# Dermatomyositis with Anti-MDA5 Autoantibodies After SARS-CoV-2 mRNA Vaccination Treated with Tofacitinib: Integrating Literature Evidence and a Novel Observation

**Authors:** Maurizio Benucci, Elisa Cioffi, Francesca Li Gobbi, Emanuele Antonio Maria Cassarà, Riccardo Terenzi, Edda Russo, Valentina Grossi, Barbara Lari, Maria Infantino, Mariangela Manfredi

PMC · DOI: 10.3390/antib15020024 · 2026-03-09

## TL;DR

A 60-year-old woman developed anti-MDA5 dermatomyositis after a fourth dose of the Pfizer/BioNTech vaccine and improved with tofacitinib and other treatments.

## Contribution

A novel case of anti-MDA5 dermatomyositis after SARS-CoV-2 vaccination and its treatment with tofacitinib is presented.

## Key findings

- Anti-MDA5 dermatomyositis can occur after SARS-CoV-2 mRNA vaccination, even without interstitial lung disease.
- Tofacitinib, a JAK inhibitor, showed marked clinical improvement in the presented case.
- The case highlights the variable clinical spectrum and diagnostic challenges of vaccine-associated anti-MDA5 DM.

## Abstract

COVID-19 mRNA vaccines activate type I interferon pathways and in genetically or immunologically predisposed individuals may trigger autoimmune responses, including autoantibodies against melanoma differentiation-associated protein 5 (MDA5). Although cases of dermatomyositis (DM), particularly anti-MDA5-positive DM, have been increasingly reported after SARS-CoV-2 vaccination, its clinical spectrum and management remain incompletely defined. We conducted a narrative review of the literature on post-vaccination dermatomyositis, focusing on clinical features, autoantibody profiles, therapeutic approaches, and outcomes. The review was enriched by the inclusion of a new case: a 60-year-old woman who developed anti-MDA5-positive dermatomyositis two weeks after receiving her fourth dose of the BNT162b2 (Pfizer/BioNTech) vaccine. She presented predominantly with cutaneous and articular manifestations in the absence of interstitial lung disease. Treatment with oral prednisone, intravenous alprostadil, and the Janus kinase inhibitor tofacitinib resulted in marked clinical improvement. This case, together with the literature review, illustrates both typical and atypical presentations of vaccine-associated anti-MDA5 DM, highlights diagnostic challenges without lung involvement, and suggests JAK inhibition as a potential therapeutic option, contributing to a more comprehensive understanding of post-vaccination dermatomyositis.

## Linked entities

- **Proteins:** IFIH1 (interferon induced with helicase C domain 1)
- **Chemicals:** tofacitinib (PubChem CID 9926791), prednisone (PubChem CID 5865), alprostadil (PubChem CID 5280723)
- **Diseases:** dermatomyositis (MONDO:0016367), COVID-19 (MONDO:0100096)

## Full-text entities

- **Genes:** PIK3C2A (phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 alpha) [NCBI Gene 5286] {aka CPK, OCSKD, PI3-K-C2(ALPHA), PI3-K-C2A, PI3K-C2-alpha, PI3K-C2alpha}, SSB (small RNA binding exonuclease protection factor La) [NCBI Gene 6741] {aka LARP3, La, La/SSB, SSB/La}, TLR7 (toll like receptor 7) [NCBI Gene 51284] {aka IMD74, SLEB17, TLR7-like}, MAVS (mitochondrial antiviral signaling protein) [NCBI Gene 57506] {aka CARDIF, IPS-1, IPS1, VISA}, HFM1 (helicase for meiosis 1) [NCBI Gene 164045] {aka MER3, POF9, SEC63D1, Si-11, Si-11-6, helicase}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, SLC17A5 (solute carrier family 17 member 5) [NCBI Gene 26503] {aka AST, ISSD, NSD, SD, SIALIN, SIASD}, IFNA1 (interferon alpha 1) [NCBI Gene 3439] {aka IFL, IFN, IFN-ALPHA, IFN-alphaD, IFNA13, IFNA@}, IFIH1 (interferon induced with helicase C domain 1) [NCBI Gene 64135] {aka AGS7, Hlcd, IDDM19, IMD95, MDA-5, MDA5}, STAT5A (signal transducer and activator of transcription 5A) [NCBI Gene 6776] {aka MGF, STAT5}, JAK3 (Janus kinase 3) [NCBI Gene 3718] {aka JAK-3, JAK3_HUMAN, JAKL, L-JAK, LJAK}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, TLR9 (toll like receptor 9) [NCBI Gene 54106] {aka CD289}, TRIM21 (tripartite motif containing 21) [NCBI Gene 6737] {aka RNF81, RO52, Ro/SSA, SSA, SSA1, TRIM21/Ro52}, IRF3 (interferon regulatory factor 3) [NCBI Gene 3661] {aka IIAE7}, STAT1 (signal transducer and activator of transcription 1) [NCBI Gene 6772] {aka CANDF7, IMD31A, IMD31B, IMD31C, ISGF-3, STAT91}, MORC3 (MORC family CW-type zinc finger 3) [NCBI Gene 23515] {aka NXP2, ZCW5, ZCWCC3}, JAK1 (Janus kinase 1) [NCBI Gene 3716] {aka AIIDE, JAK1A, JAK1B, JTK3}, TRIM33 (tripartite motif containing 33) [NCBI Gene 51592] {aka DDH4, ECTO, PTC7, RFG7, TF1G, TIF1G}, DHX58 (DExH-box helicase 58) [NCBI Gene 79132] {aka D11LGP2, D11lgp2e, LGP2, RLR-3}, MB (myoglobin) [NCBI Gene 4151] {aka MYOSB, PVALB}, SPI1 (Spi-1 proto-oncogene) [NCBI Gene 6688] {aka AGM10, OF, PU.1, SFPI1, SPI-1, SPI-A}, CCL2 (C-C motif chemokine ligand 2) [NCBI Gene 6347] {aka GDCF-2, HC11, HSMCR30, MCAF, MCP-1, MCP1}, IL21 (interleukin 21) [NCBI Gene 59067] {aka CVID11, IL-21, Za11}, TICAM1 (TIR domain containing adaptor molecule 1) [NCBI Gene 148022] {aka IIAE6, MyD88-3, PRVTIRB, TICAM-1, TRIF}, CMPK1 (cytidine/uridine monophosphate kinase 1) [NCBI Gene 51727] {aka CK, CMK, CMPK, UMK, UMP-CMPK, UMPK}, TLR3 (toll like receptor 3) [NCBI Gene 7098] {aka CD283, IIAE2, IMD83}, RNPC3 (RNA binding region (RNP1, RRM) containing 3) [NCBI Gene 55599] {aka CPHD7, IGHD5, RBM40, RNP, SNRNP65}
- **Diseases:** discoloration (MESH:D014075), RP-ILD (MESH:D012174), skin ulceration (MESH:D012883), hypoxia (MESH:D000860), SRDs (MESH:D012216), muscle soreness (MESH:D063806), cutaneous disease (MESH:D004194), chills (MESH:D023341), muscle or vascular involvement (MESH:C566343), fibrosis (MESH:D005355), hypothyroidism (MESH:D007037), Brooke-Spiegler syndrome (MESH:C536611), malignancy (MESH:D009369), shock (MESH:D012769), Raynaud's phenomenon (MESH:D011928), arthralgia (MESH:D018771), paraneoplastic (MESH:D010257), viral infections (MESH:D014777), ILD (MESH:D017563), Autoimmune Inflammatory Myopathies (MESH:D009220), erythema (MESH:D004890), allergic rhinitis (MESH:D065631), interface dermatitis (MESH:D003872), injury to (MESH:D014947), pericarditis (MESH:D010493), Gottron's papules (MESH:C538187), Ulcerative lesions (MESH:D014456), cutaneous (MESH:D018366), infections (MESH:D007239), autoimmune disorder (MESH:D001327), CT abnormalities (MESH:C000719218), blisters (MESH:D001768), diabetes mellitus (MESH:D003920), synovitis (MESH:D013585), hyperferritinemia (MESH:D000085583), headache (MESH:D006261), cutaneous vasculopathy (MESH:D000090122), systemic disease (MESH:D034721), respiratory failure (MESH:D012131), chronic pulmonary fibrosis (MESH:D011658), digital ischemia (MESH:D007511), edema (MESH:D004487), COVID-19 (MESH:D000086382), lung involvement (MESH:D008171), dyspnea (MESH:D004417), DM (MESH:D003882), digital ulcers (MESH:C000721267), Inflammatory (MESH:D007249), dysphagia (MESH:D003680), hyperkeratotic hands (MESH:D006230), rheumatoid arthritis (MESH:D001172), fever (MESH:D005334), myocarditis (MESH:D009205), CADM (MESH:C538250), infectious (MESH:D003141), critically ill (MESH:D016638), muscle weakness (MESH:D018908), sunburn (MESH:D013471), asthma (MESH:D001249), autoimmune manifestations (MESH:D012877)
- **Chemicals:** hydroxychloroquine (MESH:D006886), upadacitinib (MESH:C000613732), methotrexate (MESH:D008727), methylprednisolone (MESH:D008775), tacrolimus (MESH:D016559), mycophenolate mofetil (MESH:D009173), Janus (-), rituximab (MESH:D000069283), prednisone (MESH:D011241), alprostadil (MESH:D000527), baricitinib (MESH:C000596027), azathioprine (MESH:D001379), ciclosporin A (MESH:D016572), cyclophosphamide (MESH:D003520), Tofacitinib (MESH:C479163), steroids (MESH:D013256)
- **Species:** Human alphaherpesvirus 1 (Herpes simplex virus type 1, no rank) [taxon 10298], Severe acute respiratory syndrome coronavirus 2 (no rank) [taxon 2697049], Enterovirus B (no rank) [taxon 138949], Homo sapiens (human, species) [taxon 9606]

## Figures

1 figure with captions in the complete paper: https://tomesphere.com/paper/PMC13010631/full.md

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Source: https://tomesphere.com/paper/PMC13010631