Asymptomatic cryptosporidiosis with atypical cholangitis and eosinophilic hepatitis in X-linked hyper-IgM syndrome (XHIM)

Abstract Rationale XHIM is a rare form of immunodeficiency due to abnormally low expression of CD40 Ligand on CD4+ T-cells. XHIM patients present with variably diminished IgG, IgA, IgE and normal to high IgM levels. XHIM patients are predisposed to infections with fungi, encapsulated organisms and opportunistic organisms such as Cryptosporidium (Cry.). Cry. infection is usually associated with gastrointestinal symptoms but may also cause cholangitis in immune deficient patients. Methods 8 year old asymptomatic Hispanic male with XHIM and elevated liver enzymes was diagnosed with Cry. infection on fecal exam for oocytes and antigen. After failing metronidazole therapy, Cry. cleared from his stools after fourteen months of paromomycin therapy. Persistently elevated liver enzymes prompted an abdominal ultrasound (AUS), endoscopic retrograde cholangiopancreatography (ERCP) and liver biopsies. Results AUS showed mild dilatation throughout the biliary tract. ERCP revealed marked beading of the intrahepatic biliary tree suggesting cholangitis. Liver biopsy specimens obtained at three months and twelve months from the onset of elevated liver enzymes revealed eosinophilic inflammation with little fibrosis and no demonstrable organisms. Conclusions XHIM patients with Cry. infection and asymptomatic elevation of hepatic enzymes are at an increased risk for developing cholangitis and hepatic inflammation despite effective clearing of infection from the gastrointestinal tract. XHIM patients should be monitored closely for these complications.