Amyopathic Dermatomyositis Patients Research Articles

Clinically amyopathic dermatomyositis: Clinical, laboratory, and histopathological features.

Despite the advancements in the categorization of clinically amyopathic dermatomyositis (CADM), the classification and diagnosis of its subtypes are still challenging. The aim of our study was to describe the clinicopathological features of CADM and assess the differences between amyopathic dermatomyositis (ADM) and hypomyopathic dermatomyositis (HDM). This retrospective study included 43 patients with CADM diagnosed at our institution from 2016 to 2020. Patients were subclassed into ADM (n = 30) and HDM (n = 13) groups to assess their clinicopathological differences. All included patients had characteristic cutaneous manifestations of dermatomyositis; 67.4% had myositis-associated auto-antibodies, including ANA (32.6%), RNP (14.0%), anti-Ro52 (9.3%), anti-p155/140 (7.0%), rheumatoid factor (7.0%), anti-NXP-2 (4.7%), anti-MDA5 (2.3%), and anti-Jo-1 (2.3%) antibodies. One patient had associated interstitial lung disease, and another patient had oral squamous cell carcinoma. The histopathological findings included mucin deposition (69.8%), telangiectasia (65.1%), lymphocytic infiltrate (48.8%), vacuolar interface dermatitis (46.5%), and epidermal atrophy (14.0%). Compared to patients with HDM, ADM patients were significantly less likely to have epidermal atrophy, 3.3% versus 38.5% (p = 0.006), and more likely to have mucin deposition, 80.0% versus 46.2% (p = 0.028). We described the clinicopathological features of CADM and highlighted the distinctions between ADM and HDM dermatopathologic findings. This information may prove helpful in diagnosing ambiguous lesions.

The clinical relevance of WDFY4 in autoimmune diseases in diverse ancestral populations.

WD repeat- and FYVE domain-containing protein 4 (WDFY4), coded by a gene on 10q11.23, is a member of the BEACH (Beige and Chediak-Higashi) domain-containing family. Genome-wide association studies identified WDFY4 variants as a risk factor for SLE in Asian and European populations. WDFY4 variants are also associated with RA and primary biliary cholangitis, in different ancestry populations. The WDFY4 protein plays an essential role in the cross-presentation of classic dendritic cells, reactive oxygen species-induced apoptosis of CD8+ T cells, and non-canonical autophagic activity in B cells. A novel variant rs7919656 was identified in Japanese clinically amyopathic dermatomyositis patients, with a highly expressed truncated isoform augmenting the melanoma differentiation-associated gene 5 (MDA5) signalling pathway. The same variant was later found to be significantly associated with RP-ILD in Chinese MDA5+DM patients. Here, we briefly review the association of WDFY4 with autoimmune diseases and its known function in immune response.

Racial Disparities in Diagnosis and Treatment of Patients With Dermatomyositis of Different Skin Tones.

Delays in the diagnosis and treatment of dermatological conditions in minorities are a well-documented health disparity. We aimed to determine if there was a delay in detection and treatment initiation for dermatomyositis (DM) and amyopathic dermatomyositis (ADM) in patients of different skin tones. Patients from Montefiore Medical Center who met the criteria for DM and ADM were included in this cohort study. Records were reviewed for date of first documented rash, creatine kinase levels, muscle weakness complaints, and date of first steroid or disease-modifying antirheumatic drug initiation. The median number of days between rash documentation and therapy initiation was compared for patients of different races, including non-Hispanic White, non-Hispanic Black, Hispanic, and other (Asian and unknown). Data were compared in White versus non-White skin. Sixty-three DM and 9 ADM patients met the inclusion criteria. There was a shorter time to treatment initiation in White versus non-White patients, with a median number of 8 days compared with 21 days, respectively ( p = 0.05). Kaplan-Meier curves showed prolonged time to diagnosis and treatment in all other races when compared with White patients ( p = 0.03). It took clinicians longer to diagnose and treat DM and ADM in patients of color. The trends observed emphasize the importance of increasing dermatology education of non-White skin to improve detection and treatment of DM and ADM and minimize health disparities.

Clinical parameters of therapeutic apheresis induction in clinically amyopathic dermatomyositis patients with rapid progressive interstitial lung disease.

The purpose of this study is to clarify the clinical parameters of therapeutic apheresis (TA) induction in clinically amyopathic dermatomyositis patients with rapid progressive interstitial lung disease. Literature publications prior to November 2021 from PubMed and Ichushi-Web were used. We collected details of TA and clinical features. The data were divided into two groups determined by the outcome, survived and deceased. Then, we estimated clinical parameters between them. There were 151 cases, 134 of which had reported outcomes and 64 of which were positive for the anti-MDA5 antibody. Eighty patients survived. Forty-eight patients were treated with plasma exchange and 34 with polymyxin-B immobilized fibers direct hemoperfusion. Regarding clinical parameters, only the PaO2 to FiO2 (P/F) ratio was useful. The cut-off point of the P/F ratio was 174 on the ROC curve. The parameter for induction is considered when the P/F ratio is lower than 200.

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.

Clinical value of a [18F]-FDG PET-CT muscle-to-muscle SUV ratio for the diagnosis of active dermatomyositis.

To study a muscle-to-muscle standardised uptake value (SUV) ratio with FDG-PET/CT (FDG-PET) as a marker for the detection of disease activity in dermatomyositis (DM). Patients with DM (n = 24) who met the European Neuro-Muscular Centre diagnostic criteria were retrospectively identified over a 3-year period through a national survey. Muscle biopsy was performed in all patients. Maximum SUV was measured in proximal muscles (SUVPROX) that had the highest radiotracer uptake on visual grading as well as in the musculus longissimus thoracis (SUVMLT), whereas mean SUV was measured for the liver (SUVLIV). Muscle-to-liver SUV ratios for either muscle group were compared and a SUVPROX/SUVMLT ratio was calculated. SUVPROX/SUVMLT of DM patients were compared with age- and sex-matched control subjects (n = 24) with melanoma who had received FDG-PET scans. DM patients presented with proximal and symmetrical muscle uptake. Differences in SUVPROX/SUVLIV and SUVMLT/SUVLIV ratios in DM subjects were significant (p < 0.001). SUVPROX/SUVMLT ratios in DM and their controls also differed significantly (p = 0.0012). The SUVPROX/SUVMLT ratio threshold between DM subjects and controls was 1.73 with a sensitivity of 50% (CI95%, 29.1 to 70.9%) and specificity at 83.3% (CI95%, 62.6 to 95.3%). When amyopathic DM patients were removed from the analysis, specificity was increased to 95% (CI95%, 75.1 to 99.9%) with a likelihood ratio of 10 and an AUC of 83.4% (CI95%, 71.4 to 95.4%). A muscle-to-muscle SUVPROX/SUVMLT ratio with a cut-off value of 1.73 in FDG-PET imaging might serve as a non-invasive marker to determine disease activity in dermatomyositis. • [18F]-FDG PET-scanner standardised uptake value (SUV) could reflect disease activity in dermatomyositis (DM). • A ratio of SUV in proximal muscles (SUVPROX) to SUV in musculus longissimus thoracis (SUVMLT) could be used to determine active DM. • Active disease is suspected for SUV PROX /SUV MLT ratios greater than 1.73.

Clinical value of 18F-FDG PET/CT in assessing muscular inflammation of dermatomyositis

Objective To analyze the imaging characteristics and diagnostic value of 18F-fluorodeoxyglucose (FDG) PET/CT in muscular inflammation in dermatomyositis (DM), as well as the relationship between maximum standardized uptake value (SUVmax) and activity of muscular inflammation. Methods From July 2013 to November 2016, 17 hospitalized DM patients (8 males, 9 females, age range: 35-78 years) who underwent 18F-FDG PET/CT were retrospectively reviewed, including 13 typical DM (TDM) and 4 amyopathic DM (ADM). Seventeen healthy volunteers (8 males, 9 females, age range: 35-78 years) in the same period were enrolled as the control group. The proximal limb muscles of whole body were divided into 7 areas, and the SUVmax of each was measured and recorded. Two-sample t test, one-way analysis of variance, Dunnett-t test and Spearman correlation analysis were used to analyze data. Results Five TDM cases showed diffuse increased FDG uptake in global muscles; 8 TDM cases showed increased FDG uptake in local muscles, mainly in the shoulder and hip. The FDG uptake by muscles of 4 ADM patients was similar with that of controls. The SUVmax was lower and lower in the order of shoulder and back muscles, hip muscles, thoracic vertebra muscles, cervical vertebra muscles, biceps, proximal quadriceps and lumbar vertebra muscles in DM group. The muscle SUVmax of DM, TDM, ADM and the controls were 1.92±0.86, 2.14±0.85, 1.19±0.44 and 0.93±0.26, respectively (F=69.50, P<0.001). Muscle SUVmax of DM group was higher than that of controls, muscle SUVmax of TDM was higher than that of ADM, and muscle SUVmax of ADM was higher than that of controls (t values: 4.102-11.970, all P<0.05). Muscle SUVmax of 9 DM patients with interstitial lung disease (ILD) was lower than that of patients without ILD (1.73±0.09 vs 2.13±0.13; t=5.857, P<0.001). Muscle SUVmax of DM was positive correlated with serum levels of creatine kinase (CK) and creatine kinase isoenzyme composed by M and B subunits (CK-MB) (rs values: 0.814 and 0.751, both P<0.001). Conclusion 18F-FDG PET/CT is helpful to detect muscular inflammation of DM and it can reflect the activity and severity with SUVmax, and meanwhile evaluate the condition of ILD associated with DM. Key words: Dermatomyositis; Positron-emission tomography; Tomography, X-ray computed; Deoxyglucose

Rituximab for refractory rapidly progressive interstitial lung disease related to anti-MDA5 antibody-positive amyopathic dermatomyositis.

To report our experience in using rituximab (RTX) for treating refractory rapidly progressive interstitial lung disease (RP-ILD) complicating anti-melanoma differentiation-associated gene 5 antibody (anti-MDA5 Ab)-positive amyopathic dermatomyositis (ADM). Medical records of four ADM patients with refractory RP-ILD treated with RTX therapy were reviewed retrospectively. All four patients were tested positive for anti-MDA5 Ab and failed to respond to high-dose systemic steroid and other intensive immunosuppressive therapies. Respiratory symptoms, lung function tests, and high-resolution computed tomography (HRCT) of the chest were compared before and after the first course of RTX. After RTX treatment, all four patients had improvement in the respiratory symptoms in terms of New York Heart Association classification. Two patients successfully had their supplementary oxygen therapy weaned off. The lung function tests were significantly better in all patients. The HRCT showed improvement in three patients while the other one remained static. The recalcitrant vasculitic rashes associated with the anti-MDA5 Ab were also better in all patients. The average daily prednisolone dose dropped from 20 to 6.25mg post-treatment. None of the patients died throughout the follow-up period which ranged from 6months to 2years. However, two patients developed chest infection and one wound infection within 6months after the RTX infusion. Our results suggest that RTX may be a useful therapy for anti-MDA5 Ab-positive ADM associated with RP-ILD. However, infection is the major risk.

HRCT score and serum ferritin level are factors associated to the 1-year mortality of acute interstitial lung disease in clinically amyopathic dermatomyositis patients.

The aim of this study is to evaluate the factors associated to 1-year mortality in clinically amyopathic dermatomyositis (CADM) patients with acute interstitial lung disease (ILD). A single center of 37 cases of Chinese patients with CADM was reviewed retrospectively in Renji hospital. All CADM patients were diagnosed with ILD; there were 24 cases of acute interstitial pneumonia (AIP) and 13 cases of acute exacerbation of non-acute interstitial pneumonia non-AIP. The clinical features, including blood tests, chest high-resolution computed tomography (HRCT) score, and lung function, were analyzed, respectively. Neutrophil lymphocyte ratio (NLR), serum ferritin level, serum lactate dehydrogenase (LDH) level, and HRCT score were statistically significant factors on univariate analysis. Multivariate analysis revealed that the overall HRCT score (HR 1.134, 95 % confidence interval 1.009-1.275, P = 0.017) and serum ferritin level (HR 1.001, 95 % confidence interval 1.002-1.007, P = 0.010) were independently significant factors of 1-year mortality. C statistic value of HRCT score (c statistic value 0.867, P < 0.0001) and serum ferritin level (c statistic value 0.808, P = 0.002) were statistically significant in the classification of non-survivors. Patients with calcineurin inhibitor presented a better outcome than those without calcineurin inhibitor (log-rank test, P = 0.006). HRCT score and serum ferritin level are factors associated to the 1-year mortality of acute ILD in CADM patients. Calcineurin inhibitor might improve the outcome of CADM patients with acute ILD.

Biomarkers and Autoantibodies of Interstitial Lung Disease with Idiopathic Inflammatory Myopathies.

Various autoantibodies are seen in idiopathic inflammatory myopathies. Among myositis-specific antibodies, anti-aminoacyl-tRNA synthetase and anti-melanoma differentiation-associated protein 5 (MDA5) antibodies are associated with interstitial lung disease (ILD). Anti-MDA5 antibodies are associated with dermatomyositis (DM) or clinically amyopathic DM complicated with rapidly progressive ILD. In anti-MDA5-positive patients, a random ground-glass attenuation pattern is a characteristic finding of ILD in chest high-resolution computed tomography. Conversely, anti-aminoacyl-tRNA synthetase antibodies are not associated with rapidly progressive ILD but with chronic ILD. DM or clinically amyopathic DM patients with anti-MDA5, and characteristic high-resolution computed tomography findings are highly likely to have devastating ILD and need aggressive treatment.

Amyopathic dermatomyositis: definitions, diagnosis, and management.

Amyopathic dermatomyositis can be a challenging diagnosis because patients lack traditional muscle findings. "Clinically amyopathic" dermatomyositis (CADM) accounts for the presence of subclinical muscle disease in some of these patients. These patients represent a substantial minority of dermatomyositis cases and have similar co-morbidities to "classic" dermatomyositis patients, including interstitial lung disease and malignancy. Clinically amyopathic dermatomyositis patients should not be considered as a distinct clinical entity from "classic" dermatomyositis, as they share antibody sub-types and associated co-morbidities, likely representing clinical spectrum of a common disease. It is essential for the clinician to be familiar with the clinical presentation of clinically amyopathic dermatomyositis, in order to facilitate early, accurate diagnosis and appropriate clinical management.

THU0241 Ethnic but not gender differences in disease manifestations in dermatomyositis patients

BackgroundDermatomyositis (DM) is a subset of idiopathic inflammatory myopathies (IIM), which are heterogeneous rheumatic disorders characterized by inflammation of skeletal muscle and progressive weakness. New and improved treatment is needed...

Clinical manifestations of dermatomyositis and clinically amyopathic dermatomyositis patients with positive expression of anti–melanoma differentiation–associated gene 5 antibody

To investigate the clinical features of dermatomyositis (DM) and clinically amyopathic DM (CADM) patients with the presence of anti-melanoma differentiation-associated gene 5 (anti-MDA-5) antibodies. We screened the serum anti-MDA-5 antibody levels of 140 patients with various connective tissue diseases (CTDs), including 32 with DM and 32 with CADM, or idiopathic pulmonary fibrosis (IPF). The clinical courses of DM/CADM patients with a positive expression of anti-MDA-5 antibodies were delineated. Anti-MDA-5 antibodies were detected at a significantly higher frequency in CADM patients than in DM patients (12 of 32 versus 3 of 32; P = 0.016), but were not detected in patients with other CTDs or IPF and healthy controls. Patients with a positive expression of anti-MDA-5 antibodies developed significantly more skin ulcerations (12 of 15 versus 4 of 49; P < 0.001) and interstitial lung disease (ILD; 15 of 15 versus 31 of 49 [P = 0.003]) than those without anti-MDA-5 antibodies. High-resolution computed tomography scores of the MDA-5-positive subset were increased compared with the MDA-5-negative group (mean ± SD 117.7 ± 76.3 versus 54.4 ± 50.7; P = 0.004), and the scores correlated well with anti-MDA-5 antibody levels (r(2) = 0.582, P = 0.029). The respiratory symptoms as well as skin ulcerations were dramatically improved in patients with anti-MDA-5 antibody levels <500 units/ml after treatment, whereas patients with anti-MDA-5 antibody levels >500 units/ml were resistant to the treatment and died of respiratory failure in a short period of time. Anti-MDA-5 antibody levels closely correlate with the severity of skin ulcerations, ILD, and the prognosis of the disease. Dynamic observation of serum anti-MDA-5 antibody levels would be helpful in predicting the course of ILD and facilitating better therapeutic targeting.

Disappearance of anti-MDA-5 autoantibodies in clinically amyopathic DM/interstitial lung disease during disease remission

Autoantibodies against melanoma differentiation-associated gene 5 (MDA-5) are one of the serological markers for DM. Anti-MDA-5 antibodies are especially associated with rapidly progressive interstitial lung disease (ILD) in amyopathic DM (ADM). It is known that the antibody status of anti-ENAs does not generally change significantly with disease course. For anti-MDA-5 antibodies, however, few longitudinal studies have investigated such changes. This study aimed to establish a quantitative assay for anti-MDA-5 antibodies towards assessing the long-term outcome of ADM patients who had anti-MDA-5 antibodies. We established ELISA for measuring anti-MDA-5 antibody levels using in vitro transcription and translation recombinant protein. The antibody levels were measured at different time points in 11 clinically ADM patients who tested positive for the anti-MDA-5 antibody on their first visit (range of follow-up 3 months to 16 years). At the stage of clinical remission, six patients received no medication and the four others received low-dose CS. ELISA showed that anti-MDA-5 antibodies disappeared in nine of the patients and fell to just above the cut-off in one patient; in the patient who died, the antibodies remained. Our results suggest that anti-MDA-5 antibodies may be useful as a marker for monitoring disease activity in ILD complicated with ADM. Serial monitoring at short intervals is required to evaluate whether anti-MDA-5 antibody levels correlate with ADM disease activity.

Myositis autoantibodies in Korean patients with inflammatory myositis: Anti-140-kDa polypeptide antibody is primarily associated with rapidly progressive interstitial lung disease independent of clinically amyopathic dermatomyositis

BackgroundTo investigate the association between myositis autoantibodies and clinical subsets of inflammatory myositis in Korean patients.MethodsImmunoprecipitation was performed using the sera of classic polymyositis (PM) (n = 11) and dermatomyositis (DM) (n = 38) patients who met the Bohan and Peter criteria for definite inflammatory myositis. A panel of defined myositis autoantibodies was surveyed to investigate the association between each autoantibody and clinical subsets of inflammatory myositis.ResultsEither MSAs, anti-p140, or anti-p155/140 antibodies were found in 63.3% (31/49) of the study subjects. Anti-140-kDa-polypeptide (anti-p140) (18.4%, 9/49) and anti-155/140-kDa polypeptide (anti-p155/140) (16.3%, 8/49) antibodies were the most common, followed by anti-Mi2 (14.3%, 7/49), anti-ARS (12.2%, 6/49) and anti-SRP (2.0%, 1/49) antibodies. All MSAs and anti-p140 and anti-p155/140 antibodies were mutually exclusive. Anti-p140 (23.7%, 9/38), anti-p155/140 (21.1%, 8/38), and anti-Mi2 (18.4%, 3/38) antibodies were found exclusively in DM patients. Anti-p140 antibody was associated with rapidly progressive interstitial lung disease (ILD) (p = 0.001), with a sensitivity of 100.0% (4/4) and a specificity of 85.3% (29/34) in DM patients. Anti-p155/140 antibody was associated with cancer-associated DM (p = 0.009), with a sensitivity of 55.6% (5/9) and a specificity of 89.7% (26/29). Cancer-associated survival was significantly worse when anti-p155/140 antibody was present (19.2 ± 7.6 vs. 65.0 ± 3.5 months, p = 0.032). Finally, anti-ARS antibodies were associated with stable or slowly progressive ILD in PM and DM patients (p = 0.005).ConclusionsAnti-p140 and anti-p155/140 antibodies were commonly found autoantibodies in Korean patients with inflammatory myositis. Despite the lack of clinically amyopathic DM patients in the study subjects, a strong association was observed between anti-p140 antibody and rapidly progressive ILD. Anti-p155/140 antibody was associated with cancer-associated myositis and poor survival.

Clinical features of amyopathic dermatomyositis

The clinical features of 8 cases with amyopathic dermatomyositis (ADM) wereretrospectively compared with those of 53 cases with typical dermatomyositis ( DM). Incidence of interstitiallung disease, joint pain, fever, concurrent cancer were 4/8, 3/8, 3/8 and 0 in ADM group and those were 40% , 34% , 32% and 11 % in DM group respectively. The prevalence of interstitial lung disease in ADMgroup was significantly higher than that in DM group, which indicates that ADM patient should be properlytreated. Key words: Dermatomyositis; Pneumonia, Interstitial

Use of magnetic resonance imaging and P-31 magnetic resonance spectroscopy to detect and quantify muscle dysfunction in the amyopathic and myopathic variants of dermatomyositis.

To investigate the use of magnetic resonance imaging (MRI) and P-31 magnetic resonance spectroscopy (MRS) in characterizing the metabolic and functional status of muscles in patients with amyopathic dermatomyositis (DM) and to compare the findings with those in patients with classic myopathic DM. Nine patients with amyopathic DM, 11 patients with myopathic DM, and 11 normal individuals were studied. MRI images of thigh muscles were obtained, and T1 and T2 relaxation times were calculated. Biochemical status was quantitated with P-31 MRS, by determining concentrations of phosphate metabolites during rest and exercise. Patients with amyopathic DM showed no muscle inflammation, and MRS data obtained during rest were normal. During exercise at 25% and 50% maximum voluntary contractile force, the MRS data revealed significant differences between amyopathic DM patients and control subjects indicating inefficient metabolism. In contrast, muscles of patients with myopathic DM showed inflammation and metabolic abnormalities even during rest. Metabolic deficiencies in patients with amyopathic DM were unmasked by exercise, suggesting that the 2 DM syndromes may share muscle abnormalities. MRI/MRS may be useful in diagnosis and optimization of treatment.