Apoptotic Colonopathy under Immunosuppression: Mycophenolate-Related Effects and Beyond

Abstract

Background/Aims: Diarrhea developing in patients under immunosuppression has a variety of underlying causes. A broad spectrum of histological findings can be found in intestinal biopsies taken for the diagnostic workup of diarrhea including a pathologically increased proportion of epithelial cell apoptosis in the colon, for which the descriptive term ‘apoptotic colonopathy' was coined. In recent years, the immunosuppressive drug mycophenolate (mycophenolic acid, MPA) has been identified as a prototypical cause of apoptotic colonopathy, but other conditions may show similar or overlapping histological pictures. Methods: Cases of likely or possible MPA colonopathy (n = 18) were retrospectively identified from the archive files. Clinical information on patient history, clinical presentation and endoscopic findings were recorded. All cases were routinely processed, i.e. stained by hematoxylin and eosin (HE) stain, optionally supplemented by special histochemical and immune stains. Results and Conclusion: Histopathological hallmarks of MPA treatment-related changes in the colon mucosa are reviewed with respect to the major histopathological differential diagnoses including normal and near-normal findings, infectious diseases, graft-versus-host disease and inflammatory bowel diseases. Furthermore, the challenge of multiple concomitant pathologies while on MPA treatment, in particular infectious diseases, is discussed, and some open questions concerning the effects of MPA on colon pathology are pointed out.

Apoptotic colopathy in a pediatric autologous bone marrow transplantation patient with spontaneous colonic cast excretion: Is it due to GVHD or rotavirus infection?

“…Patients with mycophenolate-related gastrointestinal toxicity typically present with afebrile, watery diarrhea with mostly insignificant or mild endoscopic findings. The histopathological changes in crypt epithelium in patients with a history of mycophenolate use included apoptosis in crypt bases, cystically dilated atrophic crypts, surface epithelium erosion, crypt architectural distortion, and eosinophils in lamina propria [15]. Our patient did not have a history of mycophenolate use.…”

Thymoma-associated multiorgan autoimmunity with exclusive gastrointestinal tract involvement: case report and review of the literature

“…A myriad of drugs may be associated with GIT GvHD-like changes. Mycophenolate / mycophenolic acid typically shows a patchy paucicellular lamina propria, cystic crypt dilation and numerous eosinophils, microscopic features which assist in diagnosis [11]. Other offending drugs include antineoplastic agents such as 5-fluorouracil, cyclosporine A, non-steroidal anti-inflammatory drugs and newer immune modulators such as PD-1 inhibitors [12,13].…”

“…GIT viral infections, particularly cytomegalovirus (CMV) and adenovirus, may lead to prominent epithelial apoptosis but detection of characteristic cellular inclusions will confirm this diagnosis. Congenital immune deficiencies such as combined variable immunodeficiency (CVID), and acquired immune disorders including combined variable immunodeficiency (CVID), various acquired autoimmune diseases anprimary AIE of adults and HIV infection can mimic the GvHDlike GIT pathology of TAMA [9,11,14]. Lymphoid hyperplasia and a paucity of plasma cells in CVID, and the presence of other histologic patterns in the rare cases of primary adult-onset AIE are histologic a clues.…”

“…A specific diagnosis, however, necessitates close clinical correlation. Other disorders such as acute ischemia, radiation and chronic inflammatory bowel disease may be associated with prominent GIT epithelial apoptosis, but characteristic microscopic features of the underlying pathology usually make the primary diagnosis apparent [11].…”

Lymphocytic Colitis With Increased Apoptosis: A Marker of Mutation in T-Cell-Mediated Immunity?

“…Histopathologically, it is diagnosed by an increase of lymphocytes, both intraepithelial and in the lamina propria, with preserved colonic architecture. 1 Multiple etiologies including drugs, 1,2 have been hypothesized to cause lymphocytic colitis with or without apoptosis. Interestingly, cancer immunotherapy medications (especially anti-CTLA4) have been described to cause a lymphocytic-type colitis and increased apoptosis.…”