Medicine › Epidemiology

Inflammatory Myopathies and Dermatomyositis

Works Count: 36770

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Description

This cluster of papers covers the epidemiology, classification, and clinical features of inflammatory myopathies such as dermatomyositis and polymyositis. It includes discussions on autoantibodies, interstitial lung disease, cancer risk, treatment strategies, myositis-specific antibodies, juvenile dermatomyositis, and the association with malignancy.

Keywords

Inflammatory Myopathies; Dermatomyositis; Polymyositis; Autoantibodies; Interstitial Lung Disease; Cancer Risk; Treatment; Myositis-specific Antibodies; Juvenile Dermatomyositis; Malignancy

Myology: Basic and Clinical.

1986-11-01

Andrew G Eng , Betty Q. Banker

The scientific basis of myology general approaches to neuromuscular diseases diseases of muscle. The scientific basis of myology general approaches to neuromuscular diseases diseases of muscle.

Polymyositis and Dermatomyositis

1975-02-20

Anthony Bohan , James B. Peter

Laboratory FeaturesElevation of sarcoplasmic enzymes in serum (creatine phosphokinase, aldolase, transaminases and lactic dehydrogenase) is valuable both for diagnosis and for following the clinical activity and response to treatment. Although … Laboratory FeaturesElevation of sarcoplasmic enzymes in serum (creatine phosphokinase, aldolase, transaminases and lactic dehydrogenase) is valuable both for diagnosis and for following the clinical activity and response to treatment. Although some state that the transaminases are the most reliable,31,33,35 most authorities favor the creatine phosphokinase.2These serum enzymes are not infallible guidelines, for occasionally they remain entirely within the normal range despite active myositis1,51; likewise, when muscle atrophy is extensive in long standing disease, the enzymes may be normal despite active myositis. Motor-neuron diseases, Duchenne muscular dystrophy and other dystrophies, metabolic disorders, endocrinopathies, toxins . . .

Autoantibodies against 3-hydroxy-3-methylglutaryl-coenzyme A reductase in patients with statin-associated autoimmune myopathy

2010-11-19

Andrew L. Mammen , Tae Hwan Chung , Lisa Christopher‐Stine +4 more

In addition to inducing a self-limited myopathy, statin use is associated with an immune-mediated necrotizing myopathy (IMNM), with autoantibodies that recognize ∼200-kd and ∼100-kd autoantigens. The purpose of this study … In addition to inducing a self-limited myopathy, statin use is associated with an immune-mediated necrotizing myopathy (IMNM), with autoantibodies that recognize ∼200-kd and ∼100-kd autoantigens. The purpose of this study was to identify these molecules to help clarify the disease mechanism and facilitate diagnosis.The effect of statin treatment on autoantigen expression was addressed by immunoprecipitation using sera from patients. The identity of the ∼100-kd autoantigen was confirmed by immunoprecipitation of in vitro-translated 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) protein. HMGCR expression in muscle was analyzed by immunofluorescence. A cohort of myopathy patients was screened for anti-HMGCR autoantibodies by enzyme-linked immunosorbent assay and genotyped for the rs4149056 C allele, a predictor of self-limited statin myopathy.Statin exposure induced expression of the ∼200-kd/∼100-kd autoantigens in cultured cells. HMGCR was identified as the ∼100-kd autoantigen. Competition experiments demonstrated no distinct autoantibodies recognizing the ∼200-kd protein. In muscle biopsy tissues from anti-HMGCR-positive patients, HMGCR expression was up-regulated in cells expressing neural cell adhesion molecule, a marker of muscle regeneration. Anti-HMGCR autoantibodies were found in 45 of 750 patients presenting to the Johns Hopkins Myositis Center (6%). Among patients ages 50 years and older, 92.3% had taken statins. The prevalence of the rs4149056 C allele was not increased in patients with anti-HMGCR.Statins up-regulate the expression of HMGCR, the major target of autoantibodies in statin-associated IMNM. Regenerating muscle cells express high levels of HMGCR, which may sustain the immune response even after statins are discontinued. These studies demonstrate a mechanistic link between an environmental trigger and the development of sustained autoimmunity. Detection of anti-HMGCR autoantibodies may facilitate diagnosis and direct therapy.

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A novel autoantibody recognizing 200‐kd and 100‐kd proteins is associated with an immune‐mediated necrotizing myopathy

2010-05-26

Lisa Christopher‐Stine , Livia Casciola‐Rosen , Grace Hong +3 more

Abstract Objective Myofiber necrosis without prominent inflammation is a nonspecific finding in patients with dystrophies and toxic or immune‐mediated myopathies. However, the etiology of a necrotizing myopathy is often obscure, … Abstract Objective Myofiber necrosis without prominent inflammation is a nonspecific finding in patients with dystrophies and toxic or immune‐mediated myopathies. However, the etiology of a necrotizing myopathy is often obscure, and the question of which patients would benefit from immunosuppression remains unanswered. The aim of this study was to identify novel autoantibodies in patients with necrotizing myopathy. Methods Muscle biopsy specimens and serum samples were available for 225 patients with myopathy. Antibody specificities were determined by performing immunoprecipitations from 35 S‐methionine–labeled HeLa cell lysates. Selected biopsy specimens were stained for membrane attack complex, class I major histocompatibility complex (MHC), and endothelial cell marker CD31. Results Muscle biopsy specimens from 38 of 225 patients showed predominantly myofiber necrosis. Twelve of these patients had a known autoantibody association with or other etiology for their myopathy. Sixteen of the remaining 26 sera immunoprecipitated 200‐kd and 100‐kd proteins; this specificity was observed in only 1 of 187 patients without necrotizing myopathy. Patients with the anti‐200/100 autoantibody specificity had proximal weakness (100%), high creatine kinase levels (mean maximum 10,333 IU/liter), and an irritable myopathy on electromyography (88%). Sixty‐three percent of these patients had been exposed to statins prior to the onset of weakness. All patients responded to immunosuppressive therapy, and many experienced a relapse of weakness when the medication was tapered. Immunohistochemical studies showed membrane attack complex on small blood vessels in 6 of 8 patients and on the surface of non‐necrotic myofibers in 4 of 8 patients. Five of 8 patients had abnormal capillary morphology, and 4 of 8 patients expressed class I MHC on the surface of non‐necrotic myofibers. Conclusion An anti–200/100‐kd specificity defines a subgroup of patients with necrotizing myopathy who previously were considered to be autoantibody negative. We propose that these patients have an immune‐mediated myopathy that is frequently associated with prior statin use and should be treated with immunosuppressive therapy.

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Monoclonal antibody analysis of mononuclear cells in myopathies. I: Quantitation of subsets according to diagnosis and sites of accumulation and demonstration and counts of muscle fibers invaded by T cells

1984-08-01

Kiichi Arahata , Andrew G. Engel

Abstract In 76 muscle specimens (normal controls, 9; Duchenne dystrophy, 11; scleroderma, 11; dermatomyositis, 13; polymyositis, 15; inclusion body myositis, 17), mononuclear cells were analyzed at perivascular, perimysial, and endomysial … Abstract In 76 muscle specimens (normal controls, 9; Duchenne dystrophy, 11; scleroderma, 11; dermatomyositis, 13; polymyositis, 15; inclusion body myositis, 17), mononuclear cells were analyzed at perivascular, perimysial, and endomysial sites of accumulation. Monoclonal antibodies reactive for B cells, T cell subsets, killer (K) or natural killer (NK) cells, and the Ia antigen were used for cell typing. Macrophages were identified by the acid phosphatase reaction. Few extravascular mononuclear cells occurred in normal muscle. In all inflammatory myopathies, a mixed exudate of T cells, B cells, and macrophages was present. Mature K/NK cells were rare in all diseases. In dermatomyositis, polymyositis, and inclusion body myositis, there was a positive gradient for T cells, T8 + cells, and activated T cells and a negative gradient for B cells and T4 + cells between perivascular and endomysial sites. In scleroderma the predominant perimysial exudate consisted mostly of T cells and macrophages. The percentage of B cells at all sites, and the T4 + /T cell ratio in the endomysium, were significantly higher in dermatomyositis than in the other diseases. In polymyositis and inclusion body myositis. The endomysial exudate contained a large number of T cells, T8 + cells, and activated T cells but only sparse B cells. T cells accompanied by macrophages focally surrounded and invaded nonnecrotic fibers in polymyositis and inclusion body myositis. Rare fibers in Duchenne dystrophy and a very few fibers in dermatomyositis and scleroderma were similarly affected. We infer that (1) T‐B, T‐T, and T‐macrophage cooperativities are likely to exist in muscle in different myopathies; (2) T cell‐mediated fiber injury plays a role in polymyositis and inclusion body myositis; (3) T cell–mediated fiber injury can also occur in inherited diseases, such as Duchenne dystrophy; and (4) a local humoral response may occur in muscle in dermatomyositis and possibly in polymyositis and inclusion body myositis.

Interstitial lung disease in polymyositis and dermatomyositis

2002-12-12

I. Marie , É. Hachulla , P. Chérìn +7 more

Abstract Objectives To assess prevalence, characteristics, and long‐term outcome of interstitial lung disease (ILD) in polymyositis (PM) and dermatomyositis (DM). To determine predictive variables of ILD course in PM/DM, and … Abstract Objectives To assess prevalence, characteristics, and long‐term outcome of interstitial lung disease (ILD) in polymyositis (PM) and dermatomyositis (DM). To determine predictive variables of ILD course in PM/DM, and to define both clinical and biochemical features associated with ILD onset in PM/DM. Methods The medical records of 156 consecutive PM/DM patients in 3 medical centers were reviewed. Results Thirty‐six PM/DM patients (23.1%) developed ILD. We observed that 19.4% of patients with ILD had resolution of pulmonary disorders, whereas 25% experienced ILD deterioration. Morbidity and mortality rates were as high as 13.9% and 36.4%, respectively, in PM/DM patients with ILD. Parameters of PM/DM that related to ILD poor outcome were identified as follows: Hamman‐Rich–like pattern, initial diffusing capacity of carbon monoxide <45%, neutrophil alveolitis, and histologic usual interstitial pneumonia. Additionally, for the group with ILD, polyarthritis, higher values of erythrocyte sedimentation rate and C‐reactive protein, presence of anti–Jo‐1 antibody, and characteristic microangiopathy were significantly more frequent. Conclusion Our series underlines the high frequency of ILD in PM/DM patients, resulting in increased morbidity and mortality rates. It also indicates that PM/DM patients should routinely be screened for ILD, even those patients without anti–Jo‐1 antibody, because 69% of our ILD patients were seronegative for the anti–Jo‐1 antibody. Our findings further suggest that PM/DM patients presenting with factors predictive of ILD poor outcome may require more aggressive therapy.

A New Approach to the Classification of Idiopathic Inflammatory Myopathy

1991-11-01

Lori A. Love , Richard L. Leff , D. D. Fraser +4 more

The IIM are a heterogeneous group of systemic rheumatic diseases which share the common features of chronic muscle weakness and mononuclear cell infiltrates in muscle. A number of classification schemes … The IIM are a heterogeneous group of systemic rheumatic diseases which share the common features of chronic muscle weakness and mononuclear cell infiltrates in muscle. A number of classification schemes have been proposed for them, but none takes into consideration the marked immunologic, clinical, and genetic heterogeneity of the various clinical groups. We compared the usefulness of myositis-specific autoantibodies (anti-aminoacyl-tRNA synthetases, anti-SRP, anti-Mi-2 and anti-MAS) to the standard clinical categories (polymyositis, dermatomyositis, overlap myositis, cancer-associated myositis, and inclusion body myositis) in predicting clinical signs and symptoms, HLA types, and prognosis in 212 adult IIM patients. Although patients with inclusion body myositis (n = 26) differed in having significantly more asymmetric and distal weakness, falling, and atrophy than other patients, there were few other significant differences among the other clinical groups. In contrast, autoantibody status defined distinct sets of patients and each patient had only 1 myositis-specific autoantibody. Patients with anti-amino-acyl-tRNA synthetase autoantibodies (n = 47), compared to those without these antibodies, had significantly more frequent arthritis, fever, interstitial lung disease, and "mechanic's hands"; HLA-DRw52; higher mean prednisone dose at survey, higher proportion of patients receiving cytotoxic drugs, and higher death rates. Those with anti-signal recognition particle antibodies (n = 7) had increased palpitations; myalgias; DR5, DRw52; severe, refractory disease; and higher death rates. Patients with anti-Mi-2 antibodies (n = 10) had increased "V-sign" and "shawl-sign" rashes, and cuticular overgrowth; DR7 and DRw53; and a good response to therapy. The 2 patients with anti-MAS antibodies were the only ones with alcoholic rhabdomyolysis preceding myositis; both had insulin-dependent diabetes mellitus, and both had HLA-B60, -C3, -DR4, and -DRw53. These findings suggest that myositis-specific autoantibody status is a more useful guide than clinical group in assessing patients with myositis, and that specific associations of immunogenetics, immune responses, and clinical manifestations occur in IIM. Thus the myositis-specific autoantibodies aid in interpreting the diverse symptoms and signs of myositis patients and in predicting their clinical course and prognosis. We propose, therefore, that an adjunct classification of the IIM, based on the myositis-specific autoantibody status, be incorporated into future studies of their epidemiology, etiology, and therapy.

Novel Classification of Idiopathic Inflammatory Myopathies Based on Overlap Syndrome Features and Autoantibodies

2005-07-01

Yves Troyanov , Ira N. Targoff , Jean-Luc Tremblay +3 more

Our objective was to improve the currently imperfect classifications of idiopathic inflammatory myopathies (IIM). In clinical practice, overlap features are common in IIM. This provided a rationale for positioning overlap … Our objective was to improve the currently imperfect classifications of idiopathic inflammatory myopathies (IIM). In clinical practice, overlap features are common in IIM. This provided a rationale for positioning overlap clinical features at the core of a new classification system. We conducted a longitudinal study of 100 consecutive adult French Canadian patients with IIM. Clinical and laboratory data were obtained by retrospective chart review. Sera were analyzed for autoantibodies (aAbs) by protein A-assisted immunoprecipitation and double immunodiffusion. Overlap aAbs encompassed aAbs to synthetases, systemic sclerosis-associated aAbs, anti-signal recognition particle (SRP) and anti-nucleoporins. Patients were classified both at IIM diagnosis, based on data at presentation, and at the end of follow-up, based on cumulative findings. Three classifications were used: 1) the Bohan and Peter original classification, 2) a new version of that classification as modified by us, and 3) a novel clinicoserologic classification. As investigators were blinded to aAb results, the modified classification is strictly a clinical classification. Its core concept is the attribution of diagnostic significance to the presence of overlap features, that is, their presence resulted in a diagnosis of overlap myositis (OM). This approach allowed direct comparison with the original Bohan and Peter classification. By integrating aAb results to the modified classification, we also defined the clinicoserologic classification, which allowed to examine the added value of aAbs to diagnostic, therapeutic and prognostic stratification. Whereas polymyositis (PM) was the most common IIM according to the original classification, accounting for 45% of the cohort at diagnosis, its frequency fell to 14% with the modified classification. Conversely, while the frequency of myositis associated with connective tissue disease was 24% according to the original classification, the frequency of OM was 60% when using the modified classification. At last follow-up, the frequency of PM fell further to only 9%, while the frequency of OM rose to 67%. Systemic sclerosis was the most common connective tissue disease associated with IIM, accounting for 42.6% of OM patients and 29% of the cohort. The frequencies of overlap aAbs in the cohort and in OM patients were 48% and 70.5% (n =48/68), respectively. The presence of overlap aAbs at IIM diagnosis identified additional OM patients unrecognized by the modified classification. The sensitivity of the modified classification for OM at diagnosis was 87%, suggesting that clinicians may rely on the modified classification for identification of most OM patients, while awaiting results of aAb assays. The new classifications predicted the response to prednisone and IIM course. Using stringent definitions, IIM was classified as responsive or refractory after an adequate initial corticosteroid therapy, and the disease course as monophasic or chronic after a single adequate trial of prednisone. PM was always chronic and was associated with the highest rate (50%) of refractoriness to initial corticosteroid treatment. Dermatomyositis was almost always chronic (92% rate); however, its responsiveness to initial corticosteroid treatment was high (87%). OM was almost always responsive to corticosteroids (89%-100% rates). When OM patients were divided according to aAb subsets, anti-synthetase, SRP, or nucleoporin aAbs were markers for chronic myositis, whereas aAbs to U1RNP, Pm-Scl, or Ku were markers for monophasic myositis. We conclude that the original Bohan and Peter classification should be abandoned as it leads to misclassification of patients. Much of IIM is composed of OM. The proposed modified and clinicoserologic classifications have diagnostic, prognostic, and therapeutic value. Abbreviations: aAbs = autoantibodies, ACR = American College of Rheumatology, ANA = antinuclear autoantibodies, antitopo I = anti-DNA topoisomerase I, CAM = cancer-associated myositis, CHUM = Centre Hospitalier de l'Université de Montréal, CK = creatine kinase, CTM = myositis with another connective tissue disease, DM = dermatomyositis, EMG = electromyogram, IIM = idiopathic inflammatory myopathies, MAA = myositis-associated autoantibodies, MSA = myositis-specific autoantibodies, OM = overlap myositis, OR = odds ratio, PM = polymyositis, RA = rheumatoid arthritis, SLE = systemic lupus erythematosus, SRP = signal recognition particle.

Autoantibodies to a 140‐kd polypeptide, CADM‐140, in Japanese patients with clinically amyopathic dermatomyositis

2005-05-01

Shinji Sato , Michito Hirakata , Masataka Kuwana +6 more

To identify novel autoantibodies specific for dermatomyositis (DM), especially those specific for clinically amyopathic DM (C-ADM).Autoantibodies were analyzed by immunoprecipitation in 298 serum samples from patients with various connective tissue … To identify novel autoantibodies specific for dermatomyositis (DM), especially those specific for clinically amyopathic DM (C-ADM).Autoantibodies were analyzed by immunoprecipitation in 298 serum samples from patients with various connective tissue diseases (CTDs) or idiopathic pulmonary fibrosis (IPF). Antigen specificity of the sera was further examined by immunoblotting and indirect immunofluorescence (IF). The disease specificity and clinical features associated with the antibody of interest were determined.Eight sera recognized a polypeptide of approximately 140 kd (CADM-140 autoantigen) by immunoprecipitation and immunoblotting. Immunoreactivity was detected in the cytoplasm, and indirect IF revealed a granular or reticular pattern. Anti-CADM-140 antibodies were detected in 8 of 42 patients with DM, but not in patients with other CTDs or IPF. Interestingly, all 8 patients with anti-CADM-140 antibodies had C-ADM. Among 42 patients with DM, those with anti-CADM-140 autoantibodies had significantly more rapidly progressive interstitial lung disease (ILD) when compared with patients without anti-CADM-140 autoantibodies (50% versus 6%; P = 0.008).These results indicate that the presence of anti-CADM-140 autoantibodies may be a novel marker for C-ADM. Further attention should be directed to the detection of rapidly progressive ILD in those patients with anti-CADM-140 autoantibodies.

HLA-DPB1 Glutamate 69: a Genetic Marker of Beryllium Disease

1993-10-08

Luca Richeldi , Rosa Sorrentino , Cesare Saltini

Chronic beryllium disease (CBD) is a lung disorder related to beryllium exposure and is characterized by the accumulation in the lung of beryllium-specific CD4 + major histocompatibility complex (MHC) class … Chronic beryllium disease (CBD) is a lung disorder related to beryllium exposure and is characterized by the accumulation in the lung of beryllium-specific CD4 + major histocompatibility complex (MHC) class II-restricted T lymphocytes. Evaluation of MHC class II genes in 33 CBD cases and 44 controls has shown a negative association with HLA-DPB1 * 0401 ( P < 0.001) and a positive association with HLA-DPB1 * 0201 ( P < 0.05) alleles, which differ at residues 36, 55 to 56, and 69 of the β 1 chain. Among CBD cases, 97 percent expressed the HLA-DPB1 * 0201-associated glutamic acid (unaffected population, 30 percent; P < 0.001) at residue 69, a position involved in susceptibility to autoimmune disorders. This suggests that HLA-D P has a role in conferring susceptibility and that residue 69 of HLA-DPB1 could be used in risk assessment for CBD.

Mitochondrial Myopathy Caused by Long-Term Zidovudine Therapy

1990-04-19

Marinos C. Dalakas , Isabel Illa , G. Pezeshkpour +3 more

Both infection with the human immunodeficiency virus type 1 (HIV) and zidovudine (formerly called azidothymidine [AZT]) cause myopathy. To identify criteria for distinguishing zidovudine-induced myopathy from that caused by primary … Both infection with the human immunodeficiency virus type 1 (HIV) and zidovudine (formerly called azidothymidine [AZT]) cause myopathy. To identify criteria for distinguishing zidovudine-induced myopathy from that caused by primary HIV infection, we reviewed the histochemical, immunocytochemical, and electron-microscopical features of muscle-biopsy specimens from 20 HIV-positive patients with myopathy (15 of whom had been treated with zidovudine) and compared the findings with the patients' clinical course and response to various therapies. Among the zidovudine-treated patients, the myopathy responded to prednisone in four, to the discontinuation of zidovudine in eight, and to nonsteroidal anti-inflammatory drugs in two.

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119th ENMC international workshop: Trial design in adult idiopathic inflammatory myopathies, with the exception of inclusion body myositis, 10–12 October 2003, Naarden, The Netherlands

2004-03-30

Jessica E. Hoogendijk , Anthony A. Amato , Bryan Lecky +6 more

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Simple method for measurement of lower extremity muscle strength

1985-01-01

Maryellen Csuka , Daniel J. McCarty

INCLUSION BODY MYOSITIS

1989-01-01

Barend P. Lotz , Andrew G. Engel , H Nishino +2 more

SUMMARY Inclusion body myositis (IBM) was suspected on light microscopic grounds in 48 of 170 consecutive patients with inflammatory myopathies. One or more vacuoles containing membranous material, groups of atrophic … SUMMARY Inclusion body myositis (IBM) was suspected on light microscopic grounds in 48 of 170 consecutive patients with inflammatory myopathies. One or more vacuoles containing membranous material, groups of atrophic fibres, and an autoaggressive endomysial inflammatory exudate occurred in 100, 96 and 92% of the muscle specimens All three of these features were present in 88% of the specimens Electron microscopy confirmed the presence of filamentous inclusions in 40 of 43 patients The inclusions are typically near vacuoles and a minimum of three vacuolated fibres must be scrutinized to detect them with confidence. There is no electromyographic pattern that can reliably distinguish IBM from other inflammatory myopathies The typical clinical features in the patients diagnosed by histological criteria as IBM were: insidious onset after age 50 yrs with painless, proximal lower extremity weakness, slow but relentless progression with selectively severe involvement of quadriceps, iliopsoas, tibialis anterior, biceps and triceps muscles; relatively early depression of the knee reflexes; and a normal or mildly elevated serum creatine kinase level The male : female ratio was 3 : 1. Distal weakness occurred in about 50%, but only in 35% was it as great or greater than proximal weakness. Significant associated illnesses include other autoimmune disorders (15%), diabetes melhtus (20%), and diffuse peripheral neuropathy (18%). Prednisone treatment at dose levels frequently effective in polymyositis failed to prevent disease progression in those patients observed for 2 or more years. Our findings support the notion that IBM is a distinct entity in which a set of pathological features is associated with a constellation of clinical findings.

A novel autoantibody to a 155‐kd protein is associated with dermatomyositis

2006-10-30

Ira N. Targoff , Gulnara Mamyrova , Edward P. Trieu +5 more

Abstract Objective In polymyositis and dermatomyositis (DM), identified autoantibodies occur in <50% of adult patients and in a smaller proportion of children. This study was undertaken as part of a … Abstract Objective In polymyositis and dermatomyositis (DM), identified autoantibodies occur in <50% of adult patients and in a smaller proportion of children. This study was undertaken as part of a larger effort to define novel autoantibodies that assist in the clinical evaluation of myositis. Methods Sera from children and adults satisfying criteria for idiopathic inflammatory myopathies and from patients with other connective tissue diseases (CTDs), patients with noninflammatory myopathies, and healthy individuals were tested for autoantibodies by immunoprecipitation (IP). A previously unrecognized autoantibody that immunoprecipitated a 155‐kd protein along with a weaker 140‐kd protein was seen. When the presence of this anti‐p155 autoantibody in test sera was suggested based on IP results, it was confirmed by immunoblotting of immunoprecipitates. Results Sera from 51 of 244 myositis patients (21%), including 30 with juvenile DM (29%), 5 with juvenile CTD–associated myositis (33%), 8 with adult DM (21%), 6 with cancer‐associated DM (75%), and 2 with adult CTD–associated myositis (15%), were found to have anti‐p155 autoantibody. One of 49 patients with lupus, and none of 89 others without myositis, had anti‐p155. Caucasian patients with anti‐p155 had a unique HLA risk factor, DQA1*0301 (odds ratio 5.4, corrected P = 0.004). In adults with anti‐p155, of several clinical features assessed only the frequency of V‐sign rash was increased, but patients with this antibody were clinically distinct from those with autoantibodies to aminoacyl–transfer RNA synthetases. Conclusion A newly recognized autoantibody, anti‐p155, is associated with DM and cancer‐associated DM, and is one of the most common autoantibodies in this condition, occurring as frequently in children as in adults. The clinical features and immunogenetics associated with anti‐p155 differ from those associated with antisynthetases.

RNA helicase encoded by melanoma differentiation–associated gene 5 is a major autoantigen in patients with clinically amyopathic dermatomyositis: Association with rapidly progressive interstitial lung disease

2009-06-29

Shinji Sato , Kana Hoshino , Takashi Satoh +4 more

To identify the autoantigen recognized by the autoantibody that is associated with clinically amyopathic dermatomyositis (C-ADM) and rapidly progressive interstitial lung disease (ILD).An anti-CADM-140 antibody-positive prototype serum sample was used … To identify the autoantigen recognized by the autoantibody that is associated with clinically amyopathic dermatomyositis (C-ADM) and rapidly progressive interstitial lung disease (ILD).An anti-CADM-140 antibody-positive prototype serum sample was used to screen a HeLa cell-derived complementary DNA (cDNA) library. Selected cDNA clones were further evaluated by immunoprecipitation of their in vitro-transcribed and in vitro-translated products using anti-CADM-140 antibody-positive and anti-CADM-140 antibody-negative sera. The lysates of COS-7 cells transfected with the putative antigen were similarly tested. An enzyme-linked immunosorbent assay (ELISA) to detect the anti-CADM-140 antibody was established using a recombinant CADM-140 antigen, and its specificity and sensitivity for C-ADM and rapidly progressive ILD were assessed in 294 patients with various connective tissue diseases.By cDNA library screening and immunoprecipitation of in vitro-transcribed and in vitro-translated products, we obtained a cDNA clone encoding melanoma differentiation-associated gene 5 (MDA-5). The anti-CADM-140 antibodies in patients' sera specifically reacted with MDA-5 protein expressed in cells transfected with full-length MDA-5 cDNA, confirming the identity of MDA-5 as the CADM-140 autoantigen. The ELISA, using recombinant MDA-5 protein as the antigen, showed an analytical sensitivity of 85% and analytical specificity of 100%, in comparison with the "gold standard" immunoprecipitation assay, and was useful for identifying patients with C-ADM and/or rapidly progressive ILD.Given that RNA helicase encoded by MDA-5 is a critical molecule involved in the innate immune defense against viruses, viral infection may play an important role in the pathogenesis of C-ADM and rapidly progressive ILD. Moreover, our ELISA using recombinant MDA-5 protein makes detection of the anti-CADM-140 antibody routinely available.

A COMPUTER-ASSISTED ANALYSIS OF 153 PATIENTS WITH POLYMYOSITIS AND DERMATOMYOSITIS

1977-07-01

Anthony Bohan , James B. Peter , Ralph L. Bowman +1 more

BOHAN, ANTHONY M.D.; PETER, JAMES B. M.D., Ph.D.; BOWMAN, RALPH L. B.S.; PEARSON, CARL M. M.D. Author Information BOHAN, ANTHONY M.D.; PETER, JAMES B. M.D., Ph.D.; BOWMAN, RALPH L. B.S.; PEARSON, CARL M. M.D. Author Information

Interferon‐α/β–mediated innate immune mechanisms in dermatomyositis

2005-04-25

Steven A. Greenberg , Jack L. Pinkus , Geraldine S. Pinkus +7 more

Abstract Dermatomyositis has been modeled as an autoimmune disease largely mediated by the adaptive immune system, including a local humorally mediated response with B and T helper cell muscle infiltration, … Abstract Dermatomyositis has been modeled as an autoimmune disease largely mediated by the adaptive immune system, including a local humorally mediated response with B and T helper cell muscle infiltration, antibody and complement‐mediated injury of capillaries, and perifascicular atrophy of muscle fibers caused by ischemia. To further understand the pathophysiology of dermatomyositis, we used microarrays, computational methods, immunohistochemistry and electron microscopy to study muscle specimens from 67 patients, 54 with inflammatory myopathies, 14 with dermatomyositis. In dermatomyositis, genes induced by interferon‐α/β were highly overexpressed, and immunohistochemistry for the interferon‐α/β inducible protein MxA showed dense staining of perifascicular, and, sometimes all myofibers in 8/14 patients and on capillaries in 13/14 patients. Of 36 patients with other inflammatory myopathies, 1 patient had faint MxA staining of myofibers and 3 of capillaries. Plasmacytoid dendritic cells, potent CD4 + cellular sources of interferon‐α, are present in substantial numbers in dermatomyositis and may account for most of the cells previously identified as T helper cells. In addition to an adaptive immune response, an innate immune response characterized by plasmacytoid dendritic cell infiltration and interferon‐α/β inducible gene and protein expression may be an important part of the pathogenesis of dermatomyositis, as it appears to be in systemic lupus erythematosus. Ann Neurol 2005;57:664–678

Rituximab in the treatment of refractory adult and juvenile dermatomyositis and adult polymyositis: A randomized, placebo‐phase trial

2012-11-02

Chester V. Oddis , Ann M. Reed , Rohit Aggarwal +7 more

To assess the safety and efficacy of rituximab in a randomized, double-blind, placebo-phase trial in adult and pediatric myositis patients.Adults with refractory polymyositis (PM) and adults and children with refractory … To assess the safety and efficacy of rituximab in a randomized, double-blind, placebo-phase trial in adult and pediatric myositis patients.Adults with refractory polymyositis (PM) and adults and children with refractory dermatomyositis (DM) were enrolled. Entry criteria included muscle weakness and ≥2 additional abnormal values on core set measures (CSMs) for adults. Juvenile DM patients required ≥3 abnormal CSMs, with or without muscle weakness. Patients were randomized to receive either rituximab early or rituximab late, and glucocorticoid or immunosuppressive therapy was allowed at study entry. The primary end point compared the time to achieve the International Myositis Assessment and Clinical Studies Group preliminary definition of improvement (DOI) between the 2 groups. The secondary end points were the time to achieve ≥20% improvement in muscle strength and the proportions of patients in the early and late rituximab groups achieving the DOI at week 8.Among 200 randomized patients (76 with PM, 76 with DM, and 48 with juvenile DM), 195 showed no difference in the time to achieving the DOI between the rituximab late (n = 102) and rituximab early (n = 93) groups (P = 0.74 by log rank test), with a median time to achieving a DOI of 20.2 weeks and 20.0 weeks, respectively. The secondary end points also did not significantly differ between the 2 treatment groups. However, 161 (83%) of the randomized patients met the DOI, and individual CSMs improved in both groups throughout the 44-week trial.Although there were no significant differences in the 2 treatment arms for the primary and secondary end points, 83% of adult and juvenile myositis patients with refractory disease met the DOI. The role of B cell-depleting therapies in myositis warrants further study, with consideration for a different trial design.

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Inclusion body myositis and myopathies

1995-11-01

Robert C. Griggs , Valerie Askanas , Salvatore DiMauro +4 more

The UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase gene is mutated in recessive hereditary inclusion body myopathy

2001-08-27

Iris Eisenberg , Nili Avidan , Tamara Potikha +7 more

Polymyositis–Dermatomyositis-associated Interstitial Lung Disease

2001-10-01

William W. Douglas , Henry D. Tazelaar , Thomas E. Hartman +4 more

We report findings in 70 patients with both diffuse interstitial lung disease and either polymyositis (PM) or dermatomyositis (DM). Initial presentations were most commonly either musculoskeletal (arthralgias, myalgias, and weakness) … We report findings in 70 patients with both diffuse interstitial lung disease and either polymyositis (PM) or dermatomyositis (DM). Initial presentations were most commonly either musculoskeletal (arthralgias, myalgias, and weakness) or pulmonary (cough, dyspnea, and fever) symptoms alone; in only 15 patients (21.4%) did both occur simultaneously. Pulmonary disease usually took the form of acute to subacute antibiotic-resistant community-acquired pneumonia. Chest radiographs and computed tomography most commonly demonstrated bilateral irregular linear opacities involving the lung bases; occasionally consolidation was present. Jo-1 antibody was present in 19 (38%) of 50 patients tested. Synchronous associated malignancy was present in 4 of 70 patients (5.7%). Surgical lung biopsies disclosed nonspecific interstitial pneumonia (NSIP) in 18 of 22 patients (81.8%), organizing diffuse alveolar damage (DAD) in 2, bronchiolitis obliterans organizing pneumonia (BOOP) in 1, and usual interstitial pneumonia (UIP) in 1. Treatment usually included prednisone in 40-60 mg/d dosages for initial control, followed by lower dose prednisone plus an immunosuppressive agent such as azathioprine or methotrexate for disease suppression. Survival was significantly better than that observed for historical control subjects with idiopathic UIP, and was more consistent with survival previously reported in idiopathic NSIP. There was no difference in survival between Jo-1 positive and Jo-1 negative groups.

Anti-Jo-1 antibody: a marker for myositis with interstitial lung disease.

1984-07-21

Robert M. Bernstein , Stephen H. Morgan , Jeffrey T. Chapman +4 more

An autoantibody known as anti-Jo-1 antibody is found in 25% of patients with myositis. Its prevalence in patients with both myositis and cryptogenic fibrosing alveolitis was 68% (13 out of … An autoantibody known as anti-Jo-1 antibody is found in 25% of patients with myositis. Its prevalence in patients with both myositis and cryptogenic fibrosing alveolitis was 68% (13 out of 19 patients), compared with 7.5% in patients with myositis alone (four of 53) and 3% in patients with cryptogenic fibrosing alveolitis alone (two of 62). Anti-Jo-1 antibody may be useful in indicating patients with myositis and cryptogenic fibrosing alveolitis. Raynaud9s phenomenon, the sicca syndrome, and mild arthritis are also often part of the syndrome.

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A systematic review of adult-onset clinically amyopathic dermatomyositis (dermatomyositis siné myositis): A missing link within the spectrum of the idiopathic inflammatory myopathies

2006-01-24

Pedram Gerami , J. Schöpe , Lauren McDonald +2 more

Would a new name hasten the acceptance of amyopathic dermatomyositis (dermatomyositis siné myositis) as a distinctive subset within the idiopathic inflammatory dermatomyopathies spectrum of clinical illness?

2002-04-01

Richard D. Sontheimer

The mucocutaneous and systemic phenotype of dermatomyositis patients with antibodies to MDA5 (CADM-140): A retrospective study

2011-05-01

David Fiorentino , Leland W.K. Chung , Jeff Zwerner +2 more

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Abnormal Signal Intensity in Skeletal Muscle at MR Imaging: Patterns, Pearls, and Pitfalls

2000-10-01

Dave A. May , David G. Disler , Elizabeth A. Jones +2 more

Abnormal signal intensity within skeletal muscle is frequently encountered at magnetic resonance (MR) imaging. Potential causes are diverse, including traumatic, infectious, autoimmune, inflammatory, neoplastic, neurologic, and iatrogenic conditions. Alterations in … Abnormal signal intensity within skeletal muscle is frequently encountered at magnetic resonance (MR) imaging. Potential causes are diverse, including traumatic, infectious, autoimmune, inflammatory, neoplastic, neurologic, and iatrogenic conditions. Alterations in muscle signal intensity seen in pathologic conditions usually fall into one of three recognizable patterns: muscle edema, fatty infiltration, and mass lesion. Muscle edema may be seen in polymyositis and dermatomyositis, mild injuries, infectious myositis, radiation therapy, subacute denervation, compartment syndrome, early myositis ossificans, rhabdomyolysis, and sickle cell crisis. Fatty infiltration may be seen in chronic denervation, in chronic disuse, as a late finding after a severe muscle injury or chronic tendon tear, and in corticosteroid use. The mass lesion pattern may be seen in neoplasms, intramuscular abscess, myonecrosis, traumatic injury, myositis ossificans, muscular sarcoidosis, and parasitic infection. Some of these conditions require prompt medical or surgical management, whereas others do not benefit from medical intervention. The ability to accurately diagnose these conditions is therefore necessary, and biopsy may be required to establish the correct diagnosis. Clues to the correct diagnosis and whether biopsy is necessary or appropriate are often present on the MR images, especially when they are correlated with clinical features and the findings from other imaging modalities.

Interstitial Lung Disease Associated With the Idiopathic Inflammatory Myopathies

2010-12-01

Geoffrey R. Connors , Lisa Christopher‐Stine , Chester V. Oddis +1 more

Peripheral arthropathies in inflammatory bowel disease: their articular distribution and natural history

1998-03-01

Timothy R. Orchard , B P Wordsworth , D P Jewell

Background —Peripheral arthropathy is a well-recognised complication of inflammatory bowel disease (IBD). Little is known of its natural history, but a variety of joint involvement has been described, from large … Background —Peripheral arthropathy is a well-recognised complication of inflammatory bowel disease (IBD). Little is known of its natural history, but a variety of joint involvement has been described, from large joint pauciarticular arthropathy to a rheumatoid pattern polyarthropathy. Aims —To classify the peripheral arthropathies according to pattern of articular involvement, and study their natural history and clinical associations. Methods —The case notes of all patients attending the Oxford IBD clinic were reviewed, and information on general disease characteristics, extraintestinal features, and arthropathy extracted. This was confirmed by direct patient interview using questionnaires at routine follow up. Patients with recorded joint swelling or effusion were classified as type 1 (pauciarticular) if less than five joints were involved and type 2 (polyarticular) if five or more were involved. Patients without evidence of swelling were classified as arthralgia. Results —In total, 976 patients with ulcerative colitis (UC) and 483 with Crohn’s disease (CD) were reviewed. Type 1 occurred in 3.6% of patients with UC (83% acute and self-limiting) and in 6.0% of those with CD (79% self-limiting); 83% and 76%, respectively, were associated with relapsing IBD. Type 2 occurred in 2.5% of patients with UC and 4.0% of those with CD; 87% and 89%, respectively, caused persistent symptoms whereas only 29% and 42%, respectively, were associated with relapsing IBD. Conclusion —Enteropathic peripheral arthropathy without axial involvement can be subdivided into a pauciarticular, large joint arthropathy, and a bilateral symmetrical polyarthropathy, each being distinguished by its articular distribution and natural history.

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Myositis-specific autoantibodies: an important tool to support diagnosis of myositis

2015-11-25

Zoë Betteridge , NJ McHugh

The idiopathic inflammatory myopathies are characterized by muscle weakness, skin disease and internal organ involvement. Autoimmunity is known to have a role in myositis pathogenesis, and myositis-specific autoantibodies, targeting important … The idiopathic inflammatory myopathies are characterized by muscle weakness, skin disease and internal organ involvement. Autoimmunity is known to have a role in myositis pathogenesis, and myositis-specific autoantibodies, targeting important intracellular proteins, are regarded as key biomarkers aiding in the diagnosis of patients. In recent years, a number of novel myositis autoantibodies including anti-TIF1, anti-NXP2, anti-MDA5, anti-SAE, anti-HMGCR and anti-cN1A have been identified in both adult and juvenile patients. These autoantibodies correlate with distinct clinical manifestations and importantly are found in inclusion body, statin-induced, clinically amyopathic and juvenile groups of myositis patients, previously believed to be mainly autoantibody negative. In this review, we will describe the main myositis-specific and myositis-associated autoantibodies and their frequencies and clinical associations across different ages and ethnic groups. We will also discuss preliminary studies investigating correlations between specific myositis autoantibody titres and clinical markers of disease course, collectively demonstrating the utility of myositis autoantibodies as both diagnostic and prognostic markers of disease.

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Polymyositis and Dermatomyositis

1994-01-01

Reinhard Hohlfeld , William W. Hofmann , Daniel F. Hanley

Inflammatory Muscle Diseases

2015-04-29

Marinos C. Dalakas

The four main types of inflammatory muscle disease — dermatomyositis, polymyositis, necrotizing autoimmune myositis, and inclusion-body myositis — are summarized. Pathogenesis, differential diagnosis, and treatment approaches are discussed. The four main types of inflammatory muscle disease — dermatomyositis, polymyositis, necrotizing autoimmune myositis, and inclusion-body myositis — are summarized. Pathogenesis, differential diagnosis, and treatment approaches are discussed.

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Autoantibodies in Polymyositis and Dermatomyositis

2013-04-16

Anna Ghirardello , Nicola Bassi , Lavinia Palma +4 more

Frequency of specific cancer types in dermatomyositis and polymyositis: a population-based study

2001-01-01

Catherine Hill , Yuqing Zhang , Bárður Sigurgeirsson +5 more

Polymyositis and Dermatomyositis

1975-02-13

Anthony Bohan , James B. Peter

POLYMYOSITIS is an inflammatory myopathy of unknown cause to which the term dermatomyositis is applied in the presence of the characteristic skin rash. These disorders share common features with the … POLYMYOSITIS is an inflammatory myopathy of unknown cause to which the term dermatomyositis is applied in the presence of the characteristic skin rash. These disorders share common features with the connective-tissue diseases and are usually classified together. It is said that there is an increased association with neoplasia.The Problem of DiagnosisThere are at present no generally accepted criteria for the diagnosis of polymyositis-dermatomyositis akin to the Jones criteria for rheumatic fever or to the American Rheumatism Association criteria for rheumatoid arthritis. Consequently, the basis for the diagnosis has varied widely in retrospective studies, which, . . .

A Controlled Trial of High-Dose Intravenous Immune Globulin Infusions as Treatment for Dermatomyositis

1993-12-30

Marinos C. Dalakas , Isabel Illa , James M. Dambrosia +5 more

Dermatomyositis is a clinically distinct myopathy characterized by rash and a complement-mediated microangiopathy that results in the destruction of muscle fibers. In some patients the condition becomes resistant to therapy … Dermatomyositis is a clinically distinct myopathy characterized by rash and a complement-mediated microangiopathy that results in the destruction of muscle fibers. In some patients the condition becomes resistant to therapy and causes severe physical disabilities.

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Colchicine Myopathy and Neuropathy

1987-06-18

Ralph W. Kuncl , Greg J. Duncan , Danny F. Watson +3 more

Although colchicine has been used for centuries, its neuromuscular toxicity in humans is largely unrecognized. In this report we describe a characteristic syndrome of myopathy and neuropathy and present 12 … Although colchicine has been used for centuries, its neuromuscular toxicity in humans is largely unrecognized. In this report we describe a characteristic syndrome of myopathy and neuropathy and present 12 new cases of the condition. Colchicine myopathy may occur in patients with gout who take customary doses of the drug but who have elevated plasma drug levels because of altered renal function. It usually presents with proximal weakness and always presents with elevation of serum creatine kinase; both features remit within three to four weeks after the drug is discontinued. The accompanying axonal polyneuropathy is mild and resolves slowly. Electromyography of proximal muscles shows a myopathy that is marked by abnormal spontaneous activity. Because of these features, colchicine myoneuropathy is usually misdiagnosed initially, either as probable polymyositis or as uremic neuropathy. The myopathy is vacuolar, marked by accumulation of lysosomes and autophagic vacuoles unrelated to necrosis or to the mild denervation in distal muscles. The morphologic changes in muscle suggest that the pathogenesis involves disruption of a microtubule-dependent cytoskeletal network that interacts with lysosomes. Correct diagnosis may save patients with this disorder from inappropriate therapy. (N Engl J Med 1987; 316: 1562–8.)

Muscle Biopsy: A Practical Approach

2014-04-30

Fernando Leiva‐Cepas

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Risk of Cancer in Patients with Dermatomyositis or Polymyositis

1992-02-06

Bárður Sigurgeirsson , Bernt Lindelöf , Olof Edhag +1 more

An association between polymyositis and cancer was first proposed in 1916, but the existence of the association has been disputed. An association between dermatomyositis and cancer is better accepted, but … An association between polymyositis and cancer was first proposed in 1916, but the existence of the association has been disputed. An association between dermatomyositis and cancer is better accepted, but its magnitude is not known.We undertook a study to provide accurate estimates of the risk of cancer in patients with dermatomyositis or polymyositis. We studied the incidence of cancer and the rate of mortality from cancer in a population-based cohort of 788 patients with dermatomyositis or polymyositis in Sweden from 1963 through 1983. The results were compared with those for the general population.Among the 396 patients with polymyositis, 42 cancers were diagnosed at the same time or after polymyositis was diagnosed in 37 patients (9 percent). The relative risk of cancer was 1.8 (95 percent confidence interval, 1.1 to 2.7) in the male patients and 1.7 (95 percent confidence interval, 1.0 to 2.5) in the female patients. Eighty-four males and 85 females died, and in 24 of these cases (14 percent) cancer was the principal cause of death. The mortality ratio (the rate of mortality from cancer in these patients as compared with that in the general population) was 0.90 (95 percent confidence interval, 0.6 to 1.4). Among the 392 patients with dermatomyositis, 61 cancers were diagnosed at the same time or after dermatomyositis was diagnosed in 59 patients (15 percent). The relative risk of cancer was 2.4 (95 percent confidence interval, 1.6 to 3.6) in the male patients and 3.4 (95 percent confidence interval, 2.4 to 4.7) in the female patients. Fifty-seven males and 110 females died, and in 67 of these cases (40 percent) cancer was the principal cause of death (mortality ratio, 3.8; 95 percent confidence interval, 2.9 to 4.8).The risk of cancer is increased in patients with polymyositis or dermatomyositis. In patients with dermatomyositis there is also a higher rate of mortality from cancer.

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Microvascular Deposition of Complement Membrane Attack Complex in Dermatomyositis

1986-02-06

John T. Kissel , Jerry R. Mendell , Kottil Rammohan

We examined the role of the complement system in the pathogenesis of dermatomyositis. Using an antibody against the neoantigens of the terminal C5b-9 membrane attack complex, we performed immunocytochemical studies … We examined the role of the complement system in the pathogenesis of dermatomyositis. Using an antibody against the neoantigens of the terminal C5b-9 membrane attack complex, we performed immunocytochemical studies that localized this complex to the intramuscular microvasculature (arterioles and capillaries) of muscle biopsy specimens from 10 of 12 patients (83 percent) with childhood dermatomyositis and 5 of 19 patients (26 percent) with adult dermatomyositis. Fifty-two control specimens, including 14 from patients with polymyositis and 12 from patients with denervation atrophy (a condition known to be associated with necrotic capillaries), showed no deposition of membrane attack complex in the microvasculature. These findings indicate that the complement system is deposited, bound, and activated to completion within the intramuscular microvasculature of patients with dermatomyositis. In addition to providing further evidence for the presence of vasculopathy in dermatomyositis, these findings suggest a primary role for complement in mediating vessel injury in the disease, particularly in its childhood form.

Muscle Biopsy: A Practical Approach

1986-01-01

Anthony J. Bourne

224th ENMC International Workshop:

2017-10-23

Yves Allenbach , Andrew L. Mammen , Olivier Benveniste +7 more

2017 European League Against Rheumatism/American College of Rheumatology classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups

2017-10-27

Ingrid E. Lundberg , Anna Tjärnlund , Matteo Bottai +7 more

<h3>Objective</h3> To develop and validate new classification criteria for adult and juvenile idiopathic inflammatory myopathies (IIM) and their major subgroups. <h3>Methods</h3> Candidate variables were assembled from published criteria and expert … <h3>Objective</h3> To develop and validate new classification criteria for adult and juvenile idiopathic inflammatory myopathies (IIM) and their major subgroups. <h3>Methods</h3> Candidate variables were assembled from published criteria and expert opinion using consensus methodology. Data were collected from 47 rheumatology, dermatology, neurology and paediatric clinics worldwide. Several statistical methods were used to derive the classification criteria. <h3>Results</h3> Based on data from 976 IIM patients (74% adults; 26% children) and 624 non-IIM patients with mimicking conditions (82% adults; 18% children), new criteria were derived. Each item is assigned a weighted score. The total score corresponds to a probability of having IIM. Subclassification is performed using a classification tree. A probability cut-off of 55%, corresponding to a score of 5.5 (6.7 with muscle biopsy) 'probable IIM', had best sensitivity/specificity (87%/82% without biopsies, 93%/88% with biopsies) and is recommended as a minimum to classify a patient as having IIM. A probability of ≥90%, corresponding to a score of ≥7.5 (≥8.7 with muscle biopsy), corresponds to 'definite IIM'. A probability of <50%, corresponding to a score of <5.3 (<6.5 with muscle biopsy), rules out IIM, leaving a probability of ≥50 to <55% as 'possible IIM'. <h3>Conclusions</h3> The European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for IIM have been endorsed by international rheumatology, dermatology, neurology and paediatric groups. They employ easily accessible and operationally defined elements, and have been partially validated. They allow classification of 'definite', 'probable' and 'possible' IIM, in addition to the major subgroups of IIM, including juvenile IIM. They generally perform better than existing criteria.

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2017 European League Against Rheumatism/American College of Rheumatology Classification Criteria for Adult and Juvenile Idiopathic Inflammatory Myopathies and Their Major Subgroups

2017-10-27

Ingrid E. Lundberg , Anna Tjärnlund , Matteo Bottai +7 more

To develop and validate new classification criteria for adult and juvenile idiopathic inflammatory myopathies (IIM) and their major subgroups.Candidate variables were assembled from published criteria and expert opinion using consensus … To develop and validate new classification criteria for adult and juvenile idiopathic inflammatory myopathies (IIM) and their major subgroups.Candidate variables were assembled from published criteria and expert opinion using consensus methodology. Data were collected from 47 rheumatology, dermatology, neurology, and pediatric clinics worldwide. Several statistical methods were utilized to derive the classification criteria.Based on data from 976 IIM patients (74% adults; 26% children) and 624 non-IIM patients with mimicking conditions (82% adults; 18% children), new criteria were derived. Each item is assigned a weighted score. The total score corresponds to a probability of having IIM. Subclassification is performed using a classification tree. A probability cutoff of 55%, corresponding to a score of 5.5 (6.7 with muscle biopsy) "probable IIM," had best sensitivity/specificity (87%/82% without biopsies, 93%/88% with biopsies) and is recommended as a minimum to classify a patient as having IIM. A probability of ≥90%, corresponding to a score of ≥7.5 (≥8.7 with muscle biopsy), corresponds to "definite IIM." A probability of <50%, corresponding to a score of <5.3 (<6.5 with muscle biopsy), rules out IIM, leaving a probability of ≥50-<55% as "possible IIM."The European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for IIM have been endorsed by international rheumatology, dermatology, neurology, and pediatric groups. They employ easily accessible and operationally defined elements, and have been partially validated. They allow classification of "definite," "probable," and "possible" IIM, in addition to the major subgroups of IIM, including juvenile IIM. They generally perform better than existing criteria.

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Idiopathic inflammatory myopathies

2021-12-02

Ingrid E. Lundberg , Manabu Fujimoto , Jiří Vencovský +5 more

Polymyositis and dermatomyositis

2003-09-01

Marinos C. Dalakas , Reinhard Hohlfeld

Anatomie und Physiologie der Capillaren

1929-01-01

August Krogh

Percutaneous Needle Biopsy of Skeletal Muscle in Physiological and Clinical Research

1975-11-01

Jonas Bergström

Muscle biopsy: A modern approach

1975-01-01

Victor Dubowitz

Atypical Presentation of Calcinosis Cutis in a Patient With Renal Lupus

2025-06-25

Sree Yazhini Ramar , Arun Somasundaram , Kashish Arora +2 more | American Journal of Dermatopathology

Rehospitalization to evaluate outcomes during clinical courses in patients with elderly-onset idiopathic inflammatory myositis: a retrospective single-center study

2025-06-25

Jun-ichi Kurashina , Yasuhiro Shimojima , Dai Kishida +2 more | Clinical Rheumatology

Inclusion Body Myositis (IBM) Presenting with Macroglossia: A Diagnostic Challenge

2025-06-24

Abhilasha Patel | International Journal of Oral and Maxillofacial Surgery

Unexpected Bone Resorption Due to Alloplastic Chin Implants or Hyaluronic Acid Injection into the Chin

2025-06-24

N. Yoshioka , Kuniko Kadoya , Soichiro Ibaragi | International Journal of Oral and Maxillofacial Surgery

Autonomic Denervative Dermatitis in the Chin Area Following Mandibuloplasty

2025-06-23

Jeeyoon Kim , Eun Young Rha , Jongweon Shin | Journal of Craniofacial Surgery

Autonomic denervative dermatitis (ADD) is a rare skin condition caused by autonomic nerve injury, often after surgery. It typically presents as erythematous or excoriated lesions in areas with sensory loss. … Autonomic denervative dermatitis (ADD) is a rare skin condition caused by autonomic nerve injury, often after surgery. It typically presents as erythematous or excoriated lesions in areas with sensory loss. While cases in the lower limbs are documented, facial involvement after mandibuloplasty has not been reported. The authors describe a 27-year-old woman who developed ADD 1 year after angle-body reduction mandibuloplasty. She presented with pruritic, erythematous papules on the chin and sensory deficits. The lesions resolved spontaneously, leaving scarring and contour irregularities. Diagnosis was based on clinical history and exclusion of other conditions such as contact dermatitis and seborrheic dermatitis. Autonomic denervative dermatitis arises from sudomotor dysfunction and immune dysregulation due to autonomic nerve damage. Surgeons should be aware of this potential complication, especially involving the mandibular canal. Early recognition and treatment with emollients, corticosteroids, and antihistamines may prevent permanent sequelae. This case underscores the need for awareness to avoid underdiagnosis.

Fenómeno isotópico de Wolf en un paciente con linfoma linfoblástico de células T

2025-06-20

Vanesa Garrigasait Vilaseca , Eduardo Subiela Perez , Ignasi Espadaler Fabrego +2 more | Medicina Clínica

Dasatinib-Induced Polymyositis-Like Syndrome: A Report of a Rare Case

2025-06-20

Anuja Santosh Kulkarni , Chandana Keshavamurthy , Tamim Sultani +2 more | Cureus

Benign Acute Childhood Myositis: Evaluation of Clinical and Laboratory Features

2025-06-19

Ecem İpek Altınok , Emine Yurdakul Ertürk , Taner Kasar +2 more | Cam and Sakura Medical Journal

Pediatric immune-mediated necrotizing myopathy with anti-SRP antibodies targeting 19, 68, and 72 kda subunits

2025-06-19

Daigo Kato , Yukiko Sato , Kanako Mitsunaga +5 more | Pediatric Rheumatology

Muscle Spatial Transcriptomic Reveals Heterogeneous Profiles in Juvenile Dermatomyositis and Persistence of Abnormal Signature After Remission

2025-06-19

Margot Tragin , Séverine A. Degrelle , Baptiste Periou +7 more | Cells

This study aimed to investigate the spatial heterogeneity of molecular signature in the muscle of juvenile dermatomyositis (JDM) patients before and after treatment. Unsupervised reference-free deconvolution of spatial transcriptomics and … This study aimed to investigate the spatial heterogeneity of molecular signature in the muscle of juvenile dermatomyositis (JDM) patients before and after treatment. Unsupervised reference-free deconvolution of spatial transcriptomics and standardized morphometry were performed in two JDM muscle biopsies with different clinical severity at disease onset and compared to healthy muscle. Identified signatures were scored in two additional JDM muscle biopsies from the same patient before and after remission. Disappearance of the normal muscle signature mostly corresponding to mitochondrial biology was observed in JDM. Three pathological transcriptomic signatures were isolated, related to "myofibrillar stress", "muscle remodeling" and "interferon signaling" signatures. The "myofibrillar stress signature" was prominent in the most severe biopsy while the "muscle remodeling" signature was mostly present in the biopsy from the patient with good outcome. These signatures unveiled genes not previously associated with JDM including ANKRD1 and FSLT1 for "myofibrillar stress" and "muscle remodeling" signatures, respectively. Post-treatment analysis of muscle after two years remission showed a persistence of pathological signatures. This pilot study of JDM muscle identified spatially distributed pathological signatures that persist after remission. This work paves the way for a better understanding of the pathophysiology in affected muscle and the identification of biomarkers that predict relapse.

Two Cases of Statin-Induced Immune-Mediated Necrotizing Myopathy: A Rare Side Effect of Statins

2025-06-19

Luis Angel Montero Furelos , C. Pena , Beatriz San Millan Tejedor | Rheumato

Statins are effective drugs for lowering cholesterol and reducing cardiovascular risk. Rarely, they can trigger autoimmune myopathies like immune-mediated necrotizing myopathy (IMNM), associated with anti-HMGCR antibodies. This condition may persist … Statins are effective drugs for lowering cholesterol and reducing cardiovascular risk. Rarely, they can trigger autoimmune myopathies like immune-mediated necrotizing myopathy (IMNM), associated with anti-HMGCR antibodies. This condition may persist after statin discontinuation and requires immunosuppressive treatment. Despite these rare side effects, the benefits of statins outweigh the risks for most patients.

Inverse Gottron’s sign in Anti TIF1 gamma positive juvenile dermatomyositis

2025-06-18

Subash Mohan Thulasi , Saranya Chinnadurai , Sornavalli Valliappan +1 more | Romanian Journal of Rheumatology

Dermatomyositis is a rare idiopathic inflammatory myopathy characterized by distinctive cutaneous findings and proximal muscle weakness. We describe a 15-year-old girl who presented with a six-month history of heliotrope rash … Dermatomyositis is a rare idiopathic inflammatory myopathy characterized by distinctive cutaneous findings and proximal muscle weakness. We describe a 15-year-old girl who presented with a six-month history of heliotrope rash and V-sign erythema, accompanied by symmetrical proximal muscle weakness. Further examination revealed Gottron’s papules and the rare manifestation of inverse Gottron’s papules. Laboratory evaluation revealed elevated muscle enzymes. An extended myositis antibody panel demonstrated strong anti-TIF1γ positivity, while anti-MDA5, Mi-2, Jo-1, and other myositis-specific antibodies were negative, confirming a diagnosis of dermatomyositis. Screening excluded interstitial lung disease and underlying malignancy. Inverse Gottron’s papules are usually associated with anti-MDA5 dermatomyositis and rapidly progressive interstitial lung disease; their occurrence in anti-TIF1γ–positive juvenile cases is scarcely documented. Treatment with oral prednisolone and methotrexate led to gradual resolution of cutaneous lesions and muscular symptoms. This case documents the rare coexistence of inverse Gottron’s papules and anti-TIF1γ seropositivity in juvenile dermatomyositis, underscores the diagnostic utility of this atypical palmar cutaneous sign, highlights the clinical phenotype associated with anti-TIF1γ positivity, and emphasizes the importance of continued malignancy surveillance despite the lower cancer risk in pediatric cohorts.

Association of Anti-Signal Recognition Particle Myopathy with Systemic Lupus Erythematosus

2025-06-18

Cheng‐Yin Tan , Tomica Ambang , Joo‐San Tan +3 more | Neurology India

Long-term outcome of juvenile dermatomyositis associated with lipodystrophy: experience of a university hospital

2025-06-18

Igor Kapetanović , Mirjana Gajić‐Veljic , Branka Bonači-Nikolić +1 more | Anais Brasileiros de Dermatologia

EFICÁCIA DA CICLOFOSFAMIDA NO TRATAMENTO DO LÚPUS ERITEMATOSO SISTÊMICO

2025-06-17

Davi Mamede da Luz , Heitor de Carvalho Sintra , Vitória Aparecida Monteiro Coelho | Revista Contemporânea

A ciclofosfamida (CYC) é um agente utilizado para tratar neoplasias e doenças autoimunes, administrada oralmente ou endovenosamente conforme a condição. Este estudo avalia a eficácia da CYC no tratamento do … A ciclofosfamida (CYC) é um agente utilizado para tratar neoplasias e doenças autoimunes, administrada oralmente ou endovenosamente conforme a condição. Este estudo avalia a eficácia da CYC no tratamento do Lúpus Eritematoso Sistêmico (LES), comparando sua eficácia nas manifestações da doença e investigando possíveis efeitos adversos, incluindo eventos neoplásicos. Foram realizadas buscas sistemáticas nas bases de dados BVS, PubMed, SciELO e LILACS utilizando descritores específicos sobre a eficácia da ciclofosfamida no tratamento do LES. Incluíram-se artigos em inglês e português, publicados entre 2000 e 2023, excluindo-se teses, dissertações não publicadas, artigos duplicados e anteriores a 2000. Os artigos selecionados foram avaliados quanto à relevância e qualidade, e os dados extraídos foram analisados qualitativa e quantitativamente. A busca resultou em 143 estudos, dos quais 14 foram selecionados para análise. A ciclofosfamida é amplamente utilizada no tratamento do Lúpus Eritematoso Sistêmico (LES), especialmente em casos graves como a nefrite lúpica (NL). Estudos demonstram sua eficácia na redução da atividade da doença e indução de remissão. No entanto, o uso prolongado pode levar a efeitos adversos significativos, incluindo toxicidade hematológica e riscos neoplásicos. Pesquisas revelam que altas doses estão associadas a eventos adversos graves e aumento do risco de neoplasia cervical. Estratégias como a administração de ciclofosfamida em baixa dose e combinação com outros imunossupressores têm mostrado eficácia semelhante com menos efeitos colaterais. A CYC é eficaz na redução da atividade do LES e na diminuição da necessidade de corticosteroides, com regimes de doses mais baixas apresentando menos efeitos adversos. A combinação com rituximabe pode melhorar resultados clínicos em casos refratários, mas a toxicidade prolongada exige monitoramento rigoroso e ajustes na dose.

Cell-free DNA profiles of dermatomyositis and its potential role in discriminating phenotypes

2025-06-17

Zhuangli Tang , Pengyu Chen , Heng Zhang +7 more | Frontiers in Immunology

Background Cell-free DNA (cfDNA) functions in the early-detection and monitoring of autoimmune diseases including systemic lupus erythematosus and rheumatoid arthritis. However, investigations into cfDNA profiles in dermatomyositis and their potential … Background Cell-free DNA (cfDNA) functions in the early-detection and monitoring of autoimmune diseases including systemic lupus erythematosus and rheumatoid arthritis. However, investigations into cfDNA profiles in dermatomyositis and their potential clinical implications remain scarce. Objectives To explore the overall landscape of cfDNA profiles in dermatomyositis and investigate potential roles in discriminating subtypes. Methods Following informed consent, 24 treatment-naïve patients diagnosed with dermatomyositis and 16 healthy controls were enrolled. We examined cfDNA concentrations, fragment distribution patterns, 5’-end motif frequencies and genetic variation profiles in all participants and studied potential correlation with laboratory parameters. Moreover, intergroup differences of cfDNA profiles among patients and potential correlation between extracellular DNases levels and cfDNA were investigated. Results Compared to healthy controls, dermatomyositis patients exhibited elevated cfDNA concentrations, with significantly longer cfDNA fragments, primarily centered around 180–360 bp; nonetheless, no correlation was witnessed between lab parameters and cfDNA levels. The A-end predominated the 5’-end motif, whereas the C-end was underrepresented, contrasting with the patterns observed in healthy controls. In addition, genetic variations in several genes, including PDE4DIP and BRCA2 , were commonly detected in cfDNA from dermatomyositis patients. Notably, end-motif profiles and cfDNA fragment length exhibited variations between anti-transcription intermediary factor 1-gamma positive patients with and without malignancies. However, owing to limited sample size, we failed to draw conclusions regarding extracellular DNase levels. Conclusions This study presents the first comprehensive depiction of cfDNA profiles in patients with dermatomyositis. Furthermore, cfDNA features exhibit variability across some sub-phenotypes and may serve as discriminatory indices. Finally, potential involvement of extracellular DNases in cfDNA profiles in dermatomyositis shall be further investigated.

Immune Characterization of a Vietnamese Cohort With Idiopathic Inflammatory Myopathies

2025-06-16

Yue‐Bei Luo , M. Nakazawa , N. Minh +6 more | Muscle & Nerve

ABSTRACT Introduction/Aims Idiopathic inflammatory myopathies (IIMs) are classified into five subtypes that are associated with distinct groups of myositis‐specific antibodies (MSAs). Variations in the prevalence, genetic predisposition and clinical manifestations … ABSTRACT Introduction/Aims Idiopathic inflammatory myopathies (IIMs) are classified into five subtypes that are associated with distinct groups of myositis‐specific antibodies (MSAs). Variations in the prevalence, genetic predisposition and clinical manifestations exist in patients with IIM from different ethnic backgrounds. In this study, we aimed to characterize the immunopathological changes in muscle tissue and serum cytokines in a Vietnamese IIM cohort with Kinh ethnicity. Methods Muscle biopsies, sera, clinical data, and autoantibody profiles from 64 patients with IIM were included. Muscles were stained by immunohistochemistry using antibodies that target immune cells and molecules. Serum cytokines were measured by multiplex bead arrays. Clustering analysis was performed using the partitioning around medoids algorithm. Results The anti‐MDA5 antibody was the most common MSA in this cohort (15.6%), followed by anti‐Jo‐1 (10.9%). A wide range of clinical manifestations and immunohistological features were seen within the serologically defined subgroups. There was no difference in the levels of immune cells, capillary density or dilation, or patterns of C5b‐9 expression between the myositis subgroups. MHC‐I patterns were the only immunomorphological variable that was different in these subgroups. IP‐10, IL‐17A, and APRIL were increased in patients with IIM compared to healthy controls ( p = 5.7 × 10 −3 , 6.9 × 10 −4 , 2.4 × 10 −3 , respectively) but without difference between IIM subgroups. Discussion Vietnamese patients with IIM demonstrated widely varying clinical and immunopathological features, with dermatomyositis and immune‐mediated necrotizing myopathy representing opposite ends of MHC‐I upregulation in muscle tissue. Thus classification of myositis requires comprehensive evaluation of clinical manifestations, serology profiling and muscle pathology.

Paraneoplastic Amyopathic Dermatomyositis Associated With a Bone and Medullary Location of Breast Adenocarcinoma

2025-06-15

Fadwa Haboub , Mohamed El Fadli , Othmane Zouiten +2 more | Cureus

[Clinical analysis of 4 cases of juvenile dermatomyositis complicated with massive hemorrhage of digestive tract].

2025-06-14

X N Wang , Xiaoling Wang , J R Zhang +3 more | PubMed

Objective: To investigate the clinical characteristics, treatment and prognosis of juvenile dermatomyositis (JDM) complicated by sever gastrointestinal hemorrhage in children. Methods: A retrospective analysis was conducted on 4 JDM patients … Objective: To investigate the clinical characteristics, treatment and prognosis of juvenile dermatomyositis (JDM) complicated by sever gastrointestinal hemorrhage in children. Methods: A retrospective analysis was conducted on 4 JDM patients with sever gastrointestinal hemorrhage admitted to our hospital, from January 2017 to January 2025. Data including demographics, clinical manifestations, laboratory and imaging findings, treatment courses, and outcomes were reviewed. Results: The cohort comprised 4 patients (2 males, 2 females), with onset ages of 6.1, 6.2, 10.0 and 8.0 years. All presented with rash and fatigue and were diagnosed with severe refractory JDM (strongly positive anti-NXP2 antibodies). Sever gastrointestinal hemorrhage occurred 18, 12, 51, and 2 months after JDM diagnosis. Two cases had confirmed gastrointestinal infections due to contaminated food. Abdominal pain was the initial gastrointestinal symptom and black stool was observed in all cases, hemoglobin levels dropped below 60 g/L (Case 1-4 decreased to 38, 59, 60 and 43 g/L respectively). All patients exhibited intestinal wall thickening. Active bleeding sites included the duodenum (3 cases: 2 cases near the duodenal papilla, 1 cases with diffuse duodenal oozing). Emergency endoscopic hemostasis was performed in 3 cases. One patient with diffuse duodenal bleeding required additional glucocortieoid pulse therapy after failed interventional embolization. Three patients stabilized following aggressive treatment of JDM, while 1 case died due to duodenal perforation. Conclusions: Anti-NXP2 antibody-positive JDM patients are prone to gastrointestinal involvement, particularly in chronic cases. Duodenal bleeding is common, with vascular erosion and deep mucosal ulcers posing life-threatening risks. For children with positive anti-NXP2 antibodies who present with abdominal pain and thickened intestinal walls, early endoscopic examination should be conducted as soon as possible to detect digestive tract lesions and provide timely treatment. Patients with severe digestive tract bleeding usually require active treatment for the underlying disease combined with endoscopic hemostasis therapy. Under timely treatment, the prognosis is relatively favorable.

Anti-HMGCR myopathy: observed ethnic differences in disease and disease outcomes in New Zealand

2025-06-14

Hamish Anderson , Ke Li Chow , J O'donnell | Lara D. Veeken

Abstract Objectives Anti-HMGCR myopathy is an immune-mediated necrotizing myopathy strongly associated with statin use in adults. Polynesians have a higher incidence of anti-HMGCR myopathy in New Zealand (NZ), but ethnic … Abstract Objectives Anti-HMGCR myopathy is an immune-mediated necrotizing myopathy strongly associated with statin use in adults. Polynesians have a higher incidence of anti-HMGCR myopathy in New Zealand (NZ), but ethnic differences in phenotype and outcome are not known. Methods 91 patients with anti-HMGCR myopathy were identified based on anti-HMGCR positivity by immunoprecipitation assay. Prioritised ethnicity data was used to identify 35 Polynesian and 48 NZ European patients to include in the cohort. Clinical records were accessed and information on disease phenotype, treatment, and outcome was obtained. Results Polynesian patients were younger than NZ European patients at presentation (median 64 vs 71 years p= 0.009). They were less likely to normalize their CK over the follow-up period (54.2% vs 79.2%, p= 0.016), even after controlling for length of follow-up. There were no other significant differences in disease phenotype or outcome found. Conclusion In addition to having higher incidence of anti-HMGCR myopathy, Polynesians are affected at a younger age and are less likely to achieve normal CK levels despite treatment over similar follow-up periods. The disproportionate burden of disease in this group should prompt early assessment of a Polynesian patient who presents with muscle symptoms while on a statin.

Diagnostic significance of carcinoembryonic antigen and anti-MDA5 antibodies in polymyositis/dermatomyositis-associated rapidly progressive interstitial lung disease

2025-06-13

Pengfang Tang , Wan Xing Hong , Binbin Chen +1 more | Medicina Clínica

A Case of Anti-TIF1γ Antibody-Positive Dermatomyositis Associated With Malignancy

2025-06-13

Muhammad Yasir , Abdelnassir Abdelgabar , Mohammed Elsayed +2 more | Cureus

Ruxolitinib in adult dermatomyositis with anti-TIF1γ antibody: a case report and literature review

2025-06-12

Jing Xu , Min Wang , Xia Liu +1 more | Frontiers in Immunology

Ruxolitinib is a selective JAK1/2 inhibitor, and its application in treating adult-onset dermatomyositis(DM) has rarely been described. Here, we report a case of an adult-onset DM patient with anti-TIF1γ antibody, … Ruxolitinib is a selective JAK1/2 inhibitor, and its application in treating adult-onset dermatomyositis(DM) has rarely been described. Here, we report a case of an adult-onset DM patient with anti-TIF1γ antibody, who also suffered from essential thrombocytosis related to the JAK2 V617F mutation. Her clinical symptoms of DM markedly improved after ruxolitinib treatment, whereas her platelet count did not significantly change. In addition, we reviewed previous studies on the treatment of adult DM with ruxolitinib, and summarized reports of the J AK2 V617F mutation in adult idiopathic inflammatory myopathy.

Acute exacerbation of anti-Ha antibody-positive antisynthetase syndrome-associated interstitial lung disease: a case report

2025-06-12

Yinying Li , Junyi Ke , Shu Huang +7 more | Frontiers in Immunology

Background Anti-synthetase syndrome (ASS) is a rare autoimmune myopathy, frequently associated with interstitial lung disease, and is characterized by the presence of anti-aminoacyl tRNA synthetase (ARS) antibodies. However, there have … Background Anti-synthetase syndrome (ASS) is a rare autoimmune myopathy, frequently associated with interstitial lung disease, and is characterized by the presence of anti-aminoacyl tRNA synthetase (ARS) antibodies. However, there have been limited reports of cases exhibiting positive anti-Ha antibodies. Methods This study presents a retrospective analysis of the clinical data from a patient with an acute exacerbation of ASS who tested positive for anti-Ha antibodies. Case presentation This patient initially presented with interstitial pneumonia. The initial anti-infective treatment was ineffective; however, symptoms improved following the addition of corticosteroids. Upon discontinuation of corticosteroids, the patient experienced a recurrence of cough, progressive worsening of dyspnea, and developed lower general weakness. Comprehensive autoantibody testing revealed positivity for anti-Ha antibodies, and MRI of the lower limbs indicated soft tissue edema. The patient was ultimately diagnosed with ASS with interstitial lung disease. Treatment with methylprednisolone pulse therapy, combined with cyclophosphamide, tacrolimus, tofacitinib citrate, and pirfenidone, led to an improvement in the patient’s condition, resulting in discharge. Post-discharge, the patient was maintained on regular oral prednisone, nintedanib, and tofacitinib. Follow-up to date has shown a stable condition, with resolution of pulmonary lesions observed upon re-examination. Conclusion Anti-Ha antibody is one of the specific antibodies associated with ASS, yet its positive rate remains exceedingly low. This case represents the first reported instance of an anti-Ha antibody-positive ASS in China. Misdiagnosis and missed diagnosis are prevalent in clinical practice, underscoring the importance of screening for autoantibodies when patients present with acute, unexplained interstitial lung changes and a poor response to anti-infective treatment. Furthermore, interstitial lung disease is the most common extra-muscular clinical manifestation observed in ASS patients. Differentiating between acute exacerbations of pulmonary infections and interstitial lung disease associated with rheumatic diseases poses a significant challenge, as both can occur concurrently. Therefore, during diagnosis and treatment, it is crucial to consider not only infections but also to identify the underlying causes of worsening lung lesions.

Inclusion body myositis – what are new lines of pathogenesis and therapy?

2025-06-05

Karsten Krause , Tobias Ruck , Felix Kleefeld | Current Opinion in Neurology

Purpose of review Although inclusion body myositis (IBM) is considered a rare disease, it is the most prevalent inflammatory myopathy in adults over 50 years of age. Its complex pathophysiological … Purpose of review Although inclusion body myositis (IBM) is considered a rare disease, it is the most prevalent inflammatory myopathy in adults over 50 years of age. Its complex pathophysiological background includes inflammatory and degenerative features, but it remains poorly understood. As a result, no effective therapy is currently available. In this review, we provide an update on the relevant contemporary literature addressing the clinical and pathophysiological aspects of IBM. Recent findings Recent studies have investigated drugs for IBM, including the immunosuppressant sirolimus, but haven’t shown satisfactory results. Some advancements have been made in investigating IBM pathophysiology: a cell culture model recapitulating key disease features has been established. Multiple studies have used RNA sequencing to elucidate disease-specific pathways, including selective type 2 fiber vulnerability. The importance of TDP-43 deposition and subsequent mis-splicing as a disease mechanism has been demonstrated. Further studies have shown the value of patient-reported outcome measures (PROM) and quantitative MRI as investigation tools. Research has also investigated and demonstrated the complex genetic susceptibility related to IBM. Summary In conclusion, significant discoveries have been made in the past year that enhance our clinical and pathophysiological insights into IBM. Due to the persistent lack of effective therapeutic options, additional research is essential – not only to investigate potential treatments but also to reveal the disease's underlying mechanisms.

Activated Dendritic Cell Subsets Characterize Muscle of Inclusion Body Myositis Patients and Correlate with KLRG1+ and TBX21+ CD8+ T cells

2025-06-05

Raphael A. Kirou , Iago Pinal‐Fernandez , Maria Casal‐Dominguez +7 more | medRxiv (Cold Spring Harbor Laboratory)

ABSTRACT Inclusion body myositis (IBM) is an idiopathic inflammatory myopathy characterized by muscle-infiltrating KLRG1+ and TBX21+ cytotoxic T cells and type 1 inflammation. Myeloid dendritic cells (mDCs), including type 1 … ABSTRACT Inclusion body myositis (IBM) is an idiopathic inflammatory myopathy characterized by muscle-infiltrating KLRG1+ and TBX21+ cytotoxic T cells and type 1 inflammation. Myeloid dendritic cells (mDCs), including type 1 conventional dendritic (cDC1) cells, type 2 conventional dendritic (cDC2) cells, and mature immunoregulatory dendritic (mregDC) cells, have previously been reported in skeletal muscle of IBM patients and may activate these cytotoxic T cells. Here, we analyzed single-nucleus RNA-sequencing (snRNA-seq) and bulk RNA-sequencing (RNA-seq) data from skeletal muscle of IBM, other myositis, and control patients to identify and quantify these mDC subsets and characterize their contribution to IBM inflammation. Our findings reveal that all three mDC subsets are relatively increased and activated in muscle of IBM patients and correlate with IBM-specific inflammatory markers. Our data specifically implicates cDC1 cells in CD8+ T cell activation via specific expression of both KLRG1 ligands, CDH1 and CDH2 , as well as IL12B in IBM muscle.

Risk, risk factors, and screening of malignancies in dermatomyositis: current status and future perspectives

2025-06-04

Shubei Liu , Zhihong Zhang , Shushan Yan +5 more | Frontiers in Oncology

Dermatomyositis (DM) is an idiopathic inflammatory myopathy with characteristic cutaneous inflammation and heterogeneous systemic involvements, and is strongly associated with risk of malignancy. This review summarizes the incidence of malignancies, … Dermatomyositis (DM) is an idiopathic inflammatory myopathy with characteristic cutaneous inflammation and heterogeneous systemic involvements, and is strongly associated with risk of malignancy. This review summarizes the incidence of malignancies, risk factors associated with malignancies, and cancer screening methods in DM patients. Large population-based cohort studies and meta-analyses have provided strong evidence for the significantly elevated incidence of malignancies in DM patients. Common malignancies occurring in DM patients mainly include ovarian cancer, lung cancer, breast cancer, pancreatic cancer, stomach cancer, hematologic malignancies, and colorectal cancer. Clinicians should cautiously consider the risk of malignancy in DM patients during diagnosis and treatment, conducting regular screening and monitoring to facilitate early detection and treatment of malignancies. Among myositis-specific antibodies, anti-transcription intermediary factor 1γ antibodies are strongly linked to malignancy risk. Other factors such as older age, male gender, dysphagia, skin necrosis, cutaneous vasculitis, rapid onset of the disease, elevated creatinine kinase, and elevated C-reactive protein are closely associated with the risk of malignancy. DM patients with these features need receive screening for malignant tumors or close monitoring and follow-up. DM patients, especially those within 3 years of onset, have a high risk of cancer and should receive careful cancer screening according to their risk stratification. Conventional screening tools such as imaging examinations and tumor marker tests are not effective in detecting malignancies among DM patients. Current cancer screening workflows available for DM patients largely mirror those used in the general population but may not fully address DM-specific characteristics, and the best strategy for screening cancer in DM patients is still lacking. To facilitate earlier detection and diagnosis of DM-associated cancer and thereby improve outcomes, more effective cancer detection tools and personalized malignancy screening workflows specifically tailored to the features of DM and their individual risk stratification are warranted.

High levels of EPSTI1 enhance IFN-β-mediated HLA-A expression and chemokine secretion in myoblasts in dermatomyositis

2025-06-03

Xiaojing Li , Ting Ding , Yizhi Xiao +7 more | Lara D. Veeken

Abstract Objectives Epithelial-Stromal Interaction 1 (EPSTI1), an interferon-related gene that has emerged as a gene of notable interest, plays a multifaceted role in cellular function and disease processes. However, the … Abstract Objectives Epithelial-Stromal Interaction 1 (EPSTI1), an interferon-related gene that has emerged as a gene of notable interest, plays a multifaceted role in cellular function and disease processes. However, the precise role of EPSTI1 in the context of dermatomyositis(DM) remains elusive and requires further exploration. Methods To investigate EPSTI1 expression in DM, we analyzed two transcriptome datasets, peripheral blood mononuclear cells (PBMCs) and muscle tissues from our DM cohort. We further validated the findings using RT-qPCR and immunohistochemical staining within our idiopathic inflammatory myopathy (IIM) cohort. Through Small Interfering RNA (siRNA)-mediated knockdown, we delved into the function and underlying mechanisms of EPSTI1 in DM patients. Results EPSTI1 is significantly upregulated in both PBMCs and muscle tissues of DM patients. A notable positive correlation between EPSTI1 expression and interferon-stimulating genes (ISGs) accompanies this upregulation. Furthermore, EPSTI1 levels were markedly elevated in interferon-β(IFN-β)-stimulated myoblasts. Functional studies have shown that downregulation of EPSTI1 inhibits multiple immune and inflammatory pathways, including antigen processing and presentation, chemokine-mediated signalling, interferon signalling, IL-1-mediated signalling, NIK/NF-κB signalling. EPSTI1 was involved in the expression of HLA-A and the secretion of chemokines in myoblasts mediated by IFN-β. Conclusion EPSTI1 might play an essential role in promoting muscle inflammation in DM by regulating the expression of HLA-A and the secretion of chemokines in myoblasts. Targeting EPSTI1 may represent a novel therapeutic approach for reducing muscle inflammation and damage in DM patients.

Predictive factors and clinical outcomes of progressive pulmonary fibrosis in anti-threonyl (PL7) positive anti-synthetase syndrome

2025-06-03

Xueyan Shan , Zhenguo Huang , Guochun Wang +1 more | Lara D. Veeken

Abstract Objectives Patients with anti-threonyl (PL7) positive anti-synthetase syndrome (ASS) exhibit a high prevalence of interstitial lung disease (ILD), which can progress to progressive pulmonary fibrosis (PPF) and increased mortality. … Abstract Objectives Patients with anti-threonyl (PL7) positive anti-synthetase syndrome (ASS) exhibit a high prevalence of interstitial lung disease (ILD), which can progress to progressive pulmonary fibrosis (PPF) and increased mortality. This study aims to explore the clinical characteristics, imaging features, and predictive factors for PPF. Methods A retrospective cohort of PL7-ASS patients at a single tertiary centre between January 2018 and December 2022, was analysed. Clinical, serological, and radiological data were collected at baseline and during follow-up. Results The study included 69 PL7-ASS patients with ILD (mean age: 54.5 years; 73.9% female). Baseline CT imaging revealed the following patterns: cellular nonspecific interstitial pneumonia (cNSIP, 29%), fibrotic NSIP (fNSIP, 18.8%), organizing pneumonia (OP, 14.5%), OP-cNSIP overlap (15.9%), OP-fNSIP overlap (14.5%), and usual interstitial pneumonia (UIP, 7.2%). PPF developed in 39.1% of patients. Elevated levels of lactate dehydrogenase (LDH; HR = 1.021, 95% CI: 1.002–1.04, p= 0.031) and carbohydrate antigen 125 (CA125; HR = 1.164, 95% CI: 1.023–1.326, p= 0.022) were identified as independent predictors of PPF. Patients with UIP or OP-NSIP overlap patterns exhibited worse survival (p= 0.0479) and higher PPF prevalence (p= 0.029). Patients who developed PPF had significantly lower survival rates compared with those without PPF (HR = 5.120, 95% CI: 1.566–16.740, p= 0.018). Conclusion PL7-ASS patients with ILD are at significant risk of developing PPF, which is associated with poor survival outcomes. Elevated LDH and CA125 levels may serve as reliable predictors of PPF, highlighting importance of early identification and aggressive management strategies.

New-onset dermatomyositis in a patient on nivolumab for metastatic melanoma

2025-06-01

Nina B. Curkovic , Douglas B. Johnson , Eva Rawlings Parker | BMJ Case Reports

We present a case of antitranscriptional intermediary factor 1 gamma positive dermatomyositis in a patient with metastatic malignant melanoma undergoing therapy with nivolumab. The patient was diagnosed with dermatomyositis after … We present a case of antitranscriptional intermediary factor 1 gamma positive dermatomyositis in a patient with metastatic malignant melanoma undergoing therapy with nivolumab. The patient was diagnosed with dermatomyositis after presenting with severe dysphagia, proximal muscle weakness and typical cutaneous and histologic findings. Nivolumab was discontinued, and intravenous and oral steroids, intravenous immunoglobulin and rituximab were initiated for the treatment of dermatomyositis. Both paraneoplastic dermatomyositis in patients with metastatic melanoma and dermatomyositis presenting as an immune-related adverse event in patients receiving immune checkpoint inhibitors (ICI) are rare. In this case, we highlight features that are consistent with both paraneoplastic dermatomyositis and ICI-induced dermatomyositis.

POS0278 RISK FACTORS AND PROGNOSTIC OUTCOMES OF PATIENTS WITH IDIOPATHIC INFLAMMATORY MYOPATHY COMPLICATED WITH INFECTION

2025-06-01

Lin Zhao , Kaldybaev Ma , Xianying Xing +3 more | Annals of the Rheumatic Diseases