RARE DISEASE
Dermatomyositis
Dermatomyositis
Dermatomyositis
Synonyms: Adult dermatomyositis
Synonyms: Adult dermatomyositis
Synonyms: Adult dermatomyositis
Drug discovery
18
drugs
With orphan designations
Overview
Dermatomyositis is a chronic immune-mediated inflammatory disorder characterized by progressive proximal muscle weakness and pathognomonic cutaneous manifestations (e.g., heliotrope rash, Gottron papules). Associated with myositis-specific autoantibodies, it carries increased malignancy risk and may involve interstitial lung disease. Diagnosis combines clinical findings, elevated muscle enzymes, imaging (MRI), electromyography, and biopsy. Treatment focuses on immunosuppression (corticosteroids, IVIG, disease-modifying agents) and multidisciplinary management [1][5][17].
Burden
Therapies
First-line: corticosteroids (prednisone) ± immunosuppressants (methotrexate, azathioprine, mycophenolate) [3][18]
FDA-approved IVIG for refractory cases; monoclonal antibodies (rituximab) for severe disease [3][13][18]
Adjuncts: hydroxychloroquine (skin-predominant disease), physical therapy, and rigorous sun protection [3][16]
Categories: rare neurological diseases, rare renal diseases, rare skin diseases, rare systemic and rheumatological diseases, rare transplant-related disorders
Research Papers
1,937 drug discovery papers about Dermatomyositis, with 4 first-in-class and 9 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
1,937 drug discovery papers about Dermatomyositis, with 4 first-in-class and 9 next-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
proteins
2026-06-25 | Acthar Gel treatment in patients with rheumatoid arthritis, systemic lupus erythematosus, or dermatomyositis/polymyositis: analysis of physician-reported charts.
Aim: To examine the characteristics, treatment patterns, and physicians' assessments of outcomes for patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), or dermatomyositis/polymyositis (DM/PM) who received Acthar Gel. Materials & methods: This survey-based medical chart review study asked rheumatologists who met specific inclusion criteria to abstract data from patient records covering the period from April 2022 to November 2024. Eligible patients were adults ≥18 years diagnosed with RA, SLE, or DM/PM, treated with Acthar Gel for ≤24 months. An online questionnaire screened and identified contributing physicians and collected anonymized patient data (baseline demographic, medical history, concomitant medications, Acthar Gel treatment history, and physicians' assessment of health status, symptom severity, treatment outcomes with Acthar Gel). Results: The study population comprised 73 patients with RA (average age 50 years; 49 [67%] female; 44 [60%] White/non-Hispanic), 56 with SLE (average age 42 years; 47 [84%] female; 28 [50%] African-American), and 104 with DM/PM (average age 52 years; 69 [66%] female; 62 [60%] White/non-Hispanic). Patients had received Acthar Gel for an average of 9 (RA) or 8 months (SLE, DM/PM), with most receiving treatment at the time of the study. Per physicians' assessment, health status improved in 68 (93%) patients with RA, 50 (89%) patients with SLE, and 100 (96%) patients with DM/PM after starting treatment with Acthar Gel. The most common treatment goals achieved in patients with improved overall health status were improved overall symptoms, pain, physical function, and corticosteroid use in the RA cohort; overall symptoms, pain, corticosteroid use, and fatigue in the SLE cohort; and overall symptoms, strength, physical function, and corticosteroid use in the DM/PM cohort. Conclusion: These findings support the use of Acthar Gel as a potential treatment option for appropriate patients with RA, SLE, or DM/PM.
2026-03-26 | Interleukin-2 Deprived State of Regulatory T cells and Their Recovery by Low-Dose Interleukin-2 in Patients With Inflammatory Myopathies.
Regeneration and expansion of Treg by low-dose interleukin-2 (IL-2) therapy is considered a potential treatment strategy for a wide range of autoimmune diseases. To provide a pathophysiologically-based rationale for low-dose IL-2 therapy, we investigated whether reversible defects in the Treg-IL-2 axis emerge in inflammatory myopathies. CD4+ T cell subsets from patients with polymyositis (PM) or dermatomyositis (DM) (n = 20) and healthy controls (HC) (n = 19) and peripheral blood mononuclear cells (PBMC) from eight patients that were stimulated in vitro for 24 hours with different concentrations of recombinant human IL-2 were analyzed by multicolor flow cytometry. Messenger RNA (mRNA) expressions of IL2RA, IL2RB, IL2RB, ENTPD1, IKZF2, and CTLA4 were quantified by real-time polymerase chain reaction in IL-2 stimulated PBMC (n = 6). Two patients with refractory PM/DM were treated with low-dose IL-2 therapy for eight weeks and monitored for clinical responses and changes in Treg subsets. Frequencies of Treg expressing CD25 at high levels (CD25hi Treg) and of CXCR5+ Treg were reduced in patients with PM/DM compared with HC (P = 0.0052; P = 0.0661), particularly in active myositis (P = 0.0036; P = 0.0335). Stimulation with low doses of IL-2 selectively enhanced expression of CD25 molecules by Treg, leading to an increase in the CD25hi Treg subset (P < 0.05) and augmented mRNA expression of several immunoregulatory molecules (P < 0.05). Low-dose IL-2 therapy induced decreases in muscle enzymes that were accompanied by a sustained expansion of CD25+ Treg. Our data suggest that shortage of IL-2 is pathophysiologically relevant in PM/DM. Recovery and expansion of Treg by low-dose IL-2 therapy could thus be a promising targeted treatment option.
2026-01-06 | Interferon-β Triggers Z-DNA Binding Protein 1-Mediated PANoptosis in T Cells of Anti-Melanoma Differentiation-Associated Protein 5 Antibody-Positive Dermatomyositis.
To investigate the role of PANoptosis activation in anti-melanoma differentiation-associated protein 5 (MDA5) antibody-positive dermatomyositis (anti-MDA5+ DM). Transcriptomic profiling of peripheral blood mononuclear cells (PBMCs) from 40 patients with anti-MDA5+ DM and 10 healthy controls (HCs) was performed. The PANoptosis signature score was constructed using single sample gene set enrichment analysis based on the mean enrichment scores of the pyroptosis, apoptosis and necroptosis gene sets, and the clinical associations of the PANoptosis signature score in patients with anti-MDA5+ DM were evaluated. PANoptosis markers were analysed via western blotting, and the regulatory mechanism of PANoptosis activation was studied in Jurkat cells in vitro. Transcriptomic profiling demonstrated overactivation of the PANoptosis signalling pathway in patients with anti-MDA5+ DM. The PANoptosis signature score was positively correlated with inflammatory markers, type 1 interferon (IFN) signature score, disease severity and poor prognosis in patients with anti-MDA5+ DM. Z-DNA binding protein 1 (ZBP1) was identified as a key PANoptosis-related gene in anti-MDA5+ DM. PANoptosis markers, including P-MLKL, GSDMD-N, cleaved caspase-8, cleaved caspase-3 and cleaved caspase-7, were significantly upregulated in T cells from patients with anti-MDA5+ DM. Functional assays demonstrated that IFN-β induced PANoptosis activation in T cells in vitro, which was significantly attenuated following ZBP1 knockdown. PANoptosis overactivation was associated with disease severity and prognosis in anti-MDA5+ DM. Our findings indicated that IFN-β triggered ZBP1-mediated PANoptosis in T cells, highlighting PANoptosis as a novel potential therapeutic target for anti-MDA5+ DM.
2025-10-01 | Refractory antibody-mediated rejection after high-emergency lung transplantation for dermatomyositis with anti-MDA5 antibody: a case report.
This case report describes a female with amyopathic anti-MDA5+ dermatomyositis who underwent emergency double lung transplantation due to rapidly progressive interstitial lung disease. Following transplantation, she developed acute antibody-mediated rejection (AMR). Despite multiple rounds of immunosuppressive therapy, her condition continued to deteriorate, and her donor-specific anti-human leukocyte antigen antibody levels increased markedly. An experimental treatment, imlifidase-an immunoglobulin G endopeptidase-was employed as a rescue therapy. This case highlights the complexity of posttransplant management of AMR and emphasizes the need for dedicated clinical trials to provide additional data.
2025-09-03 | Recombinant human hyaluronidase-facilitated subcutaneous immunoglobulin (hf-SCIg) for inflammatory myositis: a multicenter retrospective real-world observational study.
Subcutaneous immunoglobulin (SCIg) is a promising alternative to intravenous Ig (IVIg) for the treatment of idiopathic inflammatory myositis (IIM), thanks to its more favorable safety profile, reduced costs, and lower impact on patients' quality of life. We assessed the short- and long-term effectiveness and safety of recombinant human hyaluronidase-facilitated SCIg (hf-SCIg) in patients with IIM treated at different referral centers in Italy. A multicenter, retrospective, real-life cohort study was conducted on consecutive adult patients diagnosed with IIM according to the EULAR/ACR criteria, treated with hf-SCIg for remission induction or maintenance. Hf-SCIg effectiveness was assessed in terms of variation in the Medical Research Council (MRC) score, serum creatine kinase (CK) values, clinical disease manifestations and daily prednisone dosage. Safety data were also collected. Twenty-six patients with IIM treated with hf-SCIg for remission induction (n = 5) or maintenance (n = 21) were included in the study (18 females; median age at diagnosis of 59 (IQR 42-64) years)). In most patients, hf-SCIg was started following previous IVIg treatment (23, 89 %) and was initiated in combination with oral corticosteroids (21, 81 %) and/or traditional or biologic DMARDs. Short-term use of hf-SCIg for remission induction appeared associated with a corticosteroid-sparing effect, without worsening of MRC score. Long-term hf-SCIg treatment for up to 24 months maintained clinical stability and serum CK levels with further improvement of MRC score. Hf-SCIg was well tolerated, with mild adverse events mostly related to local site reactions. Hf-SCIg seems effective and safe for induce and maintain clinical remission in patients with IIM.
small molecules
2026-09-17 | Catching up with calcinosis: analysis of clinical characteristics, myositis-specific autoantibodies, and response to therapy in juvenile dermatomyositis.
This study aims to evaluate the clinical, laboratory, and treatment profiles of juvenile dermatomyositis (JDM) patients with calcinosis. A retrospective study was conducted at a tertiary-care referral centre in India (1992-2024), analysing JDM patients per modified Bohan and Peter criteria. Clinical data, myositis- specific autoantibody (MSA) profiles, and treatment details were compared between those with and without calcinosis. Calcinosis severity and treatment response were evaluated. Statistical analysis was performed using SPSS v. 29 software. Out of 157 JDM patients, 44 (28%) had calcinosis. These patients had a long diagnostic delay (12 months) and were more likely to be NXP2-positive (41%). Lipodystrophy was significantly associated with presence of calcinosis (39% vs. 5%). Severe calcinosis is linked to early age of onset of disease. Four children presented with calcinosis alone without clinically obvious skin or muscle disease, two of them were NXP2-positive. Patients with TIF1- gamma positivity predominantly had superficial calcinosis around large joints with skin ulceration, whereas NXP2 positivity had extensive and severe calcinosis. Among all patients with calcinosis, 39% improved while 61% had static/progressive disease. Analysis of drug response showed that the medications targeting calcium/phosphorus metabolism are linked to improvement in the calcinosis lesions over time. Calcinosis in JDM is associated with NXP2 autoantibody positivity and delayed diagnosis; however, severity correlates with early disease onset and specific MSA patterns. A subset of patients may present with calcinosis alone, underscoring diagnostic challenges. Drugs targeting calcium/phosphorus metabolism may be of benefit in reducing the severity of calcinosis in JDM.
2026-09-15 | Clinical features and a Nomogram for predicting clinical response in juvenile dermatomyositis associated interstitial lung disease.
Juvenile dermatomyositis (JDM) is a rare autoimmune disease and accompany by interstitial lung disease (ILD), a major cause of morbidity and mortality. However, data on clinical features and prognosis of JDM-ILD in Chinese pediatric populations remain limited. The aim is to characterize the clinical features, treatment options and prognosis of JDM-ILD in Chinese pediatric patients, and to develop a nomogram for predicting clinical response. We retrospectively enrolled 244 JDM-ILD patients from Beijing Children's Hospital (May 2015-January 2026). Demographic, clinical, laboratory, treatment, and prognostic data were collected. Clinical response was assessed through a combination of PRINTO-defined clinical inactive disease (CID) , respiratory symptoms and HRCT. Independent prognostic factors were identified using Cox regression analysis and incorporated into a nomogram. Model performance was assessed using C-index, calibration curves and decision curve analysis (DCA). Among 244 patients (55.7% female, median onset age 5.7 years), anti-MDA5 (32.0%) and anti-NXP2 (13.9%) were the most prevalent autoantibodies. At last follow-up visit, 202 patients (82.8%) achieved CID, with CID rates increasing progressively over time. A total of three patients who tested positive for anti-MDA5 antibody died of RP-ILD (median survival 2.7 months). Multivariable Cox regression identified combination therapy with JAK inhibitors (HR 2.09, 95%CI 1.25-3.50) or IL-6 inhibitors (HR 1.83, 95%CI 1.07-3.12) and Gottron's sign (HR 1.80, 95%CI 1.10-2.96) as favorable factors for CID, while high-risk status (HR 0.23, 95%CI 0.10-0.57), higher DAS skin score (HR 0.71, 95%CI 0.48-1.00), and higher neutrophil-to-lymphocyte ratio (NLR) (HR 0.84, 95%CI 0.72-0.97) predicted lower probability of CID. The nomogram showed predictive performance in both training cohort (AUC: 0.67, 0.77, and 0.78 at 1, 3, and 5 years) and testing cohort (AUC: 0.60, 0.78 and 0.77 at 1, 3, and 5 years). This nomogram for predicting clinical response in Chinese pediatric JDM-ILD patients integrates clinical features and treatment variables to enable individualized risk stratification. Combination therapy with JAK or IL-6 inhibitors demonstrates promising efficacy and may improve outcomes.
2026-09-11 | Therapeutic expansion of JAK inhibitors in Chinese dermatological practice: beyond atopic dermatitis to novel autoimmune frontiers.
Janus kinase inhibitors (JAKi) have demonstrated clinical utility in managing atopic dermatitis (AD), yet their broader potential across immune-mediated dermatoses remains inadequately explored, particularly within China's restrictive regulatory landscape for dermatologic indications. This review examines pathogenic mechanisms and emerging evidence supporting JAKi repositioning in seven dermatological conditions beyond AD: alopecia areata (AA), vitiligo, psoriasis, dermatomyositis (DM), pemphigus, bullous pemphigoid (BP), and chronic spontaneous urticaria (CSU)-with emphasis on therapeutic gaps and opportunities specific to Chinese practice. We delineate disease-specific JAK-STAT dysregulation, including IFN-γ-driven cytotoxicity in AA/vitiligo, IL-23/STAT3 activation in psoriasis, and type I interferon hyperactivation in DM. Key clinical findings from rigorous trials indicate that oral tofacitinib achieves PASI75 in 58% of psoriatic patients within 16 weeks and topical ruxolitinib induces facial repigmentation exceeding 75% in vitiligo. In contrast, while current evidence is substantially limited to isolated case reports, emerging data suggest that baricitinib may resolve steroid-refractory BP lesions within one month. Persistent limitations include reliance on small-scale studies for pemphigus and CSU, along with unresolved safety concerns regarding thrombosis risks in susceptible populations. Crucially, we identify therapeutic gaps in segmental vitiligo and juvenile DM where clinical data are absent. This synthesis advocates for randomized controlled trials to validate JAKi efficacy against biologics in high-burden diseases currently dependent on glucocorticoids.
2026-09-01 | Regulated cell death in autoimmune diseases: molecular mechanisms and therapeutic opportunities.
Autoimmune diseases develop from a breakdown in immune tolerance and arise through complex interactions among genetic susceptibility, environmental factors, immune dysregulation, and tissue damage. Although apoptosis has traditionally been recognized as a central mechanism for maintaining immune homeostasis, increasing evidence has identified several non-classical forms of regulated cell death (RCD) that also contribute to autoimmune disease pathogenesis. These pathways include ferroptosis, pyroptosis, necroptosis, PANoptosis, NETosis, parthanatos, and cuproptosis. Unlike classical apoptosis, many of these RCD mechanisms are strongly pro-inflammatory and promote the release of damage-associated molecular patterns (DAMPs), cytokines, oxidized lipids, and autoantigens, thereby enhancing both innate and adaptive immune responses. Recent studies indicate that dysregulation of RCD pathways contributes to chronic inflammation, impaired self-tolerance, immune cell abnormalities, and progressive tissue injury in autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, psoriasis, multiple sclerosis, sjögren's syndrome, systemic sclerosis, type 1 diabetes, ulcerative colitis, dermatomyositis, ankylosing spondylitis, Chronic Dermatitis, antiphospholipid syndrome, Nephritis, and ANCA-associated vasculitis. These pathways do not function independently but form an interconnected network with extensive molecular crosstalk and compensatory interactions that influence disease progression. This review highlights the molecular mechanisms underlying emerging RCD pathways, their cell-specific roles in autoimmune diseases, and the evidence linking their involvement to disease initiation and progression. Furthermore, it discusses current and potential therapeutic approaches targeting major regulators of ferroptosis, pyroptosis, necroptosis, PANoptosis, NETosis, cuproptosis, and parthanatos. Improved understanding of the integrated landscape of the RCD network may facilitate the discovery of novel biomarkers and support the development of innovative therapies to restore immune tolerance and control chronic inflammatory damage in autoimmune diseases.
2026-08-19 | Laryngeal Complications of Dermatomyositis: A Case Report and Comprehensive Review of the Literature.
Dermatomyositis is an immune-mediated inflammatory myopathy characterized by progressive proximal muscle weakness with sparing of distal muscles, accompanied by cutaneous manifestations. Laryngeal involvement in patients with dermatomyositis is extremely rare, with only seven cases described in the literature. We report the case of a 21-year-old man with dermatomyositis who presented with dysphonia, breathiness, and asthenia with a voice handicap index-10 score of 24/40. Laryngeal examination showed whitish mucosal patches on the upper surface of both vocal folds with bowing of the vocal folds. Video-stroboscopy revealed incomplete closure of the vocal folds during phonation, a decrease in vocal fold vibration amplitude, and diminished mucosal waves. One month after therapy with mycophenolate mofetil, the patient's voice quality improved and his VHI-10 score decreased to 16/40.
cell therapies
2026-06-13 | A window to breathe again.
In this Backstory, the authors recount how a 10-year-old girl with rapidly progressive MDA5-positive dermatomyositis survived fulminant lung failure on ECMO and received compassionate-use CD19 chimeric antigen receptor (CAR)-T therapy. The interdisciplinary team then followed her immune reconstitution and clinical recovery, ultimately supporting discharge and offering a potential blueprint for personalized cellular therapy in similarly critical cases.
2026-05-19 | Chimeric antigen receptor T-cell (CAR-T) therapy and other cellular immunotherapy treatments for idiopathic inflammatory myopathies.
Idiopathic inflammatory myopathies (IIM), including immune-mediated necrotizing myopathy (IMNM), dermatomyositis (DM), anti-synthetase syndrome (ASyS), overlap myositis and polymyositis, are heterogeneous autoimmune diseases characterized by immune-mediated skeletal muscle injury and frequent extra-muscular organ involvement. Despite recent therapeutic advances, many IIM patients have persistent disease activity, medication toxicity, or steroid dependence with current treatments. Increasing evidence implicates autoreactive B cells and autoantibody-producing plasma cells as central drivers of disease activity in several IIM subtypes, providing a strong rationale for B-cell- targeted therapies. While monoclonal antibody-based B-cell depletion strategies such as rituximab have demonstrated variable efficacy, their inability to effect persistent, intense depletion of tissue autoreactive B-cell populations often limit their success. Chimeric antigen receptor T-cell (CAR-T) and related cellular immunotherapies were originally developed against hematologic malignancies, but have recently emerged potentially transformative therapeutic options for autoimmune diseases. CAR-T cells targeting CD19 and other B-cell antigens have demonstrated the capacity to induce deep and durable B-cell depletion, and may even lead to "immune reset" with long-lived autoimmunity remission in diseases such as systemic lupus erythematosus and systemic sclerosis. Early clinical experiences now suggest that CAR-T therapy may offer similar promise in refractory IIM, particularly in phenotypes that include pathogenic autoantibodies, such as ASyS, DM, IMNM. This review provides a synopsis of current knowledge on the immunopathogenesis of IIM relevant to CAR-T and other cellular immunotherapy, outlines CAR-T technology and the mechanistic rationale for its use in IIM, and critically appraises emerging clinical CAR-T treatment data in IIM. We also discuss safety considerations, practical challenges, and future directions, with a focus on how CAR-based immunotherapies may reshape treatment paradigms for refractory inflammatory myopathies.
2026-05-11 | Case Report: Juvenile dermatomyositis complicated by acute myeloid leukemia: achievement of sustained remission through hematopoietic stem cell transplantation.
Juvenile dermatomyositis (JDM), a pediatric subtype of idiopathic inflammatory myopathy, is a relatively rare rheumatic and immune system disease among children. Although paraneoplastic dermatomyositis (DM) has been documented in adult malignancies, its association with acute myeloid leukemia (AML) in pediatric populations remains exceptionally rare. We present a male patient diagnosed with JDM at age 6, characterized by Gottron's papules and muscle weakness. Despite receiving sequential immunosuppressive therapies and biological agents, the disease followed a relapsing-remitting course over 9 years. At age 15, he developed persistent knee arthralgia accompanied by intermittent fever lasting 8 days. Hematologic evaluation revealed thrombocytopenia (platelet count: 76 ×109/L) and leukocytosis (white blood cell count: 36.46 ×109/L), prompting bone marrow aspiration confirmed AML diagnosis (French-American-British M2 subtype). Following induction chemotherapy and two consolidation cycles, allogeneic hematopoietic stem cell transplantation (HSCT) from a matched unrelated donor was successfully performed. Notably, both JDM symptoms and AML achieved sustained remission at 1-year follow-up post-HSCT. This case suggests that HSCT may represent a potential therapeutic approach for refractory autoimmune-hematologic malignancy overlap syndromes, though further studies are required to validate its efficacy.
2026-05-08 | Case Report: Lung transplantation for rare anti-MDA5-positive rapidly progressive interstitial lung disease: two cases and a narrative review.
Lung transplantation is a definitive lifesaving option for end-stage lung disease; however, its role in rapidly progressive interstitial lung disease (RP-ILD) associated with anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibodies remains debated. We retrospectively analyzed two anti-MDA5-positive RP-ILD (MDA5+ RP-ILD) patients who underwent bilateral lung transplantation and synthesized pertinent literature to evaluate clinical value and the impact of therapeutic interventions. Both patients recovered postoperatively and were discharged after symptomatic management and supportive care. One patient subsequently developed cerebral infarction and died approximately 8 months after transplantation, whereas the other remains clinically stable under regular follow-up. Given the limited efficacy of conventional therapies and the overall poor prognosis of anti-MDA5-positive dermatomyositis (MDA5+ DM) with RP-ILD, our observations-together with prior reports-support lung transplantation, with extracorporeal membrane oxygenation (ECMO) as a bridge when necessary, as a promising and reliable therapeutic strategy. Lung transplantation may offer definitive treatment in carefully selected patients, underscoring its important clinical value.
2026-02-06 | Anti-CD19 CAR T cells for pediatric patients with treatment-refractory autoimmune diseases.
Chimeric antigen receptor (CAR) T cell therapy was recently proposed as a treatment for adults with B-cell-mediated autoimmune diseases (ADs) refractory to conventional immunomodulatory therapy. We present a case series of eight children with severe/refractory AD (four systemic lupus erythematosus, three dermatomyositis, one systemic sclerosis) treated at Ospedale Pediatrico Bambino Gesù, Rome, and University Hospital Erlangen with a single infusion of 1 × 106 kg-1 point-of-care manufactured autologous CD19 CAR T cells (zorpocabtagene autoleucel), in a hospital exemption (HE) program. In Europe, the HE pathway offers the opportunity to treat patients with life-threatening or seriously debilitating disorders who lack valid therapeutic options, using an advanced therapy medicinal product (ATMP) authorized on a nonroutine, single-patient basis. In contrast to the 'compassionate use' pathway, the ATMP does not necessarily need to have undergone clinical trials or marketing authorization applications. Manufacturing was successful in all patients, yielding several drug product bags. Once infused after lymphodepletion, zorpocabtagene autoleucel cells expanded in vivo, promoting prompt B cell clearance. Grade 1 cytokine release syndrome was reported in six patients, and grade 1 immune effector cell-associated neurotoxicity syndrome was reported in one patient. Late-hematotoxicity was limited to grade 1 in two patients. All these adverse events were manageable and no severe infections occurred. With a median follow-up of 16.5 months (range = 9-24 months), all patients experienced a clinically substantial improvement/resolution of AD, as evidenced by reduction in disease activity scores and signs of reversal of organ damage. This improvement enabled sustained discontinuation of immunomodulators, even after B cell reconstitution. The activation of formal clinical trials enrolling children and adolescents is urgently needed to confirm these preliminary results and to assess the long-term safety of this approach.
antibodies
2026-08-25 | Real-world experience with obinutuzumab in difficult-to-treat myositis: concise report of a case series.
Idiopathic inflammatory myopathy (IIM) is an orphan systemic disorder with muscular, cutaneous and pulmonary involvement. B cell-directed therapies, including rituximab, belimumab and chimeric antigen receptor T-cell (CAR-T), have shown promise in altering disease outcome. We report the benefit of obinutuzumab in difficult -to- treat myositis patients. The Northwell Rheumatology database was searched for obinutuzumab-treated patients (2019-24); five of them met 2017 EULAR/ACR classification criteria for IIM and were included in the analysis. Demographic, clinical, serological and imaging data were collected. Overall response was rated as complete, partial or no response based on clinical response and physician global assessment. Total improvement score was not calculated because data were collected retrospectively. Descriptive statistics were used for analyses. Of five patients, two had antisynthetase syndrome, one dermatomyositis (DM) and two overlap myositis. Most patients failed at least three immunosuppressive agents. The reason for obinutuzumab use was rituximab allergy and worsening of interstitial lung disease (ILD) and myositis activity (3/5), arthritis (2/5) and severe rash (1/5 patients), despite rituximab. After obinutuzumab 80% of patients had overall improvement by 3-6 months. Respiratory status improved/stabilized in all ILD patients. Two patients required second obinutuzumab cycle: one for recurrence and another for persistent disease with B cell re-population. One was lost to follow-up after the second cycle and was deemed a non-responder. At last observation, 4/5 patients had achieved a complete response. No hypogammaglobulinaemia, significant infections or hospitalizations were observed. Obinutuzumab was safe and provided durable improvement in difficult-to-treat myositis patients with rituximab allergy, further highlighting targeting the B-cell pathway.
2026-08-10 | Outcomes of Immune Check Point Inhibitor Use in US Veterans With Pre-Existing Idiopathic Inflammatory Myopathies: Case Series and Literature Review.
Our objective was to identify and describe the clinical characteristics and outcomes in patients with pre-existing idiopathic inflammatory myopathies (IIMs) in the Veterans Health Administration (VHA) treated with immune checkpoint inhibitors (ICIs). All veterans receiving ICI infusions were identified. Patients with at least two International Classification of Disease codes for IIM before first ICI infusion underwent chart review to identify patients with confirmed IIM by American College of Rheumatology/EULAR criteria. The demographics, cancer diagnoses, laboratory findings, clinical course, and mortality rates were reported. IIM cases were also reviewed to determine if patients developed IIM flare following ICI treatment. We identified 29,539 veterans who received at least one ICI infusion in the VHA between June 6, 2011, and February 14, 2023. The eight patients with confirmed IIM before ICI treatment were mostly White men with an average age of 71.7 years at first ICI infusion. The IIM diagnoses were dermatomyositis in three patients, polymyositis in two, antisynthetase syndrome in two, and one rheumatoid arthritis (RA)/myositis overlap. Cancer diagnoses were lung (two), melanoma (two), head and neck (two), kidney/other urinary (one), and mesothelioma (one). Diagnosis of IIM was made on average 3.1 years before ICI treatment. One patient had an IIM flare after ICI. No IIM flares were identified in other patients. Our findings show that an IIM flare after ICI therapy can occur, but most patients did not develop a flare. These observations suggest ICIs can be considered as an option in patients with cancer with IIM with shared decision-making and close monitoring.
2026-08-06 | Unmasking dermatomyositis in a patient with hypothyroid myopathy.
Dermatomyositis (DM) and hypothyroid myopathy are both treatable causes of muscle weakness and can present with overlapping clinical and laboratory features, posing a diagnostic challenge. We report the case of a young male who presented with proximal upper and lower limb muscle weakness, calf muscle hypertrophy and elevated serum creatine kinase (CK) and was found to have hypothyroidism. Muscle weakness and hyperCKemia persisted despite normalisation of thyroid function, prompting a muscle biopsy and extended autoantibody testing, which revealed anti-Ku-positive DM characterised by perivascular inflammation, perifascicular atrophy and membrane attack complex deposition. High-dose corticosteroids led to partial improvement and subsequent rituximab therapy achieved sustained clinical and biochemical remission. This case emphasises the importance of considering dual aetiology when appropriate treatment of the primary diagnosis does not yield expected results. Early biopsy and comprehensive serological evaluation could lead to excellent clinical outcomes.
2026-08-02 | Long-Term Safety and Efficacy of Dazukibart in Dermatomyositis: Combined Phase II Results From Double-Blind and Open-Label Extension Studies.
To evaluate the long-term safety and efficacy of dazukibart, a novel antiinterferon β monoclonal antibody, in adults with moderate-to-severe dermatomyositis (DM). Participants from 2 cohorts of DM (skin-predominant [SP] and muscle-predominant [MP]) completing a 24-week phase II, double-blind study, were enrolled into a 52-week phase IIb, open-label extension (OLE) study, with a 16-week follow-up post treatment (combined study duration: 92 weeks). The pooled skin analysis set included all SP and MP DM participants with baseline Cutaneous Dermatomyositis Disease Area and Severity Index-Activity (CDASI-A) scores ≥ 14. The primary endpoint was incidence of treatment-emergent adverse events (TEAEs) from week 24 through week 92. Key secondary endpoints were change in CDASI-A and Total Improvement Score (TIS) from week 0 through week 92. Participants who received ≥ 1 dose of dazukibart (600 mg) during the OLE study (comprising 9, 15, and 16 participants from the SP cohort, MP cohort, and pooled skin analysis set, respectively) were analyzed (median age 49.5 years, 83% female, 96% White). TEAEs were mild (55%), moderate (38%), or severe (7%), with no treatment-related serious AEs or treatment discontinuations. At week 76, CDASI-A scores improved, with a median change from baseline of -24.0 (range -33 to -12), -9.0 (range -32 to 1), and -23.5 (range -33 to -12) for participants from the SP cohort, MP cohort, and pooled skin analysis set, respectively. In the MP cohort, TIS (median 65.0, range 2.5-95.0) and associated core set measures, including patient-reported outcomes, improved at week 76. Overall, the observed improvements in outcomes, as indicated by the slight reduction in outcome measures, persisted during the 16-week posttreatment follow-up. The safety and efficacy profiles of dazukibart observed at 24 weeks were sustained through 92 weeks. (ClinicalTrials.gov: NCT03181893, NCT05192200).
2026-07-23 | An Aggressive Presentation of Anti-melanoma Differentiation-Associated Gene 5 (MDA-5)-Positive Dermatomyositis With Rapidly Progressive Interstitial Lung Disease: A Case Report.
Anti-melanoma differentiation-associated gene 5 (MDA-5) dermatomyositis is an uncommon condition that is frequently complicated by rapidly progressive interstitial lung disease (RP-ILD), resulting in a poor prognosis. Due to its aggressive course, management is often challenging and requires timely interventions to improve outcomes. This case of a female patient with anti-MDA-5-positive DM and RP-ILD aims to document this unique and uncommon condition, its aggressive clinical course, associated complications, diagnostic challenges, and management considerations.
other
2026-09-13 | Antinuclear Antibody (ANA)‑Negative, Anti-melanoma Differentiation-Associated Gene 5 (MDA5)‑Positive Dermatomyositis Presenting as Rapidly Progressive Interstitial Lung Disease: A Case Report.
Dermatomyositis (DM) is a rare, autoimmune myopathy characterized by proximal muscle weakness and pathognomonic skin findings, including Gottron's papules and a heliotrope rash. Anti-melanoma differentiation-associated gene 5 (MDA5)-positive DM is a distinct subtype often associated with rapidly progressive interstitial lung disease (RP-ILD) and may lack the classic features of DM. We present the case of a 43-year-old woman who developed persistent hypoxic respiratory failure after multiple vascular surgeries requiring repeated postoperative blood transfusions. Her respiratory failure was initially attributed to transfusion-related acute lung injury with progression to acute respiratory distress syndrome. Despite appropriate treatment, her respiratory condition worsened. Infectious and autoimmune workups, including bronchoscopy and ANA testing, were unrevealing. Persistent diffuse bilateral ground-glass opacities and new fibrotic changes on imaging prompted an extended myositis panel, which revealed positive anti-MDA5 antibodies, establishing a diagnosis of RP-ILD secondary to MDA5 DM. She was treated with rituximab, mycophenolate, and IV immunoglobulin, with clinical improvement and was discharged on 4L of supplemental oxygen. This case underscores the importance of considering anti-MDA5-positive DM in unexplained, progressive respiratory failure, highlighting the importance of early recognition and multidisciplinary management.
2026-08-02 | Improvement of Refractory Cutaneous Ulcers and Pulmonary Arterial Hypertension Following Rituximab and Mycophenolate Mofetil Therapy in Anti-melanoma Differentiation-Associated Gene 5 (Anti-MDA5) Antibody-Positive Dermatomyositis.
Anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibody-positive dermatomyositis (DM) can manifest with a severe vasculopathic phenotype. We report a case of anti-MDA5 DM in a woman in her early 30s complicated by refractory cutaneous ulcers and pulmonary arterial hypertension (PAH). Despite the escalation of immunosuppressive therapy with glucocorticoids, tacrolimus, intravenous immunoglobulin, and cyclophosphamide, the cutaneous ulcers remained refractory. A progressive decline in diffusing capacity of the lung for carbon monoxide raised suspicion of PAH, which was subsequently confirmed by right heart catheterization. Consequently, combination therapy with mycophenolate mofetil (MMF) and rituximab (RTX) was initiated alongside bosentan. This regimen resulted in the prompt resolution of ulcers and improvement of PAH. Bosentan was discontinued, and azathioprine was initiated to maintain remission, allowing for a successful pregnancy and delivery of a healthy infant. This case suggests a potential role for an MMF- and RTX-containing combination regimen in refractory cutaneous ulcers and PAH associated with anti-MDA5 DM.
2026-03-28 | Management and Prognosis of Anti-MDA5 Dermatomyositis: Insights from a National Multicenter Cohort.
Background: Anti-melanoma differentiation-associated gene 5 (anti-MDA5) positive dermatomyositis is a distinct subset of idiopathic inflammatory myopathies (IIMs), often associated with unique cutaneous features and interstitial lung disease (ILD). While East Asian cohorts frequently report high mortality due to rapidly progressive ILD (RP-ILD), data regarding Central and Eastern European populations remain scarce. Methods: We conducted a retrospective multicenter study of anti-MDA5 positive Caucasian patients managed at four Hungarian rheumatology centers between 2020 and 2025. Demographic, clinical, serological, and radiological data were analyzed. Antibody profiling was performed using a standardized 16-antigen immunoblot assay. Results: Anti-MDA5 positivity was confirmed in 24 out of 742 patients (3.23%) treated in the four centers. The median age at diagnosis was 49.5 years (range: 24-81). Classic dermatomyositis was the predominant clinical phenotype (75%), followed by clinically amyopathic dermatomyositis (CADM) (12.5%) and polymyositis (12.5%). ILD was identified in 58.3% of patients, presenting with organizing pneumonia (OP), non-specific interstitial pneumonia (NSIP), and usual interstitial pneumonia (UIP) patterns. At diagnosis, median creatine kinase (CK) (193.5 U/L) and C-reactive protein (CRP) (4.24 mg/L) levels remained low even in the ILD group, whereas lactate dehydrogenase (LDH) was elevated in 91.7% of the cohort. Anti-Ro52 positivity (45.8% overall) emerged as a notable predictor of ILD (odds ratio [OR]: 22.5, 95% confidence interval [CI]: 2.10-240.48; p = 0.0045), being present in 71.4% of affected patients. RP-ILD occurred in two patients (8.3%). Therapeutic management followed an early, aggressive strategy, frequently utilizing cyclophosphamide (45.8%) and methotrexate (37.5%), with Janus kinase (JAK) inhibitors or rituximab employed in refractory cases. Overall disease-specific survival was 100% during the study period (median follow-up: 72.0 months); no mortality was directly attributable to IIM-related complications. Conclusions: Our study demonstrates that anti-MDA5 positive dermatomyositis in a Hungarian cohort is characterized by heterogeneous manifestations and a significant association between anti-Ro52 and ILD. The observed dissociation between low CK/CRP and elevated LDH underscores the necessity for a high index of suspicion, with LDH serving as a superior marker for disease activity. While ILD presents a significant risk, early and intensive multi-modal intervention may yield superior survival outcomes in European patients compared to the historical mortality rates reported in Asian cohorts.
2026-01-08 | Prolonged remission of dermatomyositis and autoantibody negativization following SARS-CoV-2 infection in an elderly patient.
This case report presents the clinical course of an 80-year-old patient diagnosed with dermatomyositis in 2014, initially managed successfully with methotrexate (MTX). In March 2022, the patient experienced a severe SARS-CoV-2 infection with significant pulmonary involvement, necessitating discontinuation of MTX. Notably, the patient maintained complete remission of dermatomyositis post-infection without relapse. Sustained negativization of autoantibodies, confirmed through multiple evaluations, was observed, while persistent capillaroscopic abnormalities suggested ongoing subclinical disease activity. This case underscores the potential immunomodulatory effects of SARS-CoV-2 on autoimmune diseases and highlights the need for further investigation into its role in immune modulation and disease quiescence.
2025-11-06 | Tacrolimus Trough Concentration-Escalating Bipartite Therapy (Glucocorticoids Combined With Tacrolimus) for Refractory MDA5 Antibody-Positive Clinically Amyopathic Dermatomyositis With Rapidly Progressive Interstitial Pneumonia.
This study aimed to determine the outcomes of patients that have refractory anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive clinically amyopathic dermatomyositis with rapidly progressive interstitial pneumonia treated with tacrolimus trough concentration-escalating bipartite therapy (glucocorticoids combined with tacrolimus). We retrospectively enrolled 19 patients that had refractory anti-MDA5 antibody-positive clinically amyopathic dermatomyositis with rapidly progressive interstitial pneumonitis who were unable to achieve disease control on intensive combination immunosuppressive therapy with glucocorticoids and immunosuppressive agents. They were treated with tacrolimus trough concentration-escalating bimodal therapy. Patients receiving tacrolimus trough concentration-escalating dual therapy were selected based on poor prognostic factors and refractoriness to the initial immunosuppressive therapy. The 19 patients included in the study were treated with tacrolimus trough concentration-escalating bipartite therapy (glucocorticoids combined with tacrolimus) immediately after diagnosis of refractory anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive clinically amyopathic dermatomyositis with rapidly progressive interstitial pneumonia. Following 17 months of treatment and subsequent follow-up, 16 patients displayed decreased ferritin and lactate dehydrogenase levels and improved oxygenation index and high-resolution lung computed tomography findings. Two patients died, and one patient (case 9) developed renal impairment on Day 14 of treatment. Renal damage occurred when the tacrolimus trough concentration was 15.68 ng/mL. After lowering the tacrolimus trough concentration, the patient's renal function gradually normalized. However, because of the addition of cyclophosphamide due to disease activity, the patient did not experience the full efficacy of the two-combination therapy. Tacrolimus-associated renal impairment and viral and fungal infections occurred in some patients treated with bimodal therapy, but it did not have serious consequences. For patients with refractory anti-MDA5 antibody-positive clinically amyopathic dermatomyositis associated with rapidly progressive interstitial pneumonia, the combination of glucocorticoids and tacrolimus is a potentially effective treatment regimen. However, there is considerable individual variation in the optimal trough concentration of tacrolimus.
proteins
2026-06-25 | Acthar Gel treatment in patients with rheumatoid arthritis, systemic lupus erythematosus, or dermatomyositis/polymyositis: analysis of physician-reported charts.
Aim: To examine the characteristics, treatment patterns, and physicians' assessments of outcomes for patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), or dermatomyositis/polymyositis (DM/PM) who received Acthar Gel. Materials & methods: This survey-based medical chart review study asked rheumatologists who met specific inclusion criteria to abstract data from patient records covering the period from April 2022 to November 2024. Eligible patients were adults ≥18 years diagnosed with RA, SLE, or DM/PM, treated with Acthar Gel for ≤24 months. An online questionnaire screened and identified contributing physicians and collected anonymized patient data (baseline demographic, medical history, concomitant medications, Acthar Gel treatment history, and physicians' assessment of health status, symptom severity, treatment outcomes with Acthar Gel). Results: The study population comprised 73 patients with RA (average age 50 years; 49 [67%] female; 44 [60%] White/non-Hispanic), 56 with SLE (average age 42 years; 47 [84%] female; 28 [50%] African-American), and 104 with DM/PM (average age 52 years; 69 [66%] female; 62 [60%] White/non-Hispanic). Patients had received Acthar Gel for an average of 9 (RA) or 8 months (SLE, DM/PM), with most receiving treatment at the time of the study. Per physicians' assessment, health status improved in 68 (93%) patients with RA, 50 (89%) patients with SLE, and 100 (96%) patients with DM/PM after starting treatment with Acthar Gel. The most common treatment goals achieved in patients with improved overall health status were improved overall symptoms, pain, physical function, and corticosteroid use in the RA cohort; overall symptoms, pain, corticosteroid use, and fatigue in the SLE cohort; and overall symptoms, strength, physical function, and corticosteroid use in the DM/PM cohort. Conclusion: These findings support the use of Acthar Gel as a potential treatment option for appropriate patients with RA, SLE, or DM/PM.
2026-03-26 | Interleukin-2 Deprived State of Regulatory T cells and Their Recovery by Low-Dose Interleukin-2 in Patients With Inflammatory Myopathies.
Regeneration and expansion of Treg by low-dose interleukin-2 (IL-2) therapy is considered a potential treatment strategy for a wide range of autoimmune diseases. To provide a pathophysiologically-based rationale for low-dose IL-2 therapy, we investigated whether reversible defects in the Treg-IL-2 axis emerge in inflammatory myopathies. CD4+ T cell subsets from patients with polymyositis (PM) or dermatomyositis (DM) (n = 20) and healthy controls (HC) (n = 19) and peripheral blood mononuclear cells (PBMC) from eight patients that were stimulated in vitro for 24 hours with different concentrations of recombinant human IL-2 were analyzed by multicolor flow cytometry. Messenger RNA (mRNA) expressions of IL2RA, IL2RB, IL2RB, ENTPD1, IKZF2, and CTLA4 were quantified by real-time polymerase chain reaction in IL-2 stimulated PBMC (n = 6). Two patients with refractory PM/DM were treated with low-dose IL-2 therapy for eight weeks and monitored for clinical responses and changes in Treg subsets. Frequencies of Treg expressing CD25 at high levels (CD25hi Treg) and of CXCR5+ Treg were reduced in patients with PM/DM compared with HC (P = 0.0052; P = 0.0661), particularly in active myositis (P = 0.0036; P = 0.0335). Stimulation with low doses of IL-2 selectively enhanced expression of CD25 molecules by Treg, leading to an increase in the CD25hi Treg subset (P < 0.05) and augmented mRNA expression of several immunoregulatory molecules (P < 0.05). Low-dose IL-2 therapy induced decreases in muscle enzymes that were accompanied by a sustained expansion of CD25+ Treg. Our data suggest that shortage of IL-2 is pathophysiologically relevant in PM/DM. Recovery and expansion of Treg by low-dose IL-2 therapy could thus be a promising targeted treatment option.
2026-01-06 | Interferon-β Triggers Z-DNA Binding Protein 1-Mediated PANoptosis in T Cells of Anti-Melanoma Differentiation-Associated Protein 5 Antibody-Positive Dermatomyositis.
To investigate the role of PANoptosis activation in anti-melanoma differentiation-associated protein 5 (MDA5) antibody-positive dermatomyositis (anti-MDA5+ DM). Transcriptomic profiling of peripheral blood mononuclear cells (PBMCs) from 40 patients with anti-MDA5+ DM and 10 healthy controls (HCs) was performed. The PANoptosis signature score was constructed using single sample gene set enrichment analysis based on the mean enrichment scores of the pyroptosis, apoptosis and necroptosis gene sets, and the clinical associations of the PANoptosis signature score in patients with anti-MDA5+ DM were evaluated. PANoptosis markers were analysed via western blotting, and the regulatory mechanism of PANoptosis activation was studied in Jurkat cells in vitro. Transcriptomic profiling demonstrated overactivation of the PANoptosis signalling pathway in patients with anti-MDA5+ DM. The PANoptosis signature score was positively correlated with inflammatory markers, type 1 interferon (IFN) signature score, disease severity and poor prognosis in patients with anti-MDA5+ DM. Z-DNA binding protein 1 (ZBP1) was identified as a key PANoptosis-related gene in anti-MDA5+ DM. PANoptosis markers, including P-MLKL, GSDMD-N, cleaved caspase-8, cleaved caspase-3 and cleaved caspase-7, were significantly upregulated in T cells from patients with anti-MDA5+ DM. Functional assays demonstrated that IFN-β induced PANoptosis activation in T cells in vitro, which was significantly attenuated following ZBP1 knockdown. PANoptosis overactivation was associated with disease severity and prognosis in anti-MDA5+ DM. Our findings indicated that IFN-β triggered ZBP1-mediated PANoptosis in T cells, highlighting PANoptosis as a novel potential therapeutic target for anti-MDA5+ DM.
2025-10-01 | Refractory antibody-mediated rejection after high-emergency lung transplantation for dermatomyositis with anti-MDA5 antibody: a case report.
This case report describes a female with amyopathic anti-MDA5+ dermatomyositis who underwent emergency double lung transplantation due to rapidly progressive interstitial lung disease. Following transplantation, she developed acute antibody-mediated rejection (AMR). Despite multiple rounds of immunosuppressive therapy, her condition continued to deteriorate, and her donor-specific anti-human leukocyte antigen antibody levels increased markedly. An experimental treatment, imlifidase-an immunoglobulin G endopeptidase-was employed as a rescue therapy. This case highlights the complexity of posttransplant management of AMR and emphasizes the need for dedicated clinical trials to provide additional data.
2025-09-03 | Recombinant human hyaluronidase-facilitated subcutaneous immunoglobulin (hf-SCIg) for inflammatory myositis: a multicenter retrospective real-world observational study.
Subcutaneous immunoglobulin (SCIg) is a promising alternative to intravenous Ig (IVIg) for the treatment of idiopathic inflammatory myositis (IIM), thanks to its more favorable safety profile, reduced costs, and lower impact on patients' quality of life. We assessed the short- and long-term effectiveness and safety of recombinant human hyaluronidase-facilitated SCIg (hf-SCIg) in patients with IIM treated at different referral centers in Italy. A multicenter, retrospective, real-life cohort study was conducted on consecutive adult patients diagnosed with IIM according to the EULAR/ACR criteria, treated with hf-SCIg for remission induction or maintenance. Hf-SCIg effectiveness was assessed in terms of variation in the Medical Research Council (MRC) score, serum creatine kinase (CK) values, clinical disease manifestations and daily prednisone dosage. Safety data were also collected. Twenty-six patients with IIM treated with hf-SCIg for remission induction (n = 5) or maintenance (n = 21) were included in the study (18 females; median age at diagnosis of 59 (IQR 42-64) years)). In most patients, hf-SCIg was started following previous IVIg treatment (23, 89 %) and was initiated in combination with oral corticosteroids (21, 81 %) and/or traditional or biologic DMARDs. Short-term use of hf-SCIg for remission induction appeared associated with a corticosteroid-sparing effect, without worsening of MRC score. Long-term hf-SCIg treatment for up to 24 months maintained clinical stability and serum CK levels with further improvement of MRC score. Hf-SCIg was well tolerated, with mild adverse events mostly related to local site reactions. Hf-SCIg seems effective and safe for induce and maintain clinical remission in patients with IIM.
small molecules
2026-09-17 | Catching up with calcinosis: analysis of clinical characteristics, myositis-specific autoantibodies, and response to therapy in juvenile dermatomyositis.
This study aims to evaluate the clinical, laboratory, and treatment profiles of juvenile dermatomyositis (JDM) patients with calcinosis. A retrospective study was conducted at a tertiary-care referral centre in India (1992-2024), analysing JDM patients per modified Bohan and Peter criteria. Clinical data, myositis- specific autoantibody (MSA) profiles, and treatment details were compared between those with and without calcinosis. Calcinosis severity and treatment response were evaluated. Statistical analysis was performed using SPSS v. 29 software. Out of 157 JDM patients, 44 (28%) had calcinosis. These patients had a long diagnostic delay (12 months) and were more likely to be NXP2-positive (41%). Lipodystrophy was significantly associated with presence of calcinosis (39% vs. 5%). Severe calcinosis is linked to early age of onset of disease. Four children presented with calcinosis alone without clinically obvious skin or muscle disease, two of them were NXP2-positive. Patients with TIF1- gamma positivity predominantly had superficial calcinosis around large joints with skin ulceration, whereas NXP2 positivity had extensive and severe calcinosis. Among all patients with calcinosis, 39% improved while 61% had static/progressive disease. Analysis of drug response showed that the medications targeting calcium/phosphorus metabolism are linked to improvement in the calcinosis lesions over time. Calcinosis in JDM is associated with NXP2 autoantibody positivity and delayed diagnosis; however, severity correlates with early disease onset and specific MSA patterns. A subset of patients may present with calcinosis alone, underscoring diagnostic challenges. Drugs targeting calcium/phosphorus metabolism may be of benefit in reducing the severity of calcinosis in JDM.
2026-09-15 | Clinical features and a Nomogram for predicting clinical response in juvenile dermatomyositis associated interstitial lung disease.
Juvenile dermatomyositis (JDM) is a rare autoimmune disease and accompany by interstitial lung disease (ILD), a major cause of morbidity and mortality. However, data on clinical features and prognosis of JDM-ILD in Chinese pediatric populations remain limited. The aim is to characterize the clinical features, treatment options and prognosis of JDM-ILD in Chinese pediatric patients, and to develop a nomogram for predicting clinical response. We retrospectively enrolled 244 JDM-ILD patients from Beijing Children's Hospital (May 2015-January 2026). Demographic, clinical, laboratory, treatment, and prognostic data were collected. Clinical response was assessed through a combination of PRINTO-defined clinical inactive disease (CID) , respiratory symptoms and HRCT. Independent prognostic factors were identified using Cox regression analysis and incorporated into a nomogram. Model performance was assessed using C-index, calibration curves and decision curve analysis (DCA). Among 244 patients (55.7% female, median onset age 5.7 years), anti-MDA5 (32.0%) and anti-NXP2 (13.9%) were the most prevalent autoantibodies. At last follow-up visit, 202 patients (82.8%) achieved CID, with CID rates increasing progressively over time. A total of three patients who tested positive for anti-MDA5 antibody died of RP-ILD (median survival 2.7 months). Multivariable Cox regression identified combination therapy with JAK inhibitors (HR 2.09, 95%CI 1.25-3.50) or IL-6 inhibitors (HR 1.83, 95%CI 1.07-3.12) and Gottron's sign (HR 1.80, 95%CI 1.10-2.96) as favorable factors for CID, while high-risk status (HR 0.23, 95%CI 0.10-0.57), higher DAS skin score (HR 0.71, 95%CI 0.48-1.00), and higher neutrophil-to-lymphocyte ratio (NLR) (HR 0.84, 95%CI 0.72-0.97) predicted lower probability of CID. The nomogram showed predictive performance in both training cohort (AUC: 0.67, 0.77, and 0.78 at 1, 3, and 5 years) and testing cohort (AUC: 0.60, 0.78 and 0.77 at 1, 3, and 5 years). This nomogram for predicting clinical response in Chinese pediatric JDM-ILD patients integrates clinical features and treatment variables to enable individualized risk stratification. Combination therapy with JAK or IL-6 inhibitors demonstrates promising efficacy and may improve outcomes.
2026-09-11 | Therapeutic expansion of JAK inhibitors in Chinese dermatological practice: beyond atopic dermatitis to novel autoimmune frontiers.
Janus kinase inhibitors (JAKi) have demonstrated clinical utility in managing atopic dermatitis (AD), yet their broader potential across immune-mediated dermatoses remains inadequately explored, particularly within China's restrictive regulatory landscape for dermatologic indications. This review examines pathogenic mechanisms and emerging evidence supporting JAKi repositioning in seven dermatological conditions beyond AD: alopecia areata (AA), vitiligo, psoriasis, dermatomyositis (DM), pemphigus, bullous pemphigoid (BP), and chronic spontaneous urticaria (CSU)-with emphasis on therapeutic gaps and opportunities specific to Chinese practice. We delineate disease-specific JAK-STAT dysregulation, including IFN-γ-driven cytotoxicity in AA/vitiligo, IL-23/STAT3 activation in psoriasis, and type I interferon hyperactivation in DM. Key clinical findings from rigorous trials indicate that oral tofacitinib achieves PASI75 in 58% of psoriatic patients within 16 weeks and topical ruxolitinib induces facial repigmentation exceeding 75% in vitiligo. In contrast, while current evidence is substantially limited to isolated case reports, emerging data suggest that baricitinib may resolve steroid-refractory BP lesions within one month. Persistent limitations include reliance on small-scale studies for pemphigus and CSU, along with unresolved safety concerns regarding thrombosis risks in susceptible populations. Crucially, we identify therapeutic gaps in segmental vitiligo and juvenile DM where clinical data are absent. This synthesis advocates for randomized controlled trials to validate JAKi efficacy against biologics in high-burden diseases currently dependent on glucocorticoids.
2026-09-01 | Regulated cell death in autoimmune diseases: molecular mechanisms and therapeutic opportunities.
Autoimmune diseases develop from a breakdown in immune tolerance and arise through complex interactions among genetic susceptibility, environmental factors, immune dysregulation, and tissue damage. Although apoptosis has traditionally been recognized as a central mechanism for maintaining immune homeostasis, increasing evidence has identified several non-classical forms of regulated cell death (RCD) that also contribute to autoimmune disease pathogenesis. These pathways include ferroptosis, pyroptosis, necroptosis, PANoptosis, NETosis, parthanatos, and cuproptosis. Unlike classical apoptosis, many of these RCD mechanisms are strongly pro-inflammatory and promote the release of damage-associated molecular patterns (DAMPs), cytokines, oxidized lipids, and autoantigens, thereby enhancing both innate and adaptive immune responses. Recent studies indicate that dysregulation of RCD pathways contributes to chronic inflammation, impaired self-tolerance, immune cell abnormalities, and progressive tissue injury in autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, psoriasis, multiple sclerosis, sjögren's syndrome, systemic sclerosis, type 1 diabetes, ulcerative colitis, dermatomyositis, ankylosing spondylitis, Chronic Dermatitis, antiphospholipid syndrome, Nephritis, and ANCA-associated vasculitis. These pathways do not function independently but form an interconnected network with extensive molecular crosstalk and compensatory interactions that influence disease progression. This review highlights the molecular mechanisms underlying emerging RCD pathways, their cell-specific roles in autoimmune diseases, and the evidence linking their involvement to disease initiation and progression. Furthermore, it discusses current and potential therapeutic approaches targeting major regulators of ferroptosis, pyroptosis, necroptosis, PANoptosis, NETosis, cuproptosis, and parthanatos. Improved understanding of the integrated landscape of the RCD network may facilitate the discovery of novel biomarkers and support the development of innovative therapies to restore immune tolerance and control chronic inflammatory damage in autoimmune diseases.
2026-08-19 | Laryngeal Complications of Dermatomyositis: A Case Report and Comprehensive Review of the Literature.
Dermatomyositis is an immune-mediated inflammatory myopathy characterized by progressive proximal muscle weakness with sparing of distal muscles, accompanied by cutaneous manifestations. Laryngeal involvement in patients with dermatomyositis is extremely rare, with only seven cases described in the literature. We report the case of a 21-year-old man with dermatomyositis who presented with dysphonia, breathiness, and asthenia with a voice handicap index-10 score of 24/40. Laryngeal examination showed whitish mucosal patches on the upper surface of both vocal folds with bowing of the vocal folds. Video-stroboscopy revealed incomplete closure of the vocal folds during phonation, a decrease in vocal fold vibration amplitude, and diminished mucosal waves. One month after therapy with mycophenolate mofetil, the patient's voice quality improved and his VHI-10 score decreased to 16/40.
cell therapies
2026-06-13 | A window to breathe again.
In this Backstory, the authors recount how a 10-year-old girl with rapidly progressive MDA5-positive dermatomyositis survived fulminant lung failure on ECMO and received compassionate-use CD19 chimeric antigen receptor (CAR)-T therapy. The interdisciplinary team then followed her immune reconstitution and clinical recovery, ultimately supporting discharge and offering a potential blueprint for personalized cellular therapy in similarly critical cases.
2026-05-19 | Chimeric antigen receptor T-cell (CAR-T) therapy and other cellular immunotherapy treatments for idiopathic inflammatory myopathies.
Idiopathic inflammatory myopathies (IIM), including immune-mediated necrotizing myopathy (IMNM), dermatomyositis (DM), anti-synthetase syndrome (ASyS), overlap myositis and polymyositis, are heterogeneous autoimmune diseases characterized by immune-mediated skeletal muscle injury and frequent extra-muscular organ involvement. Despite recent therapeutic advances, many IIM patients have persistent disease activity, medication toxicity, or steroid dependence with current treatments. Increasing evidence implicates autoreactive B cells and autoantibody-producing plasma cells as central drivers of disease activity in several IIM subtypes, providing a strong rationale for B-cell- targeted therapies. While monoclonal antibody-based B-cell depletion strategies such as rituximab have demonstrated variable efficacy, their inability to effect persistent, intense depletion of tissue autoreactive B-cell populations often limit their success. Chimeric antigen receptor T-cell (CAR-T) and related cellular immunotherapies were originally developed against hematologic malignancies, but have recently emerged potentially transformative therapeutic options for autoimmune diseases. CAR-T cells targeting CD19 and other B-cell antigens have demonstrated the capacity to induce deep and durable B-cell depletion, and may even lead to "immune reset" with long-lived autoimmunity remission in diseases such as systemic lupus erythematosus and systemic sclerosis. Early clinical experiences now suggest that CAR-T therapy may offer similar promise in refractory IIM, particularly in phenotypes that include pathogenic autoantibodies, such as ASyS, DM, IMNM. This review provides a synopsis of current knowledge on the immunopathogenesis of IIM relevant to CAR-T and other cellular immunotherapy, outlines CAR-T technology and the mechanistic rationale for its use in IIM, and critically appraises emerging clinical CAR-T treatment data in IIM. We also discuss safety considerations, practical challenges, and future directions, with a focus on how CAR-based immunotherapies may reshape treatment paradigms for refractory inflammatory myopathies.
2026-05-11 | Case Report: Juvenile dermatomyositis complicated by acute myeloid leukemia: achievement of sustained remission through hematopoietic stem cell transplantation.
Juvenile dermatomyositis (JDM), a pediatric subtype of idiopathic inflammatory myopathy, is a relatively rare rheumatic and immune system disease among children. Although paraneoplastic dermatomyositis (DM) has been documented in adult malignancies, its association with acute myeloid leukemia (AML) in pediatric populations remains exceptionally rare. We present a male patient diagnosed with JDM at age 6, characterized by Gottron's papules and muscle weakness. Despite receiving sequential immunosuppressive therapies and biological agents, the disease followed a relapsing-remitting course over 9 years. At age 15, he developed persistent knee arthralgia accompanied by intermittent fever lasting 8 days. Hematologic evaluation revealed thrombocytopenia (platelet count: 76 ×109/L) and leukocytosis (white blood cell count: 36.46 ×109/L), prompting bone marrow aspiration confirmed AML diagnosis (French-American-British M2 subtype). Following induction chemotherapy and two consolidation cycles, allogeneic hematopoietic stem cell transplantation (HSCT) from a matched unrelated donor was successfully performed. Notably, both JDM symptoms and AML achieved sustained remission at 1-year follow-up post-HSCT. This case suggests that HSCT may represent a potential therapeutic approach for refractory autoimmune-hematologic malignancy overlap syndromes, though further studies are required to validate its efficacy.
2026-05-08 | Case Report: Lung transplantation for rare anti-MDA5-positive rapidly progressive interstitial lung disease: two cases and a narrative review.
Lung transplantation is a definitive lifesaving option for end-stage lung disease; however, its role in rapidly progressive interstitial lung disease (RP-ILD) associated with anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibodies remains debated. We retrospectively analyzed two anti-MDA5-positive RP-ILD (MDA5+ RP-ILD) patients who underwent bilateral lung transplantation and synthesized pertinent literature to evaluate clinical value and the impact of therapeutic interventions. Both patients recovered postoperatively and were discharged after symptomatic management and supportive care. One patient subsequently developed cerebral infarction and died approximately 8 months after transplantation, whereas the other remains clinically stable under regular follow-up. Given the limited efficacy of conventional therapies and the overall poor prognosis of anti-MDA5-positive dermatomyositis (MDA5+ DM) with RP-ILD, our observations-together with prior reports-support lung transplantation, with extracorporeal membrane oxygenation (ECMO) as a bridge when necessary, as a promising and reliable therapeutic strategy. Lung transplantation may offer definitive treatment in carefully selected patients, underscoring its important clinical value.
2026-02-06 | Anti-CD19 CAR T cells for pediatric patients with treatment-refractory autoimmune diseases.
Chimeric antigen receptor (CAR) T cell therapy was recently proposed as a treatment for adults with B-cell-mediated autoimmune diseases (ADs) refractory to conventional immunomodulatory therapy. We present a case series of eight children with severe/refractory AD (four systemic lupus erythematosus, three dermatomyositis, one systemic sclerosis) treated at Ospedale Pediatrico Bambino Gesù, Rome, and University Hospital Erlangen with a single infusion of 1 × 106 kg-1 point-of-care manufactured autologous CD19 CAR T cells (zorpocabtagene autoleucel), in a hospital exemption (HE) program. In Europe, the HE pathway offers the opportunity to treat patients with life-threatening or seriously debilitating disorders who lack valid therapeutic options, using an advanced therapy medicinal product (ATMP) authorized on a nonroutine, single-patient basis. In contrast to the 'compassionate use' pathway, the ATMP does not necessarily need to have undergone clinical trials or marketing authorization applications. Manufacturing was successful in all patients, yielding several drug product bags. Once infused after lymphodepletion, zorpocabtagene autoleucel cells expanded in vivo, promoting prompt B cell clearance. Grade 1 cytokine release syndrome was reported in six patients, and grade 1 immune effector cell-associated neurotoxicity syndrome was reported in one patient. Late-hematotoxicity was limited to grade 1 in two patients. All these adverse events were manageable and no severe infections occurred. With a median follow-up of 16.5 months (range = 9-24 months), all patients experienced a clinically substantial improvement/resolution of AD, as evidenced by reduction in disease activity scores and signs of reversal of organ damage. This improvement enabled sustained discontinuation of immunomodulators, even after B cell reconstitution. The activation of formal clinical trials enrolling children and adolescents is urgently needed to confirm these preliminary results and to assess the long-term safety of this approach.
antibodies
2026-08-25 | Real-world experience with obinutuzumab in difficult-to-treat myositis: concise report of a case series.
Idiopathic inflammatory myopathy (IIM) is an orphan systemic disorder with muscular, cutaneous and pulmonary involvement. B cell-directed therapies, including rituximab, belimumab and chimeric antigen receptor T-cell (CAR-T), have shown promise in altering disease outcome. We report the benefit of obinutuzumab in difficult -to- treat myositis patients. The Northwell Rheumatology database was searched for obinutuzumab-treated patients (2019-24); five of them met 2017 EULAR/ACR classification criteria for IIM and were included in the analysis. Demographic, clinical, serological and imaging data were collected. Overall response was rated as complete, partial or no response based on clinical response and physician global assessment. Total improvement score was not calculated because data were collected retrospectively. Descriptive statistics were used for analyses. Of five patients, two had antisynthetase syndrome, one dermatomyositis (DM) and two overlap myositis. Most patients failed at least three immunosuppressive agents. The reason for obinutuzumab use was rituximab allergy and worsening of interstitial lung disease (ILD) and myositis activity (3/5), arthritis (2/5) and severe rash (1/5 patients), despite rituximab. After obinutuzumab 80% of patients had overall improvement by 3-6 months. Respiratory status improved/stabilized in all ILD patients. Two patients required second obinutuzumab cycle: one for recurrence and another for persistent disease with B cell re-population. One was lost to follow-up after the second cycle and was deemed a non-responder. At last observation, 4/5 patients had achieved a complete response. No hypogammaglobulinaemia, significant infections or hospitalizations were observed. Obinutuzumab was safe and provided durable improvement in difficult-to-treat myositis patients with rituximab allergy, further highlighting targeting the B-cell pathway.
2026-08-10 | Outcomes of Immune Check Point Inhibitor Use in US Veterans With Pre-Existing Idiopathic Inflammatory Myopathies: Case Series and Literature Review.
Our objective was to identify and describe the clinical characteristics and outcomes in patients with pre-existing idiopathic inflammatory myopathies (IIMs) in the Veterans Health Administration (VHA) treated with immune checkpoint inhibitors (ICIs). All veterans receiving ICI infusions were identified. Patients with at least two International Classification of Disease codes for IIM before first ICI infusion underwent chart review to identify patients with confirmed IIM by American College of Rheumatology/EULAR criteria. The demographics, cancer diagnoses, laboratory findings, clinical course, and mortality rates were reported. IIM cases were also reviewed to determine if patients developed IIM flare following ICI treatment. We identified 29,539 veterans who received at least one ICI infusion in the VHA between June 6, 2011, and February 14, 2023. The eight patients with confirmed IIM before ICI treatment were mostly White men with an average age of 71.7 years at first ICI infusion. The IIM diagnoses were dermatomyositis in three patients, polymyositis in two, antisynthetase syndrome in two, and one rheumatoid arthritis (RA)/myositis overlap. Cancer diagnoses were lung (two), melanoma (two), head and neck (two), kidney/other urinary (one), and mesothelioma (one). Diagnosis of IIM was made on average 3.1 years before ICI treatment. One patient had an IIM flare after ICI. No IIM flares were identified in other patients. Our findings show that an IIM flare after ICI therapy can occur, but most patients did not develop a flare. These observations suggest ICIs can be considered as an option in patients with cancer with IIM with shared decision-making and close monitoring.
2026-08-06 | Unmasking dermatomyositis in a patient with hypothyroid myopathy.
Dermatomyositis (DM) and hypothyroid myopathy are both treatable causes of muscle weakness and can present with overlapping clinical and laboratory features, posing a diagnostic challenge. We report the case of a young male who presented with proximal upper and lower limb muscle weakness, calf muscle hypertrophy and elevated serum creatine kinase (CK) and was found to have hypothyroidism. Muscle weakness and hyperCKemia persisted despite normalisation of thyroid function, prompting a muscle biopsy and extended autoantibody testing, which revealed anti-Ku-positive DM characterised by perivascular inflammation, perifascicular atrophy and membrane attack complex deposition. High-dose corticosteroids led to partial improvement and subsequent rituximab therapy achieved sustained clinical and biochemical remission. This case emphasises the importance of considering dual aetiology when appropriate treatment of the primary diagnosis does not yield expected results. Early biopsy and comprehensive serological evaluation could lead to excellent clinical outcomes.
2026-08-02 | Long-Term Safety and Efficacy of Dazukibart in Dermatomyositis: Combined Phase II Results From Double-Blind and Open-Label Extension Studies.
To evaluate the long-term safety and efficacy of dazukibart, a novel antiinterferon β monoclonal antibody, in adults with moderate-to-severe dermatomyositis (DM). Participants from 2 cohorts of DM (skin-predominant [SP] and muscle-predominant [MP]) completing a 24-week phase II, double-blind study, were enrolled into a 52-week phase IIb, open-label extension (OLE) study, with a 16-week follow-up post treatment (combined study duration: 92 weeks). The pooled skin analysis set included all SP and MP DM participants with baseline Cutaneous Dermatomyositis Disease Area and Severity Index-Activity (CDASI-A) scores ≥ 14. The primary endpoint was incidence of treatment-emergent adverse events (TEAEs) from week 24 through week 92. Key secondary endpoints were change in CDASI-A and Total Improvement Score (TIS) from week 0 through week 92. Participants who received ≥ 1 dose of dazukibart (600 mg) during the OLE study (comprising 9, 15, and 16 participants from the SP cohort, MP cohort, and pooled skin analysis set, respectively) were analyzed (median age 49.5 years, 83% female, 96% White). TEAEs were mild (55%), moderate (38%), or severe (7%), with no treatment-related serious AEs or treatment discontinuations. At week 76, CDASI-A scores improved, with a median change from baseline of -24.0 (range -33 to -12), -9.0 (range -32 to 1), and -23.5 (range -33 to -12) for participants from the SP cohort, MP cohort, and pooled skin analysis set, respectively. In the MP cohort, TIS (median 65.0, range 2.5-95.0) and associated core set measures, including patient-reported outcomes, improved at week 76. Overall, the observed improvements in outcomes, as indicated by the slight reduction in outcome measures, persisted during the 16-week posttreatment follow-up. The safety and efficacy profiles of dazukibart observed at 24 weeks were sustained through 92 weeks. (ClinicalTrials.gov: NCT03181893, NCT05192200).
2026-07-23 | An Aggressive Presentation of Anti-melanoma Differentiation-Associated Gene 5 (MDA-5)-Positive Dermatomyositis With Rapidly Progressive Interstitial Lung Disease: A Case Report.
Anti-melanoma differentiation-associated gene 5 (MDA-5) dermatomyositis is an uncommon condition that is frequently complicated by rapidly progressive interstitial lung disease (RP-ILD), resulting in a poor prognosis. Due to its aggressive course, management is often challenging and requires timely interventions to improve outcomes. This case of a female patient with anti-MDA-5-positive DM and RP-ILD aims to document this unique and uncommon condition, its aggressive clinical course, associated complications, diagnostic challenges, and management considerations.
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2026-09-13 | Antinuclear Antibody (ANA)‑Negative, Anti-melanoma Differentiation-Associated Gene 5 (MDA5)‑Positive Dermatomyositis Presenting as Rapidly Progressive Interstitial Lung Disease: A Case Report.
Dermatomyositis (DM) is a rare, autoimmune myopathy characterized by proximal muscle weakness and pathognomonic skin findings, including Gottron's papules and a heliotrope rash. Anti-melanoma differentiation-associated gene 5 (MDA5)-positive DM is a distinct subtype often associated with rapidly progressive interstitial lung disease (RP-ILD) and may lack the classic features of DM. We present the case of a 43-year-old woman who developed persistent hypoxic respiratory failure after multiple vascular surgeries requiring repeated postoperative blood transfusions. Her respiratory failure was initially attributed to transfusion-related acute lung injury with progression to acute respiratory distress syndrome. Despite appropriate treatment, her respiratory condition worsened. Infectious and autoimmune workups, including bronchoscopy and ANA testing, were unrevealing. Persistent diffuse bilateral ground-glass opacities and new fibrotic changes on imaging prompted an extended myositis panel, which revealed positive anti-MDA5 antibodies, establishing a diagnosis of RP-ILD secondary to MDA5 DM. She was treated with rituximab, mycophenolate, and IV immunoglobulin, with clinical improvement and was discharged on 4L of supplemental oxygen. This case underscores the importance of considering anti-MDA5-positive DM in unexplained, progressive respiratory failure, highlighting the importance of early recognition and multidisciplinary management.
2026-08-02 | Improvement of Refractory Cutaneous Ulcers and Pulmonary Arterial Hypertension Following Rituximab and Mycophenolate Mofetil Therapy in Anti-melanoma Differentiation-Associated Gene 5 (Anti-MDA5) Antibody-Positive Dermatomyositis.
Anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibody-positive dermatomyositis (DM) can manifest with a severe vasculopathic phenotype. We report a case of anti-MDA5 DM in a woman in her early 30s complicated by refractory cutaneous ulcers and pulmonary arterial hypertension (PAH). Despite the escalation of immunosuppressive therapy with glucocorticoids, tacrolimus, intravenous immunoglobulin, and cyclophosphamide, the cutaneous ulcers remained refractory. A progressive decline in diffusing capacity of the lung for carbon monoxide raised suspicion of PAH, which was subsequently confirmed by right heart catheterization. Consequently, combination therapy with mycophenolate mofetil (MMF) and rituximab (RTX) was initiated alongside bosentan. This regimen resulted in the prompt resolution of ulcers and improvement of PAH. Bosentan was discontinued, and azathioprine was initiated to maintain remission, allowing for a successful pregnancy and delivery of a healthy infant. This case suggests a potential role for an MMF- and RTX-containing combination regimen in refractory cutaneous ulcers and PAH associated with anti-MDA5 DM.
2026-03-28 | Management and Prognosis of Anti-MDA5 Dermatomyositis: Insights from a National Multicenter Cohort.
Background: Anti-melanoma differentiation-associated gene 5 (anti-MDA5) positive dermatomyositis is a distinct subset of idiopathic inflammatory myopathies (IIMs), often associated with unique cutaneous features and interstitial lung disease (ILD). While East Asian cohorts frequently report high mortality due to rapidly progressive ILD (RP-ILD), data regarding Central and Eastern European populations remain scarce. Methods: We conducted a retrospective multicenter study of anti-MDA5 positive Caucasian patients managed at four Hungarian rheumatology centers between 2020 and 2025. Demographic, clinical, serological, and radiological data were analyzed. Antibody profiling was performed using a standardized 16-antigen immunoblot assay. Results: Anti-MDA5 positivity was confirmed in 24 out of 742 patients (3.23%) treated in the four centers. The median age at diagnosis was 49.5 years (range: 24-81). Classic dermatomyositis was the predominant clinical phenotype (75%), followed by clinically amyopathic dermatomyositis (CADM) (12.5%) and polymyositis (12.5%). ILD was identified in 58.3% of patients, presenting with organizing pneumonia (OP), non-specific interstitial pneumonia (NSIP), and usual interstitial pneumonia (UIP) patterns. At diagnosis, median creatine kinase (CK) (193.5 U/L) and C-reactive protein (CRP) (4.24 mg/L) levels remained low even in the ILD group, whereas lactate dehydrogenase (LDH) was elevated in 91.7% of the cohort. Anti-Ro52 positivity (45.8% overall) emerged as a notable predictor of ILD (odds ratio [OR]: 22.5, 95% confidence interval [CI]: 2.10-240.48; p = 0.0045), being present in 71.4% of affected patients. RP-ILD occurred in two patients (8.3%). Therapeutic management followed an early, aggressive strategy, frequently utilizing cyclophosphamide (45.8%) and methotrexate (37.5%), with Janus kinase (JAK) inhibitors or rituximab employed in refractory cases. Overall disease-specific survival was 100% during the study period (median follow-up: 72.0 months); no mortality was directly attributable to IIM-related complications. Conclusions: Our study demonstrates that anti-MDA5 positive dermatomyositis in a Hungarian cohort is characterized by heterogeneous manifestations and a significant association between anti-Ro52 and ILD. The observed dissociation between low CK/CRP and elevated LDH underscores the necessity for a high index of suspicion, with LDH serving as a superior marker for disease activity. While ILD presents a significant risk, early and intensive multi-modal intervention may yield superior survival outcomes in European patients compared to the historical mortality rates reported in Asian cohorts.
2026-01-08 | Prolonged remission of dermatomyositis and autoantibody negativization following SARS-CoV-2 infection in an elderly patient.
This case report presents the clinical course of an 80-year-old patient diagnosed with dermatomyositis in 2014, initially managed successfully with methotrexate (MTX). In March 2022, the patient experienced a severe SARS-CoV-2 infection with significant pulmonary involvement, necessitating discontinuation of MTX. Notably, the patient maintained complete remission of dermatomyositis post-infection without relapse. Sustained negativization of autoantibodies, confirmed through multiple evaluations, was observed, while persistent capillaroscopic abnormalities suggested ongoing subclinical disease activity. This case underscores the potential immunomodulatory effects of SARS-CoV-2 on autoimmune diseases and highlights the need for further investigation into its role in immune modulation and disease quiescence.
2025-11-06 | Tacrolimus Trough Concentration-Escalating Bipartite Therapy (Glucocorticoids Combined With Tacrolimus) for Refractory MDA5 Antibody-Positive Clinically Amyopathic Dermatomyositis With Rapidly Progressive Interstitial Pneumonia.
This study aimed to determine the outcomes of patients that have refractory anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive clinically amyopathic dermatomyositis with rapidly progressive interstitial pneumonia treated with tacrolimus trough concentration-escalating bipartite therapy (glucocorticoids combined with tacrolimus). We retrospectively enrolled 19 patients that had refractory anti-MDA5 antibody-positive clinically amyopathic dermatomyositis with rapidly progressive interstitial pneumonitis who were unable to achieve disease control on intensive combination immunosuppressive therapy with glucocorticoids and immunosuppressive agents. They were treated with tacrolimus trough concentration-escalating bimodal therapy. Patients receiving tacrolimus trough concentration-escalating dual therapy were selected based on poor prognostic factors and refractoriness to the initial immunosuppressive therapy. The 19 patients included in the study were treated with tacrolimus trough concentration-escalating bipartite therapy (glucocorticoids combined with tacrolimus) immediately after diagnosis of refractory anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive clinically amyopathic dermatomyositis with rapidly progressive interstitial pneumonia. Following 17 months of treatment and subsequent follow-up, 16 patients displayed decreased ferritin and lactate dehydrogenase levels and improved oxygenation index and high-resolution lung computed tomography findings. Two patients died, and one patient (case 9) developed renal impairment on Day 14 of treatment. Renal damage occurred when the tacrolimus trough concentration was 15.68 ng/mL. After lowering the tacrolimus trough concentration, the patient's renal function gradually normalized. However, because of the addition of cyclophosphamide due to disease activity, the patient did not experience the full efficacy of the two-combination therapy. Tacrolimus-associated renal impairment and viral and fungal infections occurred in some patients treated with bimodal therapy, but it did not have serious consequences. For patients with refractory anti-MDA5 antibody-positive clinically amyopathic dermatomyositis associated with rapidly progressive interstitial pneumonia, the combination of glucocorticoids and tacrolimus is a potentially effective treatment regimen. However, there is considerable individual variation in the optimal trough concentration of tacrolimus.
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Drug Discovery Landscape
18 orphan drug designations for Dermatomyositis, including 2 approved therapies.
18 orphan drug designations for Dermatomyositis, including 2 approved therapies.
Drug | Therapy type | Orphan designation | Clinical trial status | Sponsor |
|---|---|---|---|---|
reversible and selective small molecule TYK2 inhibitor | small molecules | FDA | Galapagos NV | |
brepocitinib [Lisraya] | small molecules | FDA | Approved | Priovant Therapeutics, Inc. |
Glucagon like peptide-1 (GLP-1) Elastin like peptide (ELP)-120 fusion protein | proteins | FDA | ImmunoForge Co., Ltd. | |
begelomab | antibodies | FDA | ADIENNE SA | |
Begelomab | antibodies | EMA | Adienne S.r.l. | |
Humanised IgG1K monoclonal antibody against interferon beta | antibodies | EMA | Pfizer Europe MA EEIG | |
Recombinant humanized monoclonal antibody (immunoglobulin gamma-1 with kappa light chains, IgG1kappa) directed against human soluble cytokine interferon beta. | antibodies | FDA | Pfizer Inc. | |
(2S,3R)-N-[(2S)-3-(cyclopent-1-en-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[(2S)-2-[2-(morpholin-4-yl)acetamido]propanamido]propanamide maleate | small molecules | FDA | Kezar Life Sciences, Inc. | |
humanized anti CD20 monoclonal antibody | antibodies | FDA | — | Biocon Limited |
Lenabasum | small molecules | EMA | Pharma Gateway AB | |
immune globulin subcutaneous (Human) | proteins | FDA | CSL Behring | |
lenabasum | small molecules | FDA | Corbus Pharmaceuticals, Inc. | |
Immune Globulin Intravenous (Human) [Octagam 10%] | antibodies | FDA | Approved | OCTAPHARMA USA, Inc. |
Siponimod [BAF312] | small molecules | EMA | Novartis Europharm Limited | |
sodium thiosulfate | small molecules | FDA | Hope Pharmaceuticals | |
siponimod | small molecules | FDA | Novartis Pharmaceuticals Corporation | |
Human normal immunoglobulin [Gammagen] | antibodies | EMA | [INACTIVE] Orfagen | |
Eculizumab | antibodies | FDA | Alexion Pharmaceuticals, Inc. |
“Terminated” – programs with discontinued clinical trials, or with no updates reported for 5 years after completion or 12 years after the last trial started.
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