Paris Charilaou MD1 Devendra Enjamuri MD1 Andrew Korman MD2 1Gastroenterology & Hepatology Fellows, 2Gastroenterology & Hepatology Attending, Director of Advanced Therapeutic Endoscopy, Division of Gastroenterology & Hepatology Department of Medicine Saint Peter’s University Hospital/Rutgers, RWJ Medical School, New Brunswick, NJ
A previously healthy 38 year-old male from the Philippines immigrated to the United States months prior to presenting to the emergency department with a three-month history of diarrhea and diffuse, crampy abdominal pain associated with tenesmus and hematochezia. The diarrhea has been progressive with up to 10 watery, small-volume bowel movements a day. He has experienced a 20-pound weight loss over that period. There was no nausea, vomiting, fever, rash or arthralgias. He had not been taking any non-steroidal anti-inflammatory medications or antibiotics. On further history, he disclosed that he was homosexual. He had no family history of malignancy or inflammatory bowel disease. He did not smoke, drink alcohol or used illicit drugs.
His physical exam was unremarkable, other than severe pain and nodularity of the rectal mucosa, without blood or other palpable masses, on rectal exam.
Basic laboratory testing included a normal complete blood count and a comprehensive metabolic panel. Initial routine stool studies, including ova and parasites, were negative.
On colonoscopy, there were multiple erosions in the terminal ileum and multiple well-demarcated ulcers throughout the colon (Figure 1, blue arrows). Several nodules were found in the anus and rectum. Moderate architectural distortion with acute and chronic inflammation, reactive epithelial changes, with intracytoplasmic and intranuclear inclusions were seen on histopathology. (Figure 2)
Question 1. What is the most likely diagnosis?
Question 2. What is the next step in the management of this patient?
Question 3. What is the most important consultation you should consider at this time?
Question 4. What are the other gastrointestinal manifestations of this pathogen?
In this adult patient with chronic diarrhea, we need to consider infectious and inflammatory bowel disease as the top two diagnostic categories. Considering the complete history and presentation of this patient, including his immigrant status, sexual practices and weight loss, human immunodeficiency virus (HIV) infection, and its potential complications, should be entertained. In doing so, one should consider the different entities that may be encountered depending on whether a patient has received highly active anti-retroviral therapy (ART) or not (see Table 1).1,2 Our patient was found to be HIV positive, with a CD4+ count of 69/µL, consistent with acquired immunodeficiency syndrome (AIDS).During the post-ART era, complications encountered are usually medication-associated adverse effects (Table 1).1,2 The pre-ART complications that need to be considered in an AIDS patient with chronic diarrhea include cytomegalovirus (CMV) colitis, cryptosporidiosis, microsporidiosis, mycobacterium avium complex (MAC), Shigella, Campylobacter jejuni, Clostridium difficile.2 Idiopathic AIDS-related enteropathy should also be considered if all diagnostic studies are negative. The most likely diagnosis at that time was CMV colitis, as it is the most common pathogen leading to chronic diarrhea in patients with AIDS and a CD4+ < 100/µL. The colonic biopsies stained positive for CMV and a diagnosis of CMV colitis was made.
CMV serum antigen, antibodies and polymerase chain reaction (PCR) cannot be used to determine invasive gastrointestinal CMV infection.3,4 Most patients have already been colonized by CMV and have seroconverted. The clinical picture,
endoscopic and pathologic findings are indicative of an invasive CMV infection that warrants treatment. CMV DNA levels have been shown to predict disease severity but do not play a role in diagnosing active gastrointestinal disease.3 In patients with diarrhea on ART, medications such as protease inhibitors, nucleoside reverse transcriptase inhibitors, delavirdine, maraviroc, raltegravir, cobicistat, and elvitegravir/cobicistat have been implicated and should be considered as potential etiologies1.
The patient should be started on treatment for invasive CMV infection (Table 2) and also on ART for HIV. His diarrhea resolved after approximately three weeks of valganciclovir, while receiving ART.
Every patient diagnosed with CMV infection should have fundoscopy to exclude CMV retinitis. Thus, an ophthalmology consult is mandated. CMV retinitis, if present, needs close follow-up to ensure remission and to prevent blindness.
CMV can affect multiple gastrointestinal (GI) organs, most commonly in immunocompromised patients. CMV esophagitis, gastritis and enteritis are other luminal, gastrointestinal manifestations. Esophagitis usually presents with odynophagia (rather than dysphagia) and endoscopy may reveal multiple, shallow ulcers, which can be confirmed with biopsies taken from their center. At least three biopsies can have a sensitivity of 80%, reaching 98% with 10 biopsies.5 The differential diagnosis of CMV esophagitis includes HIV-associated idiopathic ulcers and herpes simplex (HSV) esophagitis. Gastritis will often present with non-specific symptoms of epigastric pain, nausea and vomiting. A specific, yet less common presentation, is that of postural epigastric pain with relief in supine position.6 Endoscopy may reveal ulcerations with erythematous mucosa in the antro-pyloric region. Enteritis, including duodenitis, may present with severe diarrhea, especially in post-transplant patients. Differential diagnosis includes lymphoma and graft-vs-host disease, which requires serial biopsies to differentiate from the latter.7 Potentially fatal complications include perforation and peritonitis.
CMV hepatitis may be seen in immunocompetent patients, commonly presenting as subclinical liver enzyme elevation, typically as a hepatocellular pattern. In symptomatic cases, liver enzyme elevations will be more severe, with signs of hepatic dysfunction and even portal vein thrombosis.8 Differential diagnosis should include hepatic granulomas, especially in patients with prolonged unexplained fevers. In post-liver transplant patients, CMV hepatitis from reactivation can lead or resemble acute allograft rejection, especially in sero-mismatched donor/recipient pairs (i.e. CMV-positive donor with CMV-negative recipient).9
In patients with chronic diarrhea and a clinical suspicion for HIV/AIDS, CMV colitis should be suspected as it is the most common pathogen implicated in these cases. Once the diagnosis is made and treatment is started, the patient should be referred to an ophthalmologist to rule out retinal involvement, which would otherwise necessitate close follow-up during the treatment period.