Abstract

Hepatotoxicity during high-dose cyclophosphamide (CYC) therapy has been reported,^1,2 but hepatitis due to low-dose CYC treatment has rarely been described.³ We report a 40-year-old male patient diagnosed with primary scleroderma, treated with D-penicillamine (D-PEN) followed by cyclophosphamide. The patient was treated with D-PEN for 1.5 years and responded well to treatment. He did not take any other medications for the following 2.5 years. When the patient developed polyarthralgia and sinusitis, he was treated and responded well to low-dose steroids and oral CYC (100 mg/d). The same dose of CYC was continued for 45 days and the total cumulative dose of CYC was estimated to be 4.5 g. Because of progressive jaundice lasting for one week, the patient was readmitted. Laboratory findings revealed an albumin of 3.3 mg/dL, globulin 2.9 mg/dL, alkaline phosphatase 206 U/L, aspartate aminotransferase 1806 U/L, alanine aminotransferase 2407 U/L, gamma glutamyl transferase 202 U/L, lactate dehydrogenase 818 U/L, direct bilirubin 6.3 mg/dL, indirect bilirubin 4.2 mg/dL, partial thromboplastin time 14.2 seconds, Cu 134 U/L (70–153 U/L) and ceruloplasmin 409 U/L (280–570 U/L). Ultrasonography of the hepatobiliary system did not reveal any obstructive lesions. Serology for hepatitis A, B and C, toxoplasma IgM, cytomegalovirus IgG and IgM, herpes simplex virus Type 1 and Type 2 IgM, Brucella IgM and IgG, antimitochondrial antibody M2, anti-Sp100, anti-LKM-1, and anti-SLA were all found to be negative. Hepatitis C virus RNA was performed with real time PCR and was found to be negative. Liver function tests returned to normal levels 11 weeks following discontinuation of CYC. No other reason was found for the hepatic injury, and the patient's cyclophosphamide therapy was determined to be the cause.