GI in the Immunocompromised Host: GI in the Immunocompromised Host: HIV as a Host

0:00Welcome to Board Pearls. This is episode three of four of the GI in the Immunocompromised Host chapter, in the Special Populations and Acute or Supportive Care module. This episode is human immunodeficiency virus, HIV, as a host: the gastrointestinal, GI, problems set by how weak the immune system is rather than by any one organism, followed in one newly diagnosed man with a very low CD4 count. His case shows how the CD4 count reorders the differential, what acquired immunodeficiency syndrome, AIDS, cholangiopathy is and why its papillary stenosis needs a sphincterotomy when everything else improves on antiretroviral therapy, how Kaposi sarcoma is diagnosed when the biopsy looks normal, when antiretroviral therapy starts, what it means when he worsens after starting it, and whether he needs prophylaxis.

0:52Here's the patient. A thirty-eight-year-old man is newly diagnosed with HIV after months of weight loss, with a CD4 count of forty. He's had six weeks of watery diarrhea and two weeks of right upper quadrant pain, with a high alkaline phosphatase, a normal bilirubin, and no fever. Ultrasound shows a dilated common bile duct, and upper endoscopy showed several violaceous nodules in his stomach.

1:17He has advanced HIV disease, AIDS, and his findings point to two diagnoses: his diarrhea, biliary pain, raised alkaline phosphatase, and dilated duct suggest AIDS cholangiopathy, and his purple gastric nodules suggest Kaposi sarcoma. About one point two million people in the United States live with HIV, and effective antiretroviral therapy has made the opportunistic GI infections of the early epidemic uncommon. They still appear in people diagnosed late, like him, and in those with poor adherence or treatment failure.

1:49His CD4 count of forty decides how broad his workup is. The CD4 count turns a long list of pathogens into tiers. Above five hundred, the differential is essentially normal. Between two hundred and five hundred, oropharyngeal candidiasis emerges. Below two hundred, herpes simplex ulcers, esophageal candidiasis, and Cystoisospora become likely. Below one hundred, Cryptosporidium, microsporidia, and cytomegalovirus, CMV, enter the list, and below fifty, disseminated CMV and Mycobacterium avium complex, MAC, appear. So the probability behind every GI symptom changes with the count, and the workup follows the count rather than the symptom alone.

2:33At forty, every tier is open, so his diarrhea needs a broad workup, including the specific stool stains from chapter thirty-three, and if Cystoisospora were found, he'd need secondary prophylaxis after treatment, because his count is below two hundred. A man with the same diarrhea and a count of three hundred fifty would be expected to have only thrush among the opportunistic problems, and ordinary causes of diarrhea would come first.

3:00His biliary findings fit AIDS cholangiopathy, a cholangitis caused by opportunistic infection of the bile ducts. It was a defining problem of the era before antiretroviral therapy, affecting about a quarter of late-stage patients with a CD4 count below one hundred, and it's now uncommon. Its causes, roughly in order of frequency, are Cryptosporidium parvum, microsporidia, CMV, and Cyclospora cayetanensis, all organisms of the lowest CD4 tiers. So the organism causing the cholangiopathy is often the one causing the diarrhea, and finding one prompts a search for the other.

3:39It presents with right upper quadrant or epigastric pain plus diarrhea, and fever and jaundice are less common, so their absence in him doesn't argue against it. Endoscopic retrograde cholangiopancreatography, ERCP, shows one of three patterns: sclerosing cholangitis with papillary stenosis, the most common, sclerosing cholangitis alone, or papillary stenosis alone. His ERCP shows papillary stenosis with sclerosing changes, and his stool shows Cryptosporidium.

4:08His cholangiopathy is treated mainly by restoring his immunity, but the stenosis needs a mechanical fix. Antiretroviral therapy is the main treatment, because immune reconstitution drives most of the resolution, with treatment for the specific pathogen added. Papillary stenosis is different: it's fixed scarring left by earlier cryptosporidial inflammation, and it doesn't reverse with antiretroviral therapy, so only cutting the sphincter restores drainage. He has an ERCP sphincterotomy for his symptomatic stenosis during the same procedure.

4:40His purple gastric nodules are Kaposi sarcoma until proven otherwise. Kaposi sarcoma is driven by human herpesvirus eight, also called Kaposi sarcoma-associated herpesvirus, and in HIV it appears below a CD4 count of two hundred as violaceous mucosal nodules anywhere in the GI tract, most often the stomach and small bowel. Most are asymptomatic, though they can bleed.

5:05His normal biopsies don't exclude it. A pinch biopsy of a typical nodule is often non-diagnostic, because the tumor lies in the submucosa, so recognition comes from the appearance, and confirmation comes from immunohistochemistry for the latency-associated nuclear antigen one, LANA-1, of human herpesvirus eight. His gastric biopsies showed only mild gastritis, so LANA-1 staining is requested, with deeper samples taken if needed.

5:32His Kaposi sarcoma is also treated mainly by restoring immunity. The lesions depend on angiogenic and proliferative signals driven by human herpesvirus eight, and restored cytotoxic T-cell control suppresses them, so antiretroviral therapy is the main treatment. Advanced disease that doesn't regress gets intralesional or systemic chemotherapy, with liposomal doxorubicin the preferred systemic agent, because its liposomes accumulate in this highly vascular tumor and deliver the drug selectively. If his lesions shrink as his CD4 count rises, he needs nothing more. If they grow despite immune recovery, he gets liposomal doxorubicin.

6:09Because antiretroviral therapy is the main treatment for his cholangiopathy, his Cryptosporidium, and his Kaposi sarcoma, its timing matters. Antiretroviral therapy starts within two weeks of an opportunistic infection diagnosis, because earlier initiation reduced mortality and AIDS progression in trials. The major exception is cryptococcal meningitis, in which therapy is deliberately delayed four to six weeks to reduce deaths from immune reconstitution in the central nervous system. He has no meningitis, so he starts within two weeks.

6:41Then he worsens after starting treatment. Five weeks in, with his CD4 count rising and his viral load falling, he develops high fever, painful enlarged abdominal lymph nodes, and worse abdominal pain, and blood cultures grow Mycobacterium avium complex.

6:58He has immune reconstitution inflammatory syndrome, IRIS. It occurs two to twelve weeks after antiretroviral therapy starts in patients who began with severe lymphopenia, as the recovering immune system unmasks a hidden infection or paradoxically worsens a treated one. Its GI presentations include flares of MAC, CMV colitis, hepatic tuberculosis, and Kaposi sarcoma. It's a clinical diagnosis and not a treatment failure, so antiretroviral therapy continues without interruption, the infection is treated with its own regimen, and corticosteroids are added in severe cases. His rising CD4 count is causing the reaction, and it's also what will clear the infection, so his antiretrovirals continue, and his MAC is treated with a macrolide plus ethambutol, as chapter thirty-three describes.

7:47His count of forty would once have called for MAC prophylaxis at diagnosis. Primary prophylaxis below a CD4 count of fifty historically used azithromycin, one thousand two hundred milligrams weekly, or clarithromycin, five hundred milligrams twice daily, and weekly azithromycin remains the historical standard regimen. Current United States guidelines no longer routinely recommend primary prophylaxis for patients starting effective antiretroviral therapy, because MAC risk falls quickly with viral suppression. So at diagnosis, before his MAC appeared, he didn't need routine prophylaxis, because he was starting effective therapy.

8:24Here are the traps the boards set in these patients. Working up a GI symptom in HIV without the CD4 count. Missing Cryptosporidium and CMV below one hundred, or MAC below fifty. Dismissing cholangiopathy because there's no fever or jaundice. Expecting antiretroviral therapy alone to open papillary stenosis. Excluding Kaposi sarcoma on a negative pinch biopsy. Delaying antiretroviral therapy beyond two weeks for most opportunistic infections, or starting it early in cryptococcal meningitis. Stopping antiretroviral therapy for IRIS. And giving routine MAC prophylaxis to a patient starting effective therapy.

9:05So, start to finish. The CD4 count sets the HIV differential: two hundred to five hundred brings thrush; under two hundred, herpes simplex, esophageal Candida, and Cystoisospora; under one hundred, Cryptosporidium, microsporidia, and CMV; and under fifty, disseminated CMV and MAC. AIDS cholangiopathy, with papillary stenosis and sclerosing changes, needs antiretroviral therapy plus sphincterotomy for the stenosis. Kaposi sarcoma is recognized on sight, confirmed with human herpesvirus eight LANA-1 staining, and treated with antiretroviral therapy, adding liposomal doxorubicin for advanced disease.

9:46Antiretroviral therapy starts within two weeks of most opportunistic infections, and four to six weeks after cryptococcal meningitis. It continues through IRIS, with the infection treated and steroids added if severe. And routine MAC prophylaxis isn't given when effective therapy is starting.

10:03Episode four, the last of the chapter, is the checkpoint inhibitor toxicities: colitis, hepatitis, and the other immune-related adverse events.

10:13For the full chapter, the practice vignettes, and the topic-tagged question bank, head to board pearls dot com. You'll find the rest of the series on Apple Podcasts, Spotify, or wherever you listen to podcasts. That brings us to the end of episode three of four of chapter thirty-four, and I'll see you in the next one.