mercaptopurine and Sclerosis

Thiopurines play a pivotal role in the management of inflammatory bowel disease. Azathioprine and mercaptopurine have been associated with a number of liver abnormalities, including hepatitis, veno-occlusive disease, nodular regenerative hyperplasia, and peliosis hepatitis. Patients treated with azathioprine and mercaptopurine have their liver chemistry tests routinely checked due to this potential for hepatotoxicity. Hepatoportal sclerosis is a cause of non-cirrhotic portal hypertension that is increasingly being recognized; its etiopathogenesis is not well defined. We present the first case report of mercaptopurine-induced hepatoportal sclerosis leading to non-cirrhotic portal hypertension in a patient with Crohn's disease. He had been treated with mercaptopurine for five years, and his liver chemistry tests were always within normal limits. This case underscores the potential serious liver adverse events that may arise silently and go undetected during treatment with mercaptopurine, and should alert clinicians as to the potential need to discontinue mercaptopurine in this setting.

Topics: Ascites; Crohn Disease; Humans; Hypertension, Portal; Immunosuppressive Agents; Intestinal Obstruction; Liver Function Tests; Male; Mercaptopurine; Portal System; Sclerosis; Young Adult

Topics: Blood Protein Disorders; Drug Therapy, Combination; Humans; Male; Mercaptopurine; Middle Aged; Mucins; Myxedema; Sclerosis; Syndrome

The following differential effects of immunosuppressive therapy with Cyclophosphamide (CYCLOPH) and 6-mercaptopurine (6-MP) in the female NZB-NZW F1 hybrid strain have been observed: (1) CYCLOPH but not 6-MP significantly decreased antinuclear antibody level. (2) Both CYCLOPH and 6-MP significantly decreased glomerular cell proliferation. (3) Both CYCLOPH and 6-MP significantly arrested progression of glomerulosclerosis. (4) While CYCLOPH significantly diminished Ig deposition in the glomeruli, 6-MP had no effect on this phenomenon. (5) While CYCLOPH decreased subepidermal globulin deposition in the skin, 6-MP appeared actually to enhance subepidermal staining. Thus, the present studies demonstrated that CYCLOPH was superior to 6-MP in four of the five parameters studied. In the case of one parameter, Ig staining of the skin, 6-MP actually produced enhancement of the staining. Both CYCLOPH and azathioprine which is a derivative of 6-MP, are currently being used for the treatment of human SLE. The present findings suggest that of the two, CYCLOPH may be the drug of choice.

Topics: Animals; Antibodies, Antinuclear; Cell Division; Cyclophosphamide; Female; Fluorescent Antibody Technique; Glomerulonephritis; Immunoglobulins; Kidney; Mercaptopurine; Mice; Mice, Inbred NZB; Sclerosis; Skin

Topics: Adult; Anti-Glomerular Basement Membrane Disease; Autoimmune Diseases; Biopsy; Follow-Up Studies; Glomerulonephritis; Humans; Kidney Function Tests; Kidney Glomerulus; Male; Mercaptopurine; Prednisone; Proteinuria; Sclerosis