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Inflammatory bowel disease (IBD) is a chronic, immune-mediated disease characterized by intestinal inflammation and extraintestinal symptoms. The chronic and fluctuating nature of the disease, as well as side effects and immunosuppression from medication regimens necessitates consistent follow-up. Current guidelines detailing proper care of these patients are often written through a highly specialized lens or provide a detailed review of a specific topic. There is limited educational material written to assist primary care providers (PCP) in caring for these complex patients. This article aims to provide a holistic, centralized, and practical reference to guide PCPs in more confidently managing preventative medicine and disease monitoring for their patients with IBD.

Inflammatory bowel disease (IBD) is a chronic, immune-mediated disease of the gastrointestinal (GI) tract that usually presents with varied symptoms including abdominal pain, diarrhea, increased stool frequency, urgency, rectal bleeding, weight loss and other extraintestinal symptoms. IBD can be further categorized into ulcerative colitis (UC), Crohn’s disease (CD), and IBD-unspecified (IBD-U). There are multiple guidelines available on how to care for patients with IBD, although limited direction for the primary care provider (PCP) audience. This article is written to provide guidance for PCPs, with a specific focus on health maintenance and prevention in patients with IBD (Table 1).

Disease Evaluation

Similar to other chronic conditions, symptom assessment and laboratory testing should be obtained at annual physical exams or in an individual, problem-directed clinic visit. Visits may include characterization of bowel frequency, consistency, urgency, rectal bleeding, abdominal pain, nausea, assessment of oral intake and evaluation of medication and substance use. However, it is important to note that symptom assessment alone cannot ensure adequate control of inflammation.

Table 1. Health Maintenance and Prevention Recommendations for Patients with Inflammatory Bowel Disease

Topic	Recommendations
DISEASE EVALUATION
Clinical symptom assessment	At every visit. Can employ clinical assessment tools such as Harvey-Bradshaw Index for Crohn’s disease and Simple Colitis Activity Index for ulcerative colitis.
Inflammation assessment	Routine blood work: CBC, CMP, CRP, iron studies, Vitamin D, Vitamin B12 (if ileal disease), fecal calprotectin.
MEDICATION REVIEW
Review of all medications and recreational substance use	At every visit. Includes but not limited to steroid use, steroid-sparing IBD therapy, analgesics, alcohol, tobacco, and cannabis use.
VACCINATIONS
Vaccination review	Review at time of diagnosis and with every subsequent visit. Patients with IBD should be up to date on all recommended vaccinations ideally prior to starting IS therapy. Please refer to Table 2 for more guidance.
CANCER PREVENTION
Cervical cancer screening	Annual for patients on thiopurines and JAK inhibitors. Q3 years with cervical cytology alone in women aged 21-29. Q5 years with HPV co-testing with cytology in women aged 30-65 years of age.
Skin cancer screening	Baseline examination for all patients with IBD. Annually, especially for patients on thiopurines and JAK inhibitors.
Colorectal cancer screening	Colonoscopy is gold-standard. Beginning 8 years after diagnosis of IBD (>1/3 colon involvement). At diagnosis of those with primary sclerosing cholangitis. Interval afterwards varies on degree of colonic inflammation and dysplastic findings on initial colonoscopy.
OTHER RECOMMENDED SCREENINGS
Bone mineral density testing	DEXA bone scanning should be completed in patients with IBD who meet any of the high-risk criteria.
Vitamin D monitoring	Annual monitoring of Vitamin D OH-25 level is recommended. Supplementation with combined calcium and vitamin D therapy is recommended in patients with vitamin D deficiency.
Mental health screening	Annual screening for anxiety and depression with PHQ-2 and GAD7 questionnaires.
FERTILITY CONSIDERATIONS
Contraceptives	Intrauterine devices are the first line for women with IBD. Increased risk of VTE for oral contraceptives but not contraindicated. Preconceptual counseling in all women with IBD.
Perimenopausal	Hormonal replacement therapy can be a safe option to reduce menopausal and IBD symptoms.
NUTRITIONAL ASSESSMENT
Evaluation of nutritional status	Reviewed at every visit [body weight, body mass index, oral intake, unintended weight loss, edema and fluid retention, fat, and muscle loss]. Patients with any signs of poor nutritional status warrant referral to dietician for further assessment.
Vitamin & mineral deficiency evaluation	Annually or more frequently if concerned for malnutrition.
Dietitian referral	Consider all patients with IBD, especially if concerned for moderate to severe malnutrition.

References: 3, 8, 13, 15, 16, 17, 21, 22, 23, 24, 28, 29 CBC- complete blood count; CMP- complete metabolic panel; CRP- C-reactive protein; DEXA- dual-energy x-ray absorptiometry; GAD7- generalized anxiety disorder 7; HPV- human papillomavirus; IBD- inflammatory bowel disease, JAK- Janus kinase; PHQ-2- patient health questionarre-2; VTE- venous thromboembolism.

Laboratory Studies

Basic labs, vitamin, and mineral levels should be monitored at least annually in patients with IBD and more frequently if active inflammation or on immunosuppressive (IS) therapy. Non-invasive biomarkers, such as serum C-reactive protein (CRP) and fecal calprotectin (FCP), are used for monitoring inflammation.¹ CRP is not specific for GI inflammation but is a useful non-invasive biomarker to monitor at baseline, for treatment response, and relapse of active inflammation.¹

FCP or fecal lactoferrin are more specific for GI inflammation or infection.^1,2 FCP is a reliable marker of intestinal inflammation and superior to CRP as a surrogate biomarker to endoscopic disease activity.¹ Like CRP, FCP can be used to monitor response to treatment, however it is noted to be more sensitive for colonic inflammation over small bowel inflammation.¹

Symptom Assessment and When to Refer to a Specialist

Patients can have chronic abdominal pain and extraintestinal symptoms which can impact quality of life. Extraintestinal symptoms are due to the pathophysiology of IBD-associated inflammation and the impact it can have on multiple organ systems. This highlights the importance of obtaining a thorough physical exam and review of systems in patients with IBD.³

As part of a detailed history, it is essential to characterize abdominal pain, including changes in bowel movement consistency or bowel frequency. Symptoms may be a sign of superimposed infection or recurrence of inflammation. In this situation, stool cultures, Clostridium difficile toxin testing, GI pathogen PCR, CRP, FCP and other infectious workup should be completed prior to initiation of corticosteroids when able.

Recommendations

Disease evaluation should be assessed at least annually (assessment for active clinical symptoms and biomarkers for inflammation). Concern for active inflammation, persistent or severe disease activity, or superimposed infection warrants prompt evaluation by a gastroenterologist or IBD specialist. Extraintestinal manifestations should trigger inflammatory workup and referral to appropriate specialist.

Medication Review And Substance Use

Analgesics

Use of nonsteroidal anti-inflammatory drugs (NSAIDs) is not recommended for patients with IBD.⁴ While there is conflicting data around NSAIDs and risk for relapse of inflammation, NSAIDs increase the risk of bleeding and ulcer development which could exacerbate anemia when used regularly.⁴

Similarly, there has been a long-standing recommendation to avoid opioid-based pain medications for chronic pain management.⁵ Despite this recommendation up to 13% of patients with IBD are prescribed chronic opioid pain medications.^5,6 Opioid use has been associated with dependency, increased risk for hospitalization, narcotic bowel syndrome, toxic megacolon (especially in active UC), and surgery in patients with IBD.⁵ This is important to note, as PCPs are usually the first to see patients post-hospitalization, some with a prescription for opioid pain medications upon discharge. It is important to collaborate with the patient and gastroenterologist to develop a non-opioid based pain regimen.^5,6

Corticosteroid Use

Patients with active inflammation are frequently started on corticosteroids to reduce symptoms and inflammation. When encountering these patients, there are several considerations including: steroid dosage, duration, and common adverse reactions. Short-term use is associated with truncal obesity, skin hyperpigmentation, acute myopathy, mood disturbances, and insomnia.⁷ Hyperglycemia, transient leukocytosis, and hypokalemia are objective findings associated with short-term corticosteroid use and should be monitored.⁷ Risks of long-term use include osteoporosis, adrenal insufficiency, exacerbation of peptic ulcer disease, glaucoma, hyperlipidemia, increased risk of infections, and death.⁷ Patients on chronic steroids should be referred to their gastroenterologist for discussion of steroid-sparing therapy.

Alcohol

Screening of unhealthy alcohol use is recommended for all patients over 18-years by the US Preventive Services Task Force (USPSTF).⁸ Alcohol is pro-inflammatory and has been associated with higher frequency of relapses of inflammation.⁶ Despite this finding, the prevalence of alcohol consumption in patients with IBD is similar to the general population.⁶

Tobacco

Tobacco use is discouraged in all individuals as there is overwhelming data incriminating tobacco use in causing cancer.⁹ In patients with IBD studies have shown that tobacco has a positive effect on UC in some patients whereas tobacco use is associated with increased inflammation and adverse events in patients with CD.⁹

Cannabis

There has been rising popularity of medical cannabis use, especially in patients with IBD.¹⁰ Although indications vary by state, CD and UC are approved indications for medical cannabis use in many states.¹⁰ Although cannabis use in patients with IBD has shown to improve clinical symptoms including abdominal pain, nausea, vomiting and diarrhea, randomized controlled trials have not shown improvement in inflammatory markers associated with IBD.^6,11There is conflicting data to suggest cannabis use may be associated with decreased analgesic use including opioid medications.⁶

Table 2. Vaccination Recommendations for Patients with Inflammatory Bowel Disease

Vaccination	Frequency	Recommendations
Inactivated Vaccines
COVID (SARS-CoV-2)	At least one dose of the current COVID-19 vaccine	All patients, including those on IS therapy.
Influenza	Annually	All patients (nasal spray contraindicated in IS patients).
Tetanus, diphtheria, and whooping cough (Tdap)	1 booster every 10 years	All patients.
Respiratory Syncytial Virus (RSV)	1 dose	All adults over 75 years of age and at-risk patients over 60 years of age.
Recombinant Zoster (Shingles)	2 doses	All adults > 50 years of age and consider in adults > 18 years old on IS .
Human Papillomavirus (HPV)	2-3 doses	All patients ages 9-26, at risk patients ages 27-45.
Pneumococcal Conjugate Vaccine (PCV) 15, 20, 21 & Pneumococcal Polysaccharide Vaccine (PPSV) 23	1-2 doses, depending on prior vaccination. See CDC website for further guidelines	All patients on IS therapy or with risk factors for pneumococcal disease. All patients age 65+.
Hepatitis A	2, 3, or 4 doses, depending on vaccine used	All adult patients.
Hepatitis B	2, 3, or 4 doses, depending on vaccine used	Check hepatitis B serologies before initiating advanced therapy. If not immune, vaccination is recommended.
Meningococcal	1 dose	All at-risk patients (military recruits or college students).
Live-attenuated Vaccines
Measles, Mumps, and Rubella (MMR)	1-2 doses	Contraindicated in immunosuppressed adults or those planning to start IS within 4 weeks.
Varicella Vaccine (Chickenpox)	2 doses	Check varicella zoster virus IgG. If negative, consider vaccination. Contraindicated in immunosuppressed adults or those planning to start IS within 4 weeks.

References: 13-16, 28, 29 COVID-19- coronavirus 2019; HPV- human papillomavirus; IgG- immunoglobulin G; IS- immunosuppression; MMR- measles, mumps, rubella; PCV- pneumococcal conjugate vaccine; PPSV- pneumococcal polysaccharide vaccine; RSV- respiratory syncytial virus; Tdap- Tetanus; diphtheria, and acellular pertussis.

Recommendations

A medication review should be done at each visit including over-the-counter treatments and alternative medications. Acetaminophen is recommended over NSAIDs as analgesic when indicated. Opioids are not recommended in patients with IBD for management of chronic pain. If patients are having symptoms severe enough to necessitate opioid treatment, further evaluation is indicated to identify etiology of pain.⁵ Recommend review and counseling on limiting alcohol use in patients with IBD.

Vaccinations

Prior vaccination history should be addressed at the time of diagnosis and reviewed annually.^12,13 All appropriate vaccinations, especially live attenuated vaccines, should be given as soon as possible to not delay immunosuppression (IS) therapy (Table 2).¹³ There is no evidence that vaccinations increase the risk for disease relapse in patients with IBD.¹³ IBD is not a contraindication to receiving inactivated vaccines, but being on IS therapy may suppress vaccination response.¹² Live-attenuated vaccines are contraindicated if patients are on IS therapy, prolonged courses of corticosteroids, or have significant protein calorie malnutrition.^12,13 Family members should be counseled on vaccinations to provide further protection.

The vaccination schedule should be followed as normal with a few special considerations; (a) The pneumococcal vaccine is recommended in individuals < 65 years of age if on IS therapy, (b) the inactivated herpes zoster vaccine is recommended in individuals <50 years of age and on a Janus kinase (JAK) inhibitor, (c) the respiratory syncytial virus (RSV) vaccination is recommended for at-risk individuals (i.e. patients with IBD) who are 60 years and older.^13-15

Cancer Prevention

Special Considerations

Cancer screening is a crucial part of annual exams and there are a few differences in patients with IBD. Contrary to the USPSTF Q3-5-year cervical cancer screening recommendation, patients on thiopurines and JAK inhibitors should undergo annual pap smears.^8,16 Similarly, patients on thiopurines and JAK inhibitors require annual skin exams.¹⁶ A skin exam is necessary for all patients, especially prior to the initiation of therapy.⁸ For colorectal cancer screening, patients with IBD (>1/3 colonic involvement) are at increased risk and often require earlier screening typically 8 years after symptom onset or diagnosis of IBD.¹⁷ Severe inflammation may obscure pre-cancerous lesions and can be associated with atypia or dysplasia on pathology; therefore, it is ideal for colorectal cancer surveillance to occur during endoscopic remission.¹⁷ Fecal occult blood test and multitarget stool DNA testing are not recommended for colon cancer screening in patients with IBD.^8,17

Recommendations

Patients with IBD should be up to date on all age-appropriate cancer screenings recommended by the USPSTF.⁸ Annual pap smears for patients on thiopurines and JAK inhibitors.^8,16Annual skin cancer screening in all adults, especially those on JAK inhibitors and thiopurines.^8,16 Colorectal cancer screening within 8-10 years after diagnosis if >1/3^rd of the colon is affected or at time of diagnosis of primary sclerosing cholangitis (PSC) with colonoscopy.¹⁷

Other Screenings

Bone Health

Osteoporosis screening with dual-energy X-ray absorptiometry (DEXA) bone density scan is recommended in women over 65-years-old or in postmenopausal women who are at increased risk.⁸For patients on >2.5mg prednisone (or prednisone equivalent) per day for >3 months, history of chronic steroid use for at least 1-year but within the past 2-years, maternal history of osteoporosis, malnourished or very thin, amenorrheic, or post-menopausal women regardless of disease statusshould undergo DEXA once off corticosteroids.^8,16 Annual assessment of Vitamin D (25-hydroxy (25-OH) Vitamin D) levels and supplementation should be started in patients found to have a vitamin D deficiency (<30 ng/mL).¹⁶

Recommendations

Osteoporosis screening in patients with IBD is recommended if risk factors are present. Annual monitoring of vitamin D 25-OH level is recommended in all patients to evaluate for vitamin D deficiency.¹⁶

Mental Health

Anxiety and depression are common in patients with IBD; in fact, depression has been associated with a more aggressive presentation of IBD.¹⁸ Symptoms can present at any time of disease, highlighting the importance of annual screening.¹⁹ Generalized anxiety disorder 7-item scale (GAD-7) and patient health questionnare-2 (PHQ-2) are validated tools that can be used to assess symptom severity.¹⁹ Selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, and tricyclic antidepressants are the most used medications for depressive and anxiety disorders. Studies have shown the use of antidepressants in patients with IBD may positively impact the course of the disease and assist with neuropathic symptom control.¹⁹

Recommendations

Annual screening for anxiety and depression is recommended for all adults.⁸ Screening is usually performed by PHQ-2 and GAD-7 surveys.⁸

Fertility and Contraception

Fertility in IBD

Women with IBD in remission without prior surgery have equivocal fertility rates to the general population.²¹ There is no evidence to suggest IBD alone or treatments decrease fertility.^21,22 Reduced fertility may be seen in patients with active disease and post-pelvic surgery due to inflammation and scarring of the fallopian tubes.^21,22 More women with IBD (17%) are voluntarily childless as compared to 6% of the general population.²¹ The fear of genetic risk of IBD in offspring is often exaggerated and can be addressed by meeting with genetic counselors.²¹

Contraceptive Recommendations

IBD is not an absolute contraindication to hormonal contraceptives, although it is important to note a few special considerations. Patients with IBD are at increased risk of venous thromboembolism (VTE) and there is insufficient data to extrapolate whether this risk is compounded by oral contraceptive (OCP) use.²² Due to this uncertainty, intrauterine devices (IUDs) are first line in women with IBD.²² Low dose hormonal therapy is still an option for women with IBD and the benefit may outweigh the risk, specifically in those with low-risk disease.²³ Depot medroxyprogesterone acetate (Depo-Provera) injections should be avoided in most patients with IBD, especially as they are at increased risk of osteopenia.²²In peri and post-menopausal women, hormonal replacement therapy is a viable option to combat menopausal symptoms and reduce IBD symptoms.²⁴

Recommendations

Annual evaluation for fertility/family planning in patients with IBD. IUDs are the first line for women with IBD. Increased risk of VTE with OCPs. Depo-Provera should be avoided in patients with increased risk of osteoporosis.²²

Nutritional Assessment

Nutritional status in patients with IBD should be evaluated at every appointment. A comprehensive assessment includes, but is not limited to, body composition, weight change, dietary intake, energy expenditure, and vitamin and mineral levels.²⁵ A multidisciplinary approach is crucial for patients with IBD, and often a dietitian referral is helpful. Malnutrition in IBD is multifactorial, due to decreased food intake, increased nutritional demand, malabsorption, maldigestion, increased losses, surgical resection and medication-induced vitamin deficiencies.²⁵ Inadequate vitamin and mineral intake (especially vitamin A, C, D, E, calcium, folate, and iron) is common in patients with IBD.²⁵ Forty percent of patients with IBD have had iron-deficiency anemia (IDA) and half of patients with IBD have vitamin D deficiency, requiring supplementation.²⁵ Treatment of IDA with IV (if active inflammation or intolerance) or oral (inactive inflammation or tolerance) administration is strongly recommended.²⁶ In serious cases where oral intake is not sufficient, patients may require enteral or parenteral nutrition.²⁵ Enteral nutrition is recommended over parenteral nutrition unless enteral nutrition has failed or there is intestinal obstruction.²⁶

Recommendations

Review nutritional status at every visit and serial testing for mineral and vitamin deficiencies is recommended.²⁵ When indicated, enteral nutrition is recommended over parenteral nutrition.²⁶

CONCLUSIONS

Historically, there is a limited role for IBD management by PCPs. This gap is exacerbated by the minimal amount of supportive education tools specific for PCPs.²⁶ IBD is a chronic disease and requires a multidisciplinary approach with the PCP on the frontline. Health maintenance visits focusing on disease evaluation, medication review, vaccination status, cancer prevention, and nutritional assessment are crucial to provide quality preventative care for patients with IBD. The aim of this paper is to empower PCPs with the tools they need to better care for these patients and encourage partnership with the patient’s treating gastroenterologist for improved multidisciplinary approach to managing the entire patient.

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NUTRITION REVIEWS IN GASTROENTEROLOGY, SERIES #24

Selenium: A Micronutrientwith a Macro-Impact

Sebastian Dobrow,

Rangesh Modi

Selenium, a naturally occurring trace element, serves many bodily functions through its role in a family of proteins called selenoproteins. The average daily intake in the United States is about 116 mcg/day, well above the recommended dietary reference intake of 55 mcg/day for adults. Thus, deficiency is rare among Americans. Deficiency can occur in areas of low environmental selenium or in disease states that impair intestinal absorption, such as short bowel syndrome or inflammatory bowel disease, and affects the cardiovascular, respiratory, immune/hematologic, gastrointestinal, reproductive, central nervous, and neuromusculoskeletal systems. This review will briefly summarize the general physiologic roles of selenium, emphasizing deficiency due to various gastrointestinal disorders, monitoring, and replenishment. A summary of recent investigations into selenium levels of those on parenteral nutrition is also provided.

Introduction

Selenium is a non-metallic trace element, named for Selene, the Greek goddess of the moon.¹ It is found naturally in foods and is widely available as a dietary supplement. In the United States (US), the most selenium-deficient areas are the Northwest, the Great Lakes region, and the Northeast and Atlantic coastal areas, particularly Florida.² Selenium is an essential component in a family of proteins called selenoproteins. There are 25 known human selenoproteins, and each helps carry out diverse functions, namely redox reactions. A few of the most well-described selenoproteins include glutathione peroxidases, thyroid hormone deiodinases, and thioredoxin reductases.^3,4

Selenoproteins function largely as antioxidants and have multiple physiologic roles. These roles include the protection of cells and DNA; supporting thyroid function, modulating inflammation, and regulating the nervous and immune systems. Selenoproteins also promote muscle (heart and skeletal), bone, and cartilage health, support male reproductive function and testosterone synthesis, assist in regulating lipid metabolism, and may even play a role in cancer prevention.^4-7

Selenoproteins Vital to Human Health

Glutathione peroxidases are a family of eight (thus far discovered) selenoproteins, abbreviated GPx1, GPx2, and so on. Each serves slightly different biological roles; however, they function primarily as antioxidants – reducing hydrogen peroxide and lipid peroxides to protect cells from oxidative stress and apoptosis.⁸ Genetic differences in genes coding these proteins have been associated with cardiovascular disorders, including coronary and peripheral vascular disease, hypertension, aneurysm, and stroke, as well as Keshan and Kashin-Beck disease, which are described below. Malignancies such as colorectal cancer, thyroid, and breast cancer have also been associated with variations in glutathione peroxidase genetics.⁹

Iodothyronine deiodinases (Dio) are selenoproteins responsible for proper thyroid function. Dio proteins are responsible for converting thyroid hormone from its inactive T4 to its active T3 form and between inactive forms (T4 to reverse T3; and T3 and reverse T3 to T2).⁹ T2 is the only form of thyroid hormone available as an over-the-counter supplement to stimulate metabolism.¹⁰ T2 supplementation is likely to cause disruption of normal thyroid hormone regulation before desired metabolic effects and is not recommended.¹⁰

Thioredoxin reductases (TrxR) are another family of redox selenoproteins with antioxidant functions that are vital to DNA synthesis. TrxR enzymes are crucial to proper cardiac cell function and appear to play a role in disease states such as familial amyotrophic lateral sclerosis (ALS, or Lou Gehrig’s Disease) and gastrointestinal cancers, among others.⁹

Other selenoproteins, including Selenoproteins P, S, N, and 15kDa selenoprotein, also have human health implications moderating the risk and progression of various cancers, fertility, and cardio- and neurovascular disease.⁹

Selenium Homeostasis – Uptake, Metabolism, and Excretion

Uptake and Metabolism

Selenium, found largely in soil, is incorporated into humans through the intake of both dietary plants and animals. Plants, especially wheat and grains, are the predominant source of selenium for humans; however, red meat, poultry, and fish represent other dietary sources.¹ Selenium uptake occurs mainly in the duodenum, proximal jejunum, and cecum.^1,4,11 Absorption occurs via various mechanisms involving both organic and inorganic forms of selenium. The organic forms, bound to amino acids such as selenomethionine (predominantly) and selenocysteine (less commonly), are more readily absorbed than inorganic forms and likely occur via active transport similar to their corresponding amino acids.¹² Several inorganic forms, predominantly selenite and selenate, are less readily bioavailable when consumed.^3,8 Selenate absorption occurs in an energy-dependent fashion, whereas selenite occurs by passive diffusion.¹² Several elements impair selenium absorption through various mechanisms, including iron (specifically in the ferric state), calcium, mercury (which may reduce selenium uptake from fish sources), sulfur, lead, and arsenic.⁴

Once absorbed, the liver takes up selenium via the portal system, where much of it is incorporated into the 10 selenocysteine residues present on the hepatically synthesized selenium transporter, selenoprotein P (SELENOP). SELENOP is secreted into plasma for delivery to the tissues.¹² Bound selenium is then taken up by receptors on target tissues for local use. It has been shown that the brain and testes uptake SELENOP via the apolipoprotein E receptor-2 (ApoER2), a low-density lipoprotein (LDL) receptor. ApoER2 is present in several other tissue types and thus may be involved in SELENOP uptake. Lipoprotein receptor megalin appears responsible for renal reuptake of SELENOP from glomerular filtrate, preventing excess selenium loss in urine.¹²

Selenium circulates in plasma bound to other liver-synthesized proteins in lesser quantities, such as albumin, alpha and beta globulins, and cholesterols, namely LDL.^4,13 Selenium storage occurs mainly in the form of selenomethionine and takes place largely in the liver and muscle (about 30% each), kidney (15%), and plasma (10%).⁴

Excretion

Selenium excretion occurs primarily through urine (with decreased excretion in low glomerular filtration states) and feces; however, losses can occur through expired air in states of excess consumption.^1,4 Breast milk contains relatively low amounts; however, levels rise with increased selenium intake.⁴

Selenium Deficiency

Signs and Symptoms

According to data from the United States National Health and Nutrition Examination Survey (NHANES) 2017-2022, the average daily dietary selenium intake is 116 mcg/day, with men taking in slightly more than women.¹⁴ Assuming adequate absorption, the average American is in a safe range.

Recent analysis of the United Kingdom Biobank data revealed a significant correlation between low dietary selenium levels and increased irritable bowel syndrome incidence.¹⁵ Mouse model studies have shown that a low selenium diet causes disturbances in the gut microbiota, characterized by an increase in Faecalibaculum and Helicobacter and a decrease in Bifidobacterium and Akkermansia.¹⁵ Lower selenium levels have also been linked to increased risk for gastric and esophageal cancers.¹⁶

As the biological roles of selenoproteins vary, so do the features of selenium deficiency. These are illustrated in Figure 1 and include:^4,7,17,18

Fatigue
Nausea, vomiting
Headache, confusion
Decreased muscle tone and neuromuscular conduction issues
Hair thinning
Nail changes (especially leukonychia)
Anemia
Male infertility
Necrotizing cardiomyopathy
Increased susceptibility to infections including, bacterial infections, progression from HIV to AIDS, COVID-19, and many others
Increased cancer susceptibility

Decreased Intake

As selenium content in foods depends largely on soil levels, individuals living in regions with low soil selenium, especially those with volcanic soil, such as regions of Europe, Russia, and China, are at risk for selenium deficiency.⁴ In the US, the most selenium-deficient areas are the Northwest, Northeast, Atlantic coastal area, Florida, and the Great Lakes. Obesity and poverty may be risk factors for low selenium levels, possibly owing to poor quality of nutritional intake.^1,5 Chronic insufficient dietary intake can result in major endemic syndromes:

Keshan disease – cardiomyopathy typically found in the Keshan region of rural China and Tibet, where the soil is volcanic and selenium deficient. Selenium supplementation has proven effective in protecting residents against the disease.¹
Kashin-Beck disease (KBD) – osteochondropathy characterized by short stature, joint deformities, and osteoarthritic changes endemic to parts of eastern Russia (Siberia), China, Tibet, and North Korea. Selenium deficiency is considered one of the major risk factors for KBD; however, fungal toxins, genetic susceptibilities, and many other factors are thought to play roles. A Chinese interventional study found that KBD rates and other bone cartilage measures improved with selenium supplementation; however, it did not prevent the disease.⁷

Impaired Absorption and Selenium Wasting

Patients with altered intestinal anatomy, including short-bowel syndrome and post-bariatric surgery, are at particular risk for selenium deficiency. Restrictive procedures such as a sleeve gastrectomy and gastric banding may reduce intake to the point of causing deficiency, while combination restrictive-malabsorptive procedures such as Roux-en-Y gastric bypass and duodenal switch result in an even higher risk of deficiency due to reduced absorptive capacity.¹¹

Other malabsorptive states, including inflammatory bowel disease (especially Crohn’s disease and celiac disease), may lead to selenium deficiency, with some studies suggesting potential use of selenium levels as a biomarker for disease activity.^19-21 Those on renal replacement therapy are also at risk for low selenium levels due to excess removal during dialysis.²² Importantly, chyle contains large amounts of selenium; chylous loss due to various conditions can lead to deficiency.²³

Table 1. Studies of Selenium Deficiency in Patients with CIF on HPN24-27

Study	Population	Study Details	Key findings
Culkin et al.24	93 adult patients on HPN for CIF Mean age (range): 54 years (21-81 years)	Retrospective cohort study (25 months long) Etiology for HPN: IBD (30%), mesenteric ischemia (25%), motility disorder (24%), surgical complication (6%), others (14%) Patients on stable micronutrient dosing for at least 6 months Excluded CRP >15 mg/L or changes in micronutrients within 6 months of study	13% patients had selenium deficiency despite standard trace elements Highest risk in patients with surgical complications
Uzzan et al.25	73 patients on HPN for CIF Mean age (range): 49 years (18-86 years)	Prospective cohort study Etiology: SBS (63%), dysmotility (23%), others (14%) Included patients needing HPN at least 8 times/month, stable formula for at least 1 month and serum trace element dosage available Excluded if no available trace element dosage or unstable HPN formula Median follow-up was 19.6 months	21.9% had selenium deficiency despite standard trace minerals No difference in deficiency risk based on anatomy type Low serum selenium associated with higher infection risk (HR 2.65, 95% CI [1.01-6.97])
Rannem et al.26	165 patients (CD, ulcerative colitis, or other GI illnesses) 27 (16%) HPN patients Mean age (range): 43 years (15-75 years)	Case control study Cases included CD (52%), UC (24%), ischemia or obstruction (9%), others (15%) Controls were 50 healthy subjects	85% of PN patients had reduced selenium vs 20% on EN 26% of CD patients had reduced selenium Strongest predictors were stool mass, vitamin B12 absorption, and small-bowel resection length
Fleming et al.27	12 patients with IF pre-PN 26 on HPN (mean 29 months) Age group not mentioned	Case control study Cases included CD (37%), non-specific SBS (18%), ischemia (10%), others (35%) Controls were 30 CD patients not on HPN and 27 healthy subjects	92% of pre-PN patients had low selenium levels (42 ng/mL) vs. controls (88 ng/mL) and Crohn’s controls (76 ng/ml) 85% of patients on HPN for 2–109 months had low selenium (mean 38.4 ng/mL)

Table 1 summarizes studies looking at selenium deficiency in patients with chronic intestinal failure (CIF) on home parenteral nutrition (HPN).^19–22 Although deficiency is rare overall in healthy adults eating a balanced diet, patients who receive the majority of their nutrition from parenteral nutrition (PN) are at the highest risk for developing selenium deficiency, irrespective of etiology. This is true despite standard trace element supplementation.

Excess Selenium

Despite its essential role in human health, chronically high selenium levels can also be toxic. Selenosis is a syndrome that can result from brittle or loss of hair and nails, GI issues, rashes, garlic-smelling breath, and nervous system dysfunction. Selenosis has been reported in China in cases of those consuming >850 mcg/day. This has influenced the recommendations for the upper tolerated range of 400 mcg/day set by the US Institute of Medicine and 300 mcg/day by the World Health Organization.¹ Patients with chronic kidney disease are particularly susceptible to selenium toxicity.

Measuring Selenium Levels

Plasma selenium levels are often measured and represent short-term status, while red blood cell levels can be used to determine longer-term status. In inflammatory states with an elevated erythrocyte sedimentation rate or C-reactive protein (CRP), interpretating plasma selenium levels becomes difficult due to the down-regulation of carrier and storage proteins. According to the European Society for Clinical Nutrition and Metabolism (ESPEN), depending on the severity of the inflammatory response, a “correction” of the value is required: CRP concentrations of 10-40, 41-80, and greater than 80 mg/L would be expected to produce falls in plasma selenium of approximately 15-25%, 35%, and 50% respectively. Normal plasma selenium levels are 110-165 mcg/L in the US, though reference ranges vary between laboratories.

Urinary selenium concentration can also be measured, and usually correlates with daily intake.²⁸ Concentration in toenails can be used to measure longer-term storage, as can hair; however, selenium content in many shampoos often limits accuracy.^1,28 Activity levels of certain selenoproteins such as glutathione peroxidase and SELENOP may also be used; however, the availability of such assays may be limited. In general, ascertaining functional selenium status may be difficult given the numerous forms and functions selenium takes on.²⁸

Repletion and Supplementation

Oral and Enteral Support

The recommended daily intake of selenium for adult men and women in the US (over 4 years) is 55 micrograms (mcg).²⁹ Pregnant women should increase their intake to about 60 mcg/day and to 70 mcg/day if lactating or breastfeeding.²⁹ Table 2 summarizes some foods rich in selenium and percent daily values (DV).³⁰

For people living in geographic regions with selenium deficient soil and water, daily supplementation of 60 -100 mcg of selenium should be sufficient to prevent deficiency. Generally, over-the-counter (OTC) selenium supplements are selenium-amino acid compounds (e.g., L-Selenomethionine or L-Selenocysteine). The supplements are available in tablet or capsule form and can be swallowed whole, crushed, or opened and sprinkled over food or liquids.

Patients with selenium deficiency from malabsorption or low dietary intake can try oral (or via enteral tube) repletion. Most OTC selenium supplements provide 200 mcg/capsule or tablet, though multi-mineral supplements range from 50-200 mcg selenium/capsule or tablet. The recommended safe, upper limit for selenium is 300-400 mcg/day for adults.¹

Table 2. Selenium Content of Selected Foods30

Food	Micrograms per serving	Percent DV (%)
Brazil nuts 1 ounce (6-8 nuts)	544	989
Tuna, yellowfin, cooked 3 ounces	92	167
Shrimp, cooked 3 ounces	42	76
Pork chop, bone-in, broiled 3 ounces	37	67
Beef steak, bottom round, roasted 3 ounces	37	67
Spaghetti, cooked 1 cup	33	60
Beef liver, pan fried 3 ounces	28	51
Cottage cheese, 1% milkfat 1 cup	20	36
Egg hard boiled 1 large	15	27
Oatmeal, cooked with 1 cup water	13	24
Baked beans 1 cup	13	24
Mushrooms, portabella, grilled ½ cup	13	24
Brown rice, cooked 1 cup	12	22

Parenteral Dosing

In the US, selenium is available in the IV form as selenious acid injection in 6 mcg/mL or 60 mcg/mL. The neonatal/pediatric trace element mixture used for body weight under 10 kg is Multrys^TM, and each vial contains 6 mcg of selenium. For children with weights above 10 kg and adults, Tralement^TM is used, which has 60 mcg of selenium in a 1 mL vial.³¹

Recommended selenium dosing in PN per the American Society for Parenteral and Enteral Nutrition (ASPEN) is:³²

2 mcg/kg for babies under 10 kg
2 mcg/kg for children with weight 10-40 kg with a maximum dose of 100 mcg
40-60 mcg for adolescents with
weight >40 kg
60-100 mcg for adults

No consensus exists for selenium repletion in states of deficiency for patients requiring enteral nutrition (EN) formulas or PN.

According to ESPEN:²²

The typical adult EN regimen containing 1500 kcal should include 50-150 mcg of selenium/day. (GRADE B*)
The typical PN regimen should include 60-100 mcg of selenium for adults. Doses of 100 mcg selenium/day, whether IV or oral (depending on absorption capacity), are usually sufficient to replenish selenium levels within 2 weeks. (GRADE B*)
Post PN initiation, selenium must be measured every 3 to 6 months along with CRP levels. (GRADE B*)
Patients with selenium levels <60 mcg/L and CRP<20 mg/L should also get additional selenium supplementation promptly; the route depends on intestinal absorption capacity, and IV is a more reliable route for rapid repletion. (No GRADE^)
Patients with selenium levels of <32 mcg/L require prompt supplementation with 100 mcg selenium/day. (No GRADE^)
Patients with selenium levels <30 mcg/L can be treated with high dose IV selenium 400 mcg/day for 7-10 days and then recheck levels. (No GRADE^)
No clear guidelines exist on rechecking selenium levels when being treated for deficiency.

*GRADE B was provided if the recommendation came from a body of evidence including well-conducted cohort or case-control studies directly applicable to the target population and demonstrating overall consistency of results or extrapolated evidence from high-quality or well-conducted studies

^No GRADE was considered as a good practice point and was provided if the guideline group found that there is an important practical point that they wish to emphasize but for which there is not, nor is there likely to be, any research evidence but only evidence from clinical experience.

Selenium in Acute Illness

Higher needs may exist in some illnesses; however, existing evidence is weak:^33,34

Burn patients with selenium losses, benefit from large IV supplies of around 375 mcg/day, with more rapid healing and fewer infections.
Patients with major trauma and cardiac surgery may similarly benefit from a supplement of 275 mcg/day.
Patients with continuous renal replacement therapy (CRRT) or intermittent hemodialysis require higher doses (60-100 mcg) in PN given losses during dialysis.^35,36 Given impaired excretion, lower doses of 40 mcg are generally used in patients with renal failure, not on CRRT.

Retrospective studies with adequate numbers of patients on home PN have shown that standard amounts of selenium in routine home PN formulas may not be sufficient for all patients to replenish selenium levels or prevent deficiencies even after several months of PN. In addition, no clear guidelines exist to point to the correct dose of selenium in patients with IF receiving PN. Most authors recommend 100 mcg/day to as high as 400 mcg/day in deficiency. However, the duration of treatment for deficiency and ideal monitoring guidelines do not exist. Lastly, it is difficult to determine if low plasma selenium levels correlate with reduced whole-body stores or at what levels a person may develop clinical signs and symptoms of selenium deficiency. Each individual is unique, and genetic polymorphisms play a key role in selenium metabolism. Hence, more research and randomized trials are required to better understand selenium supplementation, especially in patients with IF receiving long-term PN.

Conclusion

Most healthy adults in the US consume enough dietary selenium to prevent clinically relevant deficiency. Selenium is absorbed in the duodenum, jejunum, and partly in the cecum; hence altered surgical anatomy, IF, and inflammatory bowel disease are associated with an increased risk of deficiency, even when receiving PN support. While some signs and symptoms of deficiency are difficult to measure (increased risk of infection or cancer, for example), dilated cardiomyopathy is well-described in certain individuals with selenium deficiency.

For patients receiving EN or PN, an average of 60-100 mcg/day of selenium oral supplements or parenteral trace elements is usually sufficient to avoid deficiency. However, despite standard trace element dosing in home PN, patients remain at risk for selenium deficiency. Plasma selenium levels along with CRP must be monitored every 3-6 months for routine screening purposes, or sooner if the patient is being actively treated for selenium deficiency. The rising selenium cost may influence infusion, and insurance companies may reduce or omit it from PN formulations. However, given the deficiency risks, home PN providers must advocate for inclusion.

References

References
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5. Hassan Zadeh M, Mohammadi Farsani G, Zamaninour N.
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6. Labunskyy VM, Hatfield DL, Gladyshev VN. Selenoproteins:
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7. Guo X, Ma WJ, Zhang F, Ren FL, Qu CJ, Lammi MJ. Recent
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9. Rayman MP. Selenium and human health. The Lancet.
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10. Hernandez A. 3,5-diiodo-L-thyronine (t2) in dietary supplements:
what are the physiological effects? Endocrinology. 2015;156(1):5-7.
11. Gasmi A, Bjørklund G, Mujawdiya PK, et al. Micronutrients deficiences
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https://ods.od.nih.gov/factsheets/Selenium-HealthProfessional/
15. He Z, Chen H, Chen Y, et al. Selenium deficiency induces irritable
bowel syndrome: Analysis of UK Biobank data and experimental
studies in mice. Ecotoxicol Environ Saf. 2024;281:116604.
16. Hashemi SM, Mashhadi M, Moghaddam AA, et al. The Relationship
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17. Kieliszek M. Selenium. In: Advances in Food and Nutrition
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18. Yun JW, Woo YR, Kim M, Chung JH, Jung MH, Park HJ. Image
Gallery: Leukonychia induced by selenium deficiency related to
long-term parenteral nutrition in a patient with Hirschsprung disease.
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19. Stazi AV, Trinti B. [Selenium deficiency in celiac disease: risk of
autoimmune thyroid diseases]. Minerva Med. 2008;99(6):643-653.
20. Yan W, Meihao W, Zihan S, et al. Correlation Between Crohn’s
Disease Activity and Serum Selenium Concentration. Clin Ther.
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21. Chalcarz M, Grabarek BO, Sirek T, et al. Evaluation of Selenium
Concentrations in Patients with Crohn’s Disease and Ulcerative
Colitis. Biomedicines. 2024;12(10):2167.
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guideline. Clin Nutr Edinb Scotl. 2022;41(6):1357-1424.
23. de Berranger E, Colinet S, Michaud L, et al. Severe selenium deficiency
secondary to chylous loss. JPEN J Parenter Enteral Nutr.
2006;30(2):173-174.
24. Culkin A, Brundrett D, Pearson M, Gabe S. A one size vial does
not fit all: An evaluation of the micronutrient status of adult patients
receiving home parenteral nutrition (HPN). Clin Nutr ESPEN.
2023;57:676-682.
25. Uzzan M, Kirchgesner J, Poupon J, Corcos O, Pingenot I, Joly F.
Antioxidant trace elements serum levels in long-term parenteral
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a retrospective study from a tertiary home-PN center. Clin
Nutr. 2017;36(3):812-817.
26. T. Rannem KL E Hylander, J Hegnhøj, M Staun. Selenium
Depletion in Patients with Gastrointestinal Diseases: Are There
Any Predictive Factors? Scand J Gastroenterol. 1998;33(10):1057-
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Petz J. Selenium status in patients receiving home parenteral nutrition.
JPEN J Parenter Enteral Nutr. 1984;8(3):258-262.
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2025. http://archive.org/details/encyclopedia-of-food-sciences-andnutrition-
2nd-edition-10-volume-set-2003
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nal.usda.gov/
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Practice-Tool.pdf
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0044_seleniousacid_dosingguide_-019-_21jun2022.pdf
33. Berger MM, Baines M, Raffoul W, et al. Trace element supplementation
after major burns modulates antioxidant status and clinical
course by way of increased tissue trace element concentrations. Am
J Clin Nutr. 2007;85(5):1293-1300.
34. Berger MM, Soguel L, Shenkin A, et al. Influence of early antioxidant
supplements on clinical evolution and organ function in
critically ill cardiac surgery, major trauma, and subarachnoid hemorrhage
patients. Crit Care Lond Engl. 2008;12(4):R101.
35. Lumlertgul N, Cameron LK, Bear DE, Ostermann M. Micronutrient
Losses during Continuous Renal Replacement Therapy. Nephron.
2023;147(12):759-765.
36. Gómez de Oña C, Martínez-Morillo E, Gago González E, Vidau
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499.

Frontiers in Endoscopy, Series #96

Role of EUS and ERCP in Diagnosis and Management of Idiopathic Pancreatitis

Parth Patel,

Douglas G. Adler

Introduction

Gallstones/choledocholithiasis and alcohol use/abuse are the most common causes of acute pancreatitis (AP).¹ When the cause of acute pancreatitis remains unidentified despite a thorough history, physical examination, laboratory tests, review of medications, and imaging studies, it is classified as idiopathic acute pancreatitis (IAP). IAP can present in two patterns: isolated, where no recurrence occurs after an initial episode, and idiopathic acute recurrent pancreatitis (IARP). IARP is characterized by two or more episodes of IAP.² The incidence of IAP varies widely, ranging from 10%-30%; primarily due to missed diagnoses of underlying conditions that may become apparent during subsequent investigations.^2,3 With the growing understanding of etiologies and advancements in diagnostic technologies, IAP should account for no more than 20% of AP cases in any given population.⁴ The initial evaluation of IAP includes screening for alcohol use disorder, ultrasound imaging to assess for gallstones or sludge, measurement of triglyceride levels, serum immunoglobulin G4 levels, contrast enhanced computed tomography and a review of medications and recent medical procedures or interventions to identify potential iatrogenic causes.⁵ A negative initial evaluation warrants consideration for further testing such as genetic testing and advanced pancreaticobiliary imaging, including magnetic resonance cholangiopancreatography (MRCP), endoscopic ultrasound (EUS), and endoscopic retrograde cholangiopancreatography (ERCP).^5,6

Role of EUS in Diagnosis and Management of Idiopathic Pancreatitis

2.1. EUS Technology

EUS combines a flexible endoscope with a high-frequency miniature ultrasound probe at its distal end, enabling direct visualization of mucosal lesions, the gastrointestinal tract, and extramural structures. Unlike other cross-sectional imaging techniques, EUS offers a closer proximity to tissue, minimizing interference from subcutaneous tissue, bones, and gas.⁷ With advancements in technology, EUS produces high-resolution, real-time images, allowing for the assessment of minute lesions and pancreaticobiliary structures.⁸ This makes EUS one of the most important diagnostic tools for the evaluation of IAP.⁹

2.2. Timing of EUS

Guidelines recommend repeating a right upper quadrant (RUQ) ultrasound after discharge to improve the diagnostic yield in patients with presumed IAP due to microlithiasis or sludge.⁹ EUS is the next step in evaluating the etiology of IAP; however, the optimal timing for performing EUS after an episode of acute pancreatitis is uncertain and different operators may have varying opinions on this issue. Performing EUS too soon after an episode of acute pancreatitis may result in missed subtle lesions or undiagnosed CP, as residual inflammation (which reduces tissue resolution and increases artifacts) in the pancreas could obscure these findings. Additionally, ongoing inflammation may affect the safety of the procedure.^6,9 Various studies have examined different intervals for performing EUS, but most experts suggest a short delay of 2 to 6 weeks to ensure complete resolution of inflammation.^9,10 A recent single-center retrospective study evaluated the EUS appearance of pancreatic tissue at 4 and 6 weeks in patients with IAP. The study found that 84% of patients had normal-appearing pancreatic tissue at 6 weeks, compared to 73% at 4 weeks.¹¹Additionally, a higher CT severity index score at the time of diagnosis was associated with an increased likelihood of detecting inflamed pancreatic tissue during the EUS examination at 4 to 6 weeks.¹¹ Cortes et al. developed a scoring system (DORM65) using five variables, which includes delayed EUS (at least 82 days) as one of the factors, to predict positive EUS findings after an episode of IAP. A score of 3 or more was associated with a positive predictive value of 86%, with sensitivity and specificity of 35% and 92%, respectively.¹² The scoring system is not in widespread use, but can be considered.

2.3. Sensitivity and Diagnostic Accuracy of EUS

The diagnostic yield of EUS in identifying one or more potential etiologies of IAP varies widely, ranging from 32% to 88%.¹³ This variation can be attributed to several factors, including the efficacy of EUS in detecting specific etiologies (e.g., gallstones, neoplastic, or anatomical), operator expertise, and the timing of the procedure in relation to the episode of pancreatitis in question.^11,14–16 Additionally, the diagnostic yield may be influenced by whether other diagnostic evaluations were performed prior to EUS, which might have already identified the underlying cause.¹³

2.3.1. Microlithiasis and Choledocholithiasis

Microlithiasis (stones <3 mm) or larger stones could explain up to 75% presumed IAP in patients with an intact gallbladder.¹⁷ (Figures 1 and 2) Patients with a first episode of AP and/or those with an intact gallbladder have a higher likelihood of biliary microlithiasis or sludge being detected on EUS compared to patients with IARP and/or prior cholecystectomy.¹⁸ Studies have shown a significant reduction in the risk and severity of recurrent acute pancreatitis in patients who underwent cholecystectomy and removal of CBD stones, if present.^5,19

A meta-analysis of 22 studies involving 1,490 patients with IAP reported that EUS identified the etiology in 59% of cases, with biliary causes accounting for 30%. However, none of the included studies conducted the complete standard diagnostic workup as per IAP/APA guidelines prior to EUS study. This is important as repeat transabdominal ultrasound after the discharge can increase the diagnostic yield, especially when the underlying etiology is biliary lithiasis/sludge.^9,20

In a prospective study of 35 patients with biliary colic, both initial and repeat abdominal ultrasound examinations were normal or inconclusive. Subsequent EUS detected gallbladder sludge or small stones in 33 patients and common bile duct (CBD) sludge or microlithiasis in 21 patients.²¹

Compared to imaging modalities such as MRCP, EUS demonstrates a higher diagnostic yield in identifying presumed IAP due to biliary etiology, including cholelithiasis, choledocholithiasis, microlithiasis, and biliary sludge. Wan et al. reported a diagnostic yield of 34% for EUS, compared to just 9% for MRCP, in detecting biliary etiologies of IAP. ^14,15

2.3.2. Chronic Pancreatitis

Chronic pancreatitis (CP) is the second most common cause of IAP in patients with an intact gallbladder and the most common cause in those without a gallbladder.^16,20 EUS is one of the most accurate techniques for diagnosing CP, owing to its ability to position the transducer close to the pancreatic parenchyma.²² Previously unknown or unanticipated CP is identified as the underlying cause of IAP in approximately 7% to 12% of patients undergoing EUS evaluation.²³ EUS is either superior to or comparable with other diagnostic imaging modalities, such as MRCP and CT.^10,24 Early CP often involves changes in ductal side branches, sparing the main pancreatic duct (PD). Combining EUS and MRCP significantly improves sensitivity and specificity for the diagnosis of CP.²⁵

2.3.3. Neoplasia

Pancreatic neoplasms can cause AP by transiently or permanently obstructing the pancreatic or common bile duct (or both) and/or by inducing local inflammation in the pancreatic parenchyma. A retrospective study utilizing clinical and insurance claim data reported that 11% of patients experienced one or more episodes of AP within the three years preceding a diagnosis of pancreatic ductal carcinoma. On EUS, pancreatic neoplasms are identified as the underlying cause in 2% to 6% of presumed IAP cases.^4,16 Bartell et al. reported that EUS-guided fine-needle aspiration (EUS-FNA) identified pancreatic cancer in 5.3% of cases (out of 530 patients) with presumed IAP or idiopathic CP, despite negative initial CT and/or MRCP findings for a pancreatic mass lesion.²⁶

2.3.4. Pancreatic Anatomical Abnormalities

Among congenital pancreatic anomalies, pancreatic divisum is the most common.²⁷ It should be noted that many patients are told that pancreatic divisum is an illness, but it is not. Bernard et al. reported a 7.5% incidence of pancreatic divisum in a study of 1,825 ERCPs. Pancreatic divisum was significantly more frequent in patients presenting with acute idiopathic pancreatitis than in controls or the general population.²⁸ ERCP is considered the gold standard for diagnosing pancreatic divisum; however, its use is generally limited to cases where therapeutic intervention is also needed. EUS, particularly with a linear array echoendoscope, is increasingly used for diagnosis due to its higher sensitivity and lower adverse event rate compared to ERCP.²⁹ Kushnir et al. reported an 84% diagnostic sensitivity of EUS for pancreatic divisum among patients evaluated for idiopathic acute pancreatitis (58%), unexplained pancreatic-type abdominal pain (35%), and CP (7%).³⁰ A meta-analysis by Umans et al. identified pancreatic divisum as the underlying etiology of IAP in 87 out of 1,490 patients.²⁰ Less common pancreatic anomalies, such as annular pancreas, pancreaticobiliary maljunction a.k.a. anomalous pancreaticobiliary junction, and high confluence of the pancreaticobiliary ducts, have been reported as etiologies of IAP in only a few studies.^31,32 Annular pancreas is best diagnosed using cross-sectional abdominal imaging, whereas pancreaticobiliary maljunction and high confluence of the pancreaticobiliary ducts are typically identified via ERCP.³¹ Studies evaluating the sensitivity of EUS in diagnosing these anomalies are lacking.

2.4. Therapeutic Role of EUS

EUS has a limited direct therapeutic role in idiopathic pancreatitis. It facilitates ERCP in difficult cannulation through techniques like EUS-Rendezvous when ERCP alone is unsuccessful.³³ It is useful in performing celiac plexus blocks to manage chronic pain in patients with IARP progressed to CP.¹⁰ While not routinely used, interventions such as EUS-guided sphincterotomy for CBD stones and alcohol ablation of pancreatic cysts have been reported. With advancements in EUS-guided therapies, it may become possible to perform therapeutic interventions while simultaneously investigating the etiology of IAP in select cases.^10,34

Role of ERCP in Diagnosis and Management of Idiopathic Pancreatitis

ERCP has played both a diagnostic and therapeutic role in the management of IARP. Earlier studies demonstrated that ERCP-based evaluations, such as bile analysis for microcrystals, minor papilla cannulation, and sphincter of Oddi manometry, identified the underlying etiology in up to 79% of cases.³⁵ However, with the advent of high-resolution imaging techniques like EUS and MRCP, the diagnostic role of ERCP has declined, and it is now primarily used for therapeutic interventions.¹⁵

3.1 Sphincter of Oddi Dysfunction

In older studies, reflecting a different era of thinking, Sphincter of Oddi dysfunction (SOD) has been reported in 15% to 73% of patients undergoing ERCP with sphincter of Oddi manometry (SOM) for the evaluation of IARP in previous studies.³⁶ SOM was the gold standard for diagnosing SOD; however, it is invasive, carries high risks of serious adverse events and its accuracy is operator-dependent with limited inter-reader reliability. Non-invasive tests, such as secretin-stimulated MRCP (ss-MRCP), quantitative hepatic scintigraphy, and fatty meal sonography, are less sensitive compared to SOM.^36,37 In current clinical practice, the diagnosis of SOD and the practice of SOM have essentially been abandoned due to high risks, limited data showing clinical efficacy, and questions about the validity of the concept of SOD as a whole.^38,39

3.2 Microlithiasis

Due to the high diagnostic sensitivity of EUS for detecting microlithiasis, ERCP is no longer recommended for evaluating IAP suspected to be caused by microlithiasis.⁹ If transabdominal imaging and EUS fail to identify microlithiasis, bile microscopy during an ERCP may be considered but is rarely performed in practice.³⁵ The definitive treatment for microlithiasis causing recurrent AP is laparoscopic cholecystectomy to prevent recurrent pancreatitis and gallbladder related symptoms. In elderly patients or those with severe comorbidities that increase surgical risk, sphincterotomy alone can be an effective alternative. However, the role of sphincterotomy alone in preventing recurrent pancreatitis due to microlithiasis remains controversial among patients who are good surgical candidates.^40,41

3.3 Pancreatic Divisum and Annular Pancreas

ERCP is the gold standard for diagnosing pancreatic divisum; although this anatomic variant can be detected on EUS and MRI/MRCP as well.^9,42 (Figure 3) Endoscopic therapy (ERCP) is the first-line treatment for patients deemed to have true symptomatic pancreatic divisum. Previous retrospective studies have reported a 70-80% efficacy rate for endoscopic therapy in IARP patients with pancreatic divisum.³⁵ It is well established that the risk of recurrent pancreatitis is higher among pancreatic divisum patients with associated genetic mutations (the “two hit” hypothesis). Endoscopic therapy should be considered for IARP patients without any identifiable etiology other than pancreatic divisum, especially if the PD in the body and tail is dilated (suggesting obstruction at level of the duct of Santorini and/or the minor papilla).^6,9

Endoscopic techniques include minor papilla endoscopic sphincterotomy (mPES), balloon dilation, and trans-minor papilla dorsal duct stenting. mPES is well established for symptomatic pancreatic divisum and techniques to perform this maneuver include Wire-Guided Pull-Type Sphincterotomy, Needle-Knife Over Pancreatic Stent, Wire-Assisted Access Sphincterotomy, and Free-Hand Pre-Cut Needle-Knife Sphincterotomy.⁴² While mPES is effective, it is associated with a high risk of post-ERCP pancreatitis, which can be mitigated by prophylactic stenting and the use of rectal indomethacin.⁴³ Endoscopic therapy has comparable efficacy to surgical treatments, such as minor papilla sphincterotomy or sphincteroplasty, with the advantage of lower adverse event rates and mortality.⁴⁴

Annular pancreas is a rare condition and is associated with pancreatic divisum in 30-45% of cases. It commonly presents as duodenal obstruction (often in childhood) and IARP.^35,45 Gromski et al. reported a technical success rate of 91% for ERCP on the initial attempt, increasing to 100% with a second procedure when necessary.⁴⁵ Pancreaticobiliary symptoms, including recurrent pancreatitis, are frequently seen in adults and, when indicated, are effectively managed with pancreatic sphincterotomy, with or without stenting.⁴⁶

Other congenital anomalies, such as choledochocele (Type II choledochal cysts) and pancreaticobiliary maljunction, infrequently present as IARP. They are often identified on MRCP, and symptomatic cases are managed with biliary sphincterotomy.^35,47

3.4. Pancreatic Duct Strictures and Stones

Strictures in the main PD are found in 5-10% of IARP cases.³⁵ Management depends on whether the stricture is benign or malignant. Benign etiologies include chronic pancreatitis, sequelae of acute pancreatitis, pseudocyst, trauma, or surgical complications.⁴⁸ EUS-FNA/FNB is often used for diagnostic evaluation, especially when a malignant etiology is suspected. Symptomatic benign PD strictures, such as those causing recurrent acute pancreatitis, are treated with PD sphincterotomy, stricture dilation, and stenting using plastic or metal stents.⁴⁸

PD stones are recognized as a cause of recurrent pancreatitis, which can progress to chronic pancreatitis. Floating PD stones <5 mm can be extracted using standard ERCP with pancreatic sphincterotomy, followed by balloon or basket retrieval. Larger stones may be more difficult to remove and may fail standard retrieval techniques.⁹ PD stones are typically harder to fracture than biliary stones, lowering success rates for ERCP-directed lithotripsy. Pancreatoscopy-directed lithotripsy, however, has shown greater success and is increasingly used for managing PD stones. Extracorporeal shockwave lithotripsy (ESWL) is not available at most centers but can help fragment stones prior to ERCP to increase clearance rates.^9,49

3.5 Role of Empiric Sphincterotomy

Empiric sphincterotomy (ES) is defined as biliary or pancreatic sphincterotomy based on clinical suspicion without definitive evidence of obstructive etiology, aimed at preventing IARP or recurrent biliary pain from presumed choledocholithiasis/microlithiasis. (Figure 4) The role of ES in preventing recurrent pancreatitis in patients with standard pancreatic ductal anatomy remains controversial.⁹ It has not been shown to reduce the frequency of recurrent acute pancreatitis episodes or alter the natural history of IARP.⁵⁰ ES is a reasonable alternative for patients at high risk for cholecystectomy, particularly when there is concern about future stone passage. ES should be considered after a discussion of its benefits and potential procedure-related risks. If performed, ERCP with biliary sphincterotomy alone may be preferable to dual sphincterotomy.

Conclusion

Increasing accessibility and continuous advancements in EUS technology have significantly improved the identification of the etiology of acute pancreatitis in cases initially considered idiopathic. The sensitivity and diagnostic accuracy of EUS often surpass traditional cross sectional imaging modalities like CT and MRI/MRCP. While primarily therapeutic, ERCP remains the gold standard for diagnosing and managing pancreaticobiliary anatomic abnormalities. Current diagnostic algorithms for IARP incorporate early EUS to effectively identify common etiologies such as microlithiasis and neoplasia. Future studies should focus on exploring the role of EUS in diagnosing pancreaticobiliary anatomical abnormalities. Optimizing the timing of EUS and ensuring careful patient selection for ERCP are crucial for enhancing diagnostic yield and minimizing complications among IARP patients.

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14. Safari MT, Miri MB, Ebadi S, Shahrokh S, Alizadeh AHM. Comparing the Roles of EUS, ERCP and MRCP in Idiopathic Acute Recurrent Pancreatitis. Clin Med Insights Gastroenterol. 2016;9:35-39. doi:10.4137/CGast.S37927

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21. Mirbagheri SA, Mohamadnejad M, Nasiri J, Vahid AA, Ghadimi R, Malekzadeh R. Prospective Evaluation of Endoscopic Ultrasonography in the Diagnosis of Biliary Microlithiasis in Patients With Normal Transabdominal Ultrasonography. J Gastrointest Surg. 2005;9(7):961-964. doi:10.1016/j.gassur.2005.03.002

22. Irisawa A, Katakura K, Ohira H, et al. Usefulness of endoscopic ultrasound to diagnose the severity of chronic pancreatitis. J Gastroenterol. 2007;42(17):90-94. doi:10.1007/s00535-006-1916-9

23. Aronen A, Guilabert L, Hadi A, et al. Idiopathic acute pancreatitis (IAP)—a review of the literature and algorithm proposed for the diagnostic work-up of IAP. Transl Gastroenterol Hepatol. 2024;9:71. doi:10.21037/tgh-23-125

24. Issa Y, Kempeneers MA, van Santvoort HC, Bollen TL, Bipat S, Boermeester MA. Diagnostic performance of imaging modalities in chronic pancreatitis: a systematic review and meta-analysis. Eur Radiol. 2017;27(9):3820-3844. doi:10.1007/s00330-016-4720-9

25. Ito T, Ikeura T, Tanaka T, et al. Magnetic resonance cholangiopancreatography findings in early chronic pancreatitis diagnosed according to the Japanese Diagnostic Criteria. Pancreatology. 2020;20(4):596-601. doi:10.1016/j.pan.2020.04.008

26. Bartell N, Bittner K, Vetter MS, Kothari T, Kaul V, Kothari S. Role of Endoscopic Ultrasound in Detecting Pancreatic Cancer Missed on Cross-Sectional Imaging in Patients Presenting with Pancreatitis: A Retrospective Review. Dig Dis Sci. 2019;64(12):3623-3629. doi:10.1007/s10620-019-05807-z

27. V SK, Sangu P, C K, R P, Chidambaranathan S, Lakshmanamoorthy NBO. Congenital Anomalies of the Pancreas: Various Clinical Manifestations and Their Impact on Pancreatic Diseases and Outcomes. Cureus. 2022;14(8):e27915. doi:10.7759/cureus.27915

28. Jp B, J S, M G, H S. Pancreas divisum is a probable cause of acute pancreatitis: a report of 137 cases. Pancreas. 1990;5(3). doi:10.1097/00006676-199005000-00002

29. Sahakian AB, Aslanian HR. Diagnosis of Pancreas Divisum Using Linear-Array Endosonography. Video J Encycl GI Endosc. 2014;2(1):36-39. doi:10.1016/j.vjgien.2013.11.001

30. Kushnir VM, Wani SB, Fowler K, et al. SENSITIVITY OF ENDOSCOPIC ULTRASOUND, MULTIDETECTOR COMPUTER TOMOGRAPHY AND MAGNETIC RESONANCE CHOLANGIOPANCREATOGRAPHY IN THE DIAGNOSIS OF PANCREAS DIVISUM: A TERTIARY CENTER EXPERIENCE. Pancreas. 2013;42(3):436. doi:10.1097/MPA.0b013e31826c711a

31. Takuma K, Kamisawa T, Hara S, et al. Etiology of recurrent acute pancreatitis, with special emphasis on pancreaticobiliary malformation. Adv Med Sci. 2012;57(2):244-250. doi:10.2478/v10039-012-0041-7

32. Huddleston VS, Lippuner V, Dyer AW. Annular Pancreas in an Adult Presenting with Acute Pancreatitis. J Radiol Case Rep. 2018;12(10):11-16. doi:10.3941/jrcr.v12i10.3461

33. Tsuchiya T, Itoi T, Sofuni A, Tonozuka R, Mukai S. Endoscopic ultrasonography-guided rendezvous technique. Dig Endosc Off J Jpn Gastroenterol Endosc Soc. 2016;28 Suppl 1:96-101. doi:10.1111/den.12611

34. Artifon ELA, Kumar A, Eloubeidi MA, et al. Prospective randomized trial of EUS versus ERCP-guided common bile duct stone removal: an interim report (with video). Gastrointest Endosc. 2009;69(2):238-243. doi:10.1016/j.gie.2008.05.020

35. MD PS, MD UN. Role of ERCP in Patients With Idiopathic Recurrent Acute Pancreatitis. Curr Treat Options Gastroenterol. 2016;14(3):327-339. doi:10.1007/s11938-016-0096-9

36. McLoughlin M, Mitchell R. Sphincter of Oddi dysfunction and pancreatitis. World J Gastroenterol WJG. 2007;13(47):6333-6343. doi:10.3748/wjg.v13.i47.6333

37. Villavicencio Kim J, Wu GY. Update on Sphincter of Oddi Dysfunction: A Review. J Clin Transl Hepatol. 2022;10(3):515-521. doi:10.14218/JCTH.2021.00167

38. Cotton PB, Durkalski V, Romagnuolo J, et al. Effect of endoscopic sphincterotomy for suspected sphincter of Oddi dysfunction on pain-related disability following cholecystectomy: the EPISOD randomized clinical trial. JAMA. 2014;311(20):2101-2109. doi:10.1001/jama.2014.5220

39. López-Cossio JA, Murcio-Pérez E, López Arce-Ángeles G, Borjas-Almaguer OD, Téllez-Ávila FI. The efficacy and safety of endoscopic sphincterotomy in patients with Sphincter of Oddi dysfunction: a systematic review and meta-analysis. Surg Endosc. 2023;37(12):9062-9069. doi:10.1007/s00464-023-10539-3

40. Wang HH, Portincasa P, Liu M, Tso P, Wang DQH. Similarities and differences between biliary sludge and microlithiasis: Their clinical and pathophysiological significances. Liver Res. 2018;2(4):186-199. doi:10.1016/j.livres.2018.10.001

41. Levy MJ. The hunt for microlithiasis in idiopathic acute recurrent pancreatitis: Should we abandon the search or intensify our efforts? Gastrointest Endosc. 2002;55(2):286-293. doi:10.1067/mge.2002.121224

42. Gutta A, Fogel E, Sherman S. Identification and Management of Pancreas Divisum. Expert Rev Gastroenterol Hepatol. 2019;13(11):1089-1105. doi:10.1080/17474124.2019.1685871

43. Moffatt DC, Coté GA, Avula H, et al. Risk factors for ERCP-related complications in patients with pancreas divisum: a retrospective study. Gastrointest Endosc. 2011;73(5):963-970. doi:10.1016/j.gie.2010.12.035

44. Liao Z, Gao R, Wang W, et al. A systematic review on endoscopic detection rate, endotherapy, and surgery for pancreas divisum. Endoscopy. 2009;41:439-444. doi:10.1055/s-0029-1214505

45. Gromski MA, Lehman GA, Zyromski NJ, et al. Annular pancreas: endoscopic and pancreatographic findings from a tertiary referral ERCP center. Gastrointest Endosc. 2019;89(2):322-328. doi:10.1016/j.gie.2018.09.008

46. Zyromski NJ, Sandoval JA, Pitt HA, et al. Annular Pancreas: Dramatic Differences Between Children and Adults. J Am Coll Surg. 2008;206(5):1019-1025. doi:10.1016/j.jamcollsurg.2007.12.009

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48. Dawod E, Kahaleh M. Management of Benign and Malignant Pancreatic Duct Strictures. Clin Endosc. 2017;51(2):156-160. doi:10.5946/ce.2017.085

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50. Das R, Clarke B, Tang G, et al. Endoscopic sphincterotomy (ES) may not alter the natural history of idiopathic recurrent acute pancreatitis (IRAP). Pancreatology. 2016;16(5):770-777. doi:10.1016/j.pan.2016.07.009

FELLOWS’ CORNER

Superior Mesenteric Artery Syndrome

by Archit Garg, Lara Calegari

A 35-year-old Hispanic woman, who had endometriosis surgery in 2018, experienced worsening epigastric pain, severe nausea, vomiting, and diarrhea for one day. The patient had no history of prior episodes, personal or family history of IBS, IBD, or cancers. Over four months, she experienced unintentional 25-pound weight loss, poor appetite causing her to stop eating early, and significant emotional distress after losing her job and getting divorced. Her symptoms consisted of severe, diffuse abdominal pain aggravated by recumbency, with temporary relief following emesis. Although she had no fever, sick contacts, or recent travel, she did report chills. On physical examination, the abdomen was distended and mildly tender to the touch. Laboratory findings indicated leukocytosis in the absence of bandemia. Please see the abdominal CT scan in the Figure 1 and 2.

Question 1: Which of the Following Diagnoses is Most Likely in this Case?

A) Celiac disease

B) Superior mesenteric artery syndrome

C) Crohn’s disease

D) Lactose Intolerance

The Correct answer is B.

Explanations:

This patient’s symptoms strongly suggest Superior Mesenteric Artery (SMA) syndrome. Rapid, substantial weight loss may cause the retroperitoneal fat pad and connective tissue to shrink, narrowing the angle of the aorta and superior mesenteric artery. This anatomical alteration may later lead to duodenal blockage.

Duodenal dilation proximally, with contrast unable to pass the duodenum’s third part (usually at a defined point of obstruction), is a diagnostic criterion. Typically, CT scans, the most sensitive diagnostic method, will show an aorto-superior mesenteric artery angle less than 25° and an aortomesenteric distance under 8 mm.

Option A:

Celiac disease, an autoimmune disorder, triggers an immune response when gluten is consumed. Celiac disease’s typical symptoms—chronic diarrhea, bloating, and malabsorption—don’t explain this patient’s sudden onset of cramps, pain, nausea, vomiting, and diarrhea. A CT scan won’t diagnose celiac disease. Confirmation requires serological testing (for anti-gluten, anti-gliadin, and anti-endomysial antibodies) plus a small intestine biopsy to look for villous atrophy.

Option C:

Characterized by chronic diarrhea, abdominal pain, fatigue, weight loss, and alternating relapses and remissions, Crohn’s disease is a chronic inflammatory disorder of the gastrointestinal tract.

Option D:

A lactase enzyme deficiency, which is characteristic of lactose intolerance, prevents the breakdown of complex carbohydrates present in food. Bloating, diarrhea, and abdominal discomfort are common after dairy consumption for those with lactose intolerance. Lactose intolerance shows unremarkable CT imaging, in contrast to SMA syndrome, where the aorto-SMA angle is reduced.

Conclusion

Characterized by duodenal compression from the SMA and aorta, SMA syndrome is a rare gastrointestinal disorder causing nausea, vomiting, positional abdominal pain, and weight loss. Diagnosis rests on CT or MRI imaging showing compression of the duodenum due to a narrowed aorto-SMA angle. Severe cases may necessitate surgery; otherwise, treatment is supportive.

Question 2:
What is the pathogenesis of this entity?

SMA syndrome is a potential complication in patients experiencing rapid weight loss due to various factors such as burns, prolonged immobility, bariatric surgery, cancer, or aortic aneurysm. The loss of retroperitoneal fat and connective tissue due to a sharp decrease in weight can narrow the aortomesenteric angle, potentially causing duodenal obstruction.¹

Question 3: How do you make the diagnosis?

The diagnosis of SMA syndrome is confirmed with imaging. Contrast imaging studies, either barium studies or CT imaging with oral contrast, can be used. A diagnostic criterion includes proximal duodenal enlargement and contrast medium inability to pass the third part of the duodenum, showing a specific blockage. An aorto-superior mesenteric artery angle under 25° is the best diagnostic indicator, especially when the aortomesenteric distance is below 8 mm.²

Question 4: What is the Management?

SMA syndrome treatment depends on the individual patient. It can be managed conservatively with emphasis given on weight gain. To relieve duodenal pressure, a nasogastric tube can be used to empty the stomach and duodenum. Treatment starts with high-calorie nutritional drinks and a special diet.³ Tube feeding or total parenteral nutrition may be used if needed. Postural therapy, using a left lateral position, helps avoid duodenal compression from the superior mesenteric artery and aorta. Surgery is needed when conservative management proves ineffective.³
This could be gastrojejunostomy, transabdominal or laparoscopic duodenojejunostomy, or a more involved procedure.

References

1. Mathenge N, Osiro S, Rodriguez II, et al. Superior mesenteric artery syndrome and its associated gastrointestinal implications. Clin Anat. 2014;27(8):1244-1252.

2. Neri S, Signorelli SS, Mondati E, et al. Ultrasound imaging in diagnosis of superior mesenteric artery syndrome. J Intern Med. 2005;257(4):346-351.

3. Oka A, Awoniyi M, Hasegawa N, et al. Superior mesenteric artery syndrome: Diagnosis and management. World J Clin Cases. 2023;11(15):3369.

Dispatches from the GUILD Conference, Series #68

Eosinophilic Esophagitis: Tips for the Primary Care Provider

Evan S. Dellon

Eosinophilic esophagitis (EoE) is a chronic allergic clinicopathologic condition with a rapidly increasing incidence and prevalence and is being increasingly seen in both specialty and primary care settings. Left untreated, EoE progresses from an inflammation-predominant to fibrostenotic condition in most patients. Diagnosis requires a combination of clinical symptoms, esophageal eosinophilia on biopsies obtained during upper endoscopy, and exclusion of other potential causes of eosinophilia. Treatments include dietary elimination, medications (proton pump inhibitors, swallowed/topical steroids, or biologics), and esophageal dilation (when strictures are present). Long-term therapy and monitoring are also required. This review discusses how commonly EoE is seen in the primary care setting, when to suspect a diagnosis of EoE, how EoE is treated, and how primary and specialty care can intersect management of this chronic disease; practical tips for the primary care provider are also presented.

Introduction

Eosinophilic esophagitis (EoE), a chronic allergic condition first described about three decades ago, has transitioned from a rare and case-reportable disease to one that is being increasingly seen, not just in gastroenterology and allergy specialty settings, but in the primary care setting as well. EoE is defined as a clinicopathologic disease, meaning that diagnosis requires both clinical symptoms and the presence of esophageal eosinophilia.¹ Similar to asthma and atopic dermatitis, EoE is a type 2 inflammatory condition, and the current pathogenic model holds that food or environmental allergens interact with an impaired esophageal epithelial barrier, which then triggers a T-cell mediated cascade of typical allergic cytokines and mediators resulting in accumulation of eosinophils and mast cells in the esophagus, activation of fibroblasts, and esophageal remodeling.² Left untreated, EoE will progress from an inflammation-predominant to fibrostenotic condition in most patients, with complications including food impaction, esophageal stricture, and, in children, poor growth and nutrition.³ There are multiple treatment options for EoE, with more in the drug development pipeline, and patients require long-term therapy and monitoring. This review will discuss how commonly EoE is seen in the primary care setting, when to suspect a diagnosis of EoE, how EoE is treated and how primary and specialty care can intersect management of this chronic disease. It also presents practical tips for the primary care provider. (Table 1)

How Commonly is EoE Seen in Primary Practice Settings?

The incidence of EoE has been rising at a rate that outpaces increases in awareness and frequency of performing endoscopy and biopsy, suggesting ongoing environmental changes are driving this disease.³ Because the condition is chronic and does not increase mortality, prevalence has been rapidly rising as well. Fifteen years ago, the prevalence was ~1/2000, but the most recent estimates are 1/700 with almost a half million diagnosed cases in the U.S.⁴ However, this might only be the tip of the iceberg, as recent studies suggest there is likely a large undiagnosed EoE patient population that could double to triple the current prevalence,⁵ as well as a long delay between symptom onset and diagnosis.⁶

The implication of this rising prevalence is that primary care providers will see known EoE patients in clinic as well as symptomatic patients who may yet to be diagnosed. In addition, the prevalence of EoE is quite a bit higher in certain populations.³ For patients undergoing upper endoscopy (EGD) for any reason (including open access referrals), the prevalence may be ~5%; for those undergoing EGD for dysphagia, the prevalence could be as high as 20-25%; for those who have a food impaction and require an emergency department visit, the prevalence is >50%. Additionally, patients with other atopic conditions have an increased prevalence of EoE as well,⁷ and this can be an important clue when considering EoE diagnosis, as below.

When Should Primary Providers Suspect EoE as a Diagnosis?

The symptoms of EoE are not pathognomonic, which can make diagnosis challenging. In adolescents and adults, dysphagia is the hallmark symptom. However, many patients may not realize or report they are having trouble swallowing (outside of an overt food impaction) because symptom onset can be slow in EoE, and patients can subconsciously adapt their eating behaviors to minimize symptoms. This is highlighted by the “IMPACT” acronym,⁸ where they “Imbibe” a lot of fluids while eating to help food go down; “Modify” foods by cutting into small pieces, lubricating foods, or pureeing; “Prolong” meal times by eating slowly or are the last one at the table; “Avoid” foods that might get stuck; “Chew” excessively to make food mushy and easy to swallow; or “Turn away” tablets or pills, as not being able to swallow pills or having pills stick is a subtle but common symptom. Therefore, for patients with reported or suspected dysphagia, asking specifically about the IMPACT symptoms can increase the suspicion for EoE, highlight a substantial burden of symptoms, and facilitate diagnosis. Other symptoms in adolescents and adults can include atypical chest pain and heartburn which is often unresponsive to antiacid therapy. Prior to referring a patient with refractory gastroesophageal reflux disease (GERD) for anti-reflux surgery, EoE should be excluded as it is a cause of refractory reflux symptoms in a few percent of patients.³ For children, symptoms are also non-specific. Infants and toddlers can have failure-to-thrive and poor growth or feeding difficulties such as failure to progress with consistencies. In school age children, abdominal pain and vomiting are common, and it is important to distinguish if vomiting is “true” vomiting or a manifestation of regurgitation of food stuck in the esophagus. Symptoms of chest pain, reflux, and heartburn can also be seen in this age group.

While EoE is on the differential diagnosis for all of these symptoms, what can increase the suspicion of EoE on a practical basis? First, if a patient has concomitant atopic conditions, such as asthma, eczema, immediate type (IgE-mediated) food allergies, or allergic rhinitis, in the presence of upper GI symptoms (or feeding issues for younger children), EoE should rise on the differential diagnosis. This is because there is a marked increase of EoE in patients with atopic disease.⁷ For example, 5% of children with food allergies can have EoE,⁹ and the more atopic conditions in one patient, the higher the chance of EoE (>10% with 3 or more allergic diseases).¹⁰ Similarly, if a patient has reported food impaction, then EoE should be suspected. While the general perception is that EoE is more common in younger patients, and in white males, it can affect patients of any age, sex, race, or ethnicity.³ Predictive models have been developed for both adults and children,^11,12 and an online calculator is available for adults to help understand the potential for EoE in a given patient (https://gicenter.med.unc.edu/cedas/index.php?page=CtrlNewEOE&action=showNewEOE).

How is EoE Diagnosed?

In order to diagnose EoE, a patient needs to have appropriate symptoms (as discussed above), at least 15 eosinophils per high-power field (eos/hpf) on esophageal biopsy obtained during upper endoscopy, and no other conditions that could cause esophageal eosinophilia.¹ Therefore, EGD with biopsy is currently required for EoE diagnosis; there are no non-invasive methods currently available. In the primary care setting, when EoE is suspected, referral to a gastroenterologist or for open access endoscopy should be made. In addition, the suspicion of EoE should be specifically mentioned. For open access endoscopy, while it is guideline-recommended to obtain esophageal biopsies for procedures done for an indication of dysphagia,¹³ if there are less typical symptoms, biopsies may not always be taken and a diagnosis could be missed. When a gastroenterologist performs an upper endoscopy and EoE is suspected, the key endoscopic findings of EoE, though not part of the diagnostic criteria, will increase the possibility of the diagnosis.¹⁴ These include esophageal edema (decreased vascularity), fixed rings, exudates (white plaques), furrows (longitudinal lines), stricture, narrowing, or crepe-paper mucosa (a sign of mucosal fragility). (Figure 1) It is recommended that the most common findings (edema, rings, exudates, furrows, and stricture) are reported using the EoE Endoscopic Reference Score (EREFS),¹⁵ which typically ranges 0-9 with higher scores indicating more severe findings, and which can be followed in addition to biopsy results to track treatment response. Once EoE is diagnosed, initial management is usually done by the gastroenterologist or an allergist. The diagnosis may also be suspected by an allergist, and an allergist is important to help manage the concomitant allergic conditions associated with EoE.

Table 1. Tips For Primary Care Providers Related to Eosinophilic Esophagitis

Tip	Rationale
Expect to see patients with EoE as it is no longer a rare disease	The incidence and prevalence of EoE continue to rapidly rise
Ask about more than trouble swallowing	Patients will often modify their eating with adaptive strategies, which can be highlighted on history by asking about the “IMPACT” behaviors
Think about EoE in patients with allergic conditions and upper GI symptoms	EoE is more common in patients with allergic conditions than in the general population, and the more allergic conditions that are present, the more likely a diagnosis of EoE will be
Consider whether a report of an “allergic reaction” to a food might be due to a transient food impaction	Patients may interpret food getting stuck (with associated discomfort, hypersalivation, and perceived trouble breathing or anxiety) as an allergic reaction, when in fact it is a sign of EoE
Refer to a gastroenterologist for upper endoscopy and biopsy to diagnose EoE	While diagnosis requires the correct clinical symptoms, it also requires demonstration of esophageal eosinophilia (at least 15 eos/hpf), which requires upper endoscopy and biopsy for assessment
Refer to an allergist for management of multiple concomitant atopic conditions	Concomitant atopic conditions are seen in 60-80% of patients with EoE, and allergists are key members of the multidisciplinary team required for optimal EoE management
Assess disease activity by considering multiple domains including symptoms, endoscopic features, and histologic findings	It is not sufficient to monitor symptoms alone in EoE, as symptoms are often discordant with biologic disease activity noted on endoscopy and histology, so all three domains should be assessed
Some topical steroid treatments for EoE adapt asthma preparation and might appear to duplicate other medications on patients’ medication lists	Budesonide and fluticasone have traditionally been swallowed (rather than inhaled from asthma devices), and at different doses than used for asthma; while there is an FDA-approved budesonide now available for EoE, it is important to assess EoE medications (which also include PPIs and dupilumab) to make sure the dosing and use is correct for a given indication

How is EoE Treated?

Goals of EoE treatment are to decrease symptoms, improve endoscopic and histologic findings, normalize growth and nutrition, and prevent complications such as esophageal stricture, food impaction, and esophageal perforation. Guidelines recommend a treatment approach where an anti-inflammatory option is paired with esophageal dilation of strictures, when they are present and cause dysphagia.¹⁶ Initial anti-inflammatory options include pharmacologic and dietary therapies, and a shared decision-making framework is recommended for a patient to select a treatment. Dietary elimination is based on food allergens causing EoE in the majority of patients.¹⁷ However, because current allergy tests (e.g. skin prick, blood IgE or IgG testing) do not correlate with food triggers in EoE, performing these is not recommended.¹⁶ Instead, an empiric elimination diet that removes the most common food triggers of EoE is the first step. These can be less restrictive (removing dairy only, or dairy and wheat), or more restrictive depending on patient preference.¹⁷ Initial medication options include proton pump inhibitors (PPIs) and topical or swallowed corticosteroids (tCS). Though off-label, PPIs are effective in ~30-40% of patients and work via non-acid-dependent mechanisms, so it is important to explain to patients that they are not using them for the typical GERD indication.¹⁸ tCS coat the esophagus to provide a local effect, and are effective in 50-70% of patients.¹⁹ Traditionally, budesonide or fluticasone asthma preparations were modified to be swallowed off-label, but recently a budesonide oral suspension has been FDA-approved for treatment of EoE.²⁰ For patients who do not respond to these medications, the FDA-approved biologic dupilumab²¹ can be considered as step-up therapy in most cases; in some patients with severe atopic conditions that would warrant dupilumab use, the medication can be considered earlier in the treatment algorithm.¹⁶

How is EoE Managed Long-Term and How Does this Intersect with Primary Care?

After an initial treatment is selected, repeat upper endoscopy and biopsy should be performed to assess response.¹⁶ If there is no response to first-line therapy, treatment can be switched or escalated and then endoscopy is repeated. When a response is achieved, and the goal is improvement across symptom, endoscopic, and histologic domains, the treatment should be maintained long term.²² Data from multiple sources demonstrate that when treatment is stopped in EoE the disease activity universally recurs, with many patients flaring as soon as three months. In addition, in contrast to some other atopic diseases, patients do not “grow out of EoE”.²²

Long-term EoE care, while often requiring GI or allergist input and monitoring, may overlap with the primary care setting. When patients with EoE come to clinic, it is important to know what medications or diet elimination they are on and what the rationale is for each treatment so adherence can be assessed and refills provided if necessary. For diet, the distinction between food elimination for EoE and food elimination for an immediate-type food allergy is important. In the latter case, foods cannot be added and any amount can trigger a severe reaction; in EoE, strict elimination is needed for disease control, but inadvertent exposure to a food trigger will not cause immediate harm. Further, because some medications like PPIs, budesonide, and dupilumab have multiple uses and doses differ across diseases, it is important to understand which is being used for EoE, whether it is at the appropriate dose, and whether it is doing “double duty” for a different condition. Finally, EoE is often managed in a multidisciplinary way, with allergists, gastroenterologists, pathologists, dieticians, feeding therapists, psychologists, and others contributing to care, and this group, which is typically not in the same clinic, can be coordinated by the primary provider.

Conclusions

EoE is a chronic allergy/inflammatory condition of the esophagus that is rapidly rising in incidence and prevalence and is still likely underdiagnosed. A primary care provider will therefore encounter an increasing number of patients with established EoE as well as patients with symptoms suggestive of EoE, and can play a major role in facilitating diagnosis. Situations that can increase the suspicion of EoE in clinic go beyond typical adolescent/adult symptoms of dysphagia and food impactions, to the “IMPACT” adaptive eating behaviors, and to patients with atopic conditions who also have upper GI symptoms. Prompt referral to GI for endoscopy and biopsy, with specific mention of the concern for EoE, is needed for timely diagnosis. While the initial treatment and monitoring of EoE are often performed by GI and allergy, long-term monitoring and reinforcement of appropriate treatment strategies can also be achieved in the primary care setting.

References

1. Dellon ES, Liacouras CA, Molina-Infante J, et al. Updated international consensus diagnostic criteria for eosinophilic esophagitis: Proceedings of the AGREE conference. Gastroenterology. 2018;155:1022-33.e10. Epub 2018/07/17.

2. Kennedy KV, Muir AB, Ruffner MA. Pathophysiology of Eosinophilic Esophagitis. Immunol Allergy Clin North Am. 2024;44(2):119-28. Epub 2024/04/05.

3. Dellon ES, Hirano I. Epidemiology and Natural History of Eosinophilic Esophagitis. Gastroenterology. 2018;154:319-22.e3. Epub 2017/08/05.

4. Thel HL, Anderson C, Xue AZ, et al. Prevalence and Costs of Eosinophilic Esophagitis in the United States. Clin Gastroenterol Hepatol. 2024. Epub 2024/11/02 23:12.

5. Lam AY, Lee JK, Coward S, et al. Epidemiologic Burden and Projections for Eosinophilic Esophagitis-Associated Emergency Department Visits in the United States: 2009-2030. Clin Gastroenterol Hepatol. 2023. Epub 2023/05/11.

6. Reed CC, Koutlas NT, Robey BS, et al. Prolonged Time to Diagnosis of Eosinophilic Esophagitis Despite Increasing Knowledge of the Disease. Clin Gastroenterol Hepatol. 2018;16(10):1667-9. Epub 2018/01/29.

7. Weir AA, Iweala OI, Dellon ES. High prevalence of eosinophilic gastrointestinal disorders in patients with atopic disease. Ann Allergy Asthma Immunol. 2024. Epub 2024/12/10.

8. Hirano I, Furuta GT. Approaches and Challenges to Management of Pediatric and Adult Patients With Eosinophilic Esophagitis. Gastroenterology. 2020;158(4):840-51. Epub 2019/12/15.

9. Hill DA, Dudley JW, Spergel JM. The Prevalence of Eosinophilic Esophagitis in Pediatric Patients with IgE-Mediated Food Allergy. J Allergy Clin Immunol Pract. 2017;5(369-375). Epub 2017/01/04.

10. Hill DA, Grundmeier RW, Ramos M, et al. Eosinophilic Esophagitis Is a Late Manifestation of the Allergic March. J Allergy Clin Immunol Pract. 2018;6(5):1528-33. Epub 2018/06/30.

11. Cotton CC, Betancourt R, Randall C, et al. A Model Using Clinical and Endoscopic Characteristics Identifies Patients at Risk for Eosinophilic Esophagitis According to Updated Diagnostic Guidelines. Clin Gastroenterol Hepatol. 2021;19:1824-34.e2. Epub 2020/07/08.

12. Borinsky SA, Miller TL, Dellon ES. A clinical predictive model identifies pediatric patients at risk for eosinophilic esophagitis. Dig Liver Dis. 2024;56(12):2045-51. Epub 2024/07/08.

13. Aceves SS, Alexander JA, Baron TH, et al. Endoscopic approach to eosinophilic esophagitis: American Society for Gastrointestinal Endoscopy Consensus Conference. Gastrointest Endosc. 2022;96(4):576-92.e1. Epub 2022/08/15.

14. Kim HP, Vance RB, Shaheen NJ, et al. The Prevalence and Diagnostic Utility of Endoscopic Features of Eosinophilic Esophagitis: A Meta-Analysis. Clin Gastroenterol Hepatol. 2012;10:988-96.e5.

15. Hirano I, Moy N, Heckman MG, et al. Endoscopic assessment of the oesophageal features of eosinophilic oesophagitis: validation of a novel classification and grading system. Gut. 2013;62:489-95. Epub 2012/05/24.

16. Dellon ES, Muir AB, Katzka DA, et al. ACG Clinical Guideline: Diagnosis and Management of Eosinophilic Esophagitis. Am J Gastroenterol. In press, 2025.

17. Chang JW, Kliewer K, Haller E, et al. Development of a Practical Guide to Implement and Monitor Diet Therapy for Eosinophilic Esophagitis. Clin Gastroenterol Hepatol. 2023;21:1690-8. Epub 2023/03/19.

18. Franciosi JP, Mougey EB, Dellon ES, et al. Proton Pump Inhibitor Therapy for Eosinophilic Esophagitis: History, Mechanisms, Efficacy, and Future Directions. J Asthma Allergy. 2022;15:281-302. Epub 2022/03/08.

19. Franciosi JP, Gordon M, Sinopoulou V, et al. Medical treatment of eosinophilic esophagitis. Cochrane Database Syst Rev. 2023;7(7):Cd004065. Epub 2023/07/20.

20. Hirano I, Collins MH, Katzka DA, et al. Budesonide Oral Suspension Improves Outcomes in Patients With Eosinophilic Esophagitis: Results from a Phase 3 Trial. Clin Gastroenterol Hepatol. 2022;20:525-34.e10. Epub 2021/04/23.

21. Dellon ES, Rothenberg ME, Collins MH, et al. Dupilumab in Adults and Adolescents with Eosinophilic Esophagitis. N Engl J Med. 2022;387(25):2317-30. Epub 2022/12/23.

22. von Arnim U, Biedermann L, Aceves SS, et al. Monitoring Patients With Eosinophilic Esophagitis in Routine Clinical Practice – International Expert Recommendations. Clin Gastroenterol Hepatol. 2023;21:2526-33. Epub 2022/12/27.

Nutrition Reviews in Gastroenterology, SERIES #23

Kidney Stones in Short Bowel Syndrome: Causes and Preventive Measures

Melanie Betz

Short bowel syndrome (SBS) occurs from either surgical resection or malfunction of a significant amount of small bowel. An estimated 42-50% of patients with SBS will develop kidney stones in their lifetime.^1,2 Both uric acid and calcium oxalate stones are common. Increased kidney stone risk stems from a combination of possible factors including inability to maintain adequate hydration, reduced alkali absorption, enteric hyperoxaluria, hypomagnesemia, altered gut microbiome, and poor food and beverage intake. Treatment must be individualized to each patient’s 24-hour urine collection results as the cause of kidney stones will differ based on etiology of SBS and natural variations. Evidence based treatments for stone prevention in SBS include improving hydration status, oral calcium to reduce oxalate absorption, reducing dietary fat and/or oxalate, alkali supplementation, and the correction of hypomagnesemia. Dietary recommendations should be made by a registered dietitian after a complete nutrition assessment to ensure the recommendations are appropriate.

Introduction

Short bowel syndrome (SBS) is defined as “a clinical condition associated to having less than 200 centimeters of residual small bowel (SB) in continuity, measured from the duodenojejunal flexure (ligament of Treitz), with or without colon, in an adult and for children (<18 years), less than 25% of the normal length SB for their respective age.” ³ SBS can result when surgical resection of the bowel leaves the remaining bowel with an insufficient length to support adequate digestion and absorption of oral nutrients. Additionally, SBS can occur as a consequence from dysfunction from the remaining bowel, even if the length is sufficient. Most often, SBS arises due to bowel resection resulting from trauma, inflammation, or ischemia; congenital disorders; or resulting from bariatric surgery.⁴

The most significant concern with SBS is malabsorption, making it challenging to maintain adequate nutrition and hydration. The extent of malabsorption largely depends on the length and location of the remaining bowel. If less than 50% of the SB is removed, the remaining bowel can adapt, minimizing risk of long-term complications.⁴ Complications of SBS include high volume stool or ostomy output, fluid and electrolyte imbalances, vitamin and mineral deficiencies, bone disease, hepatobiliary diseases, kidney stones, small intestinal bacterial overgrowth, and possibly the need for parenteral support.^4,5 This review will focus on mechanisms of how SBS increases the risk of kidney stones and the nutrition therapies for its prevention.

Prevalence of Kidney Stones

Kidney stones occur in 43-50% of patients with SBS.^1,2 This is remarkably higher than the estimated 10% of the general population with kidney stones.⁶Reduced kidney function is also common; one study found 28% of patients with SBS developed some level of renal impairment.⁷ Kidney stones, along with infections and dehydration are likely responsible for kidney damage.

Both uric acid and calcium oxalate kidney stones are common in SBS, highlighting the need for metabolic urine testing to direct prevention.^8,9Patients with a SB ostomy may be at greatest risk of uric acid stones due to massive bicarbonate loss, leading to acidic urine and those with some colon-in-continuity are at higher risk of developing calcium oxalate stones.^1,10

Mechanism of Stone Formation

Kidney stones are prevalent in SBS due to a combination of factors stemming from malabsorption and dehydration. The exact cause of stone formation is different for each patient depending on the amount and location of bowel that is remaining and natural variations across people.

Reduced Fluid Absorption

The hallmark of SBS is high volume stool or ostomy output and difficulty maintaining hydration due to endogenous losses of both fluid and electrolytes. Additionally, poor appetite and GI symptoms related to eating and drinking can contribute to reduced fluid intake. Limited absorption/resorption of oral fluids and endogenous secretions are problematic in many with SBS and often leads to reduced urine volume and increased saturation of lithogenic compounds. Reducing urine saturation is key to prevent all types of kidney stones.

Patients with a proximal SB ostomy have the most difficulty with enteric fluid absorption and often struggle with chronic dehydration leading to kidney injury and kidney stones.¹⁰ Patients with SBS that have their distal ileum and/or some colon-in-continuity tend to have more efficient fluid absorption and higher urine output, though risk for dehydration persists as rapid transit of fluid through the remnant SB may exceed the absorptive capacity of the remnant SB and colon.

Inhibited Intestinal Alkali Absorption

A key tenet of calcium kidney stone prevention is maintenance of adequate urine citrate. Citrate complexes with calcium to form a soluble compound in the urine, reducing calcium available to complex with other compounds to form kidney stones.¹¹Kidney stone prevention may include alkalizing urine pH via medications such as potassium citrate or sodium bicarbonate and reducing the dietary acid load.^11,12 Urine alkalization helps prevent uric acid stones as low urine pH is the biggest driver of uric acid kidney stone formation. For calcium-based stones, dietary or medicinal alkali helps increase urine citrate as well as alkalize urine, which may help prevent calcium oxalate kidney stone formation.

Patients with SBS tend to have low urine pH and low urine citrate, increasing risk of both uric acid and oxalate kidney stones.¹⁰ In SBS, alkali precursors such as potassium, magnesium and calcium are poorly absorbed by the residual SB, which may result in highly acidic urine predisposing patients to uric acid kidney stones.¹⁰ In addition, when alkali is not absorbed by the GI tract – from either alkali malabsorption or a high dietary acid load – the kidney will reabsorb more citrate to buffer the higher acid load, resulting in lower urine citrate.¹⁰ Examples of dietary sources of alkali and acid precursors and exact potential renal acid load (PRAL) values are provided in Table 1.

Enteric Hyperoxaluria

In non-stone formers, only 5-10% of dietary oxalate is absorbed. This varies widely based on dietary intake of calcium, fiber and other nutritional factors.¹³ The more calcium consumed, the more calcium binds with dietary oxalate in the gut causing reduced oxalate absorption and ultimately lower urine oxalate. By this mechanism, adequate dietary calcium is widely known to reduce the risk of forming oxalate kidney stones.¹⁴

Enteric hyperoxaluria is the over absorption of oxalate from the colon and can develop whenever fat malabsorption is present.¹⁵ Malabsorbed fat sequesters calcium in the SB, leaving oxalate to be absorbed in the colon and excreted in urine.¹⁵Given the high frequency of fat malabsorption in SBS, enteric hyperoxaluria is common. The extent of bowel resection or dysfunction is correlated with the extent of hyperoxaluria.¹⁰ Enteric hyperoxaluria is of particular concern for patients with SBS that have partial or complete colon-in-continuity as oxalate is exclusively absorbed in the colon.¹⁰ There is very little risk of enteric hyperoxaluria in those with a SB ostomy (without colon-in-continuity).

Hypomagnesemia

Magnesium is a novel target for oxalate kidney stone prevention due to its ability to bind oxalate both in the intestine and urine to create a soluble complex. Both blood and urine magnesium levels tend to be lower in stone formers.^16,17 Hypomagnesemia is common in patients with
SBS, especially in those without the distal ileum, where a majority of magnesium absorption occurs and likely contributes to risk of oxalate kidney stone formation.⁵

A 2024 study found that magnesium supplementation reduced urine oxalate in individuals with elevated baseline urine oxalate levels.¹⁸However, in SBS, oral magnesium supplementation can worsen GI fluid losses, increasing stool/ostomy output, and thus worsening dehydration with increased risk of stone formation. Therefore, oral magnesium supplementation should be monitored closely, dose adjusted, and if necessary transitioned to parenteral supplementation to optimize fluid balance and serum magnesium levels.

Altered Gut Microbiome

There is a clear role of the gut microbiome in kidney stone formation.^19,20 Most of the research has focused on the role that oxalate degrading bacteria play on reducing urine oxalate and therefore reduce oxalate kidney stone risk. The gut microbiome is altered in SBS, likely as a result of both dietary and physiological changes; it is likely that the alteration of the gut microbiome contributes to the increased prevalence of kidney stone formation. More research is needed to determine how and if the gut microbiome can be modulated to reduce kidney stone formation in patients with SBS.

Table 1. Dietary Sources of Alkali and Acid Precursors

Dietary Precursors	Potential Renal Acid Load (mEq)
Alkali Producing Foods
All Fruits Examples:
Banana (1 medium)	8.2
Blueberries (1 cup)	1.5
Peach (1 each)	4.7
All Vegetables Examples:
Broccoli (1 cup, cooked)	5.5
Green Beans (1 cup, cooked)	3.5
Tomato (1/2 cup, raw)	3.7
Acid Producing Foods
All Meat & Seafood Examples
Beef (4oz, cooked)	12.9
Chicken (4oz, cooked)	16.3
Cod (4oz, cooked)	13.5
Most Cheeses
Example:
Cheddar Cheese	3.5
Minimal Acid or Alkali Production Potential
Most Beans, Nuts, Seeds, Legumes & Plant Protein Foods Examples:
Black Beans (1/2 cup, cooked)	2.6
Lentils (1/2 cup, cooked)	1.5
Walnuts (1/2 cup)	1.7
Grains Examples:
Whole Grain Bread (1 slice)	1.8
White Bread (1 slice)	0.8
Brown Rice (1/2 cup cooked)	2.2
Fats & Oils Examples:
Olive oil (1 tablespoon)	0.0
Butter (1 tablespoon)	0.1
Milk & Yogurt Examples:
2% milk (1 cup)	1.5
Low Fat Yogurt (1 cup)	0.4

Poor Oral Intake

Patients with SBS may control their stool output by limiting oral intake. As stated above, low volume of oral fluid intake contributes to dehydration, low urine volume, and kidney stone risk. Additionally, an unbalanced diet that is low in alkali precursors (fruits and vegetables) along with nutrient malabsorption can exacerbate low urine citrate and pH, all contributing to the risk of kidney stone formation.

Prevention and Treatment of Kidney Stones

Given the complexity and variation of kidney stones in patients with SBS, it is crucial to individualize interventions to prevent stone formation based on 24-hour urine collections. Table 2 provides suggested interventions based on common urine risk factors for kidney stone formation.

Improve Hydration

The American Urological Association recommends consuming adequate fluid to produce at least 2 ½ liters of urine output/day for kidney stone prevention.¹¹ This volume of urine may be difficult to achieve for patients with SBS as increase in oral fluid intake often results in higher ostomy/stool output with reduced urine volume. Patients with SBS and low urine output (e.g., <1200 mL/24-hours) should be encouraged to sip fluids slowly throughout the day and to periodically measure 24- hour urine volume in response to oral fluid intake; small increases in urine volume can incrementally reduce kidney stone risk despite not producing the recommended amount of urine.

Table 2.
Kidney Stone Prevention Interventions Based on 24-hr Urine Collection Parameters

Urine Collection Result	Diet and Hydration Strategies
Low urine volume (<2.5 liters)	• Increased oral fluids, ideally from water or unsweetened beverages • Oral rehydration solution as appropriate • IV fluids as appropriate • Avoid dietary sodium restriction • Avoid excess simple carbohydrate
Hyperoxaluria	• Supplemental calcium of 200-300mg/meal to be taken with meals (if no hypercalciuria) • Increase intake of calcium-rich foods with meals for a total of 1,000-1,200mg calcium/day • Limit intake of very high oxalate foods • Consider low fat diet (20-30% calories from fat) • Trial bile acid sequestrant
Low urine pH or citrate	• Potassium citrate, sodium bicarbonate or other citrate supplements dosed based on 24-hour urine collection pH and citrate • Consider increased dietary alkali
Hypomagnesemia	• Supplementation of 300-400mg/day as necessary • Monitor for increased GI losses

Some patients with SBS, especially those with SB ostomy, can benefit from drinking oral rehydration solutions (ORS). ORS are iso-osmolar glucose-electrolyte solutions that utilize the sodium-glucose transport mechanism to pull water across the SB mucosa and help to correct fluid and electrolyte losses. Patients can purchase ORS products or make ORS at home (Table 3). In some cases, parenteral fluids are necessary to maintain adequate hydration and increase urine volume.

For those with SBS, avoidance of excess simple sugar is recommended to prevent rapid emptying of hypertonic fluid into the proximal SB; this results in jejunal water secretion to dilute the chyme to isotonicity, and often causes osmotic diarrhea with a net fluid loss (a.k.a. dumping syndrome). This is particularly important for individuals without the terminal ileum and/or cecum as these are the normal sites of significant fluid reabsorption. It is also advisable to avoid sugar-laden beverages (e.g., fruit juices, sodas), oral nutrition supplements, and concentrated sweets (e.g., cookies, cake, ice cream) to reduce the osmotic effect on the SB.

Dietary Sodium

Typically, a limit of 2,300 mg of sodium per day is recommended for calcium stone prevention for those with high urine calcium as higher dietary sodium increases renal excretion of calcium.¹¹ However, in SBS, especially for patients with a sodium wasting SB ostomy, dietary sodium should be unrestricted to promote water absorption, urinary fluid output, and to prevent hyponatremia related to sodium loss in ostomy effluent.

Low Fat Diet

If a patient with SBS has enteric hyperoxaluria, avoiding excess dietary fat can help reduce sequestration of calcium and thereby reduce the absorption of oxalate and urine oxalate. The American Society of Parenteral and Enteral Nutrition (ASPEN) recommends 20-30% of calories from fat for patients with SBS and colon-in-continuity.⁴ This does not eliminate fat from the diet and allows for 44-67 grams fat/day on a 2,000 calorie diet. It is important to have a registered dietitian assess a patient’s habitual diet to determine the need for dietary changes.

Alkali Supplementation

As stated above, a major cause of kidney stones in SBS is limited absorption of alkali leading to acidic urine and low urine pH. Given the reduced absorptive capacity of alkali for patients with SBS, it is unlikely that reducing the dietary acid load will significantly impact urine citrate or pH levels. In fact, Bianco et al. found that clinical advice to increase dietary alkali to patients with SBS did not raise urine pH, but prescriptive, oral supplementation of alkali and citrate did increase urine pH (0.34 ± 0.53 vs. 0.22 ± 0.55, p=0.26 and 83 ± 256mg/day vs. 98± 166mg/day, p= 0.74, respectively).²¹

Table 3.
Commercial and Homemade Oral Rehydration Solutions

Commercially Available Powders and Liquids	Homemade Beverage Recipes
Ceralyte 70^®	Ingredients: • 1 liter water • 6 teaspoons sugar • ½ teaspoon salt Instructions: Combine all ingredients and mix until completely dissolved Add sugar-free flavoring as needed Refrigerate Sip throughout the day
Drip Drop^® Fast Hydration	Ingredients: • ¾ cup fruit juice • 3 ¼ cups water • ¾ teaspoon table salt Instructions: Combine all ingredients and mix until completely dissolved Refrigerate Sip throughout the day
Liquid IV^® Hydration Multiplier	Ingredients: • 2 ½ cups tomato juice • 1 ½ cups water Instructions: Combine ingredients Refrigerate Sip throughout the day
Trioral^® Rehydration Electrolyte Powder	Ingredients: • 2 packets of Gatorlyte® powder • 4 cups of water • ¼ teaspoon of table salt Instructions: Combine all ingredients and mix until completely dissolved Refrigerate Sip throughout the day
Note: Patients with SBS should drink the sugar-containing oral rehydration solutions (ORS) to most efficiently promote water absorption. Do not add ice to chill ORS as it will dilute the solution changing the sodium and sugar concentration to less favorable levels.

Oral supplementation of citrate is the most common strategy to increase urine pH and citrate levels for patients with SBS. Potassium citrate and sodium bicarbonate are most commonly prescribed. If not tolerated, over the counter citrate supplements such as Moonstone^® or Litholyte^®can be used in place of prescription alkali, at the discretion of the physician, to ensure adequate alkali absorption, based on 24-hour urine collection results. It is important to periodically monitor 24-hour urine collection results to determine adequacy of dosing.

Dietary Calcium

In the general kidney stone population, avoidance of calcium supplements is typically recommended due to concern about exacerbating hypercalciuria, especially when calcium supplements are taken away from meals.^11,22 However, in patients with SBS, urine calcium is typically not elevated and calcium supplements with meals may help reduce oxalate absorption. All forms of calcium supplements can reduce oxalate absorption.

For those with SBS, including foods high in calcium, or taking calcium supplements, with each meal can help to reduce intestinal oxalate absorption, reduce urine calcium levels, and ultimately reduce oxalate kidney stone formation.¹³ For those with SBS and risk of kidney stones it is recommend they take 600-2000 mg per day, in split doses, with meals, e.g. 400-500 mg calcium per meal.²⁰

Dietary Oxalate

Limiting dietary oxalate is frequently recommended for patients with SBS to reduce their urine oxalate levels. However, there is debate as to whether a low oxalate diet is beneficial for oxalate stone prevention due to the inevitable restriction of beneficial components that are in oxalate-containing foods such as alkali, magnesium, phytate and fiber.²³ Noori et al. found urinary magnesium, citrate and pH increased in patients without SBS following a DASH (Dietary Approaches to Stop Hypertension) style diet compared to a low oxalate diet.²⁴ Siener et al. found that by providing meals that were “balanced” with less oxalate, protein and sodium, along with more fiber and magnesium, patients with SBS had reduced urine oxalate.²⁵Finally, Bianco et al. found that advice to reduce dietary oxalate given in the clinic did not lower urine oxalate in a group of patients with SBS.²²As such, a strict low oxalate diet for patients with SBS should also be questioned.

Although avoidance of eating foods that are very high in oxalate is prudent for patients with enteric hyperoxaluria, a strict low oxalate diet should not be recommended as it will limit beneficial components for stone prevention and general health.^23,24 Also, it is hard for patients to adhere to a prescribed amount of dietary oxalate given the difficulty of quantifying oxalate in food (especially prepackaged foods), incomplete lists of oxalate content of foods, discrepancies between lists of food oxalate composition, and the prevalence of misinformation.²⁵ In addition, oxalate exists in both soluble and insoluble forms; soluble oxalate has a much larger impact on urine oxalate levels, yet this distinction is not usually made on food composition lists.²⁷ Table 4 provides a short list of foods with moderate and high oxalate concentration (>70 mg oxalate per standard portion as measured by the 2023 Harvard Oxalate Table).²⁸Practically, ensuring adequate dietary calcium is a more effective and healthy way to reduce urine oxalate.

Table 4. Very High Oxalate Foods & Substitutes²⁹

Food Item	Oxalate (mg)	Lower Oxalate Substitutions	Oxalate (mg)
Spinach, ½ cup cooked	547	Kale, ½ cup cooked	1
Navy beans, ½ cup cooked	96	Kidney beans, ½ cup cooked	10
White potato with skin, 1 medium	92	Mashed or boiled potatoes, 1 cup	30
Beets, ½ cup cooked	76	Parsnip, ½ cup cooked	15
Almonds, 1 ounce (1/4 cup)	72	Pistachios, 1 ounce, ¼ cup	9

Bile acid sequestrants, such as cholestyramine, are also used to bind oxalate in the SB and reduce urine oxalate.^29,30 However, the use of bile acid sequestrants can lead to bile salt deficiency which will worsen fat malabsorption, hence increasing risk of oxalate absorption. Therefore, in patients with SBS it is necessary to provide clinical monitoring of the effectiveness of a bile salt sequestrant to determine if the resin improves or worsens a patient’s malabsorption.

Correction of Hypomagnesemia

Given the prevalence of hypomagnesemia, and the role that magnesium plays in oxalate stone prevention, the correction of hypomagnesemia may help prevent oxalate stones. Foods highest in magnesium include nuts, seeds, beans, and green leafy vegetables. Unfortunately, these foods may not be tolerated by some patients with SBS. In addition, dietary magnesium is unlikely to significantly raise serum magnesium levels in SBS patients with limited absorptive capacity and oral magnesium supplements may worsen stool output and dehydration. Therefore, parenteral magnesium replacement may be necessary to raise urinary magnesium levels and reduce stone formation.⁵

“Do No Harm”

Given the high risk of malnutrition, maldigestion, and malabsorption in patients with SBS, it is imperative that nutrition recommendations do not become so onerous that they make it more difficult for patients with SBS to balance their diet. Restrictive diets have been shown to reduce total calorie intake in frail populations.³¹ Ideally, nutrition recommendations should be devised, communicated and monitored by a registered dietitian to optimize patient adherence and prevent malnutrition.

Summary

Short bowel syndrome significantly increases the risk of kidney stone formation due to a combination of possible factors including reduced urine volume, magnesium, citrate, pH and increased oxalate. Kidney stone prevention interventions should be personalized to 24-hour urine collection results and patient preferences. A comprehensive nutrition assessment should be completed prior to providing dietary recommendations given the high risk of malnutrition. All patients with SBS that have or are at risk for kidney stone formation should be followed by a team that is knowledgeable in the prevention and management of kidney stones.

References

1. Nightingale JM, Lennard-Jones JE, Gertner DJ, Wood SR, Bartram CI. Colonic preservation reduces need for parenteral therapy, increases incidence of renal stones, but does not change high prevalence of gall stones in patients with a short bowel. Gut. 1992;33(11):1493-1497.
2. Teichman JMH. Acute Renal Colic from Ureteral Calculus | NEJM. New England Journal of Medicine. 2004;350:684-693.
3. Pironi L. Definition, classification, and causes of short bowel syndrome. Nutr Clin Pract. 2023;38 Suppl 1:S9-S16.
4. Matarese LE, O’Keefe SJ, Kandil HM, Bond G, Costa G, Abu-Elmagd K. Short Bowel Syndrome: Clinical Guidelines for Nutrition Management. Nutrition in Clinical Practice. 2005;20(5):493-502.
5. Bering J, DiBaise JK. Short bowel syndrome: Complications and management. Nutrition in Clinical Practice. 2023;38(S1):S46-S58.
6. Chewcharat A, Curhan G. Trends in the prevalence of kidney stones in the United States from 2007 to 2016. Urolithiasis. 2021;49(1):27-39.
7. Wang P, Yang J, Zhang Y, Zhang L, Gao X, Wang X. Risk Factors for Renal Impairment in Adult Patients With Short Bowel Syndrome. Front Nutr. 2021;7.
8. Deren JJ, Porush JG, Levitt MF, Khilnani MT. Nephrolithiasis as a complication of ulcerative colitis and regional enteritis. Ann Intern Med. 1962;56:843-853.
9. Maratka Z, Nedbal J. Urolithiasis as a complication of the surgical treatment of ulcerative colitis. Gut. 1964;5(3):214-217.
10. Worcester EM. Stones from bowel disease. Endocrinol Metab Clin North Am. 2002;31(4):979-999.
11. Pearle MS, Goldfarb DS, Assimos DG, et al. Medical Management of Kidey Stones: AUA Guideline. J Urol. 2014;192:316-324.
12. Haghighatdoost F, Sadeghian R, Clark CCT, Abbasi B. Higher Dietary Acid Load Is Associated With an Increased Risk of Calcium Oxalate Kidney Stones. Journal of Renal Nutrition. 2021;31(5):467-474.
13. Holmes RP, Goodman HO, Assimos DG. Contribution of dietary oxalate to urinary oxalate excretion. Kidney International. 2001;59(1):270-276.
14. Borghi L, Schianchi T, Meschi T, et al. Comparison of two diets for the prevention of recurrent stones in idiopathic hypercalciuria. N Engl J Med. 2002;346(2):77-84.
15. Witting C, Langman CB, Assimos D, et al. Pathophysiology and Treatment of Enteric Hyperoxaluria. CJASN. 2021;16(3):487-495.
16. Wu J, Yang Z, Wei J, Zeng C, Wang Y, Yang T. Association Between Serum Magnesium and the Prevalence of Kidney Stones: a Cross-sectional Study. Biol Trace Elem Res. 2020;195(1):20-26.
17. Deshmukh SR, Khan ZH. Evaluation of urinary abnormalities in nephrolithiasis patients from Marathwada region. Indian J Clin Biochem. 2006;21(1):177-180.
18. Taheri M, Jalali S, Borumandnia N, Tavasoli S, Basiri A, Taheri F. Effect of magnesium oxide or citrate supplements on metabolic risk factors in kidney stone formers with idiopathic hyperoxaluria: a randomized clinical trial. Magnes Res. 2024;37(1):12-21.
19. Galán-Llopis JA, Sánchez-Pellicer P, Navarro-López V. Role of microbiome in kidney stone disease. Current Opinion in Urology. 2023;33(2):84-89.
20. Johnson E, Vu L, Matarese LE. Bacteria, Bones, and Stones: Managing Complications of Short Bowel Syndrome. Nutr Clin Pract. 2018;33(4):454-466.
21. Bianco J, Chu F, Bergsland K, Coe F, Worcester E, Prochaska M. What treatments reduce kidney stone risk in patients with bowel disease? Urolithiasis. 2022;50(5):557-565.
22. Curhan GC, Willett WC, Speizer FE, Spiegelman D, Stampfer MJ. Comparison of dietary calcium with supplemental calcium and other nutrients as factors affecting the risk for kidney stones in women. Ann Intern Med. 1997;126(7):497-504.
23. Penniston KL. Is It Time to Retire the Low-Oxalate Diet? Yes. J Endourol. 2021;35(10):1431-1434.
24. Noori N, Honarkar E, Goldfarb DS, et al. Urinary Lithogenic Risk Profile in Recurrent Stone Formers With Hyperoxaluria: A Randomized Controlled Trial Comparing DASH (Dietary Approaches to Stop Hypertension)-Style and Low-Oxalate Diets. American Journal of Kidney Diseases. 2014;63(3):456-463.
25. Siener R, Ernsten C, Welchowski T, Hesse A. Metabolic Profile of Calcium Oxalate Stone Patients with Enteric Hyperoxaluria and Impact of Dietary Intervention. Nutrients. 2024;16(16):2688.
26. Attalla K, De S, Monga M. Oxalate Content of Food: A Tangled Web. Urology. 2014;84(3):555-560.
27. Ritter MMC, Savage GP. Soluble and insoluble oxalate content of nuts. Journal of Food Composition and Analysis. 2007;20(3):169-174.
28. Harvard T. H Chan School of Public Health. Oxalate Table. Published online November 2023. Accessed September 30, 2024. https://www.hsph.harvard.edu/nutrition-questionnaire-service-center/wp-content/uploads/sites/2637/2023/11/OXALATE-TABLE-1.xlsx
29. Kapral C, Wewalka F, Praxmarer V, Lenz K, Hofmann AF. Conjugated bile acid replacement therapy in short bowel syndrome patients with a residual colon. Z Gastroenterol. 2004;42(7):583-589.
30. Emmett M, Guirl MJ, Santa Ana CA, et al. Conjugated bile acid replacement therapy reduces urinary oxalate excretion in short bowel syndrome. Am J Kidney Dis. 2003;41(1):230-237.

From the Pediatric Literature

Intestinal Ultrasound Use in Pediatric IBD

Pediatric inflammatory bowel disease (IBD) in children requires endoscopic intervention for initial diagnosis and for continued disease surveillance. Intestinal ultrasound (IU) has the potential to be less invasive while also accurate when used as a diagnostic modality for IBD. The authors of this study evaluated IU in comparison to pediatric endoscopy and fecal calprotectin testing in the diagnosis of pediatric IBD via a prospective study performed over one year.

Pediatric patients (age 2-21 years) who had previously undergone colonoscopy (including terminal ileum intubation) were divided into 2 groups consisting of patients with IBD and patients without IBD. A subsequent IU occurred one month after colonoscopy, and five segments of the intestine were evaluated (terminal ileum, ascending colon, transverse colon, descending colon, and rectum). IU studies were read by three pediatric radiologists, and all radiologists and gastroenterologists involved in the study were blinded to each other’s findings. IU documentation included bowel wall thickness, hyperemia, presence of fatty proliferation, and absence of wall stratification. A modified ultrasound-ulcerative colitis index was used as a scoring system to determine bowel wall inflammation, and bowel wall thickness was scored based on millimeter thickness. For example, a score of “0” was given for normal thickness; “1” was given for a thickness of 3 to 5 millimeters; “2” was given for a thickness of 5 to 7 millimeters; and “3” was given for a thickness greater than 7 millimeters. The presence of hyperemia, fatty proliferation, and absence of wall stratification were each given a score of “1” if present. A Mayo score was used to document endoscopic colon inflammation for ulcerative colitis while a Simple Endoscopic Score for Crohn Disease (SES-CD) was used to determine endoscopic colon inflammation for Crohn disease. Individual patient data including assessments for disease activity were collected. Disease activity was assessed by fecal calprotectin level, the Pediatric Ulcerative Colitis Activity Index (PUCAI), and the Pediatric Crohn Disease Activity Index (PCDAI).

In total, 50 patients were included in the study (median age 13.5 years; 58% female). Half of these patients were diagnosed with IBD in which 12 patients had ulcerative colitis, 12 patients had Crohn disease, and 1 patient had IBD unclassified. The other 25 patients had no IBD, and there was no difference in age distribution between these two groups. Patients with ulcerative colitis had a median PUCAI of 52.5 and a Mayo score of 8.5. Patients with Crohn disease had a median PCDAI of 42.5 and a SES-CD of 16.5. IU demonstrated bowel wall thickness in 23 patients (46%) for which 19 of these patients had IBD (82.6%). A bowel inflammation score of at least “1” was associated with 76% sensitivity, 84% specificity, 83% positive predictive value (PPV), 78% negative predictive value (NPV), and a Pearson’s chi-square being <0.001when patient with IBD were compared to patients without IBD.

Sensitivity, specificity, PPV, and NPV improved further if only moderate or severe endoscopic disease was included. Pearson correlation coefficient testing demonstrated a significant correlation between IU scoring and fecal calprotectin levels as well as IU and endoscopic scoring (Mayo score and SES-CD). No such correlation existed between IU and clinical scoring (PUCAI and PCDAI).

IU appears to have potential utility in the diagnosis of pediatric IBD, especially since this study noted good correlation with fecal calprotectin levels and endoscopic scoring systems. It also may prove to be a good non-interventional testing technique to follow up on disease activity after a diagnosis of IBD is made in a child.

Khan H, Munden M, Spence L, Jones R, Whatley J, Suppa C. Intestinal ultrasound at diagnosis of pediatric inflammatory bowel disease compared to endoscopy. Journal of Pediatric Gastroenterology and Nutrition. 2024; doi: 10.1002/jpn3.12444.\Online ahead of print.

More Data on Exclusive Enteral Nutrition as Treatment for Crohn Disease in Children

One potential therapy for some cases of Crohn disease in children is exclusive enteral nutrition (EEN). Although EEN can be effective in the treatment of Crohn disease, its associated dietary limitations potentially can lead to eating disorders. The authors of this study determined the risk of eating disorder development in the setting of EEN therapy for pediatric Crohn disease. This retrospective study occurred over a four-month period at a children’s hospital in Paris, France. A questionnaire was developed which covered basic patient information, EEN use (including duration and how it was administered), potential difficulties with EEN use, follow-up data, long-term risks, and patient opinion on EEN therapy.

Out of the 450 pediatric patients with Crohn disease that were evaluated, 92 patients (20%) were receiving EEN and only 32 patients (7%) completed the survey. Survey respondents were 32% female, and most patients (84%) were 10 years of age or older. Ileocolonic disease was present in 50% of patients, and 75% of patients had non-stricturing/non-penetrating disease. Normal growth was present in 84% of patients. All patients who completed the survey had at least one eating difficulty associated with EEN for which the main difficulty was loss of eating desire. Enteral therapy discontinuation occurred in 12 patients receiving EEN (38%) for which the primary cause was intolerance of EEN treatment. Gastrointestinal symptom continuation was present in 8 patients (25%). The average time for patients to have an improvement while on EEN was 6 weeks, and most patients (62%) received continuing support from a multidisciplinary healthcare team.

Persistent eating difficulties remained in 10 patients (32%) after a median of 5 years post EEN, and patients receiving behavioral therapy during EEN did not develop long-term feeding issues. It was noted that 19 patients (59%) recommended use of EEN as treatment for Crohn disease mainly because it avoided use of medication.

This small study demonstrated that although EEN was effective and tolerable for many pediatric patients with Crohn disease, a sizable group of patients did not tolerate EEN and had persistence of eating difficulties long after EEN had been stopped. These findings suggest that psychological therapy is essential during EEN for pediatric Crohn disease, and frequent screening for the development of possible eating disorders during EEN is required.

Sandrine C, Emmanuelle D, Jerome V, Christine M. Exclusive enteral nutrition for induction of remission in pediatric Crohn＊s disease: short- and long-term tolerance and acceptance. JPGN Reports. 2024; https://doi.org/10.1002/jpr3.12163. Online ahead of print.

Constipation in Children with Inflammatory Bowel Disease

Children with inflammatory bowel disease (IBD) typically present with abdominal pain, blood in the stool, diarrhea, and weight loss. However, such children also can have constipation which can delay a diagnosis of IBD. Since the worldwide prevalence of pediatric functional constipation (FC) may be as high as 29.6%, it is imperative to be able to delineate children with sole FC from patients with FC and organic gastrointestinal disease. The authors of this Italian study attempted to determine the prevalence of constipation in children who eventually were diagnosed with IBD.

This study was retrospective, observational, and cross-sectional in which children diagnosed with either Crohn disease or ulcerative colitis over an 8-year period were reviewed. Initial patient characteristics were obtained, including IBD symptom duration, disease location (per the Paris Classification), the Pediatric Crohn’s Disease Activity Index (PCDAI) score, the Pediatric Ulcerative Colitis Activity Index (PUCAI) score, the Ulcerative Colitis Endoscopic Index of Severity (UCEIS) score, and the Simplified Endoscopic Score for Crohn disease (SES-CD) score. Patients with IBD who also had FC based on Rome IV Criteria at the initial follow-up clinic visit or phone call were included in the study.

Full data regarding a patient’s IBD diagnosis was present in 238 patients for which 104 patients (44%) had Crohn disease, 130 patients (56%) had ulcerative colitis, and 4 patients (0.016%) had IBD Unclassified. The mean age of patients was 174 ± 47 months, and 53% of these patients were male. A total of 41 of all patients with IBD met Rome IV criteria for FC. The authors noted that 18.2% of patients with Crohn disease, 21.5% of patients with ulcerative colitis, and none of these patients with IBD Unclassified had FC. None of the patients with IBD and FC had other autoimmune diseases, and there was no statistical difference in age, gender, extra-intestinal manifestations of IBD, age at IBD diagnosis, surgery, use of induction therapy, and IBD relapse when patients with IBD with FC were compared to patients with IBD and no FC. However, patients with IBD and FC were statistically more likely to have a delay in IBD diagnosis. Patients with IBD and no FC were statistically more likely to have diarrhea or bloody diarrhea. Initial PUCAI scoring also was statistically higher for patients with ulcerative colitis and no FC. Patients with Crohn disease and FC were statistically more likely to have perianal disease changes. Patients with ulcerative colitis and FC were statistically more likely to have proctitis and left-sided colitis. Serum testing and stool testing, including fecal calprotectin levels, were similar between patients with IBD with or without FC.

Laxatives were used in 69% of patients prior to an IBD diagnosis in patients with IBD and FC with 65% of these patients receiving PEG3350 medication. A statistically significant higher serum erythrocyte sedimentation rate (ESR) level was present in patients with IBD and FC who had not received PEG3350. Interestingly, there was a statistically significant delay in IBD diagnosis in patients with IBD and FC who did not receive PEG3350 therapy.

This study demonstrates that FC can occur in a sizable percentage of children with IBD. If a child with FC is not improving on laxative therapy, further testing, including a good anal/rectal examination and possible endoscopy is warranted.

Sabrina C, Antonio C, Salomone S, Daniela P, Marianna C, Pietro B, Massimo M, Erasmo M, Annamaria S, Caterina S. The prevalence of constipation in children with new diagnosis of inflammatory bowel disease (IBD): a retrospective study. Journal of Pediatric Gastroenterology and Nutrition 2025; doi: 10.1002/jpn3.70005.\Online ahead of print.

PFAPA Outcomes in Children

Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis syndrome (PFAPA) affects children and typically is associated with recurring fevers, stomatitis, pharyngitis, and cervical adenitis. Pediatric gastroenterologists often see such patients as children with PFAPA also can have associated abdominal pain, emesis, and diarrhea. Although the cause of PFAPA is unknown, tonsillectomy seems to be effective in relieving PFAPA symptoms. The authors of this study evaluated the long-term symptoms of PFAPA after tonsillectomy.

This retrospective study occurred over a 14-year period and included all patients who had been diagnosed with PFAPA and also who had undergone a subsequent tonsillectomy. All patients with PFAPA met the Marshall criteria for this disorder. Patients who met inclusion criteria initially were contacted by mail or by phone and subsequently had data collected by phone interview. Initial symptoms prior to tonsillectomy were obtained by medical record review. Included patients and their families were queried regarding the presence of fever (defined as temperature greater than 38⁰ Celsius) as well as the persistence of any other symptoms associated with PFAPA after tonsillectomy. Patients were divided into 4 groups: symptom resolution, persistence of PFAPA-symptoms but no fever, less/milder febrile episodes, or no clinical change.

A total of 101 patients had data available for which 82 patients participated in the study. The median patient age at the time of interview was 14.8 years (range 6 – 28.8 years). The median age of developing PFAPA symptoms was 1.8 years (range 0.1 – 16 years). The median age of tonsillectomy was 5.1 years (range 2.3 – 18.8 years). Five patients had undergone genetic testing for periodic fever syndromes in the setting of PFAPA, but no associated genetic syndromes were detected. Median long term follow-up time after tonsillectomy was 8.8 years (range 2.8 – 16.1 years). It should be noted that gastrointestinal symptoms prior to tonsillectomy included abdominal pain (35% of patients) and nausea and emesis (16% of patients).

Resolution of fever episodes 6 months after tonsillectomy occurred in 52% of patients. Persistence of non-febrile PFAPA symptoms 6 months after tonsillectomy was present in 22% of patients.The most common non-febrile PFAPA symptoms were low-grade fever, malaise, aphthous ulcers, pharyngitis, cervical adenitis, arthralgias, abdominal pain, and headache. Persistence of less/milder febrile episodes was present in 20% of patients 6 months post tonsillectomy while 1% of patients had no clinical change 6 months post tonsillectomy. Children with PFAPA symptom resolution at 6 months post tonsillectomy were significantly more likely to maintain symptoms response long term compared to those patients with a partial response 6 months post tonsillectomy. Long-term data demonstrated that 89% of patients who had initial symptom resolution post tonsillectomy still maintained symptom resolution. It was noted that 26% of patients with initial persistence of non-febrile PFAPA symptoms still had associated symptoms. Also, 35% of patients with initial less/milder febrile episodes still had symptoms. Long-term gastrointestinal symptoms after tonsillectomy consisted of abdominal pain (40%) and nausea and emesis (33%) in patients with persistent fever symptoms as well as abdominal pain (12%) and nausea and emesis (29%) in patients with non-febrile symptoms.

This study demonstrates that tonsillectomy can ameliorate periodic fever in most pediatric patients with PFAPA. However, non-febrile symptoms can continue long term, even after tonsillectomy. Such symptoms can be gastrointestinal in nature, and it is imperative to make sure non-PFAPA conditions, such as inflammatory bowel disease, are not occurring in this patient population.

Moberg T, Rydenman K, Berg S, Fasth A, Wekell P. Long-term symptoms in periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis syndrome after tonsillectomy. Journal of Pediatrics; 2025: 114424.

FRONTIERS IN ENDOSCOPY, SERIES #93

Ablation of the Gastric Cardia for GERD: A Comprehensive Technical and Clinical Review

Sheza Malik,

Douglas G. Adler

Anti-Reflux Mucosal Ablation (ARMA) is an innovative endoscopic intervention for managing PPI-refractory GERD by enhancing the structural integrity of the gastroesophageal junction (GEJ). Utilizing controlled thermal ablation, ARMA induces localized mucosal fibrosis to reinforce the anti-reflux barrier. Clinical studies demonstrate significant improvements in GERD symptoms, acid exposure time, and DeMeester scores, with over 70% clinical success in one year. The procedure is well-tolerated, with manageable complications such as transient stenosis treated via endoscopic dilation. ARMA offers advantages over surgical fundoplication due to its reduced procedural complexity and minimally invasive nature. While early outcomes are promising, larger multicenter trials are needed to validate long-term efficacy and define optimal patient selection, particularly in those with mild to moderate GEJ abnormalities.

Introduction

Gastroesophageal reflux disease (GERD) is a highly prevalent condition. GERD is characterized by the retrograde movement of gastric contents into the esophagus, leading to symptoms such as heartburn, regurgitation, and atypical presentations like cough, chest pain, hoarseness, and laryngitis. GERD affects an estimated 20% of adults in Western populations and incurs significant healthcare costs while impairing quality of life.^1,2

Despite the widespread use of proton pump inhibitors (PPIs) as the first-line therapy, 30–40% of patients continue to experience symptoms despite adequate acid suppression.^3,4 Surgical interventions such as laparoscopic Nissen fundoplication are highly effective but are associated with complications like dysphagia and gas bloat syndrome and have a significant failure rate, necessitating the exploration of less invasive alternatives.^5,6,7

Anti-reflux mucosal interventions, including Anti-Reflux Mucosectomy (ARMS) and Anti-Reflux Mucosal Ablation (ARMA), have emerged as innovative endoscopic procedures aimed at improving the anatomical and functional integrity of the gastroesophageal junction (GEJ). These techniques are gaining traction as viable options for managing PPI-refractory GERD.⁸ This article will review the current status of ARMS and ARMA.

Pathophysiology of GERD and Role of the GEJ

The pathogenesis of GERD is multifactorial, involving structural and functional abnormalities of the GEJ.⁹ Key contributors include:

Impaired Lower Esophageal Sphincter (LES) Pressure: A hypotensive LES facilitates retrograde reflux.¹⁰

Hiatal Hernia: Alters the anatomical configuration of the GEJ and diaphragm, reducing its anti-reflux competency, and allowing acid-producing gastric mucosa above the diaphragm.¹¹

Transient LES Relaxations (TLESRs): Excessive, non-swallowing LES relaxations increase reflux events.¹²

Esophageal Clearance Dysfunction: Impaired peristalsis delays the clearance of refluxed material.¹³

Hill’s classification (grades I–IV) of the gastroesophageal flap valve provides a structural assessment of the GEJ, with grades II-IV associated with an increased risk of PPI-refractory GERD.^1,7 Endoscopic therapies like ARMA directly target the structural deficiencies of the GEJ, offering a minimally invasive alternative to surgical fundoplication

Evolution of Endoscopic Therapies

Endoscopic approaches to GERD management have advanced significantly, offering effective alternatives to traditional medical and surgical treatments.¹⁴ These approaches can be categorized into several techniques, as shown in Table 1.

1. Reconstructive Therapies:

○ Transoral Incisionless Fundoplication (TIF):Creates full-thickness plications to mimic surgical fundoplication. While effective, it is technically demanding, time-consuming, and requires specialized training and equipment.¹⁵

○ Magnetic Sphincter Augmentation (LINX): Places a ring of magnetic beads around the LES via laparoscopy. It has shown promise but is limited by MRI incompatibility, specific anatomical requirements, and risk of adverse events including dysphagia and device breakage, among others.¹⁶

2. Ablative Therapies:

○ Radiofrequency Ablation (RFA): Remodels LES muscle fibers using devices like Stretta but has variable efficacy.¹⁷

○ ARMS: Involves partial mucosal resection at the gastric cardia to induce scar-mediated tightening of the GEJ.⁸

○ ARMA: Focuses on controlled thermal ablation of the gastric cardia mucosa, leading to scar formation and enhanced flap valve integrity.⁸

Technical Considerations of ARMA

ARMA is a minimally invasive endoscopic procedure aimed at reinforcing the GEJ by inducing targeted mucosal scarring to enhance the anti-reflux barrier.¹⁸

The procedure begins with the patient positioned in the left lateral decubitus position. General anesthesia is typically used to ensure patient comfort and procedural safety, although conscious sedation may suffice in select cases based on the patient’s clinical status and tolerance. A high-definition gastroscope fitted with a transparent hood enhances visualization and precision. Ablation zones are marked in a butterfly-shaped pattern along the gastric side of the cardia, leaving two non-ablated segments to avoid circumferential scarring and mitigate the risk of stenosis. This pattern is crucial for ensuring localized scar formation without excessive narrowing of the lumen. Submucosal injection of saline mixed with indigo carmine dye is performed to lift the mucosa and create a protective cushion, safeguarding deeper layers from thermal injury during ablation.^17,18

Table 1. Comparative Analysis of Endoscopic Therapies for GERD

Therapy	Mechanism of Action	Ideal Patient Profile	Advantages	Challenges and Limitations
Transoral Incisionless Fundoplication (TIF)	Uses polypropylene fasteners to create full-thickness plications at the GEJ, replicating a partial fundoplication	– PPI-refractory GERD with Hill grade II/III – Hiatal hernia ≤2 cm – Normal esophageal motility	– Mimics surgical fundoplication – Avoids surgical incisions – Reduces regurgitation and improves LES function	– Requires specialized equipment and technical expertise – Limited by anatomical constraints (e.g., large hiatal hernias) – Recurrence rates in patients with anatomical defects
Radiofrequency Ablation (RFA)	Delivers radiofrequency energy to the LES, inducing controlled fibrosis and hypertrophy	– PPI-dependent GERD – Hypotensive LES without major anatomical defects	– Outpatient procedure – Minimal invasiveness – No need for general anesthesia	– Variable outcomes in symptom relief – Limited data on long-term efficacy – Less effective in patients with severe reflux or large hiatal hernias
Anti-Reflux Mucosectomy (ARMS)	Partial mucosal resection at the gastric cardia induces scar formation, creating a tighter GEJ	– PPI-refractory GERD with Hill grade II/III – GERD post-bariatric surgery – Moderate anatomical abnormalities	– Demonstrated efficacy in PPI-refractory cases – Improves acid exposure and esophagitis – Enhances flap valve mechanism	– Higher technical difficulty – Increased risk of perforation and post-procedural strictures – Requires expertise in endoscopic mucosal resection
Anti-Reflux Mucosal Ablation (ARMA)	Controlled thermal ablation of gastric cardia mucosa induces contraction and scarring to strengthen the GEJ	– PPI-refractory GERD with Hill grade II/III – Small (<3 cm) hiatal hernia – Normal or mildly impaired LES tone	– Safe and reproducible technique – Lower complication rates compared to ARMS – Effective in symptom relief and acid control	– Limited long-term follow-up data – Risk of transient stenosis (13.2%) treated with endoscopic dilation – Unsuitable for severe anatomical defects
Antireflux Mucosal Valvuloplasty (ARMV)	Combines mucosal resection with flap reconstruction to mimic natural anti-reflux barriers	– GERD with moderate anatomical GEJ disruption – Patients intolerant to long-term PPI use	– Innovative dual mechanism (scar contraction + mucosal flap) – Potentially superior anatomical restoration	– Experimental stage – Limited data from randomized controlled trials – Requires advanced endoscopic skills
Magnetic Sphincter Augmentation (LINX®)	Places a magnetic ring around the LES to enhance closure and reduce reflux	– PPI-refractory GERD without major anatomical abnormalities – Small (<2 cm) hiatal hernia	– Outpatient or short-stay procedure – Preserves normal swallowing and belching mechanisms	– Incompatible with MRI – Device erosion and migration risks – High costs and limited long-term outcome data

Mucosal ablation is typically conducted using electrocautery in spray coagulation mode. The generator settings commonly used for electrocautery include effect 2 and 50 W power, which deliver controlled thermal energy for uniform ablation. In some studies, argon plasma coagulation (APC) has been employed as an alternative, providing effective mucosal ablation while reducing the risk of deep thermal injury. When APC is used, the same generator settings are often applied to ensure consistent outcomes. While radiofrequency ablation (RFA) devices may be considered, APC remains the preferred method based on safety, availability, and efficacy data in the literature.^18,21 (Figure 1)

A crucial patient selection criterion is the presence and size of a hiatal hernia. ARMA is most effective in patients with small hernias (<2 cm). Larger hernias (>2 cm) typically require surgical repair, as ARMA does not address the anatomical displacement of the GEJ associated with larger hernias. Thus, a pre-procedure assessment, including endoscopy and esophageal manometry, is essential. Post-procedurally, patients are prescribed PPI therapy for 4 – 6 weeks to promote mucosal healing, minimize inflammation, and reduce the risk of complications such as ulcers or delayed bleeding. Follow-up includes reassessment of symptoms using validated GERD questionnaires, endoscopic examination, and, if indicated, 24-hour pH monitoring.¹⁸

Clinical Outcomes

ARMA has shown significant efficacy in improving GERD-related symptoms and objective reflux control. A 2024 international bi-center study reported a reduction in median GERD-HRQL scores from 26 to 11 at six months (P < 0.001), Acid Exposure Time (AET) fell from 5.3% to 0.7% (P = 0.003), alongside significant improvements in DeMeester scores. Follow-up data at 12 months indicated a clinical success rate of 70%, defined as a greater than 50% reduction in validated GERD questionnaire scores, suggesting durable symptomatic and reflux improvements over time.²³

A meta-analysis of 15 nonrandomized studies (n = 461) demonstrated a technical success rate of 100% and clinical success rates of 78% at six months, 72% at one year, and 73% at three years, with consistent outcomes across ARMS and ARMA. At one year, 64% of patients were off PPIs, with significant improvements observed in symptom scores, esophagitis resolution, and acid exposure time (P < 0.01). These findings underscore ARMA’s ability to potentially deliver durable symptom relief and effective reflux control, offering a promising therapeutic option for refractory GERD.⁸

Safety and Adverse Events

The safety profile of ARMA, while promising, reflects the early stages of adoption and ongoing evaluation of this emerging technology. In clinical studies, transient stenosis was observed in 13.2% of cases, all of which were effectively managed with endoscopic balloon dilation. Other adverse events included minor bleeding and mucosal ulceration, both of which resolved with conservative management, including short-term PPI therapy. Importantly, no perforations or severe adverse events, such as significant bleeding requiring transfusion or long-term complications, were reported in the available data. These findings highlight the need for ongoing studies to validate the long-term safety and risk profile of ARMA while acknowledging its manageable short-term complications.^23,24

Comparative Effectiveness of ARMA

Compared to ARMS and other endoscopic therapies, ARMA offers distinct clinical advantages. Its controlled thermal ablation approach avoids full-thickness mucosal resection, resulting in lower technical complexity, significantly shorter procedure times, and a reduced risk of perforation. This makes ARMA more accessible and less invasive for a broader range of patients. The procedure is particularly effective in patients with prior gastric cardia fibrosis (e.g., due to previous interventions or inflammation) or anatomical modifications, such as post-bariatric surgery anatomy or hiatal hernias smaller than 2 cm, thereby broadening its applicability.^{17, 21}

In a randomized trial comparing ARMA to PPI therapy, ARMA demonstrated superior symptom control, improved mucosal integrity, and significant reductions in acid reflux parameters, including acid exposure time and DeMeester scores. These findings support its role as an effective treatment for GERD refractory to pharmacological therapy. While short-term PPI therapy (approximately 4 – 6 weeks) is typically recommended post-procedure to promote mucosal healing, many patients experience reduced long-term dependence on PPIs due to the durable improvements provided by ARMA.

Limitations and Future Directions

While ARMA has shown promising short-term outcomes, several limitations remain. Most studies provide data for up to 12 months, leaving long-term durability uncertain. Additionally, the majority of evidence comes from single-center and small-scale trials, necessitating larger, multicenter randomized controlled trials to validate findings. Current studies also focus primarily on PPI-refractory GERD in patients with mild to moderate anatomical abnormalities, limiting generalizability. Future research should explore ARMA’s long-term durability, comparative efficacy with surgical fundoplication, emerging endoscopic techniques such as antireflux mucosal valvuloplasty (ARMV), and its cost-effectiveness in routine clinical practice.²⁷ Optimization of patient selection criteria, particularly anatomical and functional predictors of success, is crucial to further refine its role in GERD management.²⁵

Conclusion

ARMA is a novel endoscopic technique that is promising in the minimally invasive management of GERD. By targeting the gastroesophageal junction (GEJ) to enhance its structural integrity, ARMA has demonstrated effectiveness in reducing GERD symptoms, particularly in patients with PPI-refractory disease. However, as a relatively new intervention, its long-term efficacy and safety profile require further validation through robust, multicenter studies. While early evidence suggests ARMA may serve as a valuable addition to the therapeutic arsenal for GERD, its role relative to established medical and surgical treatments will be further defined as additional studies and data emerge.

References

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14. Hopkins J, Switzer N J, Karmali S. Update on novel endoscopic
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Published 2020 May 21.
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Augmentation for Gastroesophageal Reflux After
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Ablation for the Treatment of GERD. Gastroenterol Hepatol
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ablation (ARMA) as a new treatment for gastroesophageal
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1022.

April 2025 • Volume XLIX, Issue 4

Dispatches from the GUILD Conference, Series #67

What do Gastroenterologists Need to Know About Stomas?

Gilad Alon,

Michael Goldenshluger,

Stefan D. Holubar,

Miguel Regueiro

Intestinal stomas, whether from the small or large bowel, are the cornerstone of the surgical management of various gastrointestinal conditions, particularly in patients with inflammatory bowel disease (IBD) and rectal cancer. This review provides an overview of stoma types, indications, complications, and the critical role of preoperative and postoperative care. This highlights the necessity for collaboration between colorectal surgeons and gastroenterologists to optimize surgical planning, manage complex cases, and prevent complications. Stomas play a pivotal role in treating refractory diseases, high-risk surgical scenarios, and emergencies. Comprehensive care involving multidisciplinary teams that include stoma nurses, dietitians, and mental health professionals is essential for addressing stoma-related challenges, minimizing complications, and improving patient outcomes. By integrating medical and surgical expertise, healthcare teams can empower patients to adapt successfully and maintain high quality of life.

Introduction

Intestinal stomas involve the surgical exteriorization of either the small or large bowel through the anterior abdominal wall. These stomas, whether small or large, play vital roles in the treatment and management of various gastrointestinal diseases. In the United States, the estimated number of patients living with a stoma (ostomates) ranges from 750,000 to 1 million, with approximately 150,000 new ostomies constructed each year.¹ A comprehensive understanding of the surgical planning and decision-making processes involved in constructing ostomies, the different types of stomas, their potential complications, and the preoperative and postoperative care required, are essential for the successful treatment of patients with ostomies.²

1. Know the anatomy	Exactly what kind of stoma?
	How much proximal and distal bowel?
	Plans for restoration of intestinal continuity?
2. Stoma complications	Poor pouching? Refer to Ostomy nursing
	Anatomic issue? Refer to surgeon
	Manifestation of systemic disease? Treat as appropriate
3. High output enterostomy	Avoid sugar (diarrheogenic)
	Isotonic oral rehydration solutions
	Stool bulking “thicken it up”
	Antimotility agents “slow it down”
	Parental fluid and/or nutritional support as needed

Table 1. Key points:
What do Gastroenterologists Need to Know About Stomas?

A summary of key points and stoma-related terms is presented in Tables 1 and 2. Stoma is the Greek word for mouth and is defined as an artificial opening of a hollow organ; an ostomy refers to an opening of the bowel brought to the skin to allow egress of intestinal fluids through the os, but “-ostomy” may also refer to tubes placed in GI organs that cannot reach the skin (i.e., duodenostomy, gastrostomy).

Types of Stomas

Large bowel stoma: colostomy

Colostomies are constructed using the large intestine, most commonly the distal transverse, descending, or sigmoid colon. The more distal the colostomy, the better the functional outcomes, as stool consistency becomes more dehydrated, and stool frequency decreases.³ Compared to small bowel ostomies, colostomies have firmer stool consistency, easier pouch management, and a lower incidence of systemic complications such as electrolyte disturbances and dehydration, which are more common in small bowel ostomies.³ Colostomies generally offer better functionality given the ability of the large bowel proximal to the colostomy to absorb water and electrolytes with a resultant neutral pH (as opposed to the mildly acidic succus from ileostomies which results in universal skin irritation and the need for maturation of the os in a budded manner). Given the neutral pH of stool from a colostomy, it may be budded (matured) and protrude a few centimeters above the skin or lie flush with the skin surface, depending on patient-specific factors, such as body habitus, surgical technique, and the bowel’s length of reach to make a tension-free colocutaneous anastomosis whenever possible. Right colonic or proximal transverse colostomies are generally avoided, resulting in feculent diarrheal output as opposed to the thicker stool from distal colostomies or non-feculent succus entericus output from an ileostomy (which is generally preferred compared to a right-sided colostomy). A rare form of large-bowel stoma is an appendicostomy which may be used for antegrade colonic irrigation (i.e., the Malone antegrade continent enema [MACE] procedure).

Colostomies (Figure 1) can be fashioned as a loop colostomy, an end colostomy, or a “double barrel” colostomy depending on the clinical indication and surgical approach. A mucus fistula is an ostomy of the defunctionalized distal segment that is matured as a complete or partial opening to allow drainage of mucus and secretions from the distal segment and is critical to decompress the distal segment when a distal obstruction is present. An end colostomy is typically chosen when making a permanent colostomy, such as during an abdominoperineal resection for low rectal cancer or may be chosen in an emergency surgery after a segmental resection (e.g., surgery for perforated diverticulitis). In contrast, a loop colostomy or double-barrel colostomy may be selected when future bowel reconstruction is anticipated or when there is a need for distal decompression. A double-barrel colostomy is distinguished from a loop colostomy by its separation into two distinct stomas, one for the proximal bowel to divert feces and the other for the distal bowel to allow mucus drainage, whereas a loop colostomy typically involves a single stoma with two openings.

Category	Organ	Ostomy
Ostomies	Jejunum	Jejunostomy
	Ileum	Ileostomy
	Appendix	Appendicostomy
	Colon	Colostomy
	Urinary tract	Urostomy
Tubes	Stomach	Gastrostomy
Tubes	Duodenum	Duodenostomy
Intestinal anastomoses	Small bowel	Enteroenterostomy
	Ileocolic	Ileocolostomy
	Colon	Colocolostomy
	Colorectum	Coloproctostomy
	Total colectomy	Ileoproctostomy (aka ileorectal anastomosis)

Table 2. Summary of Ostomy Terminology

Small bowel stoma: enterostomy (Ileostomy and Jejunostomy)

Small bowel ostomies such as ileostomies and jejunostomies are constructed using the small intestine. They are most commonly fashioned from the terminal ileum but can be created from any part of the small bowel, depending on the clinical scenario. Generally, the more proximal the small bowel ostomy, the higher the sensitivity to systemic complications.¹ Ileostomies are indicated for conditions requiring bowel diversion or resection of either the small or large intestine when anastomosis to restore bowel continuity is not feasible, either temporarily or permanently. Jejunostomies are made from the more proximal jejunum and avoided as much as possible due to their morbid nature, given their significantly higher output of acidic, electrolyte-rich succus entericus resulting in total parenteral nutrition dependence and may be classified as low- or high- jejunostomies, less than or greater than 30 cm from the ligament of Treitz, respectively.

Compared to colostomies, ileostomies result in liquid to semi-liquid stool output (ideally yogurt consistency) owing to the lack of colonic reabsorption of water and electrolytes. Consequently, patients with ileostomies are at a higher risk of dehydration and electrolyte disturbances (e.g., hypokalemia and hyponatremia), as well as local issues such as skin irritation due to frequent stool output. Therefore, ileostomies must be matured such that the os is ideally 2 cm above the skin in a “spigot” manner (Figure 2) such that the stool egresses directly into the ostomy appliance bag to minimize skin irritation. Ileostomies (and jejunostomies) may be fashioned as an end ileostomy, loop ileostomy, or end loop.

An end ileostomy (Figure 2) involves bringing the ileum through the abdominal wall to create a single stoma and is often permanent and is typically performed after total proctocolectomy or when bowel continuity cannot be restored. End ileostomies may be fashioned in several ways (Figure 3). An end-loop ileostomy made by bringing a loop proximal to the stapled-off distal segment is brought out, often chosen when there are difficulties in getting the bowel to reach 2 cm above the surface due to the shorter divided mesentery associated with a true end ileostomy, while in an end-loop the intact mesentery supplying the loop allows for additional length. When there is a distal obstruction, an end ileostomy may be performed with a mucus fistula as an additional small opening to allow drainage of mucus and secretions from the distal bowel segment when necessary.

A loop ileostomy (Figure 4) is commonly used for temporary bowel diversion to protect the downstream anastomosis after intestinal resection. A loop of the small bowel is brought to the surface and opened, creating a stoma with two openings; the proximal limb diverts stool to the exterior, while the distal limb allows mucus drainage from the downstream bowel. Loop ileostomies are typically easier to reverse than end ileostomies, making them the preferred choice for temporary diversion.

Continent ileostomy (Figure 5), although less commonly performed today, involves the creation of an internal reservoir, such as a Kock pouch. This reservoir allows stool to be stored and drained via intermittent catheterization. Continent ileostomies are typically chosen by patients who wish to avoid a traditional end ileostomy and are not candidates for restorative surgery with an ileal pouch-anal anastomosis (IPAA) after total proctocolectomy or personal preference.

Indications for Stoma Creation

Temporary diversion

Temporary bowel diversion is frequently required in specific clinical scenarios in which protecting the distal anastomosis is critical. For example, in patients undergoing low rectal anastomosis after neoadjuvant radiotherapy or after IPAA, a temporary stoma diverts the fecal stream to allow the pouch to heal. Risk factors for anastomotic leakage include high-dose/prolonged corticosteroids, malnutrition, anemia, smoking, and other risk factors.⁴ Of note, ileostomies do not decrease anastomotic leak rates but rather decrease the severity of leaks when they occur, thus allowing less invasive treatment and facilitating successful leak management and healing by methods such as percutaneous drains and endoluminal vacuum therapy.^5-8 In cases of extensive perianal disease, such as severe perianal Crohn’s disease or complex fistulas, temporary diversion may be necessary to facilitate perineal wound healing and reduce ongoing inflammation. Similarly, in the presence of active pelvic infections and inflammation — such as colovesical and colovaginal fistulas secondary to diverticulitis or malignancy — temporary diversion before or at the time of definitive surgical repair is often required to facilitate successful restoration of intestinal continuity.⁹

Permanent ostomies

In some cases, a permanent ostomy is planned from the outset, whereas in others, an initial temporary ostomy may become permanent due to unforeseen clinical factors or patient preference. Abdominoperineal resection (APR) is a common indication for permanent colostomy in patients with low rectal cancer, where sphincter preservation is not feasible. Another scenario requiring permanent bowel diversion is total proctocolectomy without ileal pouch creation, typically performed in patients with ulcerative colitis or familial adenomatous polyposis who are either not candidates for or decline an ileal pouch-anal anastomosis.

Emergencies

In emergency settings, primary bowel reconstruction is often contraindicated, which necessitates stoma creation. Emergency bowel resection, frequently required for patients presenting with perforation, obstruction, or ischemia, may necessitate a stoma when factors such as hemodynamic instability, active infection, or poor tissue perfusion preclude a safe anastomosis. Trauma, whether from penetrating or blunt abdominal injuries, may also warrant temporary or permanent stoma creation to manage bowel injuries and prevent further complications.

Stomas in Inflammatory Bowel Disease (IBD)

Despite advances in medical therapy, including biologics and small molecules, a subset of patients with IBD still require surgical intervention. Surgery remains necessary for those with refractory disease, abdominal complications such as strictures, perforations, or abscesses, and severe perianal Crohn’s disease.^10-12 It is estimated that approximately 20–30% of ulcerative colitis patients will require a colectomy during their lifetime, while up to 58% of Crohn’s disease patients will undergo at least one major abdominal surgery within 20 years of diagnosis.^11-13

Stomas, typically ileostomies, are often indicated in IBD cases where anastomosis is either high-risk or should be avoided. Factors that increase the risk of anastomotic leakage include severe malnutrition, prolonged steroid use, and emergency surgical indications such as abdominal sepsis or bowel obstruction.

Stoma in Ulcerative Colitis

Total proctocolectomy is typically performed with or without IPAA for ulcerative colitis (UC). To optimize outcomes and reduce morbidity, this procedure is usually staged. The 3-staged approach is most common these days, starting with a total abdominal colectomy with end ileostomy (Stage 1), leaving the rectum intact, followed by a completion proctectomy with IPAA and temporary diverting loop ileostomy (Stage 2); finally, diverting loop ileostomy reversal (Stage 3) after pouch healing is confirmed. Other staging strategies include a 2-stage, starting with a total proctocolectomy with IPAA and temporary loop ileostomy (Stage 1), followed by ileostomy reversal, and a modified 2-stage which is similar to a 3-stage, but the diverting loop ileostomy is omitted in the 2nd stage. Of note, approximately 10% of UC patients after Stage 1 of a 3-stage will have such a dramatic improvement in their health and quality of life they choose to keep it permanently and forgo IPAA, while others who are not candidates for IPAA choose a continent ileostomy. Another 5-10% of patients will require pouch excision and end ileostomy due to treatment-refractory leaks or Crohn’s-like disease of the pouch.

Agent	Adult Oral Dose	Maximum Daily Dose	Notes
Loperamide	1 – 4 two mg tablets or caplets (not capsules) QID 30 min. before meals & QHS	16 tabs	OTC but can also prescribe for some
Diphenoxylate-atropine	1 – 2 2.5 mg tabs QID 30 min. before meals & QHS	8 tabs	Opioid script, non-sedating
Codeine	15 – 60 mg QID 30 min. before meals & QHS	240 mg	Opioid script
Deodorized tincture of opium	0.3 – 0.6 mL sublingual QID 30 min. before meals & QHS	6 mL	Opioid script
Octreotide	300 – 1200 ug IV/day divided	1200 ug	Provided in TPN; monitor LFTs
Sandostatin	10, 20, or 30 mg IM q28 days	30 mg/ month	Depot injection; monitor LFTs & glucose

Table 4. Antimotility Agents

Stoma in Crohn’s disease

In Crohn’s disease, stomas are frequently necessary to manage complications such as strictures, fistulas, abscesses, and perforations.^14,15 “Temporary” diversion with an ileostomy or colostomy may also be required in severe perianal disease to facilitate wound healing and symptom control, but become permanent in the vast majority.^16,17 Additionally, in high-risk conditions such as malnutrition or sepsis, primary anastomosis carries an unacceptably high failure rate, making stoma creation the preferred surgical option.⁵ Ultimately, the decision to create a stoma in IBD should be guided by both the patient’s clinical status and long-term disease trajectory.

Endoscopy in Stoma Patients

Prior to performing ileoscopy or colonoscopy in ostomates, it is important for the endoscopist to focus on the exact anatomy of the ostomy and the segments that need endoscopic interrogation. For example, if a patient has undergone Hartmann’s colostomy, it also has a distal segment known as Hartmann’s pouch (rectal stump), which requires assessment prior to colostomy reversal and routine endoscopic surveillance if the stump is kept in place permanently. For ileostomies, it should be kept in mind the bowel wall is thinner and more prone to incidental perforation compared with the colon. When scoping an apparent loop ileostomy, it may be an end-loop, and in this case, excessive pressure trying to intubate the stapled distal limb may result in perforation and enterocutaneous fistula formation.

Stoma Complications

The construction of an ostomy, whether a small bowel or colonic stoma, is associated with a substantial morbidity rate, with reported complication rates ranging from 20% to 80%.¹ Among the most common issues are peristomal skin complications and parastomal hernias. One large population-based study analyzing over 4,200 patients found an overall surgical complication rate of 37% in elective ostomy cases and 55% in emergency ostomy cases.¹⁸

Peristomal skin irritation, hyperplastic granulation tissue, and mucocutaneous separation

(Figure 6) Peristomal skin is particularly vulnerable to irritation and breakdown due to stool leakage or ill-fitting appliances. Contact dermatitis may occur secondary to appliance adhesive. Hyperplastic granulation tissue may result from the use of a tight-fitting appliance. Treatment involves optimizing pouching techniques, applying barrier creams, and revising the stoma if necessary. Mucocutaneous separation and peristomal ulceration (Figure 7) may be thought of as a failure of enterocutaneous anastomosis to heal, and fastidious skin care may expedite healing.

Stoma retraction and strictures

(Figure 7) Retraction below the skin level can cause a poor fit and difficulty in waste elimination. Less commonly, stenosis may develop because of mechanical causes (such as scar formation) or inflammatory changes, leading to impaired stoma function. Management options include dietary modification, dilation, or surgical revision.

Peristomal fistulae

(Figure 8) Peristomal infections can develop due to local inflammation or stool leakage, potentially resulting in abscess or fistula formation. Management may require surgical drainage and optimization of stoma care.

Peristomal pyoderma gangrenosum

(Figure 9) Chronic irritation can lead to inflammatory skin conditions including pyoderma gangrenosum (PG), which presents as painful ulcerations around the stoma. Management typically requires topical or intralesional corticosteroids and may require surgical revision in refractory cases. Surgical repositioning of the stoma is performed in severe cases, particularly when bowel continuity cannot be restored but is prone to recurrence if the underlying inflammatory disorder is not addressed with systemic advanced therapies. A stepwise algorithmic approach for management and treatment of peristoma PG is shown in Figure 10.

Prolapse and parastomal hernias

(Figure 11) Excessive protrusion of the stoma beyond the abdominal wall may lead to cosmetic concerns, difficulty in pouching, ischemia, or even bowel obstruction. Treatment depends on the severity and ranges from non-surgical interventions (e.g., manual reduction, application of sugar to draw out the edema from the prolapsed segment, and support belts) to surgical revision. Prolapse is typically secondary to a parastomal hernia.

A parastomal hernia is defined as an incisional hernia that occurs at the site of an abdominal wall stoma. The reported incidence of parastomal hernias varies widely, depending on factors such as the length of follow-up and the type of stoma created. The incidence of end colostomies is slightly higher, reaching up to 48%, whereas that of loop ileostomies is reported to be up to 30.8%.^18,19 Although most parastomal hernias are asymptomatic and can therefore be treated conservatively, parastomal hernias can significantly impair the quality of life and cause symptoms such as pain, discomfort, and, in severe cases, bowel obstruction. Compared with other incisional hernias, parastomal hernias are more challenging to repair because of the permanent defect in the abdominal wall created by the stoma. This complexity often necessitates careful preoperative planning and use of specialized surgical techniques for hernia repair.^20,21

Nutrition in Ostomates

Dietary adjustments for ostomates can be divided into the early and late postoperative phases. In the early phase, the primary considerations were the patient’s preoperative nutritional status and underlying condition. In cases of severe metabolic deconditioning, 10–14 days of enteral or parenteral nutritional therapy may be beneficial before surgery and directly affect postoperative recovery.²² Early physiological enteral nutrition after surgery improves intestinal adaptation, preserves the intestinal flora and enteric immune system, and is cost effective when compared with parenteral feeding.^22,23 Postoperatively, the diet is usually introduced gradually and typically consists of low-fiber foods to minimize stool production, reduce strain, and prevent obstruction, as surgical manipulation can lead to bowel edema.²⁴

In the long term, dietary adjustments for ostomates should be individualized based on three key factors: type of stoma, output volume, and the patient’s underlying condition. Generally, the aim is to maintain a healthy and rich diet, including all nutrients and fibers, as long as stoma function is optimal. After the initial recovery period (typically 6-8 weeks), it is recommended that new foods be introduced slowly and in small quantities, one at a time, as it simplifies the process of eliminating them if issues arise.²⁵

Dietary adjustments for colostomy patients

The diet of patients undergoing colostomy tends to be easier to manage than that of patients undergoing ileostomy. For long-term management, especially for patients with a permanent colostomy, maintaining a healthy BMI is crucial, as obesity and weight gain have been associated with colostomy retraction and symptomatic parastomal hernias.¹⁵ Although no specific diet has been proven effective after colostomy formation, a diet rich in complex carbohydrates and low in fat (while incorporating medium-chain triglycerides) may be beneficial. It is important to monitor for potential deficiencies in fat-soluble vitamins (A, D, E, and K), as well as in fatty acids. After the early postoperative period, including higher-fiber foods such as brown rice or whole wheat bread for patients with colostomy may help prevent constipation.²⁶

Dietary adjustments in patients with ileostomies

After the formation of an ileostomy and during the early postoperative period, stoma output is usually unpredictable and may remain elevated for 1–3 months. When the entire colon is absent or not in continuity, patients lose the endogenous vitamins and nutrients typically produced by the gut microbiota, including vitamins K and B, folic acid, and short-chain fatty acids.²⁶ In addition, the absorption of fat and niacin is much lower than that in patients with a colostomy. Hence, these patients should be monitored for their fat intake and the levels of fat-soluble vitamins (A, D, E, and K), along with vitamin B12, which is absorbed in the ileum by intrinsic factors. For ileostomy patients, especially those with a high-output stoma, the energy requirements may increase by up to 30%.²⁷ To meet these needs, it is essential to increase the caloric content of the diet, which can be achieved either through dietary modifications or oral nutritional supplements. During the first year of recovery, patients may require multivitamin supplements.²⁵ To minimize fluid loss and reduce gastric fluid production, it is recommended that patients avoid drinking fluids 30 min before and after meals. The type of fluid consumed is also important, as carbonated beverages can increase the gas in the stoma bag, leading many patients to limit or avoid them. It is helpful to reduce the amount of food consumed per meal, while increasing the number of meals throughout the day.²⁸

After the first 6–8 weeks post-surgery, patients should be encouraged to introduce more fruits and vegetables, provided their stoma output has normalized in both volume and consistency.²⁴Tolerance to fiber varies among individuals, with some patients being able to resume a high-fiber diet, while others may need to gradually reintroduce these foods or avoid certain items altogether. For ileostomy patients, some foods should be consumed with caution, as they may pose a risk of causing stoma blockages (popcorn, apple peels, whole corn, bean sprouts, dried fruit, and nuts) and excessive gas or unpleasant odors (beans/pulses, cabbage, broccoli, cauliflower, mushrooms, onions, and alcohol).²⁸ Additionally, patients with ileostomy may develop lactose intolerance after surgery due to changes in gut function. Therefore, they should avoid dairy products if they experience abdominal cramps or watery output.

High output enterostomy (HOE) and electrolyte management

Dehydration and electrolyte imbalances are the leading causes of hospital readmission following ileostomy formation and are responsible for up to 10% of readmissions within 60 days post-surgery; the most common postoperative losses in patients undergoing ileostomy are fluid, sodium, potassium, and magnesium.^29,30 Table 3 shows electrolyte replacement options. Of note, magnesium sulfate supplements are diarrheogenic, and Mag Plus Protein (Miller Pharmaceutical Group) may be recommended to avoid obligate fluid losses associated with magnesium sulfate supplementation. During the first 6–8 weeks, patients may lose 1200–2000 ml of fluid and 120–200 mmol of sodium per day. However, after approximately eight weeks, the ileum typically undergoes adaptation, leading to a reduction in fluid losses.²⁸ During the immediate postoperative period; therefore, close monitoring of renal function and electrolyte balance is essential. These assessments should be repeated at follow-up appointments within a month or sooner if any clinical signs arise. A stepwise algorithmic approach for managing HOE is recommended (Figure 12), which focuses on isotonic oral fluid repletion, stool bulking, and antimotility agents. A summary of antimotility agents is shown in Table 4. Patients with HOE, defined as producing >1500 ml/day after adaptation, are recommended to avoid sugary drinks and foods that cause osmotic diarrhea, avoid hypotonic fluids, and instead consume an additional 1000 ml of oral rehydration solution to replace the lost electrolytes.³¹ Unlike typical physiological responses, patients should be advised against increasing fluid intake of hypotonic fluids such as water, tea, or juice, as these hypotonic fluids may cause greater fluid loss from the stoma and instead use a rehydration solution.

Role of Multidisciplinary Care

Patients with ostomies, especially IBD, who require an ostomy, should be cared for by a multidisciplinary team that includes a gastroenterologist, colorectal surgeon, dietitian, pharmacist, social worker, psychologist, and a stoma therapist. Early involvement of colorectal surgeons is crucial for discussing the procedure, setting expectations, reassessing nutritional status, and possibly offering nutritional prehabilitation through enteral or parenteral feeding.

Stoma nurses are essential for providing education, support, and managing various stoma-related complications. The involvement of a mental health specialist and an ostomy nurse has been shown to enhance ostomy acceptance, reduce complications, improve quality of life, and are associated with shorter hospital stays.³²

Conclusion

Enterostomies remain a cornerstone of the surgical management of gastrointestinal conditions, particularly in patients with complex IBD. The creation of an intestinal stoma can profoundly reshape a patient’s life, often presenting unique challenges and risks, including complications and potential impacts on the quality of life. Enterostomies play a critical role in managing refractory diseases, complications, and surgical recovery in patients with IBD.

The success of stoma creation and its subsequent management relies heavily on the collaborative expertise of a multidisciplinary team that includes colorectal surgeons and gastroenterologists. This partnership ensures tailored surgical planning, precise execution, and vigilant postoperative care, which are essential for minimizing complications and supporting patients in achieving the best possible outcome. By integrating medical and surgical approaches, healthcare teams can empower ostomy patients to adapt and lead fulfilling lives, even in the face of chronic illnesses.

References

1. Malik T, Lee MJ, Harikrishnan AB. The incidence of stoma related morbidity – a systematic review of randomised controlled trials. Ann R Coll Surg Engl. Sep 2018;100(7):501-508. doi:10.1308/rcsann.2018.0126

2. Davis BR, Valente MA, Goldberg JE, et al. The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for Ostomy Surgery. Dis Colon Rectum. Oct 1 2022;65(10):1173-1190. doi:10.1097/DCR.0000000000002498

3. Gooszen AW, Geelkerken RH, Hermans J, Lagaay MB, Gooszen HG. Quality of life with a temporary stoma: ileostomy vs. colostomy. Dis Colon Rectum. May 2000;43(5):650-5. doi:10.1007/BF02235581

4. Guyton K, Kearney D, Holubar SD. Anastomotic Leak after Ileal Pouch-Anal Anastomosis. Clin Colon Rectal Surg. Nov 2021;34(6):417-425. doi:10.1055/s-0041-1735274

5. Neary PM, Aiello AC, Stocchi L, et al. High-Risk Ileocolic Anastomoses for Crohn’s Disease: When Is Diversion Indicated? J Crohns Colitis. Jul 25 2019;13(7):856-863. doi:10.1093/ecco-jcc/jjz004

6. Alipouriani A, Hull T, Lipman J, et al. Diagnosis and treatment of primary ileal pouch leaks: a 27-year experience at a referral center. J Gastrointest Surg. Jun 2024;28(6):860-866. doi:10.1016/j.gassur.2024.03.015

7. Alipouriani A, Lavryk O, Lipman J, et al. Ileoanal pouch salvage rates with endoluminal vacuum therapy for early vs late anastomotic leaks. J Gastrointest Surg. Dec 2024;28(12):1976-1982. doi:10.1016/j.gassur.2024.09.009

8. Uchino T, Lincango EP, Lavryk O, et al. Long-term ileoanal pouch survival after pouch urinary tract fistulae. Tech Coloproctol. Jun 25 2024;28(1):72. doi:10.1007/s10151-024-02948-w

9. DeLeon MF, Sapci I, Akeel NY, Holubar SD, Stocchi L, Hull TL. Diverticular Colovaginal Fistulas: What Factors Contribute to Successful Surgical Management? Dis Colon Rectum. Sep 2019;62(9):1079-1084. doi:10.1097/DCR.0000000000001445

10. Barnes EL, Lightner AL, Regueiro M. Perioperative and Postoperative Management of Patients With Crohn’s Disease and Ulcerative Colitis. Clin Gastroenterol Hepatol. May 2020;18(6):1356-1366. doi:10.1016/j.cgh.2019.09.040

11. Holubar SD, Pendlimari R, Loftus EV, Jr., et al. Drivers of cost after surgical and medical therapy for chronic ulcerative colitis: a nested case-cohort study in Olmsted County, Minnesota. Dis Colon Rectum. Dec 2012;55(12):1258-65. doi:10.1097/DCR.0b013e31826e4f49

12. Patel KV, Darakhshan AA, Griffin N, Williams AB, Sanderson JD, Irving PM. Patient optimization for surgery relating to Crohn’s disease. Nat Rev Gastroenterol Hepatol. Dec 2016;13(12):707-719. doi:10.1038/nrgastro.2016.158

13. Holubar SD, Lightner AL, Poylin V, et al. The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Surgical Management of Ulcerative Colitis. Dis Colon Rectum. Jul 1 2021;64(7):783-804. doi:10.1097/DCR.0000000000002037

14. Duraes LC, Holubar SD, Lipman JM, et al. Redo Continent Ileostomy in Patients With IBD: Valuable Lessons Learned Over 25 Years. Dis Colon Rectum. Mar 1 2023;66(3):419-424. doi:10.1097/DCR.0000000000002619

15. McKenna NP, Bews KA, Habermann EB, Dozois EJ, Lightner AL, Mathis KL. What Factors Are Associated With the Eventual Need for an Ileostomy After Total Abdominal Colectomy and Ileosigmoid or Ileorectal Anastomosis for Crohn’s Colitis in the Biologic Era? Dis Colon Rectum. Apr 2020;63(4):504-513. doi:10.1097/DCR.0000000000001556

16. Lightner AL, Steele SR, Delaney CP, et al. Colonic disease recurrence following proctectomy with end colostomy for anorectal Crohn’s disease. Colorectal Dis. Sep 2021;23(9):2425-2435. doi:10.1111/codi.15777

17. Holubar SD, Keller J, Cooper L. When Patients With IBD Require an Ostomy: Evidence-Based Answers to 10 Common Clinical Questions in IBD Surgery. Am J Gastroenterol. Feb 1 2025;120(2):268-271. doi:10.14309/ajg.0000000000002914

18. Shabbir J, Britton DC. Stoma complications: a literature overview. Colorectal Dis. Oct 2010;12(10):958-64. doi:10.1111/j.1463-1318.2009.02006.x

19. Obi M, Beffa L, Melland-Smith M, et al. The rate of ileostomy site incisional hernias: more common than we think? Hernia. Dec 2024;28(6):2311-2320. doi:10.1007/s10029-024-03163-0

20. Hansson BM, Slater NJ, van der Velden AS, et al. Surgical techniques for parastomal hernia repair: a systematic review of the literature. Ann Surg. Apr 2012;255(4):685-95. doi:10.1097/SLA.0b013e31824b44b1

21. Israelsson LA. Parastomal hernias. Surg Clin North Am. Feb 2008;88(1):113-25, ix. doi:10.1016/j.suc.2007.10.003

22. Fernandez-Galvez A, Rivera S, Duran Ventura MDC, de la Osa RMR. Nutritional and Educational Intervention to Recover a Healthy Eating Pattern Reducing Clinical Ileostomy-Related Complications. Nutrients. Aug 20 2022;14(16)doi:10.3390/nu14163431

23. Mukhopadhyay A, Maity D, Dey R, Choudhury KB, Das G, Bhattacharya U. Can Postoperative Nutrition be Favourably Maintained by Oral Diet in Patients with Emergency Temporary Ileostomy? A Tertiary Hospital Based Study. J Clin Diagn Res. Dec 2015;9(12):PC04-8. doi:10.7860/JCDR/2015/15220.6879

24. Migdanis A, Migdanis I, Koukoulis GD. Nutritional Considerations in Colorectal Surgery in Diverting Ileostomy Patients: A Review. Cureus. Nov 2023;15(11):e48102. doi:10.7759/cureus.48102

25. Michonska I, Polak-Szczybylo E, Sokal A, Jarmakiewicz-Czaja S, Stepien AE, Deren K. Nutritional Issues Faced by Patients with Intestinal Stoma: A Narrative Review. J Clin Med. Jan 8 2023;12(2)doi:10.3390/jcm12020510

26. Fulham J. Providing dietary advice for the individual with a stoma. Br J Nurs. Jan 24-Feb 13 2008;17(2):S22-7. doi:10.12968/bjon.2008.17.Sup1.28146

27. Medlin S. Nutritional and fluid requirements: high-output stomas. Br J Nurs. Mar 22-Apr 11 2012;21(6):S22-5. doi:10.12968/bjon.2012.21.Sup6.S22

28. Gasche R. Diet and stoma care. Br J Community Nurs. Sep 2 2022;27(9):444-448. doi:10.12968/bjcn.2022.27.9.444

29. Akesson O, Syk I, Lindmark G, Buchwald P. Morbidity related to defunctioning loop ileostomy in low anterior resection. Int J Colorectal Dis. Dec 2012;27(12):1619-23. doi:10.1007/s00384-012-1490-y

30. Liu C, Bhat S, Sharma P, Yuan L, O’Grady G, Bissett I. Risk factors for readmission with dehydration after ileostomy formation: A systematic review and meta-analysis. Colorectal Dis. May 2021;23(5):1071-1082. doi:10.1111/codi.15566

31. Cuerda C, Pironi L, Arends J, et al. ESPEN practical guideline: Clinical nutrition in chronic intestinal failure. Clin Nutr. Sep 2021;40(9):5196-5220. doi:10.1016/j.clnu.2021.07.002

32. Levy LC, Coburn ES, Choi S, Holubar SD. The management of the hospitalized ulcerative colitis patient: the medical-surgical conundrum. Curr Opin Gastroenterol. Jul 2020;36(4):265-276. doi:10.1097/MOG.0000000000000637

April 2025 • Volume XLIX, Issue 4

Nutrition Reviews in Gastroenterology, SERIES #22

Nutrition Therapies for Managing Gastrointestinal Symptoms During Pregnancy

Christine L. Scarcello,

Kelly Issokson,

Puja V. Khanna

Gastrointestinal symptoms of pregnancy are common and can interfere with quality of life and the ability to consume adequate oral intake. The occurrence of symptoms varies throughout pregnancy; while nausea and vomiting predominantly affect patients during the first trimester, other symptoms may progressively worsen throughout the length of gestation without relief until the postnatal period. Common symptoms prevalent during pregnancy include nausea and vomiting, gastroesophageal reflux, constipation, and diarrhea. Clinicians can introduce nutritional interventions for the management of mild symptoms prior to pharmacologic intervention, but it is important to monitor for adequate relief. Individuals with chronic GI disorders – such as inflammatory bowel disease, gastroparesis, metabolic dysfunction-associated steatotic liver disease, and irritable bowel syndrome – face an increased risk for malnutrition and may require ongoing care from a gastroenterologist and a registered dietitian during pregnancy.

Introduction

The forty-week period of gestation is a time of heightened need for nutritional optimization for both the parent and developing fetus. Changes in the gastrointestinal (GI) tract result from hormonal and physiologic intra-abdominal adaptations during pregnancy and may quickly affect quality of life as well as adequate oral nutrition. The American College of Obstetrics and Gynecology (ACOG) and former Institute of Medicine (IOM) recommendations for specific gestational weight gain ranges for pregnancy are based on pre-pregnancy Body Mass Index (BMI) (See Table 1).¹ While these ranges continue to be researched and updated, clinicians should still measure adequacy of weight gain throughout gestation to avoid over- or undernutrition. A recent systematic review of over one million pregnant individuals revealed that 23% did not meet weight gain parameters and 47% exceeded them.² Monitoring gestational weight milestones is important to prevent poor fetal development and pregnancy outcomes, such as small-for-gestational-age (SGA) infants and preterm birth when undernutrition is present.² Pregnancy-related GI symptoms can also affect quality of life,and managing mild pregnancy GI symptoms safely and adequately through diet is the recognized first-line treatment (See Table 2).^3-6 The purpose of this review is to identify the most common GI symptoms experienced during pregnancy, highlight the first-line nutrition therapies for these ailments, and discuss updates and considerations for pregnant individuals diagnosed with GI disorders.

BMI	Classification	Gestational Weight Gain Goals
<18.5	Underweight	28-40 lbs
18.5-24.9	Normal	25-35 lbs
25-29.9	Overweight	15-25 lbs
>30	Obese	11-20 lbs

Table 1.
Gestational Weight Gain per ACOG/IOM Recommendations (2013)¹

Common Gastrointestinal
Symptoms During Pregnancy

Nausea and Vomiting

Nausea and vomiting (NV) in pregnancy is the most common GI symptom that affects between 50-90% of pregnant individuals and interferes the most with adequate oral intake and ability to reach pregnancy weight goals.^3,4,7 Beginning early in the first trimester and subsiding after 20 weeks, the etiology of NV can be attributed to various hormonal changes.^8,9 For example, increased estrogen and human chorionic gonadotropin affect GI motility while progesterone inhibits motility and can cause delayed gastric emptying.^8,9 Clinicians should be sure to rule out any other causes of nausea during pregnancy, such as gastroenteritis, biliary disease, gastroparesis (GP), gastroesophageal reflux disease (GERD), peptic ulcers, pancreatitis, hepatitis, pyelonephritis, appendicitis, and irritable bowel syndrome (IBS).^4,9

Common GI Symptoms	Practical Nutrition-Related Interventions for Patients
Nausea and Vomiting	Texture modification for fruits, vegetables, and proteins to soft and small particle size: fork-tender consistency, blended, steamed, stewed, slow-baked, roasted. Smaller meals with more frequency to ensure adequate nutrient intake. Supplementation with ginger and Vitamin B6.⁸ Limit offending foods (based on smell, taste, or texture) that worsen nausea. The use of prenatal vitamin and mineral supplementation one month prior to conception can reduce occurrence and severity.⁴
Hyperemesis Gravidarum	Emphasis on calories and protein at each meal.⁴ Electrolyte and micronutrient monitoring and replacement. EN or PN support if intake remains inadequate.
Gastroesophageal Reflux Disorder	Smaller meals with more frequency to ensure adequate nutrient intake. Final meal or snack consumed 2-3 hours before bed. Limit offending foods that worsen symptoms. Common GERD triggers include caffeine/coffee, spicy foods, greasy or high-fat foods, chocolate, peppermint, acidic fruits, heavy creams or gravies, and vinegar. Limit high-volume intake and over-eating. Separating fluids from meals may help reduce the volume of items entering the stomach at one time.
Constipation	Increased fiber intake if inadequate. Aim for 25-35 grams per day and increase slowly by a few grams each day. Increased hydration if inadequate. Aim for 60-64 ounces per day.
Diarrhea	Increased soluble fiber intake (e.g., oatmeal, banana, potato). Use of oral rehydration solutions (ORS) if diarrhea is severe/persistent. Review all medications and supplements as some may cause or worsen diarrhea (such as certain antibiotics, laxatives, motility agents, magnesium citrate or oxide).

Table 2. Nutrition-Related Applications for Common GI Symptom Management

• Nutritional remedies that can be implemented for NV during pregnancy include: ^4,7,8,9
• Identifying triggering foods (based on smell, taste, or texture)
• Eating smaller and more frequent meals
• Modifying textures of foods to a smaller particle size
• Choosing bland foods and snacks that are generally higher in protein and lower in fat
• Supplementing with ginger (250 mg capsules four times per day) or vitamin B6 (10-25 mg every eight
hours) before advancing to pharmacologic treatments

If nutrition interventions to reduce NV are unsuccessful, next-line treatment includes H1-receptor antiemetics such as doxylamine, promethazine, and dimenhydrinate.⁸ Additional pharmacological intervention should be used on a case-by-case basis after identifying the certain risks and benefits of medication use in this population. The use of prenatal vitamin and mineral supplementation at least one month before conception may reduce the occurrence and severity of NV in pregnancy.⁴ Clinicians should encourage patients to do so, especially in the preconception visit and fertility clinic setting.

Hyperemesis Gravidarum

Intractable and sustained vomiting – hyperemesis gravidarum (HG) – can lead to severe complications such as metabolic disturbances, dehydration, micronutrient deficiencies, Wernicke’s encephalopathy, and even death from thromboembolism or cardiac arrest.^4,10 HG affects a much smaller percentage of pregnancies with various estimates placing its prevalence at approximately 1- 3%.^4,7 Research by Fezjo et al. in recent years has shown a causative genetic etiological component of worsening NV and HG related to a hypersensitivity to increased levels of growth and differentiation factor 15 (GDF15) from which future therapies may one day be derived.^10,11 Other contributing factors that have shown to be related to HG onset include changes to the amount of progesterone, estrogen, thyroid hormones, and leptin during pregnancy.⁴ Physiological changes during pregnancy include abnormalities with gastric transit and lower esophageal sphincter (LES) resting pressure, which may increase the severity of NV and risk of developing HG.⁴

Manifestations that may present in a clinical exam and that are used to diagnose HG include weight loss (5% or greater), dehydration, ketonuria, orthostasis, micronutrient deficiencies, inadequate oral intake (usually consuming less than 50% of needs), and electrolyte imbalances.^4,7 Some severe cases require hospitalization and parenteral administration of fluids and electrolytes. In the acute inpatient setting, a regular diet should be the primary goal with modifications as needed, with the supplementation of enteral nutrition (EN) reserved for those who continue to experience weight loss and are refractory to medical interventions.⁴

Malnutrition and inadequate gestational weight gain are concerning consequences of HG.⁴ It is important to consult a registered dietitian (RD) to monitor for these clinical repercussions and assess when escalation to EN is important. Nasogastric tubes with use of antiemetic medication are preferred first, as post-pyloric feeding tube placement requires imaging for placement confirmation that will expose the fetus to radiation.⁴ Dietitians should start with polymeric enteral formulas and evaluate tolerance before considering a transition to a semi-elemental enteral formula or an alternative access method. If vomiting remains intractable and there is persistent intolerance to oral and EN support, parenteral nutrition (PN) may become necessary to provide the adequate caloric and protein needs for fetal development and prevention of malnutrition. In lieu of clinical guidelines for this population subset, the decision to escalate to PN must be managed on a case-by-case basis.⁴ Providing treatment early for NV in pregnancy may help delay the progression to HG, and it is important for clinicians to recognize when escalation of care is essential before severe metabolic disturbances arise.^7,8

Gastroesophageal Reflux

Instances of heartburn, regurgitation, and epigastric pain during pregnancy are often related to GERD, though it is important to rule out other GI disorders that may present with similar symptomatology.⁹ GERD is a common GI disorder that currently affects 1 in 3 U.S. adults and during pregnancy it has an even higher prevalence of 50-85%with symptoms usually persisting until delivery.^8,9,12 Clinical manifestations are diagnosed just as with nonpregnant individuals, with an important note that barium imaging studies should be avoided in pregnant patients due to fetal radiation exposure.⁹

The etiology of GERD in pregnancy may be attributed to hormonal changes (for example, progesterone can affect the LES) or physiological changes to intra-abdominal pressure and motility due to an enlarging uterus.^8,9,13 The first-line treatment for reflux and associated symptoms includes changes to diet, meal planning, and sleep position.⁹ Recommendations include:⁹

• Ceasing intake a few hours before bed
• Eating smaller meals with increased frequency
• Identifying triggering and offending foods and avoiding them
• Raising head of bed during sleep
• Lying on the left side

Schuitenmaker et al. investigated sleep positions on non-pregnant individuals while measuring esophageal pH in 57 adult participants and determined that sleeping in the left lateral decubitus position offered a shorter esophageal acid exposure time and increased acid clearance when compared to right lateral or supine sleep positioning.¹⁴ The clinical practice update from the American Gastroenterological Association (AGA) lists modifications to lifestyle and diet as best practice advice.¹⁵ Weight loss is the traditional recommendation to reduce GERD symptoms but would not be appropriate to recommend during pregnancy.¹⁵

If the first-line treatment of altered diet and lifestyle change does not improve symptoms, physicians may consider antacids as a second-line therapy.¹⁴ Antacids containing aluminum, calcium, and magnesium are considered an acceptable treatment in normal doses, but those containing sodium bicarbonate or magnesium trisilicate are not.^16,17 Additional pharmacologic therapy is needed if prior interventions are not effective at managing symptoms on a case-by-case basis. There is a paucity of human study data for GI medications during pregnancy, but some medications have been classified by the Food and Drug Administration (FDA) to be acceptable or lower risk.^9,16 The FDA currently does not have a classification for antacids during pregnancy. While antacid use may be beneficial at treating GERD symptoms for 30-50% of pregnant patients, for the rest it may not be sufficient.¹⁷ After approaching symptom management with lifestyle change and antacids, clinicians can use histamine-2 receptor blockers, which are classified by the FDA as Category B and have been shown in studies to be safe during pregnancy.¹⁷ If unsuccessful, the next approach involves proton pump inhibitors; while classified as Category C, studies have largely indicated their safety during pregnancy even though there is a lack of research around their efficacy at treating symptoms in pregnant patients.¹⁷

Constipation

Constipation during pregnancy is one of the more common GI symptoms with a global prevalence of 32.4% per recent meta-analysis data.¹⁸ Contributing factors in the complex etiology may include decreasing motility and smooth muscle contractility from progesterone production, increased intra-abdominal pressure from an expanding uterus, decreased physical activity level, iron supplementation, and changes to diet such as including more fat- and protein-rich foods to meet nutritional needs during pregnancy.^18,19

Treatment for constipation during pregnancy differs based on the severity of symptoms; mild cases may be improved with lifestyle modifications involving increased dietary fiber intake and adequate hydration.^9,18 Clinicians can discuss safe bulking agents such as psyllium fiber or methylcellulose.⁸ Additionally, education and counseling on how to consume fiber in the diet can be achieved with a referral to an RD. After addressing nutrition and lifestyle changes, further medical management to include osmotic laxatives or stimulants should be started only under the discretion of a physician and for more severe cases.^8,18,19 For those suffering with co-occurring GI ailments during pregnancy, osmotic laxatives can worsen bloating, cramps, flatulence, and nausea and therefore may not be a welcomed method of constipation treatment.¹⁹

Hemorrhoids are a common complication of constipation and are prevalent in up to 80% or more of pregnancies.^5,8 The etiology can be attributed to the third trimester compression of the rectum from the expanding uterus, prolonged straining during constipation, and inadequate fiber intake to regulate bowel movements.^5,8,19The first-line treatment for hemorrhoid prevention include:⁵

• Increased fiber
• Increased fluid intake
• Improved toileting regimen to limit the amount of time and straining during defecation

Poskus et al. conducted a clinical trial researching the inclusion of dietary strategies for prevention of hemorrhoids in 260 randomized pregnant patients across three medical centers.²⁰The intervention group received education on drinking adequate fluid, increased fiber intake from bran, fruits, vegetables, and nuts, exercising 3-5 times per week for at least 30-60 minutes, spending less than three minutes on the toilet, not ignoring any urgency to use the bathroom, attempting a bowel movement 30-40 minutes after eating, and washing after bowel movements.²⁰ This group showed a significantly reduced occurrence of hemorrhoids by about 50% after receiving the education.²⁰

Diarrhea

Diarrhea and fecal incontinence are much less common GI symptoms that can occur during pregnancy compared to nausea, vomiting, reflux, and constipation.²¹ Acute infection is the most common cause for diarrhea during pregnancy so it is important to rule out viral, bacterial, or parasitic infectious etiologies first.²¹ If acute infection is not present, the noninfectious causes or factors leading to diarrhea during pregnancy may include hormonal changes, changes to diet, increased intra-abdominal pressure, and side effects of prenatal vitamins.²¹ Clinicians should also consider preexisting conditions such as pelvic floor dysfunction, inflammatory bowel disease (IBD), IBS, lactose intolerance, overflow diarrhea from constipation, a history of anorectal surgeries, or ileal pouch anal anastomosis (IPAA).²¹ Pregnant individuals with fecal incontinence may benefit from certain lifestyle modifications, which can include pelvic floor muscle training (PFMT) with or without biofeedback therapy.²¹ A referral to a specialized physical therapist for a PFMT assessment may be useful.²¹

The first-line intervention for diarrhea includes a slow introduction and increase in dietary intake of soluble fiber (e.g., banana, oatmeal, potato) or use of psyllium fiber supplementation.²¹ Important nutrition interventions include consuming smaller and more frequent meals and adequate hydration with electrolytes via oral rehydration solutions (ORS) if diarrhea is frequent and signs and symptoms of dehydration are detected. Intravenous electrolytes and hydration may be necessary for prolonged diarrhea if metabolic abnormalities are present. Excluding whole food groups or overly restrictive diets are not indicated during pregnancy as this may lead to inadequate gestational weight gain or nutritional deficiencies. A consultation with an RD can help ensure patients are consuming adequate nutrition by finding alternatives for any nutrients that are being excluded.

Pharmacologic intervention for diarrhea during pregnancy should only be used in the most persistent and severe cases, and loperamide is the antidiarrheal most preferred.^9,21 It is important to know that diphenoxylate with atropine and bismuth preparations (Pepto-Bismol^® and Kaopectate^®) are contraindicated during pregnancy due to adverse fetal effects and that probiotics and empiric antibiotics are not routinely used in this population.^9,21

Special Considerations
for Gastrointestinal Disorders

Pregnant individuals with chronic GI disorders may benefit from intervention by their healthcare team during preconception or early pregnancy. The nutrition interventions discussed above for nausea, vomiting, reflux, constipation, and diarrhea would be appropriate for those who have these symptoms superimposed upon their chronic disease, but it warrants a discussion with their healthcare provider and case-by-case evaluation. Below are special considerations during pregnancy for chronic GI disorders (See Table 3).

GI Disorder	Considerations During Pregnancy
Inflammatory Bowel Disease	Pregnancy in active IBD can include increased risks of miscarriage, premature delivery, inadequate gestational weight gain, complications during labor and delivery, and SGA infants.^22,23 The AGA recommends remission for 3-6 months prior to conception to reduce flare risk during pregnancy.²² PEN and EEN are safe nutritional interventions during pregnancy.^29,30 Working with an IBD-focused RD can help manage adequate intake and weight gain goals.
Gastroparesis	Preconception planning is prudent as GP during pregnancy can lead to nutritional consequences and deficiencies for the patient and fetus.³¹ Small particle size, low-fat, and low insoluble fiber diets.³² RD consultation to recommend more easily tolerated foods, supplements, and oral nutrition shakes to ensure adequate nutrition.
Metabolic Dysfunction-Associated Steatotic Liver Disease	Pregnancy outcomes with MASLD include higher rates of GDM, gestational hypertension, hypertensive complications, Caesarean sections, preterm births, and postpartum hemorrhage compared to other chronic liver diseases or no liver disease.³³ Weight loss is not recommended during pregnancy, but patients can adhere to ACOG/IOM gestational weight gain goals. Reduction of sugar-sweetened beverages, added sugars, and ultra-processed foods.³⁴
Irritable Bowel Syndrome	IBS is a common DGBI that may worsen during pregnancy, theoretically, due to increased hormone production or stress.³⁶ An RD during preconception is beneficial to assess diet quality and liberalization prior to becoming pregnant if currently on a restricted diet. Initiating restrictive diets, such as the high-FODMAP elimination phase if appropriate, should be done under the close guidance of an RD and if no response, then discontinued.³⁶

Table 3. Considerations for Gastrointestinal Disorders During Pregnancy

Inflammatory Bowel Disease

Risks associated with pregnancy in active IBD include miscarriage, increased risk of premature delivery, inadequate gestational weight gain, complications during labor/delivery, and SGA infants.^22,23 Adequacy of nutrition can play a vital role in reducing complications from inadequate gestational weight gain or decreased intake that may occur with active disease, GI complications, or surgical changes in GI anatomy from IBD.²² In one recent cohort study, the risk of inadequate gestational weight gain was higher among those with Crohn’s disease (34.3%) and ulcerative colitis (26.7%) compared to those without IBD (19.4%).²⁴ Twenty percent of participants with IBD in a second cohort study experienced inadequate weight gain and had increased risk for preterm birth, intrauterine growth restriction (IUGR) and SGA.²⁵Poor nutrition in early pregnancy can further affect fetal development from insufficient vitamin and mineral intake, and those with active IBD flaring are at a higher risk of food intolerance and inadequate intake.

Guidelines from the 2019 AGA IBD Parenthood Project Workgroup recommend women with IBD to be in remission for 3-6 months prior to conception to reduce the risk of flare during pregnancy.²² IBD-trained RDs can help patients navigate dietary concerns, ensure quality nutrition and micronutrient intake, and monitor for appropriate gestational weight gain if flares occur during pregnancy. Many organizations’ recent clinical guidelines and practice updates have recognized the importance of having specialized RDs as part of an IBD interdisciplinary team.^26-28A thorough nutrition assessment can determine whether certain interventions, such as steroid-sparing exclusive enteral nutrition (EEN) or other nutrition therapies, would be beneficial and safe during pregnancy. A recent case report of a 35-year-old woman eight weeks pregnant with moderately severe ileal Crohn’s disease showed clinical remission and weight gain after 6 weeks of the Crohn’s Disease Exclusion Diet (CDED) and partial enteral nutrition (PEN).²⁹ The patient gained appropriate gestational weight (10.3 kg), delivered at 40 weeks, and sustained remission up to 12 weeks postpartum.²⁹ A retrospective observational study of fifteen women with active CD showed that peptide-based EEN was effective at inducing remission in 85.7% of participants without any changes in pregnancy outcomes compared to a non-EEN group.³⁰ The women in the study were pregnant or preparing for pregnancy and had experienced a relapse or complication for which they were refractory to or contraindicated for other treatment modalities.³⁰ In addition to PEN or EEN, specialized therapeutic diets for IBD may also be beneficial for patients as long as they are robust enough to provide adequate micronutrients; monitoring and evaluation by an RD can determine on a case-by-case basis whether a specialized diet is too restrictive for a pregnant individual based on their recall of usual intake. A list of IBD-specific nutrition resources in Table 4 may be beneficial for helping patients expand their diets healthfully during pregnancy.

IBD-Specific Resources	Organization
Gut-Friendly Recipes	Crohn’s & Colitis Foundation: gutfriendlyrecipes.org
2020 Consensus Guidelines for Nutrition	International Organization for the Study of Inflammatory Bowel Disease: ioibd.org
MyIBDLife Parenthood Project	American Gastroenterological Association: myibdlife.gastro.org
Evidence-Based Nutrition Therapies	Nutrition Therapy for Inflammatory Bowel Disease: nutritionaltherapyforIBD.org

Table 4. Resources for Inflammatory Bowel Disease

Gastroparesis

GP is a chronic disorder of delayed gastric emptying that presents nutritional consequences for the patient and fetus during pregnancy. It is prudent to conduct preconception multidisciplinary planning – including diet education – for those with pre-existing disease who wish to become pregnant.³¹ There is a lack of data on the efficacy and safety of medications used to treat GP in the pregnant population.³¹ The 2022 guidelines on gastroparesis from the American College of Gastroenterology (ACG) provide nutrition interventions that include small particle size, low-fat, and low insoluble fiber diets.³² These are appropriate interventions during pregnancy so long as they are not overly restrictive and remain varied enough to provide adequate nutrition for appropriate gestational weight gain.

Nausea, vomiting, and pain associated with GP may often lead to decreased intake.³¹ A referral to an RD can help to manage suboptimal intake, oral food intolerances, micronutrient deficiency that may result, and recommendations for whether nutrition support therapies are needed. An RD can provide education on the importance of smaller meals in higher frequency, texture modification for better tolerance, and the use of oral nutrition supplements; an RD can evaluate a patient’s diet pattern and quality to ensure adequacy and recommend the best-absorbed supplements (such as liquids or chewable tablets) that will be better tolerated.

Metabolic Dysfunction-Associated
Steatotic Liver Disease

Patients with metabolic dysfunction-associated steatotic liver disease (MASLD or MASH) would benefit from preconception interdisciplinary intervention for management of this chronic disease. Over the last decade, there has been an increase in the incidence of fatty liver diseases among the U.S. population under 40 years old.³³ One study looking at 18 million U.S. pregnancies between 2012-2016 identified over 5600 pregnancies with MASLD (previously known as NAFLD) and found significantly more cases of gestational diabetes mellitus (GDM), gestational hypertension, hypertensive complications, Caesarean sections, preterm births, and postpartum hemorrhage compared to other chronic liver diseases or no liver diseases.³³

Weight loss is not recommended during pregnancy but adherence to the ACOG/IOM gestational weight gain is an appropriate intervention. Nutritional interventions include the reduction of sugar-sweetened beverages, added sugars, and ultra-processed foods as these are associated with worsened MASLD status.³⁴ The addition of a Mediterranean-style dietary pattern (which is high in dietary fiber and monounsaturated fatty acids), and reduction of red meat have also been related to a reduced incidence of MASLD.³⁴

Irritable Bowel Syndrome

IBS is classified as a disorder of gut-brain interaction (DGBI) and characterized by recurrent abdominal pain and altered bowel habits.³⁵ The subgroups of this DGBI are based on bowel status and include IBS with constipation (IBS-C), IBS with diarrhea (IBS-D), and IBS with mixed or alternative bowel habits (IBS-M).³⁵ While there is a lack of extensive study on the effect of pregnancy on IBS, a theoretical association to explain how IBS symptoms may worsen during pregnancy is the change in hormones.³⁶ Increased estrogen during pregnancy can affect gut-brain axis regulatory mechanisms, visceral hypersensitivities, and gut motility.³⁶ Luteal hormone production, which is highest in the first trimester, can affect the migrating motor complex and increase risk of both constipation and small intestinal bacterial overgrowth.³⁶ Increased stress could also play a role in IBS status during pregnancy.³⁶ Regarding pregnancy outcomes, having IBS during pregnancy was associated with increased risks of miscarriage and ectopic pregnancy compared to individuals without IBS, although this information is based on a retrospective trial and more studies of this population are needed.³⁶

A majority of patients with IBS report that their symptoms are food-related, and dietary modification for the exclusion of offending foods (such as gas-producing foods, high lactose content, or foods high in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols known as FODMAPs) remains as first-line treatment for the general IBS population.^36,37 In a survey of over 1500 gastroenterologists in the U.S., 60% reported that their patients associate their symptoms with food and were inclined to restrict foods on their own, using dietary modifications that included reducing lactose (33%), eliminating gluten (24%), lowering fat content (6%), or trying low FODMAP diet (2%).³⁷ Half of patients used ‘trial and error’ to determine which foods were problematic.³⁷ Over half of the gastroenterologists reported that they use dietary modification as a first-line treatment strategy to 75% of their patients.³⁷ The most common dietary therapy recommended to patients was a low FODMAP diet (77% of respondents), with high-fiber and lactose-reduced as the next most common (both at 45%).³⁷

The dietary modifications and recommendations for the general IBS population should involve careful consideration during pregnancy to ensure adequacy of nutrient intake.³⁶ Prior to conception, patients with IBS would benefit from consulting with an RD to evaluate baseline adequacy of their diet and to trial diet liberalization. Ongoing follow-ups during pregnancy is recommended if worsening IBS symptoms develop or affect oral intake. Restrictive diets, such as the high-FODMAP elimination phase, should only be started under the close supervision of a registered dietitian.³⁶ If no improvement is observed, the diet should be discontinued. Patients who are on restricted diets for IBS management and become pregnant should also be closely observed for appropriate gestational weight gain and micronutrient adequacy.³⁶

Conclusion

Clinicians can implement nutritional interventions as useful first-line therapies during pregnancy for many common GI symptoms. Involving an RD during early pregnancy can help those who are experiencing weight loss and inadequate intake from common ailments like nausea, vomiting, reflux, diarrhea, and constipation. Nutrition education during the preconception stages is a beneficial option for those with chronic GI disorders such as IBD, GP, MASLD, and IBS. Patients who are not meeting their gestational weight gain milestones will benefit from frequent RD follow-ups throughout gestation, particularly during the second and third trimesters. There remain gaps in knowledge with a myriad of research opportunities within the pregnant population, especially regarding disease etiology, pharmacologic management, and the role of nutrition in GI disease management.

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