Abstract
The JAK family (JAK1, JAK2, JAK3, and TYK2) have recently emerged as a potential therapeutic management in controlling severe and refractory dermatomyositis. Meanwhile, the progress in the discovery of JAK blockers is significant, with an increasing number of selective JAK inhibitors reported and some are in or prepare for clinical trials. However, the importance of each JAK in dermatomyositis is unclear, which is critical for a comprehensive understanding of dermatomyositis and significant for forming mechanism-based strategy. Here, we presented a case with clinically amyopathic dermatomyositis and essential thrombocytosis with a somatic constitutive active mutation of JAK2(V617F). The coexistence of these two uncommon diseases attracted us to investigate their underlying relationship. To this end, we characterized the clinical course and laboratory findings of this patient. Particularly, we correlated JAK2(V617F) mutation burden in affected peripheral blood subset with clinical activity score of dermatomyositis. Based on our observation, we concluded that these two diseases are independent disorders, and JAK2(V617F) mutation burden is irrelevant to the severity of dermatomyositis. Finally, we reviewed the literature and summarized them with a thorough discussion.
Similar content being viewed by others
References
Bohan A, Peter JB (1975) Polymyositis and dermatomyositis. N Engl J Med 292(7):344–347
Euwer RL, Sontheimer RD (1991) Amyopathic dermatomyositis (dermatomyositis sine myositis): presentation of six new cases and review of the literature. J Am Acad Dermatol 24(6):959–966
Bailey EE, Fiorentino DF (2014) Amyopathic dermatomyositis: definitions, diagnosis, and management. Curr Rheumatol Rep 16(12):465
Troyanov Y, Targoff IN, Tremblay J-L, Goulet J-R, Raymond Y, Senécal J-L (2005) Novel classification of idiopathic inflammatory myopathies based on overlap syndrome features and autoantibodies: analysis of 100 French Canadian patients. Medicine 84(4):231–249
Moghadam-Kia S, Charlton D, Aggarwal R, Oddis CV (2019) Management of refractory cutaneous dermatomyositis: potential role of Janus kinase inhibition with tofacitinib. Rheumatology 58(6):1011–1015
Kurtzman DJ, Wright NA, Lin J, Femia AN, Merola JF, Patel M, Vleugels RA (2016) Tofacitinib citrate for refractory cutaneous dermatomyositis: an alternative treatment. JAMA Dermatol 152(8):944–945
Wendel S, Venhoff N, Frye BC, May AM, Agarwal P, Rizzi M, Voll RE, Thiel J (2019) Successful treatment of extensive calcifications and acute pulmonary involvement in dermatomyositis with the Janus-kinase inhibitor tofacitinib–a report of two cases. J Autoimmun 100:131–136
Ghoreschi K, Laurence A, O’Shea JJ (2009) Janus kinases in immune cell signaling. Immunol Rev 228(1):273–287
Schieber M, Crispino JD, Stein B (2019) Myelofibrosis in 2019: moving beyond JAK2 inhibition. Blood Cancer J 9(9):1–11
Stijnis C, Kroes W, Balkassmi S, Marijt E, Van Rossum A, Bakker E, Vlasveld L (2012) No evidence for JAK2V617F mutation in monoclonal B cells in 2 patients with polycythaemia vera and concurrent monoclonal B cell disorder. Acta Haematol 128(3):183–186
Germer S, Holland MJ, Higuchi R (2000) High-throughput SNP allele-frequency determination in pooled DNA samples by kinetic PCR. Genome Res 10(2):258–266
Jatiani SS, Baker SJ, Silverman LR, Reddy EP (2010) Jak/STAT pathways in cytokine signaling and myeloproliferative disorders: approaches for targeted therapies. Genes Cancer 1(10):979–993
de Freitas RM, da Costa Maranduba CM (2015) Myeloproliferative neoplasms and the JAK/STAT signaling pathway: an overview. Rev Bras Hematol Hemoter 37(5):348–353
Nielsen C, Birgens HS, Nordestgaard BG, Kjaer L, Bojesen SE (2011) The JAK2 V617F somatic mutation, mortality and cancer risk in the general population. Haematologica 96(3):450–453
Hasselbalch HC, Bjørn ME (2015) MPNs as inflammatory diseases: the evidence, consequences, and perspectives. Mediat Inflamm 2015:1–16
Antovic A, Sennström M, Bremme K, Svenungsson E (2018) Obstetric antiphospholipid syndrome. Lupus Sci Med 5(1):e000197
Shi J, Li S, Yang H, Zhang Y, Peng Q, Lu X, Wang G (2017) Clinical profiles and prognosis of patients with distinct antisynthetase autoantibodies. J Rheumatol 44(7):1051–1057
Marie I, Josse S, Decaux O, Diot E, Landron C, Roblot P, Jouneau S, Hatron P-Y, Hachulla E, Vittecoq O (2013) Clinical manifestations and outcome of anti-PL7 positive patients with antisynthetase syndrome. Eur J Intern Med 24(5):474–479
Dugar M, Cox S, Limaye V, Gordon TP, Roberts-Thomson PJ (2010) Diagnostic utility of anti-Ro52 detection in systemic autoimmunity. Postgrad Med J 86(1012):79–82
Sclafani A, D’Silva K, Little BP, Miloslavsky E, Locascio J, Sharma A, Montesi S (2019) Presentations and outcomes of interstitial lung disease and the anti-Ro52 autoantibody. Respir Res 20(1):256
Brito-Zerón P, Izmirly PM, Ramos-Casals M, Buyon JP, Khamashta MA (2015) The clinical spectrum of autoimmune congenital heart block. Nat Rev Rheumatol 11(5):301–312
Salomonsson S, Sonesson S-E, Ottosson L, Muhallab S, Olsson T, Sunnerhagen M, Kuchroo VK, Thorén P, Herlenius E, Wahren-Herlenius M (2005) Ro/SSA autoantibodies directly bind cardiomyocytes, disturb calcium homeostasis, and mediate congenital heart block. J Exp Med 201(1):11–17
Sekigawa I, Seta N, Yamada M, Iida N, Hashimoto H, Ogawa H (2004) Possible importance of immunoglobulin E in foetal loss by mothers with anti-SSA antibody. Scand J Rheumatol 33(1):44–46
Prestipino A, Emhardt AJ, Aumann K, O’Sullivan D, Gorantla SP, Duquesne S, Melchinger W, Braun L, Vuckovic S, Boerries M (2018) Oncogenic JAK2V617F causes PD-L1 expression, mediating immune escape in myeloproliferative neoplasms. Sci Transl Med 10(429):eaam7729
Sage PT, Schildberg FA, Sobel RA, Kuchroo VK, Freeman GJ, Sharpe AH (2018) Dendritic cell PD-L1 limits autoimmunity and follicular T cell differentiation and function. J Immunol 200(8):2592–2602
Nishanth G, Wolleschak D, Fahldieck C, Fischer T, Mullally A, Perner F, Schnöder TM, Just S, Heidel FH, Schlüter D (2017) Gain of function in Jak2 V617F-positive T-cells. Leukemia 31(4):1000–1003
Lu LD, Stump KL, Wallace NH, Dobrzanski P, Serdikoff C, Gingrich DE, Dugan BJ, Angeles TS, Albom MS, Mason JL (2011) Depletion of autoreactive plasma cells and treatment of lupus nephritis in mice using CEP-33779, a novel, orally active, selective inhibitor of JAK2. J Immunol 187(7):3840–3853
Wang S, Yang N, Zhang L, Huang B, Tan H, Liang Y, Li Y, Yu X (2010) Jak/STAT signaling is involved in the inflammatory infiltration of the kidneys in MRL/lpr mice. Lupus 19(10):1171–1180
Hornung T, Wenzel J (2014) Innate immune-response mechanisms in dermatomyositis: an update on pathogenesis, diagnosis and treatment. Drugs 74(9):981–998
Paik JJ, Christopher-Stine L (2017) A case of refractory dermatomyositis responsive to tofacitinib. Seminars in Arthritis Rheum 46 (4): e19
Kurasawa K, Arai S, Namiki Y, Tanaka A, Takamura Y, Owada T, Arima M, Maezawa R (2018) Tofacitinib for refractory interstitial lung diseases in anti-melanoma differentiation-associated 5 gene antibody-positive dermatomyositis. Rheumatology 57(12):2114–2119
Hornig J, Weinhage T, Schmidt L, Buerke B, Schneider U, Pavenstädt H, Becker H, Gabriëls G (2018) Response of dermatomyositis with lung involvement to Janus kinase inhibitor treatment. Z Rheumatol 77(10):952–957
Chen Z, Wang X, Ye S (2019) Tofacitinib in amyopathic dermatomyositis–associated interstitial lung disease. N Engl J Med 381 (3):291–293
Hornung T, Janzen V, Heidgen F-J, Wolf D, Bieber T, Wenzel J (2014) Remission of recalcitrant dermatomyositis treated with ruxolitinib. N Engl J Med 371(26):2537–2538
Ladislau L, Suárez-Calvet X, Toquet S, Landon-Cardinal O, Amelin D, Depp M, Rodero MP, Hathazi D, Duffy D, Bondet V (2018) JAK inhibitor improves type I interferon induced damage: proof of concept in dermatomyositis. Brain 141(6):1609–1621
Aeschlimann FA, Frémond M-L, Duffy D, Rice GI, Charuel J-L, Bondet V, Saire E, Neven B, Bodemer C, Balu L (2018) A child with severe juvenile dermatomyositis treated with ruxolitinib. Brain 141(11):e80
Jalles C, Deroux A, Tardieu M, Lugosi M, Viel S, Benveniste O, Colombe B (2020) Severe MDA5 dermatomyositis associated with cancer and controlled by JAK inhibitor. Rev Med Interne 41(6):421–424
Fetter T, Niebel D, Bieber T, Wenzel J (2020) Unexpected hair regrowth in a patient with longstanding alopecia universalis during treatment of recalcitrant dermatomyositis with the janus kinase inhibitor ruxolitinib. Acta Derm Venereol:100
Papadopoulou C, Hong Y, Omoyinmi E, Brogan PA, Eleftheriou D (2019) Janus kinase 1/2 inhibition with baricitinib in the treatment of juvenile dermatomyositis. Brain 142(3):e8
Breccia M, Baratè C, Benevolo G, Bonifacio M, Elli EM, Guglielmelli P, Maffioli M, Malato A, Mendicino F, Palumbo GA (2020) Tracing the decision-making process for myelofibrosis: diagnosis, stratification, and management of ruxolitinib therapy in real-word practice. Ann Hematol 99(1):65–72
Clark JD, Flanagan ME, Telliez J-B (2014) Discovery and development of Janus kinase (JAK) inhibitors for inflammatory diseases: miniperspective. J Med Chem 57 (12):5023–5038
Genovese MC, Kremer J, Zamani O, Ludivico C, Krogulec M, Xie L, Beattie SD, Koch AE, Cardillo TE, Rooney TP (2016) Baricitinib in patients with refractory rheumatoid arthritis. N Engl J Med 374:1243–1252
Vainchenker W, Leroy E, Gilles L, Marty C, Plo I, Constantinescu SN (2018) JAK inhibitors for the treatment of myeloproliferative neoplasms and other disorders. F1000Research 7
Bose P, Verstovsek S (2017) JAK2 inhibitors for myeloproliferative neoplasms: what is next? Blood J Am Soc Hematol 130(2):115–125
Tefferi A (2012) JAK inhibitors for myeloproliferative neoplasms: clarifying facts from myths. Blood J Am Soc Hematol 119(12):2721–2730
Schwartz DM, Bonelli M, Gadina M, O'shea JJ (2016) Type I/II cytokines, JAKs, and new strategies for treating autoimmune diseases. Nat Rev Rheumatol 12(1):25–36
Acknowledgments
We appreciated our patient who gave written informed consent in accordance with the Declaration of Helsinki and the ethics committee of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine.
Funding
The work was supported by a grant from the Medical Science and Technology Project of Zhejiang Province (2020KY585 to Q.X.).
Author information
Authors and Affiliations
Contributions
Q.X. and Y.M. designed the research; Q.X., X.J., and Y.J. performed the research; Q.X. and X.D. collected clinical data; and Q.X. and Y.M. wrote the paper.
Corresponding authors
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Xu, Q., Jin, X., Jiang, Y. et al. The relationship between JAK2(V617F) mutation and dermatomyositis—a case report and literature review. Clin Rheumatol 40, 1147–1157 (2021). https://doi.org/10.1007/s10067-020-05286-y
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10067-020-05286-y