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Anti-aminoacyl-tRNA synthetase-related myositis and dermatomyositis: clues for differential diagnosis on muscle biopsy

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Abstract

Anti-synthetase syndrome is an autoimmune disease characterized by autoantibodies toward amino acyl-tRNA synthetases (ARS), anti-Jo 1 being the most commonly detected. Muscle damage develops in up to 90% of ARS-positive patients, characterized by a necrotizing myositis restricted to the perifascicular region. This topographic distribution of muscle damage may lead to a misdiagnosis of dermatomyositis (DM) at muscle biopsy. We compared morphological, immunohistochemical, and histoenzymatic features of muscle from ARS-positive patients (n = 11) with those of DM (n = 7) providing clues for their differential diagnosis. In addition, we evaluated markers of mitochondrial damage to provide a further distinction between these two entities. Necrosis occurred in the majority of ARS patients, mainly located in the perifascicular region. It was often limited to small foci of fibers, always associated with myocyte regeneration. This last often overwhelmed necrosis, representing occasionally the main finding. In DM, necrosis/regeneration was scarce while the peculiar feature was a diffuse atrophy of perifascicular fibers. These last showed decreased cytochrome c oxidase (COX) stain and mitochondrial DNA depletion, consistent with mitochondrial dysfunction. In contrast to DM, ARS displayed scattered COX-deficient fibers, not restricted to the perifascicular region. This feature occurred in up to 91% of patients, being prominent only in two.

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References

  1. Dalakas MC (2015) Inflammatory muscle diseases. N Engl J Med 372(18):1734–1747. https://doi.org/10.1056/NEJMra1402225

    Article  PubMed  Google Scholar 

  2. Hoogendijk JE, Amato AA, Lecky BR, Choy EH, Lundberg IE, Rose MR, Vencovsky J, de Visser M, Hughes RA (2004) 119th ENMC international workshop: trial design in adult idiopathic inflammatory myopathies, with the exception of inclusion body myositis, 10–12 October 2003, Naarden, The Netherlands. Neuromuscul Disord 14(5):337–345. https://doi.org/10.1016/j.nmd.2004.02.006

    Article  PubMed  Google Scholar 

  3. Troyanov Y, Targoff I, Tremblay JL, Goulet JR, Raymond Y, Senécal JL (2005) Novel classification of idiopathic inflammatory myopathies based on overlap clinical features and autoantibodies: analysis of 100 French Canadian patients with myositis. Medicine (Baltimore) 84(4):231–249. https://doi.org/10.1097/01.md.0000173991.74008.b0

    Article  Google Scholar 

  4. Love LA, Leff RL, Fraser DD, Targoff IN, Dalakas M, Plotz PH et al (1991) A new approach to the classification of idiopathic inflammatory myopathy: myositis-specific autoantibodies define useful homogeneous patient groups. Med Baltim 170:360–374

    Article  Google Scholar 

  5. Koenig M, Fritzler MJ, Targoff IN, Troyanov Y, Senécal J (2007) Heterogeneity of autoantibodies in 100 patients with autoimmune myositis: insights into clinical features and outcomes. Arthritis Res Ther 9(4):R78. https://doi.org/10.1186/ar2276

    Article  PubMed  PubMed Central  Google Scholar 

  6. Senécal JL, Raynauld JP, Troyanov Y (2017) Editorial: a new classification of adult autoimmune myositis. Arthritis Rheumatol 69(5):878–884. https://doi.org/10.1002/art.40063

    Article  PubMed  Google Scholar 

  7. Iaccarino L, Gatto M, Bettio S, Caso F, Rampudda M, Zen M, Ghirardello A, Punzi L, Doria A (2013) Overlap connective tissue disease syndromes. Autoimmun Rev 12(3):363–373. https://doi.org/10.1016/j.autrev.2012.06.004

    Article  CAS  PubMed  Google Scholar 

  8. Brouwer R, Hengstman GJ, Vree Egberts W, Ehrfeld H, Bozic B, Ghirardello A, Grøndal G, Hietarinta M, Isenberg D, Kalden JR, Lundberg I, Moutsopoulos H, Roux-Lombard P, Vencovsky J, Wikman A, Seelig HP, van Engelen BG, van Venrooij WJ (2001) Autoantibody profiles in the sera of European patients with myositis. Ann Rheum Dis 60(2):116–123. https://doi.org/10.1136/ard.60.2.116

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Mescam-Mancini L, Allenbach Y, Hervier B, Devilliers H, Mariampillay K, Dubourg O, Maisonobe T, Gherardi R, Mezin P, Preusse C, Stenzel W, Benveniste O (2015) Anti-Jo 1 antibody-positive patients show a characteristic necrotizing perifascicular myositis. Brain 138(Pt 9):2485–2492. https://doi.org/10.1093/brain/awv192

    Article  PubMed  Google Scholar 

  10. Uruha A, Suzuki S, Suzuki N, Nishino I (2016) Perifascicular necrosis in anti-synthetase syndrome beyond anti-Jo 1. Brain 139(Pt 9):e50. https://doi.org/10.1093/brain/aww125

    Article  PubMed  Google Scholar 

  11. Allenbach Y, Hervier B, Stenzel W, Benveniste O (2016) Reply: Perifascicular necrosis in anti-synthetase syndrome beyond anti-Jo 1. Brain 139(Pt 9):e51. https://doi.org/10.1093/brain/aww126

    Article  PubMed  Google Scholar 

  12. Batten FE (1912) Case of dermatomyositis in a child with pathological report. Proc R Soc Med 5(Neurol Sect):103–114

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Banker BQ, Victor M (1966) Dermatomyositis (systemic angiopathy) of childhood. Medicine 45(4):261–289. https://doi.org/10.1097/00005792-196607000-00001

    Article  CAS  PubMed  Google Scholar 

  14. Carpenter S, Karpati G, Rothman S, Watters G (1976) The childhood type of dermatomyositis. Neurology 26(10):952–962. https://doi.org/10.1212/WNL.26.10.952

    Article  CAS  PubMed  Google Scholar 

  15. Emslie-Smith AM, Engel AG (1990) Microvascular changes in early and advanced dermatomyositis: a quantitative study. Ann Neurol 27(4):343–356. https://doi.org/10.1002/ana.410270402

    Article  CAS  PubMed  Google Scholar 

  16. Lahoria R, Selcen D, Engel AG (2016) Microvascular alterations and the role of complement in dermatomyositis. Brain 139(Pt 7):1891–1903. https://doi.org/10.1093/brain/aww122

    Article  PubMed  Google Scholar 

  17. Varadhachary AS, Weihl CC, Pestronk A (2010) Mitochondrial pathology in immune and inflammatory myopathies. Curr Opin Rheumatol 22(6):651–657. https://doi.org/10.1097/BOR.0b013e32833f108a

    Article  CAS  PubMed  Google Scholar 

  18. Oldfors A, Moslemi AR, Jonasson L, Ohlsson M, Kollberg G, Lindberg C (2006) Mitochondrial abnormalities in inclusion-body myositis. Neurology 66(2 Suppl 1):S49–S55. https://doi.org/10.1212/01.wnl.0000192127.63013.8d

    Article  CAS  PubMed  Google Scholar 

  19. Miró O, Casademont J, Grau JM, Jarreta D, Urbano-Marquez A, Cardelllach F (1998) Histological and biochemical assessment of mitochondrial function in dermatomyositis. Br J Rheumatol 37(10):1047–1053. https://doi.org/10.1093/rheumatology/37.10.1047

    Article  PubMed  Google Scholar 

  20. Giordano C, Sebastiani M, Plazzi G, Travaglini C, Sale P, Pinti M, Tancredi A, Liguori R, Montagna P, Bellan M, Valentino ML, Cossarizza A, Hirano M, d’Amati G, Carelli V (2006) Mitochondrial neurogastrointestinal encephalomyopathy: evidence of mitochondrial DNA depletion in the small intestine. Gastroenterology 130(3):893–901. https://doi.org/10.1053/j.gastro.2006.01.004

    Article  CAS  PubMed  Google Scholar 

  21. Giordano C, d’Amati G (2011) Evaluation of gastrointestinal mtDNA depletion in mitochondrial neurogastrointestinal encephalomyopathy (MNGIE). Methods Mol Biol 755:223–232. https://doi.org/10.1007/978-1-61779-163-5_18

    Article  CAS  PubMed  Google Scholar 

  22. Murphy JL, Ratnaike TE, Shang E, Falkous G, Blakely EL, Alston CL, Taivassalo T, Haller RG, Taylor RW, Turnbull DM (2012) Cytochrome c oxidase-intermediate fibres: importance in understanding the pathogenesis and treatment of mitochondrial myopathy. Neuromuscul Disord 22(8):690–698. https://doi.org/10.1016/j.nmd.2012.04.003

    Article  PubMed  PubMed Central  Google Scholar 

  23. Brooke MH, Engel WK (1969) The histographic analysis of human muscle biopsies with regard to fiber types. 2. Disease of the upper and lower motor neuron. Neurology 19(4):378–393. https://doi.org/10.1212/WNL.19.4.378

    Article  CAS  PubMed  Google Scholar 

  24. Vitali C, Bombardieri S, Jonsson R, Moutsopoulos HM, Alexander EL, Carsons SE, Daniels TE, Fox PC, Fox RI, Kassan SS, Pillemer SR, Talal N, Weisman MH (2002) Classification criteria for Sjögren’s syndrome: a revised version of the European criteria proposed by the American-European Consensus Group. Ann Rheum Dis 61(6):554–558. https://doi.org/10.1136/ard.61.6.554

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Cavagna L, Nuño L, Scirè CA, Govoni M, Longo FJ, Franceschini F, Neri R, Castañeda S, Sifuentes Giraldo WA, Caporali R, Iannone F, Fusaro E, Paolazzi G, Pellerito R, Schwarting A, Saketkoo LA, Ortego-Centeno N, Quartuccio L, Bartoloni E, Specker C, Murcia TP, la Corte R, Furini F, Foschi V, Corral JB, Airò P, Cavazzana I, Martínez-Barrio J, Hinojosa M, Giannini M, Barsotti S, Menke J, Triantafyllias K, Vitetta R, Russo A, Bajocchi G, Bravi E, Barausse G, Bortolotti R, Selmi C, Parisi S, Montecucco C, González-Gay MA, AENEAS (American, European NEtwork of Antisynthetase Syndrome) collaborative group (2015) Clinical spectrum time course in anti Jo-1 positive antisynthetase syndrome: results from an international retrospective multicenter study. Medicine (Baltimore) 94(32):e1144. https://doi.org/10.1097/MD.0000000000001144

    Article  CAS  Google Scholar 

  26. Mahler M, Miller FW, Fritzler MJ (2014) Idiopathic inflammatory myopathies and the anti-synthetase syndrome: a comprehensive review. Autoimmun Rev 13(4–5):367–371. https://doi.org/10.1016/j.autrev.2014.01.022

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Cavazzana I, Fredi M, Ceribelli A, Mordenti C, Ferrari F, Carabellese N, Tincani A, Satoh M, Franceschini F (2016) Testing for myositis specific autoantibodies: comparison between line blot and immunoprecipitation assays in 57 myositis sera. J Immunol Methods 433:1–5. https://doi.org/10.1016/j.jim.2016.02.017

    Article  CAS  PubMed  Google Scholar 

  28. Troyanov Y, Targoff IN, Payette MP, Raynauld JP, Chartier S, Goulet JR, Bourré-Tessier J, Rich E, Grodzicky T, Fritzler MJ, Joyal F, Koenig M, Senécal JL (2014) Redefining dermatomyositis: a description of new diagnostic criteria that differentiate pure dermatomyositis from overlap myositis with dermatomyositis features. Medicine (Baltimore) 93(24):318–332. https://doi.org/10.1097/MD.0000000000000222

    Article  Google Scholar 

  29. Pestronk A (2011) Acquired immune and inflammatory myopathies: pathologic classification. Curr Opin Rheumatol 23(6):595–604. https://doi.org/10.1097/BOR.0b013e32834bab42

    Article  CAS  PubMed  Google Scholar 

  30. Greenberg SA, Pinkus JL, Pinkus GS, Burleson T, Sanoudou D, Tawil R, Barohn RJ, Saperstein DS, Briemberg HR, Ericsson M, Park P, Amato AA (2005) Interferon-alpha/beta-mediated innate immune mechanisms in dermatomyositis. Ann Neurol 57(5):664–678. https://doi.org/10.1002/ana.20464

    Article  CAS  PubMed  Google Scholar 

  31. Woo M, Chung SJ, Nonaka I (1988) Perifascicular atrophic fibers in childhood dermatomyositis with particular reference to mitochondrial changes. J Neurol Sci 88(1–3):133–143. https://doi.org/10.1016/0022-510X(88)90211-0

    Article  CAS  PubMed  Google Scholar 

  32. Alhatou MI, Sladky JT, Bagasra O, Glass JD (2004) Mitochondrial abnormalities in dermatomyositis: characteristic pattern of neuropathology. J Mol Histol 35(6):615–619. https://doi.org/10.1007/s10735-004-2194-6

    PubMed  Google Scholar 

  33. Rygiel KA, Miller J, Grady JP, Rocha MC, Taylor RW, Turnbull DM (2015) Mitochondrial and inflammatory changes in sporadic inclusion body myositis. Neuropathol Appl Neurobiol 41(3):288–303. https://doi.org/10.1111/nan.12149

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Colafrancesco S, Priori R, Valesini G (2015) Inflammatory myopathies and overlap syndromes: update on histological and serological profile. Best Pract Res Clin Rheumatol 29(6):810–825. https://doi.org/10.1016/j.berh.2016.02.005

    Article  PubMed  Google Scholar 

  35. Temiz P, Weihl CC, Pestronk A (2009) Inflammatory myopathies with mitochondrial pathology and protein aggregates. J Neurol Sci 278(1–2):25–29. https://doi.org/10.1016/j.jns.2008.11.010

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, Policlinico Umberto I, Viale Regina Elena 324, 00161, Rome, Italy

    Bruna Cerbelli, Annalinda Pisano, Maria Gemma Pignataro, Silvia Berni, Antonia De Luca, Giulia d’Amati & Carla Giordano

  2. Department of Internal Medicine and Medical Specialties, Rheumatology Unit, Sapienza University of Rome, 00161, Rome, Italy

    Serena Colafrancesco, Valeria Riccieri, Roberta Priori & Guido Valesini

  3. Department of Surgical Science, Sapienza University of Rome, 00161, Rome, Italy

    Marco Biffoni

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  1. Bruna Cerbelli
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Correspondence to Carla Giordano.

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Cerbelli, B., Pisano, A., Colafrancesco, S. et al. Anti-aminoacyl-tRNA synthetase-related myositis and dermatomyositis: clues for differential diagnosis on muscle biopsy. Virchows Arch 472, 477–487 (2018). https://doi.org/10.1007/s00428-017-2269-x

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