Clinical Characteristics and Management of Patients With Clinical Amyopathic Dermatomyositis: A Retrospective Study of 64 Patients at a Tertiary Dermatology Department

Background: Clinical amyopathic dermatomyositis (CADM) represents a subtype of 5–20% of patients with dermatomyositis (DM), which can be categorized into amyopathic dermatomyositis (ADM) and hypomyopathic dermatomyositis (HDM). The characteristics of patients with CADM are still limited in English literature.Objective: To investigate clinical features, cutaneous findings, diagnostic accuracy, and treatment regimen of CADM patients.Methods: Sixty-four patients diagnosed with CADM at Peking Union Medical College Hospital by dermatologists were retrospectively analyzed. Data were recorded in the electronic database at each offline clinical consultation and directly extracted from medical records. 2017 EULAR/ACR criteria for idiopathic inflammatory myositis (IIM) classification was used to identify and classify patients with CADM. Published studies were searched to extract relevant data of CADM patients.Results: This cohort included 38 ADM patients and 26 HDM patients. 2017 EULAR/ACR criteria classified 67.2% of patients with CADM into probable or definite DM. Antimalarials were given to a majority of CADM patients (72.6%, n = 45). However, 68.8% (31 out of 45) required at least one aggressive agent combined with hydroxychloroquine due to insufficient response or side effects. The median of systemic treatments in HDM was significantly higher than ADM (p = 0.007). The number of ADM patients using antimalarials as monotherapy was significantly higher than that of HDM patients (p = 0.031), while the number of HDM patients receiving steroids combined with immunosuppressants was significantly higher (p = 0.025). The median of Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI) score improvement was 11.5 and 10.5 for ADM and HDM after a median follow-up of 31.5 and 32.5 months, respectively. Six patients with normal muscle strength developed muscle weakness after a median of 10.5 months (IQR 9-13), and elevated inflammatory markers at initial visit might indicate their muscle weakness development.Conclusions: 32.8% of patients may be overlooked using the three skin variables of 2017 EULAR/ACR criteria. The response rate to single hydroxychloroquine in our cohort was 68.8%. Detailed treatment modalities were different among ADM and HDM. Long-term monitoring for the development of myositis in patients with CADM, especially those with elevated inflammatory markers at initial visit, may be warranted.

Profiling of Myositis Specific Antibodies and Composite Scores as an Aid in the Differential Diagnosis of Autoimmune Myopathies

(1) Background: Myositis specific antibodies (MSA) represent important diagnostic and stratification tools in idiopathic inflammatory myositis (IIM) patients. Here we aimed to evaluate the clinical performance of MSA profiled by a novel particle based multi-analyte technology (PMAT) in IIM and subsets thereof. (2) Methods: 264 IIM patients and 200 controls were tested for MSA using PMAT (Inova Diagnostics, research use only). Diagnostic performance was analyzed and composite scores were generated. (3) Results: The sensitivity/specificity of the individual MSA were: 19.7%/100% (Jo-1), 7.2%/100.0% (Mi-2), 3.0%/99.0% (NXP2), 3.8%/100.0% (SAE), 2.7%/100.0% (PL-7), 1.9%/99.5 (PL-12), 1.1%/100.0% (EJ), 15.5%/99.5% (TIF1ƴ), 8.3%/98.5% (MDA5), 6.1%/99.0% (HMGCR) and 1.9%/98.5% (SRP). Of all IIM patients, 180/264 tested positive for at least one of the MSAs. In the individual control group, 12/200 (6.0%) tested positive for at least one MSA, most of which had levels close to the cut-off (except one SRP and one PL-12). Only 6/264 (2.3%) IIM patients were positive for more than one antibody (MDA5/HMGCR, EJ/PL-7, 2 x MDA5/TIF1ƴ, EJ/SAE, SAE/TIF1ƴ). The overall sensitivity was 68.2% paired with a specificity of 94.0%, leading to an odds ratio of 33.8. The composite scores showed good discrimination between subgroups (e.g., anti-synthetase syndrome). (4) Conclusion: MSA, especially when combined in composite scores (here measured by PMAT), provide value in stratification of patients with IIM.

GAP Score and CA-153 Associated with One-Year Mortality in Anti-MDA-5 Antibody-Positive Patients: A Real-World Experience

Background. Anti-melanoma differentiation-associated gene 5 (MDA-5) antibody is associated with respiratory failure and death in patients with idiopathic inflammatory myositis (IIM) and interstitial lung disease (ILD). This study aimed to investigate clinical parameters associated with mortality in anti-MDA-5 antibody-positive patients. Methods. We retrospectively reviewed the clinical and laboratory data, and pulmonary function test results in 55 anti-MDA-5 antibody-positive patients. A comparison was made between the survivors and non-survivors at the 12-month follow-up. Results. A total of 13 patients (23.6%) died within 12 months. Non-survivors had higher GAP scores (gender, age, and physiology score for idiopathic pulmonary fibrosis) (1 vs. 6, p < 0.01) and CA-153 (16.4 vs. 72.9, p < 0.01). In addition, rapid progressive ILD, fever, peak ferritin, leukocyte count, lactate dehydrogenase, CT score, intravenous immunoglobulin, mycophenolic acid, CMV infections, pneumocystis pneumonia, and pneumothorax were significantly associated with increased risks of 1-year mortality, while forced vital capacity, forced expiratory volume in one second, and diffusion capacity for carbon monoxide were correlated with decreased risk of 1-year mortality. Conclusions. Our study results suggest that GAP scores and CA-153 could be prognostic factors for 1-year mortality in anti-MDA-5 antibody-positive patients. A prompt pulmonary function test and CA-153 are essential for these patients to guide further management.

Favourable Functional Outcomes In Idiopathic Inflammatory Myositis- A Single Centre Experience Over 15 Years

Background: To describe the long term clinical outcome and prognostic factors associated with outcome in a longitudinal cohort of idiopathic inflammatory myositis (IIM). Methods: In this retrospective cohort study, IIM patients were classified as per Bohan and Peter criteria. In those with ≥ 24 months of follow-up; treatment response, functional outcomes [health assessment questionnaire-disability index(HAQ-DI) and modified Rankin score(MRS)], Myositis damage index(MDI) at last follow-up was recorded. Results: The cohort consists of 175 patients, with a mean age of 40.9(+12.6) years, M:F 1:3.3; the IIM subsets were dermatomyositis(DM) 78(44.6%), overlap myositis(OM) 45(25.7%), antisynthetase syndrome(ASS) 11(6.3%), polymyositis(PM) 25(14.3%) and juvenile DM/OM in 15(8.6%) patients. Mortality rate was 13.4% and disease related deaths was 9.1%. Ninety-four patients have followed up for >24 months, the median (IQR) of 65(35,100.7) months. At last follow-up, 13.8% were in treatment free remission, 73.4%, 11.7% had complete clinical response and partial clinical response with treatment respectively. HAQ-DI and MRS were favourable in > 90% of patients. At last follow-up, one-third were off-steroids. Discontinuation of steroids was associated with HAQ-DI of 0 and lower MRS. Complete clinical response on/off medication at last follow-up was associated with HAQ-DI of 0[OR10.9; 95%CI(3.3,160)], better MRS[OR 3.2; 95%CI(1.4,7.3)] and lesser MDI[OR 1.7; 95% CI(1.1,2.7)] at the last follow-up as compared to partial response. Baseline parameters and IIM subsets did not significantly influence outcome.Conclusion: Our longitudinal cohort of IIM had a good outcome in all major myositis subsets. Partial clinical response on treatment is associated with worse functional outcomes and damage accrual.

Myositis-Related Interstitial Lung Disease: A Respiratory Physician’s Point of View

Idiopathic inflammatory myositis (IIM) is an umbrella term for diseases of unknown origin that cause muscle inflammation. Dermatomyositis and polymyositis are IIMs that commonly cause interstitial lung disease (ILD). When a patient presents with ILD, the evaluation of whether the case displays the characteristics of myositis should be determined by interview, physical examination, imaging findings, the measurement of myositis-related antibodies, and the determination of disease severity after diagnosis. Rapidly progressing anti-melanoma differentiation-associated gene 5 antibody-positive ILD may require rapid multi-drug therapy, while anti-aminoacyl tRNA synthetase (ARS) antibody-positive ILD can be treated with anti-inflammatory drugs. Importantly, however, anti-ARS antibody-positive ILD often recurs and sometimes develops into fibrosis. Early diagnosis is crucial for treatment, and we therefore need to clarify the features of myositis associated with ILD and suspect these pathologies early. This section reviews what clinicians need to look for and what findings are evaluated in patients when diagnosing myositis associated with ILD.

POS0323 ANTI PM-SCL ASSOCIATED AUTO IMMUNE DISEASES: MULTICENTRIC COHORT OF 128 PATIENTS

Background:Autoantibodies permit to classify and subgroup connective tissue diseases (CTD) in homogeneous groups of patients in terms of phenotype and prognosis. Anti PM-Scl antibodies have been associated with different CTD categories such as: idiopathic inflammatory myositis (IIM), systemic sclerosis (SSc), Sjögren’s syndrome (SjS), systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD) or undifferentiated connective tissue disease (UCTD).Objectives:To determine clinical spectrum of anti-PM-Scl associated disease and if it an homogenous condition.Methods:This multicentric (four hospitals) observational and retrospective study included all consecutive patients with positive testing for anti PM-Scl antibodies on immunoblot assay and connective tissue disease (2011 -2020). Epidemiological, biological, clinical and radiological data were collected in standard form as well as patient’s outcome.Results:One hundred twenty height patients (female n=96;75%) were included. Median [quartiles] age at diagnosis was 50 [18;84] (IQR) and follow-up duration of 7 [3.75-12] years. Seventy-six (59.3%) patients were simple anti-Pm-Scl positive, and 40.7% were associated with other antibodies: anti-SSA/Ro52 (n=13; 10.92%), SSc associated antibodies (n=21; 16.4%), anti-dsDNA for (n=9; 7%), anti-RNP (n=6; 4.7%) and anti-CCP antibodies (n=6; 4.7%). Most patients had cutaneous involvement (n=106; 83%) with skin thickening (n=47; 36%), mechanics hands (n= 28; 22%), calcinosis (n=26; 20.3%) and subcutaneous edema (n=20; 15.62%). Vascular involvement was frequent with Raynaud phenomenon (n= 89; 69%), telangiectasia (n=36; 28%), skin ulcers (n=27; 21%), pulmonary hypertension (n=8/120; 6.7%) and scleroderma renal crisis (n=2; 1.5%). A majority of patients also displayed an interstitial lung disease (ILD) (n=83; 65.8%); nonspecific interstitial pneumonia (92.7%) and/or organizing pneumonia (25.3%). ILD was characterized by a subacute onset in 37/81 (45.7%); median [quartiles] forced vital capacity (FVC) and total lung capacity (TLC) at diagnosis of 88% [73-105] and 79.5% [68.5-101] respectively. Sixty patients (47%) had muscular sign including myalgia (47%), elevated CPK (n=51; 40%) and muscular weakness (Medical Research Council score <4) (n=19/124;15%). Finally, fifty-three (41.7%) had gastroesophageal reflux. Thirty-nine patients (30.4%) experienced at least one muscular or ILD relapse and 6 (4.84%) died during follow-up (2 breast cancer, 1 pneumonia, 3 unknown etiology). Concerning patients’ prognosis, relapses were associated with skeletal (n=29, 74.4% vs n=32, 35.96%, p < 0.001) or cardiac muscle involvement (n=7, 18.4% vs n=2, 2.5%, p=0.007), and subacute ILD (n=19, 65.5% vs n=18, 34.62%, p= 0.05) with organized pneumonia pattern (n=11, 32.3% vs n=10, 13.9%, p=0.05). Strikingly, ILD occurred mainly in men (90.6% vs 57.2%, p < 0.001) and was associated with anti-Scl-70 positivity (n=14, 16.67% vs 0%, p= 0.01). Muscle involvement was associated arthralgia (n=46, 76.67% vs n=34, 50.75%, p=0.005), respiratory signs at diagnosis: dyspnea NYHA ≥3 (n=46, 75.41% vs n=30, 44.78%, p < 0.001), sub-acute ILD (n=24, 61.54% vs n=13, 30.95%, p=0.0111) with lower FVC (73% [64;88] vs 98 [76;105], p < 0.001). Ulcers were associated with Anti-Scl70 positivity (n=9, 33.33% vs n=5, 4.95%, p < 0.001), Raynaud phenomenon (n=27, 100% vs n=62, 61.39%, p < 0.001), digestive involvement (n=20, 74.07% vs n=34, 33.66%, p < 0.001), ILD with chronic onset (n=15, 78.95% vs n=29, 46.77%, p=0.027) and increased incidence of deaths (n=4, 16% vs n=2, 2.02%, p= 0.01).Conclusion:Conducted on the largest cohort of Anti-PM-Scl patients, this study highlights two main phenotypes that determine different outcome and prognosis. One was associated with muscular disease and subacute onset ILD with more frequent relapses. The second with a vascular phenotype associated with chronic ILD, digestive involvement, chronic evolution and increased incidence of death. This could lead to a reclassification of PM-Scl associated auto immune diseases.Disclosure of Interests:None declared