Evolution of diagnostic criteria for clinically amyopathic dermatomyositis / 中华皮肤科杂志

At present, the Bohan and Peter criteria are the most widely used criteria for the diagnosis of dermatomyositis, which require patients to meet at least 2 criterion items for myositis in addition to typical skin lesions before the diagnosis of dermatomyositis. Clinically amyopathic dermatomyositis (CADM) has been excluded due to the absence of myositis manifestations, resulting in a lack of early studies on this type of dermatomyositis, and little attention has been paid to it by clinicians. In addition, the diagnosis of CADM depends on the understanding of skin lesions and their histopathological manifestations. Because of atypical early skin lesions, CADM is often misdiagnosed as rosacea, seborrheic dermatitis, lupus erythematosus and other diseases, which affects the early diagnosis, treatment and prognosis of patients. This article summarizes the evolution of diagnostic criteria for CADM, in order to promote its early recognition and diagnosis, and also to provide a basis for future clinical research.

Application of imaging techniques in diagnosis and severity assessment of dermatomyositis / 中华皮肤科杂志

Dermatomyositis is an autoimmune disease involving the skin and muscles. At the onset of dermatomyositis, it is difficult to make an early diagnosis due to atypical clinical manifestations and lack of serological markers. Skin and muscle lesions are associated with disease activity and prognosis in patients with dermatomyositis or clinical amyopathic dermatomyositis. Computed tomography, magnetic resonance imaging, ultrasonography, dermoscopy and other imaging techniques may be used to assess skin and muscle involvements, which can not only improve the accuracy of early diagnosis of dermatomyositis, but also provide important reference for the assessment of disease activity and prognosis.

Differentially expressed genes in peripheral blood of patients with dermatomyositis complicated by interstitial lung disease or malignant tumors / 中华皮肤科杂志

Objective To investigate differentially expressed genes and related signaling pathways in patients with dermatomyositis/clinical amyopathic dermatomyositis (DM/CADM)complicated by interstitial lung disease or malignant tumors.Methods From January 2017 to January 2018,27 DM/CADM patients were enrolled from Department of Dermatology,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine,and divided into 3 groups according to the complications:10 with interstitial lung disease,8 with malignant tumors,and 9 without interstitial lung disease or malignant tumors.Meanwhile,7 healthy controls were enrolled into this study.High-throughput RNA sequencing was performed to screen differentially expressed genes in peripheral blood in the above 4 groups.Then,these genes were subjected to gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis.Results Compared with the healthy controls,4 820 up-regulated genes and 137 down-regulated genes were identified in DM/CADM patients;GO analysis revealed 49 significantly enriched items in the DM/CADM patients,37 (75.5％) of which were associated with biological processes;KEGG analysis showed that differentially expressed genes were mainly enriched in infection-,tumor-and immune-related pathways in DM/CADM patients.Compared with the patients without interstitial lung disease or malignant tumors,272 up-regulated genes and 158 down-regulated genes were identified in the patients with interstitial lung disease;GO analysis revealed 157 significantly enriched items,114 (72.6％)of which were associated with biological processes;KEGG analysis showed that differentially expressed genes were mainly enriched in bacterial infection-and autoimmune/inflammatory-related pathways in the patients with interstitial lung disease.Compared with the patients without interstitial lung disease or malignant tumors,398 up-regulated genes and 68 down-regulated genes were identified in the patients with malignant tumors;GO analysis revealed 117 significantly enriched items,94 (80.3％) of which were associated with biological processes;KEGG analysis showed that differentially expressed genes were mainly enriched in glycosylation-,metabolism-and tumor-related signaling pathways in the patients with malignant tumors.Conclusions Differences existed in transcriptomes and pathways between the DM/CADM patients and healthy controls,as well as between the patients with interstitial lung disease or malignant tumors and patients without these complications.Bacterial infection-and cytokine/chemokine-related pathways were significantly enriched in the patients with DM/CADM complicated by interstitial lung disease,while those pathways related to glycosylation,protein metabolism,angtigen presentation and cytotoxic effects of natural killer cells were significantly enriched in the patients with DM/CADM complicated by malignant tumors.

Classification of idiopathic inflammatory myopathies based on clinical manifestations and myositis-specific antibodies / 南方医科大学学报

OBJECTIVE@#To investigate the classification of idiopathic inflammatory myopathies (IIM) based on clinical manifestations and myositis- specific antibodies using cluster analysis.@*METHODS@#We retrospectively analyzed the data of patients with IIM admitted in Nanfang Hospital in 2015-2019. The clinical data of the patients including serum creatine kinase (CK), interstitial lung disease (ILD), cancer, and myositis-specific antibodies were collected for two-step cluster analysis to identify the distinct clusters of patients, whose clinical characteristics were subsequently analysed.@*RESULTS@#A total of 71 patients with IIM were included in this study, including 30 (42.3%) with polymyositis (PM), 20 (28.2%) with classic dermatomyositis (DM), 16 (22.5%) with amyopathic dermatomyositis (CADM), and 5 (7.0%) with immune-mediated necrotizing myopathy (IMNM). Two-step cluster analysis identified 3 distinctive subgroups: Cluster 1 of 15 (51.7%) patients characterized by rash, positive anti-MDA5 antibody and hypoproteinemia ( < 0.05) with normal or slightly elevated CK level, mainly corresponding to CADM; Cluster 2 of 4 (57.1%) patients with significantly elevated CK and positive anti-SRP antibody ( < 0.001) corresponding to IMNM; and Cluster 3 of 17 (48.6%) patients consisting primarily of patients with PM, characterized by positivity for anti- aminoacyl transfer RNA synthetases antibodies (=0.022) corresponding to antisynthetase syndrome (ASS).@*CONCLUSIONS@#Patients with IIM can be divided into 3 subgroups based on their clinical and serological characteristics (especially myositis-specific antibodies), and among them ASS may represent an independent IIM subgroup with unique clinical characteristics.

Differentially expressed genes in peripheral blood of patients with dermatomyositis complicated by interstitial lung disease or malignant tumors / 中华皮肤科杂志

Objective@#To investigate differentially expressed genes and related signaling pathways in patients with dermatomyositis/clinical amyopathic dermatomyositis (DM/CADM) complicated by interstitial lung disease or malignant tumors.@*Methods@#From January 2017 to January 2018, 27 DM/CADM patients were enrolled from Department of Dermatology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, and divided into 3 groups according to the complications: 10 with interstitial lung disease, 8 with malignant tumors, and 9 without interstitial lung disease or malignant tumors. Meanwhile, 7 healthy controls were enrolled into this study. High-throughput RNA sequencing was performed to screen differentially expressed genes in peripheral blood in the above 4 groups. Then, these genes were subjected to gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis.@*Results@#Compared with the healthy controls, 4 820 up-regulated genes and 137 down-regulated genes were identified in DM/CADM patients; GO analysis revealed 49 significantly enriched items in the DM/CADM patients, 37 (75.5%) of which were associated with biological processes; KEGG analysis showed that differentially expressed genes were mainly enriched in infection-, tumor- and immune-related pathways in DM/CADM patients. Compared with the patients without interstitial lung disease or malignant tumors, 272 up-regulated genes and 158 down-regulated genes were identified in the patients with interstitial lung disease; GO analysis revealed 157 significantly enriched items, 114 (72.6%) of which were associated with biological processes; KEGG analysis showed that differentially expressed genes were mainly enriched in bacterial infection- and autoimmune/inflammatory-related pathways in the patients with interstitial lung disease. Compared with the patients without interstitial lung disease or malignant tumors, 398 up-regulated genes and 68 down-regulated genes were identified in the patients with malignant tumors; GO analysis revealed 117 significantly enriched items, 94 (80.3%) of which were associated with biological processes; KEGG analysis showed that differentially expressed genes were mainly enriched in glycosylation-, metabolism- and tumor-related signaling pathways in the patients with malignant tumors.@*Conclusions@#Differences existed in transcriptomes and pathways between the DM/CADM patients and healthy controls, as well as between the patients with interstitial lung disease or malignant tumors and patients without these complications. Bacterial infection- and cytokine/chemokine-related pathways were significantly enriched in the patients with DM/CADM complicated by interstitial lung disease, while those pathways related to glycosylation, protein metabolism, angtigen presentation and cytotoxic effects of natural killer cells were significantly enriched in the patients with DM/CADM complicated by malignant tumors.

Comparison of clinical and immunological features between clinically amyopathic dermatomyositis and typical dermatomyositis / 北京大学学报(医学版)

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.

Detection of serum cytokines in patients with dermatomyositis and their clinical significance / 中华皮肤科杂志

Objective To explore the association of serum cytokine levels with disease activity in patients with dermatomyositis (DM) and clinically amyopathic dermatomyositis (CADM),especially their association with skin lesions and interstitial lung disease (ILD).Methods Enzyme-linked immunosorbent assay (ELISA) and cytometric beads array (CBA)were performed to detect the serum levels of interleukin (IL)-2,IL-4,IL-6,IL-10,IL-17A,IL-18,tumor necrosis factor (TNF) and interferon (IFN)-γin 40 patients with DM or CADM,as well as in 16 health checkup examinees (healthy control group).Then,the association of serum cytokine levels with skin lesions,inflammatory biomarkers and severity of ILD was analyzed.Results The patients with DM/CADM showed significantly higher serum levels of IL-6 (37.8 ±45.8 pg/ml),IL-10 (16.1 ± 7.2 pg/ml) and IL-18 (492.0 ± 193.1 pg/ml) compared with the healthy controls (12.0 ± 2.7 pg/ml,7.7 ± 1.4 pg/ml,191.1 ± 39.2 pg/ml,respectively,all P ＜ 0.001),and there were no significant differences in the serum levels of the other 5 cytokines between the above 2 groups.The serum level of IL-6 was significantly higher in patients with elevated erythrocyte sedimentation rate (ESR) than in those with normal ESR (49.7 ± 46.8 pg/ml vs.29.1 ± 45.4 pg/ml,P =0.008).The patients with raised C-reactive protein (CRP) levels showed significantly higher serum levels of IL-6 (68.7 ± 59.7 pg/ml) and IL-18 (635.1 ± 232.8 pg/ml) compared with those with normal CRP levels (IL-6:30.6 ± 40.3 pg/ml,P =0.013;IL-18:440.2 ± 164.7 pg/ml,P =0.020).Moreover,the patients with elevated levels of lactate dehydrogenase (LDH) showed significantly higher serum levels of IL-10 (18.4 ± 6.9 pg/ml),IL-17A (19.6 ±6.7 pg/ml) and IL-18 (529.4 ± 197.2 pg/ml) compared with those with normal LDH levels (IL-10:10.7 ±4.8 pg/ml,P ＜ 0.001;IL-17A:11.4 ± 6.6 pg/ml,P =0.001;IL-18:404.9 ± 158.0 pg/ml,P =0.037).No significant difference in the cytokine levels was observed between the patients with elevated creatine kinase (CK) levels and those with normal CK levels.The patients with Gottron's papules/sign showed significantly higher serum levels of IL-18 (513.7 ± 187.2 pg/ml) compared with those without Gottron's papules/sign (297.1 ± 140.4 pg/ml,P ＜ 0.05).The serum levels of IL-10 and IL-18 were significantly higher in the patients with DM/CADM complicated by ILD (18.0 ± 6.7 pg/ml,552.3 ± 192.8 pg/ml,respectively) than in those without ILD (11.6 ± 6.5 pg/ml,351.4 ± 101.0 pg/ml,respectively,both P =0.001).Conclusion Serum levels of IL-6,IL-10 and IL-18 are highly associated with inflammatory biomarkers,skin lesions and ILD in patients with DM/CADM.

Spontaneous pneumomediastinum complicating interstitial lung disease, associated with clinically amyopathic dermatomyositis and positive anti-MDA5 antibodies / Neumomediastino espontáneo como complicación de enfermedad pulmonar intersticial, asociada con dermatomiositis clínicamente amiopática y anticuerpos anti-MDA5 positivos

Abstract Clinically amyopathic dermatomyositis comprises a special group of patients within the spectrum of dermatomyositis characterized by the presence of typical skin lesions, minimal or absent muscle involvement, and increased risk of interstitial lung disease. The antibodies directed against the protein encoded by melanoma differentiation-associated gene 5 (MDA5) are present in a significant proportion of patients with clinically amyopathic dermatomyositis, who develop rapidly progressive interstitial lung disease, with high mortality and frequently complicated by the onset of spontaneous pneumomediastinum. A case is presented of an African patient with anti-MDA5 positive clinically amyopathic dermatomyositis and interstitial lung disease with tomography pattern of organizing pneumonia who developed spontaneous pneumomediastinum during its clinical course.

Resumen La dermatomiositis clínicamente amiopática comprende un grupo especial de pacientes dentro del espectro de la dermatomiositis, caracterizados por la presencia de lesiones cutáneas típicas, compromiso muscular mínimo o ausente y riesgo aumentado de enfermedad pulmonar intersticial. Los anticuerpos dirigidos contra la proteína codificada por el gen asociado con la diferenciación del melanoma 5 (MDA5), están presentes en una proporción importante de pacientes con dermatomiositis clínicamente amiopática, los cuales desarrollan enfermedad pulmonar intersticial rápidamente progresiva, con elevada mortalidad y que se complica frecuentemente con la aparición de neumomediastino espontáneo. Presentamos el caso de una paciente de origen africano con dermatomiositis clínicamente amiopática anti-MDA5 positiva y enfermedad pulmonar intersticial con patrón tomográfico de neumonía organizada, que desarrolló neumomediastino espontáneo durante su evolución.

Juvenile-onset clinically amyopathic dermatomyositis complicated with progressive interstitial pneumonia: report of one case and review of the literature / 临床儿科杂志

Objective To analyze the clinical features of juvenile-onset clinically amyopathic dermatomyositis complicated by progressive interstitial pneumonia.Methods A retrospective analysis of a case of juvenile-onset clinically amyopathic dermatomyositis on clinical features,diagnosis and treatment was performed.Data of the other three reported cases were also reviewed.Results The patient was an adolescent girl presented with Gorrton's sign.The patient did not have fatigue and got normal result in creatine kinase and elctromyogram test.The HRCT exam showed interstitial pneumonia.The mean age of the four cases at the time of onset is 12.3 years old.Gottron's sign (3/4) and fever (2/4) are the most common symptoms of onset.Anti-nuclear antibody (ANA),anti-Jo-1 antibody are 100％ negative in the four patients.Two of the four patients who received anti-Ro-52 antibody test are both positive.Three of the four patients were asymptomatic when the CT scan showed interstitial pneumonia.The interstitial pneumonia was progressive and three of the four patients died of respiratory failure within six months.Treatment with glucocorticoid and immunosuppressant was successful in one case.Conclusions Juvenile CADM can be complicated by progressive interstitial pneumonia.Children suspected CADM should perform pulmonary imaging examinations to find interstitial pneumonia.Children diagnosed as CADM complicated by interstitial pneumonia should receive glucocorticoid and immunosuppressant treatment to prevent progression.

Tumoral Calcinosis as an Initial Complaint of Juvenile-Onset Amyopathic Dermatomyositis

Calcinosis is rarely observed in juvenile-onset amyopathic dermatomyositis in contrast to juvenile-onset dermatomyositis. A 6-year-old female presented with several 0.5 to 2 cm-sized painless grouped masses on both knees for 3 years. The patient also presented with multiple erythematous scaly patches and plaques on both elbows, knuckles, buttock, ankles and cheeks. Her mother had similar skin lesions which were erythematous scaly patches on the knuckles and elbows, since her childhood. When skin biopsy was performed from a left knee nodule, liquid chalky discharge was observed. The biopsy results were consistent with calcinosis cutis. Other biopsies from erythematous patch of the patient and erythematous patch of her mother showed vacuolization of basal cell layer with inflammatory cell infiltrations. Laboratory findings showed normal range of serum phosphorus (4.5 mg/dl), calcium (9.3 mg/dl), 1,25-dihydroxy-vitamin D (10.8 ng/ml) and parathyroid hormone levels (11 pg/ml). Both patient and her mother had no history of muscle weakness and showed normal levels of muscle-specific enzyme. Both patients were diagnosed with juvenile-onset amyopathic dermatomyositis based on histopathology and cutaneous manifestations with no evidence of muscle weakness and no serum muscle enzyme abnormalities. Tumoral calcium deposits observed in daughter was diagnosed as dystrophic calcinosis which can be rarely seen in juvenile-onset amyopathic dermatomyositis. The patient is being treated with oral acetazolamide (40 mg/kg/d) for calcinosis.

The clinical characteristics of 26 cases of amyopathic dermatomyositis / 中华内科杂志

Objective To analyze the clinical characteristics of amyopathic dermatomyositis (ADM).Methods Twenty six patients diagnosed as ADM from January 2006 to January 2010 in PLA General Hospital were retrospectively analyzed.The clinical manifestation,laboratory findings,imaging manifestations,treatment and prognosis of the 26 patients were recorded.Results There were 18 females and 8 males with age of 30-68 years.Overall disease course after diagnosis was 2-18 months.All patients had Gottron rash and interstitial pneumonia.Fifteen patients had history of pulmonary infections.Three patients had comorbidity of tumor.Creatine phosphokinase,creatine phosphokinase isoenzyme,glutamicoxaloacetic transaminase and lactate dehydrogenase were normal in all 26 patients.Four patients had positive anti-Jo-1 antibodies.Antinuclear antibodies were positive in nine patients.Electromyogram was slightly abnormal in 5 patients.Muscle biopsy was abnormal in 19 patients.Twenty patients had improved after receiving corticosteroids and immunosuppressive agents.Six patients died.Conclusions It has been estimated that ADM represents approximately 20％ of all cases of dermatomyositis.It seems that patients with ADM have greater incidence of lung involvement and combined cancer.ADM patients need to be treated positively to improve the prognosis.

Detection of anti-CADM-140 antibody in patients with dermatomyositis or clinically amyopathic dermatomyositis and its clinical significance / 中华皮肤科杂志

Objective To detect anti-clinically amyopathic dermatomyositis (CADM)-140 antibody in patients with dermatomyositis (DM) or CADM,and to estimate its clinical correlation.Methods Serum samples were collected from 22 patients with DM,16 patients with CADM,46 patients with other connective tissue diseases complicated by interstitial lung disease(including 8 cases of polymyositis,15 cases of systemic lupus erythematosus,5 cases of systemic sclerosis,6 cases of Sj(o)gren syndrome,6 cases of mixed connective tissue disease,6 cases of idiopathic pulmonary fibrosis),and 5 normal human controls.Enzyme-linked immunosorbent assay (ELISA) was performed with the recombinant melanoma differentiation-associated gene 5(rMDA)as a substrate to measure the anti-CADM-140 antibody in these serum samples.Clinical manifestations were compared between patients with anti-CADM-140 antibody and those without.Results The anti-CADM-140antibody was found in 43.8% (7/16) of patients with CADM and 9.1%(2/22) of patients with DM(P<0.05),but absent in the patients with other connective tissue diseases and in the normal human controls.A significant incroase was observed in anti-CADM-140 antibody-positive patients with DM/CADM in the incidence of cutaneous ulceration and necrosis,interstitial lung disease and rapidly progressive interstitial lung disease (8/9 vs.6.9%,P<0.01;9/9 vs.48.3%,P<0.01;5/9 vs.0,P<0.05),serum lactate dehydrogenase level(328.3±104.2 vs 241.1±100.3 IU/L P<0.05),erythrocyte sedimentation rate(40.8±23.1 vs.22.5±16.8 mm/1 h,P<0.05),high resolution computed tomography score(122.9±54.8 vs.70.0±59.8,P<0.05)compared with anti-CADM-140 antibody-negative patients with DM/CADM.The ereatine kinase level was significantly lower(156.3±260.8 vs.1806.2±3737.1 IU/L P<0.05)in anti-CADM-140 antibody-positive patients with DM/CADM than in anti-CADM-140 antibody-negative patients with DM/CADM,while no significant difference was noted in the positivity rate of antinuclear antibodies or incidence of malignancies between the antibody-positive and-negative patients with DM/CADM.Conclusions Anti-CADM.140 antibody not only is useful for the diagnosis of interstitial lung disease in patients with DM/CADM,but also may serve as a serum marker for rapidly progressive interstitial lung disease.Monitoring of serum anti-CADM-140 antibody might help to predict the progression of interstitial lung disease in patients with DM/CADM.

A Case of Amyopathic Dermatomyositis / 대한피부과학회지

Amyopathic dermatomyositis is diagnosed when the biopsy-confirmed cutaneous lesions of dermatomyositis are present for longer than 2 years in the absence of muscle weakness, elevated muscle enzymes, and the history of immunosuppressive drug therapy and ingestion of drugs such as hydroxyurea that can produce dermatomyositis-like cutaneous hypersensitivity changes. We report a 36-year-old woman with a 3-year history of typical skin features of dermatomyositis with no evidences of muscle involvement.

A Case of Amyopathic Dermatomyositis

We report a 33-year-old woman with a 1-year history of typical skin features of dermatomyositis without any evidence of muscle involvement. Her skin eruption of the face (heliotrope erythema) and hands (Gottron's papules) and skin biopsy findings were typical of dermatomyositis. Levels of serum muscle enzymes were within normal ranges and electromyography showed no signs of muscle involvement. During a 1-year follow-up, she had no signs of muscle weakness. Based on these clinical and laboratory findings, our case can be diagnosed as amyopathic dermatomyositis.

Amyopathic Dermatomyositis with Interstitial Lung Disease: A Case Report / 대한류마티스학회지

Amyopathic dermatomyositis is defined by characteristic cutaneous manifestation of dermatomyositis without evidence of muscle involvement. There is no clinical difference between dermatomyositis and amyopathic dermatomyositis. Pulmonary involvement of dermatomyositis is so frequent than aggressive dianostic and therapeutic approach is needed. Early steroid or immunosuppresive treatment in pulmonary involvement of dermatomyositis gets better prognosis. Intravenous immunoglobulin treatment is an effective and safe alternative when the steroid or immunosuppresive treatment is ineffective or intolerable. We are reporting a case of amyopathic dermatomyositis with interstitial lung disease. This patient was improved with intravenous immunoglobulin treatment.