Contributed by Andrew F. Gao, MD1,3, Ophir Vinik, MD2, David G. Munoz, MD1,3
1Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada
2Division of Rheumatology, Department of Medicine, St. Michael's Hospital, Toronto, Canada
3Department of Laboratory Medicine, St. Michael's Hospital, Toronto, Canada
A 45-year-old woman presented to our institution with progressive upper and lower extremity proximal weakness of a few weeks' duration. 3 months prior, the patient received a diagnosis of systemic lupus erythematosus and started on hydroxychloroquine; she had been treated with low dose prednisone for her weakness for the last 3 weeks. Physical examination showed severe proximal weakness, grade 2/5, in the bilateral upper and lower extremities with retained strength in all other muscle groups. The patient had an erythematous rash on her face, chest, and upper back. There was no clinical evidence of involvement of other organs.
Serum creatinine kinase (CK) was >50000 U/L. CT scan of the chest/abdomen/pelvis revealed no evidence of malignancy or interstitial lung disease. Serology was positive for ANA, but with negative ENA and dsDNA. She tested positive for anti-PL-7 and anti-Mi2. The rest of the myositis-specific and-associated antibodies were negative including anti-TIF1β, anti-MDA-5, anti-NXP2, anti-SAE1, anti-Jo-1, anti-PL-12, anti-EJ, and anti-OJ.
The patient underwent a muscle biopsy of the left vastus lateralis. Prednisone was continued together with methotrexate and intravenous immunoglobulin was added. At follow-up 1 month later, she showed clinical improvement of proximal muscle strength (4- to 4/5 bilateral upper and lower extremities) and CK decreased to 1169 U/L.
Hematoxylin-phloxine-saffron stained cryostat sections showed markedly abnormal muscle with numerous atrophic, necrotic, and regenerating fibres in a striking perifascicular distribution (Figs. 1 and 2). There was fragmentation of perimysial connective tissue with infiltration by histiocytes (Fig. 3) and alkaline phosphatase staining in the perimysium (Fig. 4). Immunohistochemistry for MHC Class I showed upregulation on the sarcolemma of all fibres, with slight perifascicular accentuation (Fig. 5). Staining for C5b-9 (membrane attack complex; MAC) showed intense deposition on the sarcolemma of non-necrotic fibres in a predominantly perifascicular distribution, but not on capillaries (Fig. 6). What is your diagnosis?