Liver Enzyme Abnormalities in Patients With Atopic Dermatitis Treated With Mycophenolate Mofetil

Mycophenolate mofetil is approved by the US Food and Drug Administration for the treatment of renal allograft rejection, and recently it has received attention as an alternative steroid-sparing agent in dermatology.^{1 - 3} Dose-dependent nausea, vomiting, diarrhea, and abdominal pain are the most commonly encountered adverse effects. Bone marrow suppression and increased risk of infection are the major safety risks, and mycophenolate mofetil is generally thought to be free of hepatotoxic effects. Herein, we describe 2 patients with atopic dermatitis who developed increased levels of serum hepatic transaminases (liver function tests) following an increase in dosage of mycophenolate mofetil.

A 52-year-old woman had a long history of atopic dermatitis previously treated with prednisone and cyclosporine. Her medications included topical pimecrolimus, conjugated estrogen, fexofenadine, cetirizine, and valsartan. She denied use of alcohol or any herbal or over-the-counter medications. Her baseline levels of serum hepatic transaminases were within the reference range, and her serologic test results were negative for hepatitis C and B. She was started on a regimen of mycophenolate mofetil, 500 mg, twice a day, and after 2 weeks, her levels of serum hepatic transaminases remained in the reference range and the dosage was increased to 1 g twice a day. One month later, her atopic dermatitis had improved, but her level of serum aspartate aminotranferase was elevated at 134 U/L and her serum level of alanine aminotransferase was 289 U/L. Her bilirubin levels were always within the reference range, and she denied abdominal pain, dark urine, or light stools. Treatment with mycophenolate mofetil was discontinued, and her levels of serum hepatic transaminases returned to the reference range (aspartate aminotranferase, 21 U/L; alanine aminotransferase, 28 U/L) within 2 weeks. She was then rechallenged with a dosage of mycophenolate mofetil, 500 mg, twice a day, and within 1 month again developed increased levels of serum hepatic transaminases. Treatment with mycophenolate mofetil was discontinued, and the patient was started on a prednisone taper and azathioprine concurrently. The patient’s levels of serum hepatic transaminases have remained within the reference range since that time.

A 68-year-old man was seen for treatment of recalcitrant and severe atopic dermatitis. Other than cetirizine, he was not taking any medications or herbal products and denied alcohol use. Baseline levels of serum hepatic transaminases were within the reference range. The patient’s hepatitis serologic testing results were positive for IgG antibodies directed against hepatitis A as well as hepatitis B surface and core antigens. Results were negative for antibodies against hepatitis B surface antigen and hepatitis C. The patient was initially started on a regimen of 500 mg of mycophenolate mofetil twice a day. His serum level of hepatic transaminases were measured 1 month later and remained unchanged. The dosage of mycophenolate mofetil was increased to 1 g twice a day; 1 month later, his serum levels of aspartate aminotranferase increased from 20 to 77 U/L, and his serum level of alanine aminotransferase increased from 22 to 247 U/L. Treatment with mycophenolate mofetil was discontinued, and his serum levels of hepatic transaminases returned to reference range over the following 4 weeks and have remained within those limits since that time (more than 1 year).

Hepatic monitoring is not recommended in the package insert for mycophenolate mofetil. The 2005 Physicians Desk Reference⁴ indicates that abnormalities in serum hepatic transaminases may occur in up to 25% of patients taking mycophenolate mofetil for hepatic allograft rejection (but not for patients who have had renal or cardiac allografts), suggesting that these changes in serum levels of hepatic transaminases are due to the effects of liver transplantation rather than mycophenolate mofetil. In fact, 1 recent study reported normalization of serum levels of hepatic transaminases in patients who had undergone orthotopic liver transplantation within 2 weeks of initiating therapy with mycophenolate mofetil.⁵ We reviewed the literature regarding the use of mycophenolate mofetil for treatment of skin disease and did not find previous reports of elevated serum levels of hepatic transaminases following treatment with mycophenolate mofetil. The functional meaning of abnormalities in serum hepatic transaminases is unclear because no biopsy or hepatic imaging studies were undertaken. Despite this, toxic effects on the liver may represent an underappreciated adverse effect of treatment with mycophenolate mofetil that should be monitored in patients.

Correspondence: Dr Fiorentino, Department of Dermatology, Stanford University School of Medicine, 900 Blake Wilbur Dr, Stanford, CA 94305 (Fiorentino@stanford.edu).

Financial Disclosure: None.