Clinically Amyopathic Dermatomyositis Patients Research Articles

Coexistence of anti-KS and anti-TIF1-γ antibodies in clinically amyopathic dermatomyositis presenting with rapid progression of interstitial lung disease.

Polymyositis/Dermatomyositis (PM/DM) is an idiopathic inflammatory myopathy (IIM) manifesting mainly as symmetrical proximal muscle weakness and/or typical cutaneous features due to autoimmune mechanisms. Clinically amyopathic dermatomyositis (CADM) is a subset of DM that exhibits only the typical cutaneous features without any clinical muscle symptoms. Several autoantibodies have been found specifically in patients with PM/DM, including CADM patients. Anti-KS antibody is one of a group of anti-aminoacyl transfer RNA (ARS) antibodies that are mainly associated with fever, Raynaud's phenomenon, polyarthritis, and interstitial lung disease (ILD), whereas anti-TIF1-γantibody is frequently found in DM patients with malignancy. Here, we report a CADM patient having both anti-KS antibody and anti-TIF1-γantibody. This patient developed an acute exacerbation of ILD and was successfully treated with high dose corticosteroid pulse therapy together with immunosuppressive agents. Although earlier experience had indicated that the seminal characteristic of anti-KS-positive ILD was slowly developing disease onset with little or no progression over the clinical course, the present patient suffered rapidly progressive disease.

Clinical characteristics and symptom progression of dermatomyositis subtypes: A retrospective analysis of a prospective database

BackgroundDisease characteristics of classic dermatomyositis (DM) and clinically amyopathic DM (CADM) are well-established, but there exists limited knowledge on disease progression of these subtypes. ObjectiveTo longitudinally track and characterize classic DM and CADM patients that experience changes in disease presentation. MethodsWe conducted a retrospective review of prospectively collected data on 269 DM patients of a longitudinal database. ResultsA total of 51% had classic DM and 49% had CADM. Forty percent of the classic DM patients became post-myopathic (PmDM). Median CDASI-A score was lower in PmDM patients than classic DM patients (13.0 vs 16.0), but 45% of the PmDM patients had CDASI-A scores >14. Five percent of the CADM patients developed muscle involvement. Compared to CADM patients, those that developed muscle symptoms had milder skin disease before subtype conversion (median CDASI-A 12.0 vs 16.0) and at subtype conversion (median CDASI-A 9.0 vs 16.0). LimitationsRetrospective study conducted at a single tertiary-care dermatology clinic. Conclusion40% of classic DM patients became PmDM. The majority continue with muscle disease, and many continue to have moderate/severe skin disease. CADM has a low risk of progressing to muscle disease, with extent of skin disease as a potential predictive factor.

Efficacy and safety of plasma exchange in interstitial lung diseases with anti-melanoma differentiation-associated 5 gene antibody positive clinically amyopathic dermatomyositis

Objective Clinically amyopathic dermatomyositis (CADM) patients frequently develop refractory interstitial lung disease (ILD), with a poor prognosis. We aimed to verify the efficacy and safety of plasma exchange (PE) treatment for ILD in CADM. Method A retrospective case–control study was conducted to compare clinical outcomes with and without PE treatment in CADM-ILD patients refractory to combination therapy of high-dose glucocorticoids, calcineurin inhibitors, and cyclophosphamide. Among 19 enrolled patients, 11 were further treated with PE. We compared survival rates and other clinical characteristics. PE consisted of either fresh-frozen plasma or albumin as a replacement solution. Results Basal clinical characteristics at diagnosis, including age, gender, serum ferritin, Krebs von den Lungen-6 (KL-6), C-reactive protein, and respiratory function tests, did not differ between the two groups. The survival rate for treatment with PE was higher than for treatment without PE (91% and 50%, respectively, p < 0.05). Among PE-treated patients, anti-melanoma differentiation-associated gene-5 (anti-MDA-5) antibody titre, ferritin, and KL-6 as serological activity markers were sustainably reduced only after initiating PE. Therapeutic intervention with PE reduced the frequency of exacerbation of ILD requiring methylprednisolone pulse therapy. The occurrence of bacterial, fungal, and cytomegalovirus infection did not differ between the groups with and without PE, and adverse events associated with PE resolved with appropriate intervention. Conclusion Combination therapy with PE was associated with an improved survival rate, and may be effective for the management of refractory ILD in CADM patients. A personalized therapeutic strategy including PE could be introduced for fatal rapidly progressive ILD.

Characterization of Patients With Dermatomyositis According to Anti-Melanoma Differentiation-Associated Gene-5 Autoantibodies in Centers from 3 Latin American Countries: A Cohort Study.

The anti-melanoma differentiation-associated protein 5 (MDA5) autoantibodies have been associated with a high frequency of interstitial lung disease (ILD) and rapidly progressive ILD (RP-ILD) in dermatomyositis (DM) patients, mainly in Asian subjects. However, there is scarce information about these parameters in Latin American patients. This was a medical records review cohort study that included classic DM (CDM) and clinically amyopathic DM (CADM) patients from 3 Latin American countries (Argentina, Brazil, and Mexico). A total of 270 DM patients were evaluated: 25.9% with CADM and 74.1% with CDM. The overall prevalence of ILD and RP-ILD, respectively, was 70 (25.9%) and 4 (1.5%) of the 270 patients, and the distributions were comparable between patients with CDM and CADM. The anti-MDA5 was present in 31 (25.4%) of 122 CDM patients and in 17 (48.6%) of 35 CADM patients; it was not associated with presence of ILD and RP-ILD. However, anti-MDA5-positive CDM patients had significantly high frequency of "mechanic's hands," arthralgia, arthritis, and lower serum levels of creatine phosphokinase, whereas anti-MDA5-positive CADM patients had significantly high frequency of arthritis. Pulmonary infection and ILD are main causes of death in DM patients. In the present study, the prevalence of ILD in DM patients is comparable to that described in the literature, in contrast to the very low frequency of RP-ILD. In addition, the anti-MDA5 is not associated with ILD and RP-ILD, but anti-MDA5-positive DM patients present conditions that mimic antisynthetase syndrome. Pulmonary infection and ILD were the main causes of death in our sample.

Comparison of clinical and immunological features between clinically amyopathic dermatomyositis and typical dermatomyositis

OBJECTIVE To study the differences between clinically amyopathic dermatomyositis (CADM) and typical dermatomyositis (DM) on clinical and immunological features. METHODS By collecting clinical data of 106 CADM patients and 158 DM patients from January 2010 to June 2019 in the department of Rheumatology and Immunology, Peking University People's Hospital, the clinical characteristics and immunological features in the two groups were compared, and the distribution characters and the clinical meanings of myositis autoantibodies were discussed in the two groups respectively. Myositis autoantibodies were measured by immunoblotting according to the manufacturers' instructions. RESULTS In the aspects of clinical manifestations, CADM presented more with onset of interstial lung diseases (ILD) compared with DM (20.7% vs. 7.6%, P=0.002), and CADM-ILD was more likely to be acute ILD (58.3% vs. 26%, P < 0.001), and there were no differences between CADM and DM in cutaneous manifestations, accompanied with connective tissue disease (CTD) and malignancy. In CADM, the positive rate of rheumatoid factors and antinuclear antibodies was lower in DM. The most common myositis specific autoantibodies (MSAs) in CADM were anti-MDA5 (36%), anti-PL-7 (11.2%) and anti-TIF-1γ (10.1%). The most common MSAs in DM were anti-Jo-1 (19.2%), anti-TIF-1γ (11.5%) and anti-MDA5 (11.5%). Anti-MDA5 was correlated with acute ILD and skin ulceration both in CADM and DM; in CADM, skin ulceration was not associated with the titer of anti-MDA5; while in DM, skin ulceration was associated with high titer of anti-MDA5. In DM, anti-TIF-1γ was correlated with heliotrope eruption, V/shawl neck sign, perionychia erythma and malignancy, and higher rate of malignancy was seen in all titers of the anti-TIF-1γ positive patients. In CADM, anti-TIF1-γ showed no correlation with clinical manifestations. The most common myositis associated autoantibody was anti-Ro-52 both in CADM and DM. In CADM, anti-Ro-52 was associated with Raynaud's phenomenon and chronic ILD, while in DM, anti-Ro-52 was associated with mechanic's hands, noninfectious fever and accompanied CTD. CONCLUSION Compared with DM, ILD is more likely to be acute in CADM. It is different between CADM and DM about the distribution of myositis autoantibodies and the clinical significance of the same myositis antibody, and the clinical significance of some myositis antibodies is related to titers.

Risk factors of interstitial lung diseases in clinically amyopathic dermatomyositis.

BackgroundClinically amyopathic dermatomyositis (CADM) is a unique sub-type of idiopathic inflammatory myopathies with a high prevalence of interstitial lung disease (ILD). Poor prognosis of the patients was strongly associated with rapid progressive ILD. The aim of this study was to identify risk factors for prediction of different types of ILD in CADM.MethodsIn this study, data of 108 inpatients with CADM were collected, including 87 with ILD. The baseline clinical data and laboratory parameters, including myositis-specific and associated antibodies and tumor-associated antigens were analyzed to identify risk factors for acute or subacute interstitial pneumonitis (A/SIP) and chronic interstitial pneumonitis (CIP).ResultsIn 87 patients with CADM-ILD, 39 (36.1%) were A/SIP, and 48 (44.4%) were CIP. There were 22 (20.4%) patients with asymptomatic ILD who were detected by routine high resolution computed tomography. Cytokeratin-19 fragment (CYFRA21-1) was significantly higher in CADM-ILD than that in CADM patients without ILD; carcinoembryonic antigen and neuron-specific enolase were significantly elevated in A/SIP than that in CIP. Patients with A/SIP had a higher positive rate of anti-melanoma differentiation-associated gene 5 (MDA5), while patients with CIP had a higher positive rate of anti PL-12 and anti-Ro-52. Logistic regression analysis indicated that elevation of CYFRA21-1 was a risk factor for ILD, higher titer of anti-MDA5 indicated increased likelihood for A/SIP, and higher titer of anti-Ro-52 was also clearly associated with CIP.ConclusionsThis study indicated that the prevalence of ILD was high in CADM. Asymptomatic ILD has been previously underestimated. Anti-MDA5 was a risk factor for the presence of A/SIP, and CYFRA21-1 was a risk factor for ILD.

Noninvasive positive pressure ventilator deteriorates the outcome of pneumomediastinum in anti-MDA5 antibody-positive clinically amyopathic dermatomyositis

Anti-melanoma differentiation-associated gene 5 (MDA5) antibody (Ab)-positive clinically amyopathic dermatomyositis (CADM) with pneumomediastinum (PNM) is a life-threatening condition. We aim to determine the prognostic factors affecting survival of patients with anti-MDA5 Ab-positive CADM complicated with PNM. We retrospectively established a cohort of patients with anti-MDA5 Ab-positive CADM complicated with PNM from April 2013 to July 2019. Demographic data and clinical characteristics from medical records were analyzed and variables were compared between survivors and nonsurvivors. We performed univariate and multivariate survival analyses by Cox regression. Survival curves were depicted by the Kaplan-Meier method. Among 133 patients with anti-MDA5 Ab-positive CADM, 20 were diagnosed with PNM. The cumulative estimated Kaplan-Meier survival rate was 85% at 1week, 55% at 1month, and 40% at 1year. Univariate analysis indicated several factors associated with survival. Worse liver function (AST, p = 0.043; LDH, p = 0.002; TBIL, p = 0.038), higher CRP level (p = 0.044), higher HRCT score (p = 0.022), and using noninvasive positive pressure ventilation (NPPV) (p < 0.01) were associated with poor prognosis. In a multivariate Cox regression model, AST level and using NPPV were indicated to be independent predictors of poor prognosis. In this research, we found that the incidence rate of PNM in anti-MDA5 Ab-positive CADM was 15.5%, obviously higher than in classical DM. The application of noninvasive positive pressure ventilator (NPPV) and higher AST level were independent risk factors for survival.Key Points• Anti-MDA5 Ab-positive CADM complicated with PNM is a life-threatening condition with an incidence rate of 15.5%.• The application of NPPV and worse liver function were independent risk factors for survival of anti-MDA5 Ab-positive CADM patients complicated with PNM.

Anti-Melanoma Differentiation-Associated Gene 5 Is Associated With Rapidly Progressive Lung Disease and Poor Survival in US Patients With Amyopathic and Myopathic Dermatomyositis.

Clinically amyopathic dermatomyositis (CADM) is a subset of dermatomyositis (DM) presenting with the characteristic rash of DM without objective muscle weakness. Asian studies report that anti-melanoma differentiation-associated gene 5 (anti-MDA-5) autoantibody in CADM is associated with interstitial lung disease (ILD), particularly rapidly progressive ILD (RPILD). These associations have not been established in US myositis patients. The goal of our study was to determine the association of anti-MDA-5 autoantibody with ILD, RPILD, and survival in US patients with CADM and classic DM. CADM patients were identified in the University of Pittsburgh Myositis Center Database and matched 1:1 (sex and age) to classic DM controls. Anti-MDA-5 was measured by serum enzyme-linked immunosorbent assay. Kaplan-Meier, log rank, and chi-square tests were used for analysis. We identified 61 CADM patients (62% women, mean age 48.2 years) and 61 classic DM controls (64% women, mean age 44.8 years). The frequencies of anti-MDA-5 positivity, ILD, and RPILD were similar in the 2 cohorts (MDA-5 positive: CADM 13.1% [8 of 61] and DM 13.1% [8 of 61], ILD positive: CADM 31.1% [19 of 61] and DM 26.2% [16 of 61], and RPILD positive: CADM 8.2% [5 of 61] and DM 5% [3 of 61]; P = 1, 0.55, and 0.46, respectively). Anti-MDA-5 positivity was significantly associated with ILD, since 50% of MDA-5-positive subjects (8 of 16) had ILD versus 25.5% of MDA-5-negative subjects (27 of 106; P = 0.04). Anti-MDA-5 was strongly associated with RPILD (P < 0.001). Anti-MDA-5-positive patients with ILD had worse baseline pulmonary function testing variables compared to anti-MDA-5-negative patients. Anti-MDA-5 positivity was significantly associated with poor survival (P = 0.007). Anti-MDA-5 antibody is significantly associated with ILD, RPILD, worse pulmonary outcome, and survival in US classic DM and CADM patients.

Predictive factors of rapidly progressive-interstitial lung disease in patients with clinically amyopathic dermatomyositis.

Clinically amyopathic dermatomyositis (CADM) is a unique subset of dermatomyositis, showing a high incidence of lung involvements. The aim of this study is to identify risk factors, other than melanoma differentiation-associated protein (MDA)-5, for developing rapidly progressive-interstitial lung disease (RP-ILD) in patients with CADM. Forty CADM patients, in whom 11 patients developed RP-ILD, were enrolled. Clinical features and laboratory findings were compared between the patients with and without RP-ILD. We found that skin ulceration, CRP, serum ferritin, anti-MDA5 Ab, and lymphocytopenia were significantly associated with ILD. Multivariate logistic regression analysis indicated that anti-MDA5 Ab(+), elevated CRP, and decreased counts of lymphocyte were independent risk factors for RP-ILD, which can provide a precise predict for RP-ILD in CADM patients. When anti-MDA5 Ab(+) was removed from the multivariate regression model, using skin ulcerations, elevated serum ferritin and decreased counts of lymphocyte can also precisely predict RP-ILD. Except for MDA-5, more commonly available clinical characteristics, such as skin ulcerations, serum ferritin, and count of lymphocyte may also help to predict prognosis in CADM.

Serum IL8 and mRNA level of CD11b in circulating neutrophils are increased in clinically amyopathic dermatomyositis with active interstitial lung disease.

The objective of this study is to assess serum IL8 and the potential activity of circulating neutrophils on relative messenger RNA (mRNA) levels and their relationship with disease activity in clinically amyopathic dermatomyositis (CADM) associated with interstitial lung disease (ILD). We studied 18 CADM patients and compared them with 18 classic dermatomyositis (DM) patients and 18 healthy control subjects. Serum IL8 level and mRNA expressions of neutrophils (chemokine (C-X-C motif) receptor 1 (CXCR1), cluster of differentiation molecule 11b (CD11b), cluster of differentiation 64 (CD64), myeloid cell leukemia 1 (MCL1), interleukin-18 (IL18)) were detected. The overproduction of serum IL8 level was most significant in the CADM group with active period. The mRNA expressions of CD11b, IL18, and MCL1 were greatly increased in the neutrophils in patients with CADM compared with DM or healthy controls. Up-expressions of CD11b, IL18, and MCL1 were detected in the neutrophils in CADM patients of active period compared with remission period. A positive correlation was found between CD11b mRNA level and high-resolution computed tomography (HRCT) score, in CADM associated with ILD. Serum IL8 level and mRNA levels of CD11b, MCL1, and IL18 in circulating neutrophils are related with the disease activity of CADM-ILD. The mRNA level of CD11b is positively correlated with HRCT score in CADM-ILD.

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.

AB0615 Elevated Erythrocyte Sedimentation Rate is Associated with Pulmonary Impairment and Poor Outcome in Patients with Dermatomyositis

BackgroundInterstitial lung disease (ILD) is a common cause of death in patients with dermatomyositis (DM). Especially, patients with clinically amyopathic DM (CADM) have a worse outcome due to ILD which...

Serum interleukin 6 levels as a useful prognostic predictor of clinically amyopathic dermatomyositis with rapidly progressive interstitial lung disease

Objectives. Rapidly progressive interstitial lung disease (RP-ILD) is life-threatening in patients with clinically amyopathic dermatomyositis (CADM). Useful prognostic markers are necessary for treatment selection. This study aimed to investigate differences in clinical and laboratory characteristics between surviving and non-surviving patients.Methods. Twelve CADM patients with RP-ILD were enrolled. Six patients lived (Group A) and six patients died (Group B) after immunosuppressive treatment for RP-ILD. Clinical manifestations and laboratory data before treatment were compared between the two groups.Results. Among the clinical manifestations and laboratory data examined, serum interleukin 6 (IL-6) levels in Group B were significantly higher than those in Group A (mean ± SD 28.5 ± 21.0 vs. 7.2 ± 1.6 pg/mL; p = 0.009). Simple regression analysis showed that serum IL-6 was the only significant prognostic factor (p = 0.032). Kaplan–Meier estimates showed that the cumulative survival rate was significantly lower in patients with serum IL-6 levels of ≥ 9 pg/mL than in patients with those of < 9 pg/mL (p = 0.04).Conclusions. Serum IL-6 levels may predict the prognosis of CADM patients with RP-ILD. The intensity of immunosuppressive treatment can be decided according to serum IL-6 levels at an early phase of the disease.

AB0845 The diagnostic and prognostic significance of anti-MDA5 antibody in dermatomyositis complicated interstitial lung disease in chinese

BackgroundInterstitial lung disease (ILD) is a common complication of polymyositis/dermatomyositis (PM/DM). It is often lethal if it occurs as a rapidly progressive pattern especially in patients present as clinically amyopathic...

Down-regulation of miR-223 contributes to the formation of Gottron's papules in dermatomyositis via the induction of PKCε

Dermatomyositis (DM) is characterized by skin manifestations accompanying and preceding muscle weakness. Gottron's papules, one of the skin manifestations, are of great diagnostic value because they are specific to DM. However, the pathogenesis of Gottron's papules remains unclear. We investigated the expression pattern of miRNAs in Gottron's papules of DM patients and evaluated the possibility that miRNAs play a role in its pathogenesis. miRNAs were extracted from skin tissues and sera of patients with DM, clinically amyopathic DM (CADM) and healthy controls. To identify pathogenic miRNAs, we performed miRNA PCR array analysis. The results were confirmed by in situ hybridization, immunohistochemistry, immunoblotting and transient transfection of siRNAs or miRNA inhibitors. PCR array analysis using tissue miRNAs demonstrated the miR-223 level was markedly decreased in Gottron's papules of DM and CADM in vivo, but not in psoriasis skin. The protein expression of PKCɛ, a predicted target of miR-223, was increased in DM/CADM skin. The transfection of a specific inhibitor of miR-223 in keratinocytes led to up-regulation of the PKCɛ protein, and resulted in increased cell proliferation. On the other hand, cell numbers were significantly decreased when cells were transfected with siRNA for PKCɛ. The serum miR-223 concentration was decreased in DM/PM patients, particularly in CADM patients, compared with healthy controls. A decreased miR-223 expression and the subsequently increased PKCɛ levels may therefore play a key role in the pathogenesis of Gottron's papules.

Angiogenin expression in the sera and skin of patients with rheumatic diseases

Vascular abnormalities are one of the common features in rheumatic diseases, but their pathogenesis is still not known. Angiogenin, a molecule implicated in the angiogenic process, may play some roles in such vascular changes. Serum angiogenin concentrations were measured in 21 scleroderma patients, 10 patients with systemic lupus erythematosus (SLE), 21 patients with dermatomyositis (DM), 5 patients with polymyositis (PM), 11 patients with clinically amyopathic DM (CADM) and 12 normal subjects, with specific enzyme-linked immunosorbent assays. Angiogenin mRNA in vivo was determined in skin tissues of 5 DM patients, 4 CADM patients, 5 SLE patients and 7 normal subjects using quantitative real-time polymerase chain reactions. We could not find any significant differences in the serum angiogenin levels among normal subjects and patients with rheumatic diseases. However, when we evaluated the correlation of serum angiogenin levels with clinical features of 32 DM/CADM patients, the patients with increased angiogenin levels had significantly higher aldolase levels than those with decreased levels. On the other hand, angiogenin mRNA is significantly up-regulated in the involved skin of DM and CADM, suggesting that angiogenin expression is up-regulated locally in the skin but not in sera of patients with DM and CADM. In conclusion, dysregulated angiogenin expression may contribute to the pathogenesis of myositis as well as skin involvement via the vascular change in DM/CADM. Further studies with an increased number of patients may help to clarify the relationship between angiogenin and vascular abnormalities in rheumatic diseases and to develop new therapeutic strategies.

Interstitial lung disease in clinically amyopathic dermatomyositis (CADM) patients: a retrospective study of 41 Chinese Han patients

To study the clinical features and associated risk factors of interstitial lung disease (ILD) in clinically amyopathic dermatomyositis (CADM) in Chinese patients. Forty-one Chinese Han patients with a diagnosis of CADM in West China Hospital from August 2008 to 2011 were retrospectively analyzed. The prevalence of ILD in CADM patients is 60.98 %, in which 26.83 % for acute/subacute interstitial pneumonia (A/SIP) and 34.15 % for chronic interstitial pneumonia (CIP). Mortality of A/SIP is 63.64 %, with a 6-month survival rate of 54.50 %. Levels of erythrocyte sedimentation rate, serum ferritin, alanine aminotransferase, aspartate aminotransferase, creatine kinase, lactate dehydrogenase, hydroxybutyric dehydrogenase, and immunoglobulin A (IgA) are higher in CADM-ILD patients than CADM patients without ILD. Levels of serum ALB and lymphocyte count in peripheral blood are significant lower in A/SIP than in CIP group. Sign of ground glass opacities in high-resolution computed tomography (HRCT) images is more common in A/SIP group, and diffusion function is worse in these patients compared with CIP group. The prevalence of ILD in Chinese CADM patients is strikingly high, and A/SIP is a major cause of death in CADM patients. Laboratory findings combined with HRCT examination and pulmonary function tests can provide valuable predictive information of ILD or A/SIP in CADM patients.

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.

Epidemiologic study of clinically amyopathic dermatomyositis and anti-melanoma differentiation-associated gene 5 antibodies in central Japan

IntroductionSeveral reports have found the onset or activity of inflammatory myopathies to show spatial clustering and seasonal association. We recently detected autoantibodies against melanoma differentiation-associated gene 5 (MDA-5) in more than 20% of patients with dermatomyositis. Anti-MDA-5 antibodies were associated with the presence of rapidly progressive interstitial lung disease in clinically amyopathic dermatomyositis (CADM). The present study aims to assess the growing prevalence of CADM and the geographical incidence of anti-MDA-5-positive patients.MethodsWe reviewed medical charts and examined the presence of anti-MDA-5 antibodies in 95 patients, including 36 CADM patients. Sera were obtained from 1994 through 2011. Statistical analyses were performed to assess whether CADM development and the presence of anti-MDA-5 antibodies were associated with various parameters, including age at disease onset, season of onset, annual positivity, and population of resident city.ResultsTertiles based on the year when the sera were collected showed increasing tendencies of CADM and anti-MDA-5-positive patients among all of the dermatomyositis patients. From 1994 to 2010, the relative prevalence of CADM and anti-MDA-5 antibody-positive patients significantly increased. Interestingly, the presence of anti-MDA-5 antibodies in 26 patients was inversely associated with the population of their city of residence.ConclusionsThis is the first study to examine the distribution of anti-MDA-5-positive dermatomyositis phenotypes in Japan. Regional differences in the incidences of these phenotypes would suggest that environmental factors contribute to the production of antibodies against MDA-5, which triggers innate antiviral responses.

Clinical analysis of 29 patients with clinically amyopathic dermatomyositis

To explore the clinical features and prognosis of clinically amyopathic dermatomyositis (C-ADM). The clinical data, including skin lesion, muscle involvement, and lung disease, of 29 patients with C-ADM, 6 males and 23 females with a male/female ratio of 1:3.83, aged 44 +/- 8, were analyzed. Skin biopsy was taken in 5 patients and lung HRCT was done in all the patients. The mean age at onset was (44 +/- 8) years. All patients presented with characteristic skin lesions such as Gottron's papulae (91.3%); heliotropic periorbital erythremia (75.9%); V-sign rash (37.9%); shawl-sign rash (24.1%); and periungual erythema and telangiectasias (20.7%). Gottron's papule was most commonly seen on the dorsal aspect of elbow (86.2%), proximal interphalangeal joints (58.6%), metacarpophalangeal joints (48.3%), patellae (23.8%), hip (20.7%), shoulder (13.8%), and ankle (9.5%). The cutaneous histopathologic pictures of these patients were all compatible with the skin lesions of dermatomyositis. Interstitial lung disease (ILD) was found by lung HRCT in 19 patients (65.5%). All patients received steroids combined with immunosuppressants, but rapidly progressive ILD happened to some of the patients and finally led to death due to respiratory failure in 5 of them. C-ADM is most commonly seen in the middle-aged women. ILD is the commonest respiratory problem arising in C-ADM patients and can be fatal, therefore should be properly treated.