A 45‐Year‐Old Woman with Rash and Severe Weakness

Clinical History

A 45‐year‐old woman presented to our institution with progressive upper and lower extremity proximal weakness of a few weeks' duration. Three 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 three 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 >50 000 U/L. CT scan of the chest/abdomen/pelvis revealed no evidence of malignancy or interstitial lung disease (ILD). 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‐TIF1γ, 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 one 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.

Microscopic Pathology

Hematoxylin‐phloxine‐saffron‐stained cryostat sections showed markedly abnormal muscle with numerous atrophic, necrotic and regenerating fibres in a striking perifascicular distribution (Figure 1A and B). There was fragmentation of the perimysial connective tissue with infiltration by histiocytes (Figure 1C) and alkaline phosphatase staining in the perimysium (Figure 1D). Immunohistochemistry for MHC Class I showed upregulation on the sarcolemma of all fibres, with slight perifascicular accentuation (Figure 1E). 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 (Figure 1F). What is your diagnosis?

Figure 1.

Diagnosis

Anti‐synthetase syndrome (ASS)–associated myositis.

Discussion

Myositis is a characteristic feature of ASS, along with ILD, arthritis, Raynaud phenomenon, mechanic's hands and the presence of serum anti‐aminoacyl‐tRNA synthetase antibodies. ASS‐associated myositis has characteristic morphological features that distinguish it from other inflammatory myopathies 3. As in our case, muscle biopsies show a striking perimysial and perifascicular distribution of pathology, with perifascicular fibre necrosis/regeneration, upregulation of MHC and sarcolemmal deposition of MAC. The perimysium shows fragmentation, inflammatory infiltrates and alkaline phosphatase staining. The differential diagnosis includes dermatomyositis, but perifascicular necrosis, as opposed to atrophy, is a relatively specific feature of ASS‐associated myositis.

Clinical‐serologic‐pathologic correlation is essential in the diagnosis of inflammatory myopathies. Our patient presented with weakness and rash and had positive serology for both anti‐PL‐7 (anti‐threonyl‐tRNA synthetase) and anti‐Mi2 (dermatomyositis‐specific) antibodies. While the muscle biopsy results were consistent with the presence of anti‐PL‐7 antibodies 4, there were no other clinical features of ASS. Interestingly, the patient's clinical presentation was more suggestive of classic dermatomyositis and consistent with positive serology for anti‐Mi2 antibodies. Anti‐Mi2 is associated with classic skin findings of heliotrope rash, Gottron papules and V‐ and shawl signs (rash on chest and upper back, respectively) 1. Typically, muscle biopsy shows classic pathological findings of perifascicular atrophy and perivascular inflammation.

Because of the somewhat discordant clinical‐serologic‐pathologic features of this case, the clinical course of this patient is difficult to predict. Anti‐Mi2 is associated with good response to therapy and low risk of ILD 1. In contrast, anti‐PL‐7 is commonly associated with ILD, which increases the risk of morbidity 2. Our case therefore highlights the importance of a robust serologic workup, having low threshold for muscle biopsy, close clinical follow‐up and careful clinical‐serologic‐pathologic correlation in inflammatory myopathies.