Oligosymptomatic Herpetic Hepatitis In A Patient With Rheumatoid Arthritis Using Corticosteroid And Methotrexate

Herpetic hepatitis is an uncommon complication of herpes simplex infection. In a survey of 137 patients, two thirds progressed to liver transplant requirement or death. Male, older, and immunocompromised patients were mostly at risk of death. The disease may also occur in immunocompetent individuals. Herein, we describe an unusual case of a patient with rheumatoid arthritis (RA), where oligosymptomatic herpetic hepatitis showed a good outcome. The patient, a 73-year-old white woman, was diagnosed as having RA in 2004; rheumatoid factor and anti-cyclic cittullinated peptide antibodies were present. Low-dose deflazacort (6 mg daily) and methotrexate (15 mg weekly) had been the standard treatment for the previous 5 years. In January 2009, the patient was admitted to the hospital because of pain in the right hypochondrium and elevation of liver enzymes. There was no jaundice, fever, or mucocutaneous lesions. On admission, the transaminase concentrations were 147 U/L for aspartate aminotransferase (reference, 14Y36 U/L) and 241 U/L for alanine aminotransferase (reference, 9Y52 U/L). Despite withdrawal of methotrexate, the liver enzymes remained elevated, reaching values of 271 U/L for aspartate aminotransferase and 589 U/L for alanine aminotransferase. Alkaline phosphatase, albumin, and prothrombin time were normal. Antinuclear, antimitochondrial, and antiYsmooth muscle antibodies were absent. Serologic tests for A, B, and C hepatitis virus were negative. Immunoglobulin G (IgG) and IgM antibodies to herpesvirus type 1 were positive in an immunoenzymatic assay (IgG, 17,461 IU; reference, G500 IU; IgM index, 1.25, reference negative). The patient was treated with intravenous acyclovir for 14 days with improvement of transaminases and clearing of IgM antiherpes antibodies from circulation. The liver biopsy showed apoptotic bodieswith eosinophilicmaterial in the cytoplasm and nuclear viral inclusions. Immunohistochemistry of liver tissue confirmed the presence of herpes simplex in the nuclei of hepatocytes (Fig. 1). Herpetic hepatitis should be considered in immunocompromised patients with changes in transaminases, even oligosymptomatic. Nonspecific symptoms of hepatitis and the absence of skin lesions could delay the diagnosis. Two cases of fulminant herpetic hepatitis, one in a child and another in a young adult, have been diagnosed after a short course of corticotherapy. Our patient, on the contrary, had been on low-dose deflazacort for a long period. Interestingly, herpes simplex hepatitis was reported in a patient with psoriatic arthritis taking prednisone and methotrexate. In our patient, we could hypothesize that the combination of corticosteroid and methotrexate predisposed to herpetic hepatitis. The current description of herpetic hepatitis, confirmed by serology and liver immunohistochemistry, is probably the first case in a patient with adult RA. Immunocompromised patients such as those with RA with acute liver disease should, after the exclusion of common causes of hepatitis (drug toxicity included), be screened for herpetic infection; screening should also include patients without skin features. The incidence of herpetic hepatitis in patients with RA may be underestimated. We emphasize that abnormal liver function tests in RA patients should not be assumed to be due to methotrexate without the exclusion of other causes, such as viral infection. Herpetic hepatitis can be fatal, but early diagnosis and prompt antiviral therapy may improve prognosis. Empiric acyclovir therapy for patients with acute liver failure of obscure etiology could be indicated until herpetic hepatitis is ruled out.