Final Diagnosis -- Anti-synthetase Syndrome-associated Myositis

FINAL DIAGNOSIS

Anti-synthetase syndrome-associated myositis.

DISCUSSION

Myositis is a characteristic feature of anti-synthetase syndrome (ASS), along with interstitial lung disease (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.

Due to 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 interstitial lung disease (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.

REFERENCES

1. Allenbach Y, Benveniste O, Goebel HH, Stenzel W (2017) Integrated classification of inflammatory myopathies. Neuropathol Appl Neurobiol 43:62-81.
2. Marie I, Josse S, Decaux O, Diot E, Landron C, Roblot P, et al (2013) Clinical manifestations and outcome of anti-PL7 positive patients with antisynthetase syndrome. Eur J Intern Med 24:474-9.
3. Mescam-Mancini L, Allenbach Y, Hervier B, Devilliers H, Mariampillay K, Dubourg O, et al (2015) Anti-Jo-1 antibody-positive patients show a characteristic necrotizing perifascicular myositis. Brain 138:2485-92.
4. Uruha A, Suzuki S, Suzuki N, Nishino I (2016) Perifascicular necrosis in anti-synthetase syndrome beyond anti-Jo-1. Brain 139:e50.

Contributed by Andrew F. Gao, MD, Ophir Vinik, MD, David G. Munoz, MD