Use of Tofacitinib in Anti-Synthetase Antibodies Associated with Rapidly Progressive Interstitial Lung Disease. A Case Report

DERMATOMYOSITIS WITH RAPIDLY PROGRESSIVE INTERSTITIAL LUNG DISEASE COMPLICATED BY SPONTANEOUS PNEUMOMEDIASTINUM IN A PATIENT AFTER ASYMPTOMATIC COVID-19 INFECTION

Successful multi-target therapy including rituximab and mycophenolate mofetil in anti-melanoma differentiation-associated gene 5 antibody-positive rapidly progressive interstitial lung disease with clinically amyopathic dermatomyositis.

Early intervention of plasma exchange combined with intensive immunosuppressive treatment for anti-MDA-5 antibody–positive rapidly progressive interstitial pneumonia: Two case reports

Background: Anti-melanoma differentiation-associated gene 5 dermatomyositis (MDA5-DM) is a rare autoimmune disease, representing less than 2% of dermatomyositis cases and occurring predominantly in East Asia. It is characterized by hallmark cutaneous features and rapidly progressive interstitial lung disease (RP-ILD), which carries a high six-month mortality risk. Although many patients initially respond to therapy, relapse is uncommon. To date, no case reports have been published from the Philippines. This case adds to the limited literature and highlights the need for vigilant recognition. Case Description: A 50-year-old man with MDA5-DM and prior RP-ILD achieved one year of disease quiescence after plasma exchange, steroid pulses, intravenous cyclophosphamide, and intravenous immunoglobulin. While maintained on prednisone and tacrolimus, he developed a one-month history of fever, cough, exertional dyspnea, and polyarthralgia. Examination showed fever (38[Formula: see text]C), inspiratory crackles, mechanic’s hands, periungual erythema, and hyperpigmented patches over the anterior neck and chest (V-sign) and over the upper back, posterior neck, and shoulders (shawl sign). Investigations demonstrated usual interstitial pneumonia and severely reduced DLCO. Pulmonary tuberculosis was also detected, likely contributing to the relapse; thus, anti-tuberculosis therapy was initiated prior to re-treatment of his underlying autoimmune condition. Discussion: The clinical course of dermatomyositis is heterogeneous. The presence of anti-MDA5 antibodies, associated with rapidly progressive interstitial lung disease, confers a poor prognosis. Although many patients initially respond to glucocorticoids, relapse is common, and sustained control often requires combination therapy with glucocorticoids and other immunosuppressants. In our case, the patient developed an exacerbation after one year of quiescence while receiving prednisone and tacrolimus. Conclusion: Patients with MDA5-DM and RP-ILD may achieve remission with initial therapy, yet relapse can occur despite prior control. These findings support long-term monitoring and individualized management to address the disease’s unpredictable course.

Objective: This study was conducted to identify the characteristics and prognosis of rapidly progressive interstitial lung disease (RP-ILD) in idiopathic inflammatory myopathy (IIM) and to assess the predictors for poor survival of RP-ILD in IIM.Methods: A total of 474 patients with IIM were enrolled retrospectively according to medical records from Peking University People's Hospital. Clinical and laboratory characteristics recorded at the diagnosis of patients with RP-ILD and chronic ILD (C-ILD) were compared. The Kaplan–Meier estimator and univariate and multivariate analyses were used for data analysis.Results: ILD was identified in 65% (308/474) of patients with IIM. Patients with ILD were classified into two groups based on lung features: RP-ILD (38%, 117/308) and C-ILD (62%, 191/308). RP-ILD resulted in significantly higher mortality in IIM compared with C-ILD (27.4 vs. 7.9%, P < 0.05). In this study, by comparing IIM patients with and without RP-ILD, a list of initial predictors for RP-ILD development were identified, which included older age at onset, decreased peripheral lymphocytes, skin involvement (periungual erythema, skin ulceration, and subcutaneous/mediastinal emphysema), presence of anti-MDA5 antibody, serum tumor markers, etc. Further multivariate Cox proportional hazards model analysis identified that anti-MDA5 positivity was an independent risk factor for mortality due to RP-ILD (P < 0.05), and lymphocytes <30% in BALF might also be associated with poor survival of myositis-associated RP-ILD (P < 0.05).Conclusion: Our study shows that RP-ILD results in increased mortality in IIM. Anti-MDA5 positivity and a lower lymphocyte ratio in BALF might be the predictive factor of mortality due to RP-ILD.

INTERSTITIAL LUNG DISEASE IN A TODDLER WITH ANTI-MDA5 JUVENILE DERMATOMYOSITIS THAT IMPROVED WITH AGGRESSIVE, EARLY TREATMENT WITH STEROIDS AND MULTIPLE IMMUNOSUPPRESSANTS

LATE DIAGNOSIS OF ANTI-MDA5 ANTIBODY-POSITIVE RAPIDLY PROGRESSIVE INTERSTITIAL LUNG DISEASE WITH CUTANEOUS MANIFESTATIONS

BackgroundAnti-melanoma differentiation-associated gene five antibody positive (MDA5+) dermatomyositis (DM) is significantly associated with rapidly progressive interstitial lung disease (RP-ILD). Early detection of RP-ILD remains a major challenge. This study aims to identify and validate prognostic factors for RP-ILD in MDA5+ DM patients.MethodsPlasma samples from 20 MDA5+ DM patients and 10 healthy controls (HC) were collected for proteomic analysis using liquid chromatography-tandem mass spectrometry (LC–MS/MS) analysis. The proteins of interest were validated in independent samples (20 HC, 20 MDA5+ DM with RP-ILD, and 20 non-RP-ILD patients) with enzyme-linked immunosorbent assay (ELISA).ResultsA total of 413 differentially expressed proteins (DEPs) were detected between the MDA5+ DM patients and HC. When comparing DEPs between RP-ILD and non-RP-ILD patients, 79 proteins were changed in RP-ILD patients, implicating acute inflammatory response, coagulation, and complement cascades. Six candidate biomarkers were confirmed with ELISA. Secreted phosphoprotein 1 (SPP1), serum amyloid A1 (SAA1), and Kininogen 1 (KNG1) concentrations were significantly elevated in RP-ILD patients than those in non-RP-ILD patients and HC. In the different clinical subgroups, SPP1 was particularly elevated in the high-risk RP-ILD subgroup of MDA5+ DM.ConclusionThis study provides novel insights into the pathogenesis of RP-ILD development in MDA5+ DM and suggests the plasma protein SPP1 could serve as a potential blood biomarker for RP-ILD early warning.

BackgroundAnti-melanoma differentiation-associated protein 5 antibody positive dermatomyositis (MDA5+ DM) is an autoimmune disease related to rapidly progressive interstitial lung disease (RPILD) with high mortality. However, the pathogenesis of MDA5+ DM with RPILD remains unclear. We aimed to explore the peripheral immune landscape of MDA5+ DM with RPILD using single-cell RNA sequencing (scRNA-seq).MethodsWe performed scRNA-seq of peripheral blood mononuclear cells (PBMCs) from MDA5+ DM with RPILD (n = 4), MDA5+ DM with ILD (non-RPILD, n = 3), and healthy controls (HCs, n = 3).ResultsThe proportion of CD14+ monocytes increased, but the proportion of natural killer cells, CD4+ T cells and CD8+ T cells decreased in MDA5+ DM with RPILD compared with HCs. Obvious antiviral response was the main feature of MDA5+ DM with RPILD, and the expression of several interferon-stimulated genes (ISGs) related to RIG-I pathway increased, including IRF7, DDX60, IFI27 and IFI6. However, this antiviral response was not significant in MDA5+ DM with ILD. In addition, multiple immune pathways were downregulated in MDA5+ DM with RPILD, including antigen processing and presentation, translation initiation, mRNA splicing, and activation of T and B cells. Cell communication analysis revealed that multiple signaling pathways, including MHC-I and MHC-II, were attenuated in MDA5+ DM with RPILD. Notably, MHC-II signaling was absent in CD4+ naïve T cells from MDA5+ DM with RPILD.ConclusionsThis study demonstrates that antiviral response plays an important role in the pathogenesis of MDA5+ DM with RPILD, as well as changes in downstream immune pathways, providing potential therapeutic targets for future treatment.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13075-025-03639-z.

Objective To investigate the clinical and immunological features of rapid progressive interstitial lung disease(ILD) in patients with idiopathic inflammatory myopathy(IIM). Methods The medical records of 146 adult IIM patients associated with ILD in Peking University People's Hospital from February 1996 to February 2015 were retrospectively analyzed. They were divided into three subgroups: the classic DM, PM and the clinical amyopathic dermatomyositis(CADM), and were further stratified based on with or without rapid progressive ILD(RP-ILD). Chi-squared test was used for group comparisons of categorical data and independent-sample t test for numerical data. Results ① Among 146 patients, 62(42.5%) developed RP-ILD. The prevalence of RP-ILD in CADM was signifcantly higher than dermatomyositis(DM) and polymyositis(PM). ② ILD occurred after or at the same time with IIM in more than 90% of patients. ILD arising before or simultaneously with DM(named ILD) tended to progress rapidly. ③ For the DM group, mechanic's hands, fever, lymphopenia, hypoxemia, hypoalbuminemia, and the elevation of globulin α1 were associated with RP-ILD. CADM-ILD with weakness of swallow muscles, increasing C-reactive protein(CRP) and globulin α2, decreased vital capacity and the relatively high level of segmented granulocytes in bron-choalveolar lavage fluid tended to undergo a rapid progressive clinical course. Additionally, the decreased free triiodothyronine(FT3) and the elevation of tumor markers including carcino-embryonic antigen(CEA), neuron specific enolase(NSE), cytokerantin-19-fragment(CYFRA211) and ferritin were significantly more frequent both in DM and CADM with RP-ILD(P<0.05) patients. ④ According to multivariate analysis, mechanic's hands [HR=31.747, 95%CI(2.367, 425.817),P=0.009] and the elevation of CEA [HR=57.047, 95%CI(1.140, 2 854.885),P=0.043] and CRP [HR=31.568, 95%CI(1.818, 548.093),P=0.018] were potential predictive factors for RP-ILD in DM and CADM patients, respectively. Conclusion The prevalence of RP-ILD in CADM is higher than DM and PM. ILD usually occurs after or simultaneously with IIM, early-onset ILD in DM patients tends to progressive rapidly. Increased tumor markers and decreased FT3 indicate the deterioration of disease. Mechanic's hands and the elevation of CEA and CRP are potential predictive factors for RP-ILD in DM and CADM patients, respectively. Key words: Myositis; Lung disease, interstitial; Allergy and Immunology

We present six cases of antimelanoma differentiation-associated gene 5 antibody (anti-MDA5-Ab)-positive clinically amyopathic dermatomyositis (CADM) with rapidly progressive interstitial lung disease (RP-ILD), which is known to have a poor prognosis. The outcomes of these cases are described after treatment with therapeutic plasma exchange (TPE). Clinical and therapeutic data for patients with CADM with RP-ILD were collected retrospectively from medical records. All six patients received early intensive care including high-dose corticosteroids, intravenous cyclophosphamide, and a calcineurin inhibitor, but lung disease and hypoxia became more severe. TPE was performed over a median of 9.5 sessions (range 3-14) per patient, and the median duration from admission to TPE was 23 days. Three patients received combined direct hemoperfusion using a polymyxin B-immobilized fiber column (PMX-DHP) therapy on successive days to manage acute respiratory failure. Four patients survived and two died due to respiratory failure. In the survival cases, ferritin decreased, and ferritin and KL-6 were lower at diagnosis. The patients who died had a higher alveolar-arterial oxygen difference and more severe lung lesions at the time of initiation of TPE. These findings indicate that a combination of conventional therapy and TPE may be useful for improvement of the prognosis of CADM with RP-ILD at the early stage of onset.

Currently, no established integrated treatment regimen exists for anti-melanoma differentiation-associated gene 5 (anti-MDA5)-positive juvenile dermatomyositis (JDM) complicated by rapidly progressive interstitial lung disease (RP-ILD). We present a case of refractory anti-MDA5-positive JDM with RP-ILD that was successfully treated using a combination of tocilizumab and plasma exchange, along with a review of the relevant literature. A literature review was conducted to gain insights into the clinical features and treatment strategies for managing refractory anti-MDA5-positive JDM complicated by RP-ILD. We report a case of successful management of anti-MDA5-positive JDM complicated by RP-ILD using a combination of immunosuppressive agents, plasma exchange, and tocilizumab. Tocilizumab may serve as an effective adjunctive treatment option for patients with refractory anti-MDA5-positive JDM complicated by RP-ILD who do not respond to conventional intensive immunosuppressive therapies.

Anti-melanoma differentiation-associated gene 5 juvenile dermatomyositis (anti-MDA5 JDM) is associated with high risk of developing rapidly progressive interstitial lung disease (RP-ILD). Here we report an 11-year-old girl with anti-MDA5 JDM and RP-ILD which led to a fatal outcome, further aggravated by SARS-CoV-2 infection. She was referred to our hospital after being diagnosed with anti-MDA5 JDM and respiratory failure due to RP-ILD. On admission, fibrobronchoscopy with bronchoalveolar lavage (BAL) revealed Pneumocystis jirovecii infection so treatment with intravenous trimethoprim-sulfamethoxazole was initiated. Due to RP-ILD worsening, immunosuppressive therapy was intensified using methylprednisolone pulses, cyclophosphamide, tofacitinib and intravenous immunoglobulin without response. She developed severe hypoxemic respiratory failure, pneumomediastinum and pneumothorax, further complicated with severe RP-ILD and cervical subcutaneous emphysema. Three real-time RT-PCR for SARS-CoV-2 were made with a negative result. In addition, she was complicated with a secondary hemophagocytic lymphohistiocytosis and a fourth real-time PCR for SARS-CoV-2 performed in BAS sample was positive. Despite aggressive treatment of RP-ILD due to anti-MDA5 JDM, there was no improvement of respiratory failure in the following days and patient developed refractory septic shock and died. Anti-MDA5 JDM patients with RP-ILD have a poor prognosis with a high mortality rate. For this reason, intensive immunosuppressive therapy is essential including the use of promising drugs such as tofacitinib. COVID-19 in children with underlying health conditions like anti-MDA5 JDM may still be at risk for disease and severe complications.

Objective Antimelanoma differentiation-associated protein 5 (anti-MDA5) autoantibody has been reported in dermatomyositis (DM) to be associated with rapidly progressive interstitial lung disease (RP-ILD). Our study is aimed at determining the clinical characteristics and prognostic factors underpinning anti-MDA5-associated RP-ILD. Methods Patients with anti-MDA5-associated DM (aMDA5-DM) were identified at the Peking University People's Hospital. The presence of anti-MDA5 antibody was determined by immunoblotting. Kaplan-Meier, chi-square test, univariate, and multivariate data analyses were used. Results Out of 213 patients with DM and clinically amyopathic dermatomyositis (CADM), 20.7% (44/213) of patients were identified as aMDA5-DM. Amongst the aMDA5-DM patients, 63.6% (28/44) were identified as having anti-MDA5-associated RP-ILD. During the follow-up, 32.1% (9/28) of patients with anti-MDA5-associated RP-ILD died of respiratory failure. We identified older age and periungual erythema as two independent risk factors for RP-ILD mortality. Age ≥ 57 years at disease onset was significantly associated with poor survival (P = 0.02) in patients with anti-MDA5-associated RP-ILD, while patients with periungual erythema had a better survival rate than those without periungual erythema (P < 0.05). Conclusions Anti-MDA5-associated RP-ILD is significantly associated with poor survival rates in DM/CADM patients. More effective intervention should be administered to anti-MDA5-associated RP-ILD patients, especially to senior patients and those without periungual erythema.

A CASE SERIES OF RAPIDLY-PROGRESSIVE INTERSTITIAL LUNG DISEASE