Clinically Amyopathic Dermatomyositis Research Articles

Clinical, histologic and prognostic features of clinically amyopathic dermatomyositis.

To characterise clinical amyopathic dermatomyositis (CADM) from a clinical, histological, and prognostic perspective. We retrospectively recorded data from our DM cohort. Patients were categorised into three groups: classic DM, hypomyopathic DM (HDM), characterised by normal muscle strength and evidence of muscle involvement in laboratory tests and/or instrumental examinations and CADM, featured by normal muscle strength and unremarkable findings in both laboratory tests and instrumental examinations. Available muscle biopsies from each group were also compared. Our cohort included 63 DM (69.2%), 12 HDM (13.2%) and 16 CADM (17.6%) patients. Compared to DM, CADM patients were younger at onset and diagnosis (45.5±17 vs. 57±18, and 46±17 vs. 58±18 years, respectively; p<0.05). They were more likely to test positive for anti-MDA5 (37.5% vs. 4.8%) and anti- TIF1-γ (31.3% vs. 6.3%), had a higher incidence of arthritis (37.5% vs. 12.6%) and interstitial lung disease (ILD) (43.8% vs. 15.9%) (all comparisons with p<0.05). Muscle biopsies were available for 44 DM, 7 CADM, and 11 HDM patients, revealing similar sarcolemma MHC-I expression rates. Five-year survival rates were comparable across groups (DM: 74.6%, CADM: 75%, HDM: 83.3%). Cox analysis indicated the main mortality predictors in overall cohort were ILD (HR: 3.57, CI: 1.11-11.5) and cancer (HR: 3.67, CI: 1.17-11.5), not CADM (HR: 1.46, CI: 0.33-6.68). CADM patients differ in disease onset, autoantibody profiles, joint and lung involvement. While laboratory and instrumental tests have not shown muscle involvement in CADM, many muscle biopsies have shown MHC-I overexpression.

Clinically amyopathic dermatomyositis associated with cutaneous ulcerations: a case-based review

Introduction and importance: Dermatomyositis (DM) is an autoimmune myopathy primarily affecting both muscles and skin. When muscle weakness is not clinically apparent, but characteristic skin lesions are present, the condition is referred to as clinically amyopathic dermatomyositis (CADM). Case presentation: The authors present the case of a 52-year-old female with a typical DM rash, interstitial pneumonia, and multiple skin ulcers. The skin biopsy was consistent with DM, and there were no signs of muscle involvement. Myositis-related and myositis-specific autoantibodies were also negative. Significant improvement was not observed until the patient received successive monthly pulses of methylprednisolone and the introduction of methotrexate. This treatment regimen allowed for the complete tapering of prednisone and resulted in sustained disease control. Clinical discussion: In addition to the case presentation, a narrative literature review was conducted using the MEDLINE database, and an evidence-based treatment flowchart is proposed. CADM is a subtype of DM, related to higher incidences of interstitial lung disease, skin vasculopathy and malignancy. When ulcers or interstitial pneumonia are present, treatment should be early and aggressive. Active screening for neoplasms is recommended, particularly within the first 5 years. Conclusion: The authors presented a case of seronegative CADM featuring skin vasculopathy, successfully treated with consecutive methylprednisolone pulses. Our literature review emphasized the importance of focused CADM management trials, highlighting the need for further research.

Effectiveness and safety of plasma exchange for anti-MDA5 antibody-positive clinically amyopathic dermatomyositis with rapidly progressive interstitial lung disease refractory to intensive immune suppression therapy: A case series.

Clinically amyopathic dermatomyositis (CADM) with anti-melanoma differentiation-associated gene 5 (MDA5) antibody (Ab) with rapidly progressive interstitial lung disease (RP-ILD) is often refractory for intensive immunosuppression. In this study, we verified the effectiveness and safety of plasma exchange (PEx) for this lethal disease. We retrospectively examined the clinical course and adverse effect (AE) of 12 patients with anti-MDA5 Ab-positive CADM between January 2017 and December 2021 in our hospital. Five out of six patients treated with simple PEx using fresh frozen plasma or 5% albumin survived with or without home oxygen therapy. Multiple PEx (15-20 times) were required to achieve satisfactory improvement as well as remission of CADM. The AEs caused by PEx were resolved using conventional methods. PEx might be a promising option for controlling the disease activity of anti-MDA5 Ab-positive CADM with severe RP-ILD and may contribute to better survival.

Clinical Characteristics and Prognostic Value of Ro52/SSA Antibodies in Idiopathic Inflammatory Myopathies.

Anti-Ro52 are myositis-associated antibodies found in idiopathic inflammatory myopathies (IIMs). This chart review aims to evaluate the frequency, significance, and associated clinical characteristics of Ro52/SSA positivity in IIM patients. We performed a chart review of IIM patients diagnosed between January 2006 and December 2020. All patients met either the 1975 Bohan and Peter or the European League Against Rheumatism/American College of Rheumatology classification criteria for probable or definite myositis. Demographics, clinical and serologic parameters, treatments, and outcomes were compared in patients with anti-Ro52/SSA antibodies and patients without anti-Ro52/SSA antibodies. One hundred eighty-nine patients with IIM were tested for either Ro52 or SSA, with 45 positive for Ro52/SSA (23.8%). Patients with IIM and Ro52/SSA+ were younger at age at onset of disease (44.8 vs. 51.2 years, p = 0.008). Ro52/SSA+ was more common in antisynthetase syndrome (p < 0.001; odds ratio [OR], 4.44; 95% confidence interval [CI], 2.11-9.33) and not frequently identified in clinically amyopathic dermatomyositis (CADM) (p = 0.02; OR, 0.13; 95% CI, 0.02-0.96) or immune-mediated necrotizing myopathy (p = 0.003; OR, 0.14; 95% CI, 0.03-0.63). Of the extraskeletal muscle manifestations, interstitial lung disease (ILD) was strongly associated with Ro52/SSA+ (p < 0.001; OR, 6.61; 95% CI, 3.15-13.86), as was dysphagia (p = 0.006; OR, 2.73; 95% CI, 1.31-5.71). Interstitial lung disease pattern and pulmonary function testing impairment did not differ based on antibody status. There was no significant difference in outcomes between groups. In this myositis cohort, Ro52/SSA+ was present in nearly one-fourth of the population and had a strong association with the antisynthetase syndrome subtype, ILD, and dysphagia. Although these disease manifestations are associated with significant morbidity, in our cohort, they were not associated with increased mortality or more severe ILD.

P78 Amyopathic dermatomyositis: a retrospective review of 21 cases

Abstract Amyopathic dermatomyositis (ADM) is a clinical subtype of dermatomyositis, which can be associated with malignancy and lung disease. We report a retrospective review of 21 cases of ADM presenting to a tertiary clinic. We discuss the clinical presentations, investigation, and cancer and lung associations. Patients were included if they met the European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) criteria for ADM. We identified 21 patients with ADM (16 women and five men). Mean age at diagnosis was 61 years (range 35–81). Clinical features were as follows: Gottron papules (n = 15; 71%), nailfold involvement (n = 16; 76%), heliotrope rash (n = 12; 57%), shawl sign (n = 11; 52%), Raynaud phenomenon (n = 9; 43%), scalp disease (n = 6; 29%) and calcinosis (n = 3; 14%). Antinuclear antibody (ANA) was positive in 76% of patients (n = 16) and 41% (n = 9) had myositis-specific antibodies. Four patients had a prediagnosed malignancy. One patient had prostate cancer detected on malignancy screen. One nerve sheath tumour was diagnosed within 1 year of ADM diagnosis and one cholangiocarcinoma within 3 years. Three patients were found to have mild lung fibrosis, but none was found to have severe interstitial lung disease. Patients were treated with corticosteroids (n = 16), hydroxychloroquine (n = 11), metho­trexate (n = 10), mycophenolate (n = 6), cyclophosphamide (n = 3), rituximab (n = 3), intravenous immunoglobulin (n = 3), mepacrine (n = 2), azathioprine (n = 1), ciclosporin (n = 1) and thalidomide (n = 1). In conclusion, in our study, a female preponderance and cutaneous findings involving extremities were seen in the majority of patients (95%), in keeping with other published data (el-Azhary RA, Pakzad SY. Amyopathic dermatomyositis: retrospective review of 37 cases. J Am Acad Dermatol 2002; 46:560–5). Our study further highlights the heterogeneity of cutaneous clinical presentation of ADM, which is broadly consistent with other reported cohorts [el-Azhary and Pakzad; Tang K, Zhang H, Jin H. Clinical characteristics and management of patients with clinical amyopathic dermatomyositis: a retrospective study of 64 patients at a tertiary dermatology department. Front Med (Lausanne) 2021; 8:783416]. We report high levels of hand and nail involvement, emphasizing the need for formal assessment of hands, including dermoscopy of nails. ANA was positive in 76% of patients; other reported data suggest that it is positive in 31.6–71% (el-Azhary and Pakzad; Tang et al.). Although previous studies have found myositis-specific antibodies in 87.5% (Tang et al.), only 42% in our cohort had positive antibodies; therefore, a high index of suspicion is required to detect cases and appropriately screen for associated morbidity (lung disease and malignancy). In addition, a third of patients had associated malignancy prediagnosed or within 3 years of diagnosis, highlighting the importance of baseline screening and ongoing follow-up.

Juvenile clinically amyopathic dermatomyositis (CADM): Case-based review

Juvenile clinically amyopathic dermatomyositis (CADM): Case-based review

Case series on anti-melanoma differentiation-associated gene 5+ dermatomyositis associated with interstitial lung disease

Dermatomyositis (DM) associated with anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibody is a rare autoimmune disease. Anti-MDA5, also known as anti-CADM-140 antibodies. DM affects the skeletal muscle, skin, joints, and lungs and is a form of idiopathic inflammatory myopathy (IIM). All the 5 dermatomyositis MDA5+ positive patients had rapidly progressive interstitial lung disease (RP-ILD). DM is classified into 2 types, classic dermatomyositis (CDM) and clinically amyopathic dermatomyositis (CADM). Anti-MDA5 antibody-positive as RP-ILD without signs of DM or CADM. RP-ILD in patients with CADM associated with antibodies to MDA5 has a high mortality rate. MDA5+ DM is diagnosed by DM rashes (Gottron’s papules or Gottron’s sign and heliotrope rash) and a positive anti-MDA5. RP-ILD includes acute/subacute interstitial pneumonia, which is a progressive deterioration associated with ILD. Immunosuppressives are effective agents for the treatment of anti-MDA5-positive RP-ILD of CADM.

Clinical Characteristics of Dermatomyositis with Interstitial Lung Disease: A Retrospective Case-Control Study.

Interstitial lung disease (ILD) is a common complication of dermatomyositis (DM) and one of the main risk factors for poor prognosis in DM patients. The aim of this study was to reveal the clinical characteristics of DM patients with ILD. Clinical data from the Second Affiliated Hospital of Soochow University were used to conduct a retrospective case-control study. Univariate and multivariate logistic regression analysis were performed to identify risk factors for ILD in DM. A total of 78 DM patients were included in this study, including 38 DM patients with ILD and 40 DM patients without ILD. Compared with patients without ILD, patients with ILD were older (59.6 vs. 51.2years, P = 0.004), and had higher rates of clinically amyopathic DM (CADM) (45 vs. 20%, P = 0.019), Gottron's papules (76 vs. 53%, P = 0.028), mechanic's hands (13 vs. 0%, P = 0.018), myocardial involvement (29 vs. 8%, P = 0.014), and higher positive rates of anti-SSA/Ro52 (74 vs. 20%, P < 0.001) and anti-melanoma differentiation-associated gene-5 (MDA5) (24 vs. 8%, P = 0.048) antibodies, while albumin (ALB) (34.5 vs. 38.0g/l, P = 0.006), prognostic nutritional index (PNI) (40.3 vs. 44.7, P = 0.013), the rates of muscle weakness (45 vs. 73%, P = 0.013) and heliotrope rash (50 vs. 80%, P = 0.005) were lower. In addition, the five patients who died were all DM patients with ILD (13 vs. 0%, P = 0.018). Multivariate logistic regression showed that old age (odds ratio [OR] = 1.119, 95% confidence interval [CI] = 1.028-1.217, P = 0.009), Gottron's papules (OR = 8.302, 95% CI = 1.275-54.064, P = 0.027) and anti-SSA/Ro52 (OR = 24.320, 95% CI = 4.102-144.204, P < 0.001) were independent risk factors for ILD in DM. DM patients with ILD usually present with older age, higher rates of CADM, Gottron's papules, mechanic's hands, myocardial involvement, higher positive rates of anti-MDA5 and anti-SSA/Ro52 antibodies, lower ALB, PNI, and lower rates of muscle weakness and heliotrope rash. Old age, Gottron's papules, and anti-SSA/Ro52 were independent risk factors for ILD in DM.

New aspects of clinical and immunological characteristics in patients with anti-asparaginyl tRNA synthetase (anti-KS) autoantibody.

Anti-asparaginyl tRNA synthetase (anti-KS) antibody is present in patients with interstitial lung disease (ILD) accompanied by polymyositis/dermatomyositis. We examined clinical/immunological features of these patients. Polymyositis/dermatomyositis or ILD patients were screened for autoantibodies, and clinical/immunological data were collected retrospectively. ILD was diagnosed by computed tomography, and clinical/immunological features of anti-KS-positive patients were compared with those of anti-Jo-1-positive patients. Sixteen anti-KS-positive patients [female = 11; male = 5; average age 63.6 years (range, 40-81) years] were diagnosed: seven had ILD, four had clinically amyopathic DM (CADM) and ILD, three had Sjögren's syndrome (SS) and ILD one each had rheumatoid arthritis and ILD, or CADM/SS overlap and ILD. All patients had ILD with chronic onset and clinical course; 11/16 (69%) had nonspecific interstitial pneumonia, and five (31%) had usual interstitial pneumonia pattern. Regarding skin manifestations, 4 (27%) had typical DM rash and 11 (69%) had mechanic's hands. All anti-KS-positive patients had no clinical muscle weakness or serum creatine kinase elevation; 8/16 patients (50%) had sicca symptoms at a significantly high frequency compared with anti-Jo-1-positive patients (50% vs 11%, P = 0.01). Anti-KS-positive patients might form a distinguishable subset closely associated with sicca symptoms, CADM and chronic-type ILD with a relatively favourable prognosis.

WDFY4 polymorphisms in Chinese patients with anti-MDA5 dermatomyositis is associated with rapid progressive interstitial lung disease.

Anti-melanoma differentiation-associated gene 5 antibody positive dermatomyositis (MDA5+DM), is susceptible to development of rapidly progressive interstitial lung disease (RPILD), which has been predominantly reported in East Asia. A Japanese genome-wide study has identified a WDFY4 variant rs7919656 linkage. We sought to evaluate this genetic marker and exploit its possible clinical relevance in Chinese MDA5+DM. We genotyped and compared the minor allele A frequency of WDFY4 rs7919656 in patients with MDA5+DM (n = 254) including 190 clinically amyopathic dermatomyositis (CADM), MDA5-DM (n = 53), anti-synthetases syndrome (ASyS, n = 72) and healthy controls (n = 192). Association of the WDFY4 variant with clinical phenotype was evaluated using logistic regression. Although the minor allele A frequencies of WDFY4 rs7919656 in MDA5+DM and CADM were comparable to that in healthy controls, we observed a significant correlation between the WDFY4 variant (GA+AA genotype) and the incidence of RPILD in MDA5+DM (OR: 2.11; 95% CI: 1.21, 3.69; P = 0.007). Moreover, this variant was an independent risk factor for RPILD in multivariate analysis (OR: 4.98; 95% CI: 1.59, 17.19; P = 0.008), along with other well-recognized risk factors, i.e. forced vital capacity % predicted, diffusing capacity for carbon monoxide % predicted, serum ferritin and prednisolone exposure. In addition, this variant was associated with higher expression of WDFY4 in PBMCs of MDA5+DM, especially those with RPILD. WDFY4 overexpression was also observed in lung biopsy of MDA5+DM-RPILD bearing the variant genotype. We found that the WDFY4 variant was associated with an increased risk of RPILD, not with disease susceptibility in Chinese MDA5+DM.

A case of Hypomyopathic Dermatomyositis which subsequently developed to overt Myositis with ILD

Dermatomyositis (DM) is an inflammatory myositis. Clinically amyopathic dermatomyositis (CADM) and hypomyopathic dermatomyositis (HDM) are rare forms of DM in which skin manifestations are present with no and minimal clinical and laboratory evidence of myositis respectively. A common complication of CADM/HDM is interstitial lung disease (ILD), with the most common histopathologic variant of non-specific interstitial pneumonia (NSIP). This case highlights the development of ILD and severe muscle weakness, including proximal limb muscles, muscles of respiration and muscles of deglutition in a patient with previous diagnosis of hypomyopathic dermatomyositis.

Pathological Roles of Pulmonary Cells in Acute Lung Injury: Lessons from Clinical Practice

Interstitial lung diseases (ILD) are relatively rare and sometimes become life threatening. In particular, rapidly progressive ILD, which frequently presents as acute lung injury (ALI) on lung histopathology, shows poor prognosis if proper and immediate treatments are not initiated. These devastating conditions include acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF), clinically amyopathic dermatomyositis (CADM), epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI)-induced lung injury, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection named coronavirus disease 2019 (COVID-19). In this review, clinical information, physical findings, laboratory examinations, and findings on lung high-resolution computed tomography and lung histopathology are presented, focusing on majorly damaged cells in each disease. Furthermore, treatments that should be immediately initiated in clinical practice for each disease are illustrated to save patients with these diseases.

Incidence, Prevalence, and Mortality of Dermatomyositis: A Population-Based Cohort Study.

We aimed to determine the population-based incidence, prevalence, and mortality of dermatomyositis (DM) using European Alliance of Associations for Rheumatology (EULAR)/American College of Rheumatology (ACR) criteria. This population-based cohort study included incident DM from January 1, 1995 to December 31, 2019. We manually reviewed all individuals with at least 1 code for DM or polymyositis to determine if they met EULAR/ACR criteria, subspecialty physician diagnosis, and/or Bohan and Peter criteria. We age- and sex-adjusted incidence and prevalence estimates to the US non-Hispanic White year 2000 population and estimated prevalence on January 1, 2015. Standardized mortality ratios (SMRs) with 95% confidence intervals (95% CIs) compared observed to expected mortality adjusting for age, sex, and year. We identified 40 cases of verified DM, with 29 cases incident in Olmsted County from 1995 to 2019. The mean age was 57 years, 26 (90%) were female, and 12 (41%) had clinically amyopathic DM (CADM). The median follow-up time was 8.2 years. The overall adjusted incidence of DM was 1.1 (95% CI 0.7-1.5) per 100,000 person-years, and prevalence was 13 (95% CI 6-19) per 100,000. The SMR was significantly elevated among the myopathic DM cases (3.1 [95% CI 1.1-6.8]) but not CADM cases (1.1 [95% CI 0.2-3.3]). The positive predictive value of ≥2 DM codes was only 40 of 82 (49%). This population-based study found that DM incidence and prevalence were higher than previously reported. Mortality was significantly elevated for myopathic DM but not for CADM.

RARE CASE OF FULMINANT OF INTERSTITIAL LUNG DISEASE SECONDARY TO IDIOPATHIC INFLAMMATORY MYOSITIS

RARE CASE OF FULMINANT OF INTERSTITIAL LUNG DISEASE SECONDARY TO IDIOPATHIC INFLAMMATORY MYOSITIS

Clinically Amyopathic Dermatomyositis With Rapid Progressive Interstitial Lung Disease Diagnosed in a Patient on Extracorporeal Membrane Oxygenation

Clinically amyopathic dermatomyositis (CADM) is characterized by skin manifestations with minimal to no muscle involvement. It is a unique subset of dermatomyositis, which may create a diagnostic challenge due to its vague presentation. Establishing the diagnosis is crucial as CADM is highly associated with rapidly progressive interstitial lung disease (RP-ILD), and patients who suffer from thereof have an abysmal prognosis. Herein, we described a case of a 46-year-old male who presented with a history of skin rash and then started to experience shortness of breath. His respiratory symptoms were progressing swiftly and affected his daily life activities. The initial blood tests were normal, but his chest imaging revealed fibrotic nonspecific interstitial pneumonia. The patient required intubation due to a critical respiratory condition, and later, he needed extracorporeal membrane oxygenation (ECMO). While the patient was connected to an ECMO machine, a bedside open lung biopsy (BOLB) was performed, and the results were in keeping with RP-ILD and CADM. The patient was started on cyclophosphamide without a response, and his chest computed tomography showed acute respiratory distress syndrome. His hospital course was complicated with pneumonia, severe kidney dysfunction requiring dialysis, and candidemia, which resulted in the patient’s death.

Successful treatment with tofacitinib for relapse of rapidly progressive interstitial lung disease in anti-melanoma differentiation-associated gene 5 antibody-positive clinically amyopathic dermatomyositis.

Anti-melanoma differentiation-associated gene 5 (MDA5) antibody is associated with clinically amyopathic dermatomyositis (CADM) with rapidly progressive interstitial lung disease (RP-ILD). Recently, several studies have reported that tofacitinib (TOF), a Janus kinase inhibitor, might be effective for cases of new or refractory RP-ILD in anti-MDA5 antibody-positive CADM; however, it is unknown whether TOF can also be effective for relapsed cases. We herein report a relapsed case of RP-ILD in anti-MDA5 antibody-positive CADM, which was successfully treated by combination therapy with TOF (5 mg twice daily). Our case suggests that TOF may also be a potential treatment option for relapsed cases of this disease.

First report of an adult patient with Clinical amyopathic dermatomyositis associated rapid progressive interstitial lung disease triggered by COVID19

ILD is a common manifestation of dermatomyositis (DM) with indolent course but a unique variant of DM called clinically amyopathic DM (CADM) presents with rapid progressive interstitial lung disease (RP-ILD) and is called CADM associated RP-ILD. Here, we report a case of a 52 year old woman with CADM associated RP-ILD occurred 2 weeks after recovery from COVID19 infection but unfortunately died from RP-ILD, almost 5 months later. This is the first report of CADM associated RP-ILD triggered by COVID19 in an adult patient

Nomogram to predict dermatomyositis prognosis: a population-based study of 457 cases.

Dermatomyositis (DM) is a systemic autoimmune disease, which typically affects the striated muscle with a variable involvement of the skin and other organs. Clinically amyopathic DM (CADM) is a combination of hypomyopathic DM (HDM) and amyopathic DM (ADM), with a characteristic of skin-predominant lesions. To date, large-scale studies on the prognostic factors of DM/CADM have been limited. The aim of this study is to evaluate the prognostic values of clinical manifestations in DM/CADM and to develop a prognostic nomogram for DM/CADM. A development cohort (n=239), an internal validation cohort (n=128) and an external validation cohort (n=90) were included in this study. Overall survival (OS) was estimated by the Kaplan-Meier method. Univariate and multivariate Cox proportional hazards regression analyses were performed. Cox proportional hazards model and forward stepwise selection with the Akaike information criterion were used for multivariate analysis of prognostic factors. The concordance index (C-index) and calibration curve were calculated to evaluate the predictive accuracy of the proposed nomogram. Rapidly progressive interstitial lung disease (RP-ILD) and erythrocyte sedimentation rate (ESR) were identified as risk independent prognostic factors, with antinuclear antibodies (ANA) was identified as protective independent prognostic factors, for DM/CADM. A prognostic nomogram was formulated based on these three predictors. The C-index of the proposed nomogram in the development cohort was 0.874 (95%CI, 0.819-0.929). The predictive accuracy of the proposed nomogram was further validated in the internal validation cohort, with a C-index of 0.799 (95%CI, 0.681-0.917). Furthermore, the C-index was 0.864 (95%CI, 0.699-1.000) in the external validation cohort, indicating a good calibration ability. This proposed nomogram showed a promising predictive accuracy on the prognosis of DM/CADM. RP-ILD, ANA and ESR are prognostic factors for DM/CADM. The proposed nomogram based on these three factors could accurately predict the 10-year OS probabilities of patients with DM/CADM.

Anti-Ro52 antibodies are associated with the prognosis of adult idiopathic inflammatory myopathy-associated interstitial lung disease.

In the present study, we aimed to assess the prevalence and clinical significance of anti-Ro52 antibodies in a cohort of patients with idiopathic inflammatory myopathy-associated interstitial lung disease (IIM-ILD) with different myositis-specific autoantibodies (MSAs). A cohort of 267 IIM-ILD patients, including 62 patients with PM, 126 patients with DM and 79 patients with clinically amyopathic DM (CADM) were retrospectively analysed in this study. Clinical and laboratory findings, pulmonary function tests (PFTs), HRCT patterns and treatment information were compared between patients with and without anti-Ro52 antibodies. The association between prognosis and anti-Ro52 antibodies was also evaluated based on different MSA subgroups. Anti-Ro52 antibodies were more frequent in patients with anti-MDA5 (62.1%, P &lt; 0.01) and anti-Jo1 (64.9%, P &lt; 0.01) antibodies than in those with other MSAs. The proportion of patients with anti-Jo1 antibodies was higher in the anti-Ro52 antibody-positive group than in the anti-Ro52 antibody-negative group. Patients with anti-Ro52 antibodies were more likely to exhibit the Gottron sign than the anti-Ro52 antibody-negative group (P &lt; 0.001). Furthermore, it was a predictive factor for rapid progression interstitial lung disease (RP-ILD) (P = 0.001) and was also associated with a higher mortality rate (log-rank test, P = 0.001). Furthermore, RP-ILD was more frequently exhibited in anti-MDA5- and anti-Ro52-positive patients. Moreover, anti-Ro52 antibody positivity was closely associated with a higher mortality rate in anti-MDA5-ILD patients (log-rank test, P &lt; 0.05). Anti-Ro52 antibodies were highly prevalent in patients with anti-MDA5 and anti-Jo1 antibodies. Within all patients with IIM-ILD, those with anti-Ro52 autoantibodies had a higher frequency of RP-ILD and a poorer prognosis, especially in the anti-MDA5 antibody subgroup.

Clinical features and immune-related protein patterns of anti-MDA5 positive clinically amyopathic dermatomyositis Dutch patients.

The presence of melanoma differentiation-associated protein 5 (MDA5) antibodies in patients with DM is associated with the development of a rapidly progressive interstitial lung disease (RPILD), unresponsive to conventional treatment. We characterize patients and provide more insight into potential biomarkers to identify patients with RPILD. Patients diagnosed with anti-MDA5 positive DM between December 2015 and November 2017 were included in this study. Clinical data were retrospectively retrieved from medical records. A total of 180 immune-related markers were measured in sera of 16 patients and 15 healthy controls using proximity extension assay-based technology. Twenty patients were included, with a median time from symptoms till diagnosis of 4 months. All patients had clinically amyopathic DM. Interstitial lung disease (ILD) was present at diagnosis in 94% of the patients, 45% presented with RPILD. The mortality rate was 35% within 4 months after diagnosis and respiratory failure was the main cause of death in these patients. Furthermore, unsupervised analysis revealed that patients with RPILD show clearly different inflammatory serum profiles than healthy controls. In addition, in comparison to healthy controls, the IFN, IL1, IL10 and IL18 signalling pathways are different regulated in anti-MDA5 positive patients. In this Dutch anti-MDA5 positive clinically amyopathic DM (CADM) cohort, one-third of the patients died due to RPILD soon after diagnosis, which underlines the severity of this disease. In addition, we have found several possible pathways that are differentially regulated in RPILD vs no RPILD DM and healthy controls. These markers await further validation before clinical use.