Recurrent acalculous cholecystitis and sclerosing cholangitis in a patient with X-linked hyper-immunoglobulin M syndrome.
X-linked hyper-immunoglobulin M (IgM) syndrome (XHIGM) is a rare genetic primary immunodeficiency disease caused by mutations of the CD40 ligand (CD40L) gene with normal or elevated levels of IgM and markedly decreased serum IgG, IgA, and IgE. Liver disease may occur as a clinical manifestation in XHIGM. This complication appears to increase with age. We report an 18-year-old male patient who had recurrent episodes of acalculous cholecystitis (AC) and sclerosing cholangitis (SC). The diagnosis of XHIGM was confirmed by the finding of CD40L expression < 1% of normal and a tyrosine 169 asparaginase (t526a) mutation in exon 5 (the tumor necrosis factor domain) of the CD40L gene. The patient had direct hyperbilirubinemia (direct bilirubin 5.5 mg/dL, total bilirubin 8.7 mg/dL), cholestasis (alkaline phosphatase 1133 U/L, gamma-glutamyl transferase 1019 U/L) and elevated transaminases (aspartate aminotransferase 70 U/L, alanine aminotransferase 101 U/L). Findings on abdominal ultrasound and abdominal computed tomography were compatible with AC. After the fourth episode of cholecystitis, cholecystectomy and liver biopsy were performed. Operative cholangiography revealed poor opacification of the hepatic duct and proximal common bile duct; the upstream intrahepatic bile ducts were not visualized. The biopsy specimen showed marked fibrosis of the portal areas. Enterococcus species was cultured from the bile. Children or adolescents with recurrent AC and SC should be evaluated for an underlying immunodeficiency syndrome such as XHIGM.
Lin
Sheng-Chieh
SC
Division of Allergy and Immunology, Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan.
Shyur
Shyh-Dar
SD
Ma
Yi-Chun
YC
Huang
Li-Hsin
LH
Lee
Hung-Chang
HC
Lee
Wen-I
WI
D000293:Adolescent; D023201:CD40 Ligand / Q000235:genetics*; D015209:Cholangitis, Sclerosing / Q000209:etiology* / Q000473:pathology; D002764:Cholecystitis / Q000209:etiology* / Q000473:pathology; D041321:Chromosomes, Human, X; D008040:Genetic Linkage; D006801:Humans; D006942:Hypergammaglobulinemia / Q000150:complications* / Q000235:genetics; D007075:Immunoglobulin M / Q000097:blood*; D007153:Immunologic Deficiency Syndromes / Q000150:complications*; D008099:Liver / Q000473:pathology; D008297:Male; D012008:Recurrence
D007075:Immunoglobulin M; D023201:CD40 Ligand