GI in the Immunocompromised Host

Episode one of the GI in the Immunocompromised Host chapter starts with a single recognition move: a transplant recipient on calcineurin inhibitor plus mycophenolate plus prednisone with diarrhea could be any of five entities at once, and time since transplant is the variable that reorders the differential. The first month belongs to the surgeon, the one-to-twelve-month window belongs to opportunistic infection, and beyond a year belongs to cumulative toxicity and malignancy. From there the reasoning runs on enzymes: donor-recipient serostatus and UL97 versus UL54 for CMV resistance, CYP3A4 for the calcineurin inhibitor trap, and dose-dependent crypt exposure for mycophenolate enteropathy. Sitting over all of it, Epstein-Barr virus drives the post-transplant lymphoproliferative disorder that responds first to reducing the immunosuppression that allowed it.

Episode two takes the other host state hiding behind the word transplant: the hematopoietic cell transplant recipient whose donor immune system attacks the host. The post-transplant timeline organizes everything, with the first twenty-one days belonging to conditioning toxicity rather than graft-versus-host disease, so the timeline decides which diagnosis is even allowed. Gut disease is staged by daily stool volume on the Glucksberg-Seattle thresholds, the histology anchors on crypt apoptosis, and the biopsy-bench differential always includes CMV because apoptosis is not pathognomonic. Treatment is methylprednisolone first and ruxolitinib second on the strength of a randomized trial, and the shared move across both host states is to pair every immunosuppression escalation with an infectious workup.

Episode three covers the non-transplant immunocompromised GI host, where two settings that look unrelated share one logic: identify the host state, and the host state opens a tiered differential. In HIV that state is the CD4 count, which converts a long pathogen list into strata that drive workup and surfaces the pre-antiretroviral-era entities still seen in late presenters, AIDS cholangiopathy, gut Kaposi sarcoma, and post-treatment IRIS. In chemotherapy-related neutropenia that state is the absolute neutrophil count, which defines typhlitis as a cecum-predominant enterocolitis managed conservatively with bowel rest and broad-spectrum antibiotics. The recurring move is that the number tells you what to look for and the entity tells you what to do, from antiretroviral therapy as the dominant intervention to the narrow list of surgical indications.

Episode four closes the module on checkpoint inhibitor toxicity, one entity with many organ targets, where releasing the brakes on T cells means the same cells recognize self. Drug class predicts the toxicity rate, with anti-CTLA-4 broad and severe, anti-PD-1 focal and milder, and combination highest, while grade drives therapy through a universal seventy-two-hour escalation window. The colitis algorithm runs grade-based steroids then infliximab or vedolizumab, with the choice turning on hepatic comorbidity and CMV risk. The single most tested distinction is that steroid-refractory hepatitis goes to mycophenolate mofetil, not infliximab, because infliximab is contraindicated by its own hepatotoxicity, and the whole framework extends to pneumonitis, endocrinopathies, and the other immune-related adverse events.