Clinically Amyopathic Dermatomyositis Research Articles

Mycophenolate mofetil after tacrolimus for refractory clinically amyopathic dermatomyositis: a case report

Dermatomyositis (DM) positive for anti-melanoma differentiation-associated gene 5 (MDA5) antibodies, mainly when linked with rapidly progressive interstitial lung disease (RP-ILD), is considered a refractory disease. Our report describes a critical case of clinically amyopathic dermatomyositis (CADM) with RP-ILD that tested positive for both anti-MDA5 and anti-Ro-52 antibodies. The patient showed a limited response to a combined therapy regimen of prednisone, iguratimod, and tacrolimus. However, after adjunct therapy with mycophenolate mofetil (MMF), the patient’s condition was controlled, his serum KL-6 levels decreased, and anti-MDA5 antibodies became negative. During the 68-week follow-up, the patient’s condition remained stable, with a satisfactory quality of life. This report also discusses the potential role of inflammatory cytokines in the pathophysiology of CADM and RP-ILD. Further research is required to confirm these results and investigate the application of MMF in maintenance therapy for CADM-associated RP-ILD.

Management of anti-melanoma differentiation-associated gene 5 antibody-induced refractory dermatomyositis complicated by interstitial pneumonia using tofacitinib and its outcomes: a case report

BackgroundClinical amyopathic dermatomyositis is characterized by cutaneous symptoms but lacks muscle symptoms. Anti-melanoma differentiation-associated gene 5 antibodies are frequently found in Japanese patients with clinical amyopathic dermatomyositis. Patients with rapidly progressive interstitial lung disease with positive anti-melanoma differentiation-associated gene 5 antibodies have poor prognoses, and majority of them are treated with combination immunosuppressive therapy; however, the best treatment is yet to be determined.Case presentationA 52-year-old Asian male patient presented with a chief complaint of dyspnea on exertion. He had a typical skin rash and rapidly progressive interstitial pneumonia. Additionally, anti-melanoma differentiation-associated gene 5 antibodies were detected; therefore, he was diagnosed with dermatomyositis-associated interstitial pneumonia. Respiratory failure worsened despite administering steroid pulse therapy, tacrolimus, and cyclophosphamide. Consequently, plasma exchange was performed on day 13 of admission. After a slight improvement, the patient’s respiratory failure worsened. Thus, cyclophosphamide was replaced by tofacitinib on day 28. Although respiratory failure improved and the progression of interstitial pneumonia seemed under control, βD-glucan level increased and Aspergillus antigen was detected on day 49. Micafungin and voriconazole were administered, but the patient succumbed to worsening respiratory failure on day 61. The pathological autopsy revealed multiple nodular lesions with cavity formation in both lungs and the presence of Aspergillus with severe neutrophilic infiltration and necrosis, which supported the diagnosis of invasive pulmonary aspergillosis.ConclusionThe patient with anti-melanoma differentiation-associated gene 5 antibody-related rapidly progressive interstitial lung disease, whose disease was difficult to control after the administration of triple immunosuppressive therapy (steroids, tacrolimus, and cyclophosphamide), showed good response with tofacitinib. Unfortunately, the patient died of invasive pulmonary aspergillosis owing to severe immunosuppression; thus, the signs of complications should be promptly detected.

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.

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.

Amyopathic Dermatomyositis Presenting with Digital Ulcerations: Case Report and Literature Review.

Clinically amyopathic dermatomyositis (CADM) is a rare subtype of dermatomyositis that presents with cutaneous features and no muscle involvement. This case report describes a 26-year-old woman with recurrent and multiple digital ulcerations coinciding with the start of winter each year. There was no evidence of myopathy, and antibody testing yielded negative results. A diagnosis of CADM was ultimately made based on clinicopathologic correlation. The patient's ulcers demonstrated excellent response to a combination therapy of hydroxychloroquine and potent topical and systemic steroids. Herein, the authors discuss the pathologic and immunologic characteristics of CADM.

Prognostic analysis of MDA5-associated clinically amyopathic dermatomyositis with interstitial lung disease.

To investigate the prognostic factors of patients with anti-melanoma differentiation-associated gene 5 (MDA5) positive clinically amyopathic dermatomyositis (CADM) and interstitial lung disease (ILD). A retrospective analysis was conducted on clinical data of 125 patients with anti-MDA5 + CADM-ILD collected from 10 branches in eastern China between December 2014 and December 2022. Prognostic factors were analyzed using χ2 test, Log-rank test, COX and logistic regression analysis. In this cohort, 125 anti-MDA5 + CADM-ILD patients exhibited a rapidly progressive interstitial lung disease (RPILD) incidence of 37.6%, and an overall mortality rate of 24.8%. One patient was lost to follow-up. After diagnosis of RPILD, a mortality rate of 53.2% occurred in patients died within 3 months, and that of 5.6% appeared in those who survived for more than 3 months. Multiple factor analysis revealed that C-reactive protein (CRP) ≥ 10 mg/L (p = 0.01) and recombinant human tripartite motif containing 21 (Ro52) (+) (p = 0.003) were associated with a higher risk of RPILD in anti-MDA5 + CADM-ILD patients; CRP ≥ 10 mg/L (p = 0.018) and the presence of RPILD (p = 0.003) were identified as the factors influencing survival time in these patients, while arthritis was the protective factor (p = 0.016). Patients with anti-MDA5 + CADM-ILD will have a higher mortality rate, and the initial 3 months after diagnosis of RPILD is considered the risk window for the dismal prognosis. Patients with CRP ≥ 10 mg/L, Ro52 (+) and RPILD may be related to a shorter survival time, while patients complicated with arthritis may present with relatively mild conditions.

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.

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.

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.

Pathogenic mechanisms of disease in idiopathic inflammatory myopathies: autoantibodies as clues.

Idiopathic inflammatory myopathies (IIMs) encompass a spectrum of autoimmune diseases characterized by muscle inflammation and systemic involvement. This review aimed to synthesize current evidence on the clinical significance and pathogenic mechanisms underlying autoantibodies associated with IIMs. Autoantibodies targeting aminoacyl-tRNA synthetases (ARS) play a pivotal role in antisynthetase syndrome (ASS), highlighting associations with interstitial lung disease (ILD) and distinctive clinical features. Anti-Mi-2 antibodies in dermatomyositis (DM) are hallmarked by characteristic cutaneous manifestations and favorable prognostic outcomes. Conversely, anti-TIF1 antibodies are correlated with DM and a higher risk of malignancies, implicating CD8+ T cells in its pathogenesis. Anti-MDA5 antibodies signify clinically amyopathic DM (CADM) with severe ILD, linked to dysregulated neutrophil extracellular trap (NET) formation. In immune-mediated necrotizing myopathies (IMNMs), anti-SRP and anti-HMGCR antibodies induce complement-mediated myopathy, typically following statin exposure. Additionally, anti-TRIM72 antibodies emerge as potential diagnostic markers in IIMs. Anti-cN1A autoantibodies are linked to inclusion body myositis (IBM) and play a decisive role in muscle protein degradation. Meanwhile, anti-FHL1 autoantibodies are associated with severe disease manifestations and muscle damage, as established in experimental models. Anti-eIF3 autoantibodies, recently identified in polymyositis (PM) patients, are rarely detected (<1%) and associated with a favorable prognosis. Elucidating these autoantibodies is anticipated to not only assist in early diagnosis and disease stratification but also inform targeted therapeutic interventions, emphasizing the intricate interplay between autoimmunity, cellular dysfunction, and clinical outcomes in IIMs.

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.