Localized panniculitis secondary to subcutaneous glatiramer acetate injections for the treatment of multiple sclerosis: a clinicopathologic and immunohistochemical study.

Abstract

Glatiramer acetate has been shown to be effective in reducing the relapse and improving the disability of patients with multiple sclerosis. The most common adverse effects at the injection sites include pain, inflammation, and induration that spontaneously disappear within hours or a few days. We sought to characterize the histopathologic findings of localized panniculitis induced by glatiramer acetate at the injection sites. Seven patients receiving daily glatiramer acetate injections for treatment of multiple sclerosis developed localized panniculitis at the injection sites. The lesions were histopathologically and immunohistochemically studied. The lesions consisted of a mostly lobular panniculitis, with lipophagic granuloma, namely histiocytes engulfing the lipids from necrotic adipocytes. In many areas, scattered neutrophils and eosinophils were seen both in the septa and in the fat lobules. Connective tissue septa showed widening and fibrosis in conjunction with many lymphoid follicles, presenting with germinal center formation. Immunohistochemically, the inflammatory infiltrate of the fat lobule consisted of CD68+ histiocytes and suppressor/cytotoxic T lymphocytes. In contrast, the lymphoid follicles in the septa and at the interface between septum and fat lobule were mainly composed of B lymphocytes. Only one biopsy was performed in each patient and, therefore, it was not possible to study the histopathologic evolution of the panniculitic process. Localized panniculitis at the sites of subcutaneous injections of glatiramer acetate for treatment of multiple sclerosis seems to be a rare, but characteristic side effect of this therapy. The histopathologic pattern of these lesions consists of a mostly lobular panniculitis, with histiocytes and T lymphocytes in the fat lobule and thickened septa with scattered lymphoid follicles, which are mostly composed of B lymphocytes.