Clinical approach to diarrheal disorders in allogeneic hematopoietic stem cell transplant recipients

Table 1 Common causes of diarrhea in hematopoietic stem cell transplant recipients

Etiology	Time period	Percentage of diarrheal episodes	Tests	Management	Comments
Acute GVHD	Early post engraftment	40%-60%, particularly after engraftment	Colonoscopy and biopsy	High-dose prednisone; if no response, other immunomodulators, and extracorporeal photopheresis	Steroid-refractory gut acute GVHD can be fatal
Conditioning regimen, without other etiology	Within 5-7 d after chemotherapy	50%	No-specific tests, other etiologies need to be ruled out	Supportive care
Medications	During any time, usually within few weeks after initiation	Variable	No-specific tests, other etiologies need to be ruled out	Supportive care, medication withdrawal if possible	Usually diarrhea stops after cessation of the offending medication
Infections	Pre-engraftment for Clostridium difficile infection and typhlitis; early post-engraftment for enterovirus, adenovirus, CMV colitis	5%-10%	Microbiologic, molecular or pathologic tests; CT, CTE, or MRE; colonoscopy with biopsies	Supportive care if viral, antibiotics if bacterial, antifungal therapy if fungal	Neutropenic enterocolitis and CMV colitis can be life threating in severe cases
Cord colitis	Late post-engraftment	10% of cord transplant	Negative cultures and a colon biopsy demonstrating chronic active colitis	Metronidazole	Only occurs in recipients of umbilical cord blood transplant

Also consider other causes unrelated to transplant such as malabsorption syndrome including pancreatic exocrine insufficiency, adrenal insufficiency, lactose intolerance, or other malabsorption syndromes[2-7]. CMV: Cytomegalovirus; CT: Computerized tomography; CTE: Computerized tomography enterography; GVHD: Graft-vs-host disease; MRE: Magnetic resonance enterography.

Table 2 Most common medications and infectious etiologies causing diarrhea in hematopoietic stem cell transplant recipients

Categories	Agents
Medications	Conditioning regimen, antibiotics, mycophenolate mofetil, tacrolimus, proton pump inhibitors, promotility agents, magnesium salts
Viral infection	Cytomegalovirus, herpes simplex virus, Ebstein-barr virus, adenovirus, norovirus and other enteroviruses
Bacterial infection	Campylobacter, Escherichia coli, Salmonella, Shigella, Yersinia, Vibrio cholera, Clostridium difficile, other enteric pathogens
Others	Fungal, e.g., candida, parasitic, e.g., Cryptosporidium and Mycobacterial infections
Mixed infection	Neutropenic enterocolitis