LETTER
Methotrexate in Idiopathic Granulomatous Hepatitis
Richard J. Shea, MD;
Talley F. Culclasure, MD; and
James D. Singleton, MD
1 November 1995 | Volume 123 Issue 9 | Page 733
TO THE EDITOR:
Knox and colleagues [1] reported the successful use of low-dose oral pulse methotrexate as a steroid-sparing agent in patients with idiopathic granulomatous hepatitis. We have observed a significant steroid-sparing effect with the use of hydroxychloroquine in a patient with this disease. Our patient was first seen 5 years ago with fever, anorexia, night sweats, elevated liver enzyme levels, a Westergren erythrocyte sedimentation rate of 125 mm/h (normal, 0 to 20 mm/h), and a C-reactive protein level of 13.7 mg/dL (normal, 0.08 to 0.8 mg/dL). Granulomas were identified in liver and bone marrow biopsy specimens.
The patient responded to treatment with high-dose glucocorticoids, but symptoms and laboratory abnormalities returned whenever the steroid dose was tapered to less than 15 mg/d. Hydroxychloroquine therapy was initiated at 200 mg twice a day, and the steroid dose was decreased to 5 mg/d. The patient remained symptom free without laboratory evidence of active disease for 2 years; repeat bone marrow biopsy specimens showed no granulomas. Therapy with all drugs was discontinued, and symptoms, laboratory abnormalities, and bone marrow granulomas returned within 6 months. Once prednisone and hydroxychloroquine were restarted, the disease was rapidly controlled.
The mechanism of action of hydroxychloroquine is unknown, but the drug has been shown to suppress monocyte-mediated activation of B cells by inhibiting the release of factors required to initiate and maintain an inflammatory response, including interleukin-1 [2]. This action may specifically interrupt the activation of the macrophages required for the formation of granuloma [3]. The drug is useful in patients with sarcoidosis, another idiopathic granulomatous disease, and is not associated with the more toxic side effects seen with methotrexate. Because treatment of granulomatous syndromes can be confused by the spontaneous resolution of symptoms [4], the efficacy of novel therapy may be overstated if this phenomenon is not excluded. We recommend a trial of hydroxychloroquine in patients with idiopathic granulomatous hepatitis before more toxic drugs are considered. We also believe that the drug should be withdrawn after a period of successful treatment so that the patient can be evaluated for spontaneous resolution.
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Author and Article Information
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Fitzsimons Army Medical Center; Aurora, CO 80045-5000
1. Knox TA, Kaplan MM, Gelfand JA, Wolff SM. Methotrexate treatment of idiopathic granulomatous hepatitis. Ann Intern Med. 1995; 122:592-5.
2. Salmeron G, Lipsky PE. Immunosuppressive potential of antimalarials. Am J Med. 1983; 75:19-24.
3. Soskel NT, Fox R. Sarcoidosis ... or something like it. South Med J. 1990; 83:1190-202.
4. Friedland JS, Weatherall DJ, Ledingham JG. A chronic granulomatous syndrome of unknown origin. Medicine (Baltimore). 1990; 69:325-31.
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