Final Diagnosis -- Immune-mediated Necrotizing Myopathy


Immune-mediated necrotizing myopathy, iNM or IMNM (Synonym: necrotizing autoimmune myopathy, NAM) Most likely anti-synthetase myopathy (ASM)


Idiopathic inflammatory myopathy (IIM) is currently classified into 4 major groups including iNM, dermatomyositis (DM), inclusion body myositis (IBM) and polymyositis (PM). Without detailed clinical information and laboratory study, a combination of skin lesions and acute to subacute muscle weakness with high CK level sometimes mislead pathologists to the diagnosis of DM although clinical findings and muscle biopsy pathology are not that typical for the disease. In DM, the characteristic skin lesions include periorbital violaceous erythema (heliotrope rash) and raised violaceous scaly eruptions on the knuckles (Gottron's sign/papule). V-shape erythematous rash on anterior chest as well as erythematous rash on the face, knees, elbows, malleoli, and neck are also common, but not specific for the disease. In fact, skin lesions can be presenting symptoms of anti-synthetase myopathy (ASM), a distinct subgroup of IIM identified by specific autoantibodies directed against tRNA-synthetase eg. anti-Jo-1, anti-PL-7, anti-PL-12, anti-OJ, anti-EJ, anti-KS, anti-Zo and anti-Ha; the most common autoantibody among this group is anti-Jo-1 [1, 2]. The other clinical symptoms in ASM include interstitial lung disease, arthritis, Raynaud's phenomenon and mechanic's hands [2]. Anti-Jo-1 antibody-positive myopathy, as well as some of ASMs associated with autoantibodies against non-Jo-1 synthetases, is pathologically characterized by perifascicular necrotizing myopathy [2, 4]. This can be superficially resembling DM as the prominent findings in both entities are perifascicular pathology. Usually, perimysium and adjacent endomysium alkaline phosphatase reactivity is present in anti-Jo-1 antibody-positive myopathy, whereas endomysial microangiopathy, such as perifascicular lymphocytic infiltration and vascular C5b-9 expression, is present in DM [1]. Perifascicular COX-negative fibers are also favor the diagnosis of DM . Interestingly, perifascicular myofiber immunohistochemical positivity for MxA has been introduced as an auxiliary test for DM as MxA is one of type 1 interferon-inducible proteins highly expressed in perifascicular myofibers of DM patients [3]. Moreover, perifascicular HLA-DR expression is recently described as a unique finding in ASM [1]. In summary, our patient presented with acute onset proximal muscle weakness and skin erythema with questionable H&E pathology; absence of perifascicular COX-negative fibers, negative MxA immunostaining, increased perimysial alkaline phosphatase activity and mild perifascicular HLA-DR positivity are suggestive of ASM. In our patient, positive anti-Jo-1 antibody is confirmed. Precise distinction between ASM and DM is important because diagnostic implications of ASM and DM can significantly differ with potential of extramuscular manifestations, including life-threatening interstitial pneumonia in the former and malignancy association in the latter.


  1. Aouizerate J, De Antonio M, Bassez G, Gherardi RK, Berenbaum F, Guillevin L, et al. (2014) Myofiber HLA-DR expression is a distinctive biomarker for antisynthetase-associated myopathy. Acta Neuropathol Commun 2:154.
  2. 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 138:2485-2492.
  3. Salajegheh M, Kong SW, Pinkus JL, Walsh RJ, Liao A, Nazareno R, et al. (2010) Interferon-stimulated gene 15 (ISG15) conjugates proteins in dermatomyositis muscle with perifascicular atrophy. Ann Neurol 67:53-63.
  4. Uruha A, Suzuki S, Suzuki N, Nishino I.(2016) Perifascicular necrosis in anti-synthetase syndrome beyond anti-Jo-1. Brain 139(Pt 9):e50.

Contributed by Jantima Tanboon, MD, Akinori Uruha, MD, PhD, Kohei Hamanaka, MD, PhD, Juri Hasegawa, MD, Ichizo Nishino, MD, PhD

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