Today, we discussed a case of a 37 year old man with HIV off ARVs, who presented with acute on chronic worsening of bloody diarrhea, found to have detectable Shiga-toxin and E. coli O157! This case brought up an interesting differential diagnosis of diarrhea in HIV patients (including CMV colitis, pearls below) as well as discussion of hemolytic uremic syndrome from E. coli O157:H7 infection.
- Majority of Shiga-toxin detected in adults is due to Shiga-toxin producing E. coli, rather than Shigellosis! This has implications for antibiotic therapy, as use of antibiotics in enterohemorrhagic E. coli infection can precipitate a rare but potentially fatal complication of hemolytic uremic syndrome.
- Additional studies to send in a HIV patient with diarrhea that are not detected in routine stool cultures or O&P
- Microsporidiosis: Requires specific stains that need to be requested, as routine examination for O&P does not usually detect microsporida spores.
- E. histolytica: Requires special stool microscopy, antigen testing (both stool and serum), or parasitic DNA or RNA in feces
- Giardia: There are Giardia-specific antigen detection assays
- Listeria: Requires a special stool culture using selective media
CMV colitis in HIV patients
- 2nd most common manifestation of end organ damage after CMV retinitis
- When to suspect?
- In patients with CD4 cell counts < 50 who present with symptoms of esophagitis, gastritis, enteritis, or colitis.
- Evaluation for more common causes of GI disease is unrevealing
- Empiric therapy for a more common etiology is not effective.
- Severe symptoms of diarrhea
- Endoscopic visualization: can range from punctate and superficial erosions to deep ulcerations and necrotizing colitis
- Histopathology : characteristic histology of mucosal inflammation, tissue necrosis, and vascular endothelial cell damage : Intranuclear and intracytoplasmic inclusion bodies
- Antigen positivity : Important to remember, presence of CMV in blood OR tissue and/or a positive CMV antibody does NOT confirm a diagnosis of CMV disease in patients with HIV and advanced suppression. AIDS patients can have CMV viremia without any end organ disease. : However, CMV colitis is rare in AIDS patients who are CMV seronegative, because infection results from reactivation of latent virus. Hence, if suspicion is high, worthy checking a CMV antibody!
Hemolytic Uremic Syndrome associated with E. Coli O157:H7 infection
- Characterized by MAHA, thrombocytopenia, and acute renal injury. Rare neurologic complications can also occur.
- 6-9% of STEC (Shiga-Toxin secreting E. Coli) infections
- Pathophysiology 1) Shiga toxin released by E. coli binds to globotriaosylceramide (Gb3) on surface of vascular endothelial cells, particularly in the kidney and brain à inhibits protein synthesis à induces broad inflammatory response à releases cytokines and chemokines à thrombosis and organ damage! 2) Shiga toxin also activates alternative pathway of complement system by binding to factor H proteins!
- Best approach: Basic supportive care
- Under investigation but not standard-of-care:
- PLEX: remove Shiga-like toxin and prothrombotic factors and replace them with coagulation, tissue, and complement factors
- Oral Shiga toxin-binding agent
- Eculizumab: Monoclonal antibody to C5 complement factor blocking complement activation. There are case series demonstrating the benefit of using eculizumab in children with STEC-HUS