Can sarcoidosis be induced by interferon beta?/nThe question concerns a 37-year-old man with multip

Fråga: Can sarcoidosis be induced by interferon beta?

The question concerns a 37-year-old man with multiple sclerosis (MS). When initiating interferon beta-1a (Avonex) treatment skin rashes developed. New rashes appeared gradually, but have not caused any big trouble. Three years later the rashes are biopsy verified as sarcoidal granulomatous dermatitis.

Sammanfattning: Several cases of sarcoidosis in patients treated with interferons have been published in the literature. Most cases are during treatment with interferon-alfa for hepatitis C. For interferon-beta only a few reports of sarcoidosis have been reported.

Svar: Sarcoidosis is a systemic granulomatous disease of unknown cause. Proposed causes include infectious organisms, genetic tendency, environmental agents and autoantigens. It is supposed that sarcoidosis is a result of a dysregulation of the immunsystem with an unchecked helper T-cell proliferation triggering a cascade of immunological events subsequently leading to granuloma formation (1,2,3). Inflammatory mediators, mainly interleukin-2 and interferon (IFN)-gamma have been suggested to be involved in the pathogenesis of sarcoidosis. It has been shown that titers of IFN-gamma in patients with sarcoidosis are higher than in healthy people (4).

IFNs are divided into two classes; IFN I (including IFN-alfa and IFN-beta) and IFN II (including IFN-gamma) (2). IFNs are known to act on the modulation of the immune response and to be mediators of T-cell activity and have been proposed to induce or worsen autoimmune diseases such as thyroiditis, SLE, psoriasis and sarcoidosis (1,5). Since INFs are mediators of T-cell activity, it is possible that they can act as triggers in the immune reaction and proliferation of T-helper cells occurring in sarcoidosis (1,6).

Several case reports of sarcoidosis after IFN-alfa treatment have been reported in the literature. Most cases have been in connection with treatment for hepatitis C. In a review of eight cases of sarcoidosis, symptoms developed between 2.5 and 17 months after initiating therapy. Prompt recovery after drug discontinuation is mostly seen (3,7).

The connection between IFN-beta and sarcoidosis does not seem as clear and only four case reports have been found. One case a lot similar to the case in question, concerning a man with MS who developed sarcoidosis has been published. Two months after initiation of IFN-beta-1b treatment prurutic granulomatous eruptions on his abdomen, chest, back arms and scalp developed. A biopsy taken two years later indicated that this was sarcoidosis. IFN-beta treatment was discontinued; treatment with hydroxychloroquine, psoralen and UVA was initiated. Nine months later the eruptions had gradually subsided (5).

One case of neurosarcoidosis in a patient treated with IFN-beta for chronic hepatitis has been reported. The patient had been treated for several weeks when she noticed numbness in her back and left side, inability to shut her left eye and difficulties swallowing. IFN-beta therapy was discontinued and prednisolone therapy was started. Within four weeks the symptoms had disappeared (8). Two cases of pulmonary sarcoidosis have also been reported. One patient was treated with IFN-beta-2a, vincristine and prednisone for renal cell carcinoma the other with interferon beta-1b, vincristine, BCNU, melphalan, cyclophosphamide and prednisone for multiple myeloma. The second patient had a history of sarcoidosis in the family (1,9).

Two reports of sarcoidosis after treatment with IFN-alfa was found in the Swedish adverse drug reactions register. There are no reports of sarcoidosis for IFN-beta in this register (10).