Síndrome antisintetasa

Antisynthetase syndrome is characterized by the association of idiopathic inflammatory myositis, pulmonary disease, mechanic's hands, nonerosive artrhitis and detection of antisynthetase antibodies. The etiology and pathogenesis are unknown, but chemical agents, drugs, bacterial and autoimmune mechanisms have been implied. The response to the treatment is variable. The target antigen of antisynthetase antibodies (IgG) are cytoplasmic RNA-t synthetases, enzyme that catalyse the covalent union between the RNA-t and its corresponding aminoacid. It is found in 25-35% of PM/DM patients. The anti-histidyl-RNAt-synthetase (anti-Jo-1) antibody is the most frecuently found myositis specific atibody, representing 20-30% of patients.The detection of antisynthetase antibodies allows us to define a subgroup of patients with idiopathic inflammatory myositis and pulmonary disease as determinant prognosis factor. So, the early detection of antisynthetase antibodies is necessary in the diagnostic and management of inflammatory miopaties and idiopathic interstitial lung disease of unclear etiology with the purpose of determining an adecuate diagnosis and treatment for improving the prognosis of these diseases.     

Acute respiratory distress syndrome as the presenting manifestation of an antisynthetase syndrome

The antisynthetase syndrome is a subgroup of idiopathic inflammatory muscle diseases. Its characteristics are interstitial lung disease, myositis, polyarthritis, mechanic's hand like cutaneous involvement, and the presence of antisynthetase antibodies (anti-Jo1). The lung disease is the presenting feature in 50% of cases. We report a patient with an antisynthetase syndrome, revealed by an acute respiratory distress syndrome. This patient was already followed-up for a scleroderma and presented a probable overlap syndrome. The disease course was favourable with anti-CD20 therapy.     

Antisynthetase syndrome without myositic disease: a case report

Antisynthetase syndrome is a rare disorder, included among the idiopathic inflammatory myopathies, characterized by the presence of antisynthetase antibodies. We present a case of a patient with a suggestive clinical stage of interstitial lung disease, skin and articular disease, but without muscle involvement, with the presence of anti Jol antibodies.     

Clinical,serologic, and immunogenetic features in polish patients with idiopathic inflammatory myopathies

Objective. To determine the clinical, serologic, and immunogenetic correlations in patients with idiopathic inflammatory myopathies (IIM), and to evaluate the useful grouping of some diseases for practical clinical purposes. Methods. Patients with IIM were categorized according to clinical presentation as compared with auto-antibody specificity. Serum samples from 84 patients were screened for myositis-specific autoantibodies (MSAs) by indirect immunofluorescence and double immunodiffusion. All sera were also studied by protein A-assisted immunoprecipitation. Genomic DNA was isolated from peripheral blood mononuclear cells, and HLA-DQA1 and DRB1 alleles were determined. The patients were seen and followed up for many years in the same center. Results. MSAs were present in 19% of patients. The most common MSAs were antisynthetases in 13% of patients (Jo-1 10.7%, PL-12 1.2%, and EJ 1.2%), associated with the antisynthetase syndrome. Anti-SRP was found in 1.2% of patients, associated with polymyositis, and anti-Mi-2 in 4.9%, found exclusively in patients with dermatomyositis. The most frequent MSA was PM-Scl in 23.8% of patients, associated with scleromyositis, and Ku was present in 9.6% of patients with overlap syndromes. The alleles that were found at a significantly increased frequency were HLA-DRB1*0301 (59.4%) and DQA1*0501 (71.6%), which are in linkage disequilibrium. DQA1*0501 was present in 85.7% of patients with antisynthetases, and in 100% of patients with PM-Scl and Ku. Conclusion. The HLA-DRB1*0301; DQA1*0501 haplotype was found to be significantly increased in this population overall and in those myositis patients with antisynthetase, anti-PM-ScI, and anti-Ku antibodies. The results of this study confirm that IIM are heterogeneous syndromes, but can be divided into more useful groups on the basis of clinical, serologic, and immunogenetic features.     

Cancer-associated myositis in the presence of anti-Jo1 autoantibodies and the antisynthetase syndrome

We describe 3 patients with inflammatory myositis in association with a neoplasm whose serum also contained anti-Jo1 antibodies, one of which presented characteristic features of the antisynthetase syndrome. No patient had a rash, and muscle biopsy was suggestive of polymyositis in all 3. Immunohistochemistry confirmed the diagnosis of polymyositis in the single patient with sufficient tissue available. Our patients remind us that the presence of antisynthetase antibodies (and even antisynthetase syndrome) in a patient with inflammatory myositis does not preclude the diagnosis of cancer-associated myositis.     

Myositis‐specific and myositis‐associated antibodies in a series of eighty‐eight mediterranean patients with idiopathic inflammatory myopathy

Objective

To determine the prevalence of myositis‐specific autoantibodies (MSAs) and myositis‐associated autoantibodies (MAAs) and their clinical and immunogenetic correlations in Mediterranean patients with idiopathic inflammatory myopathies.

Methods

Sera from 88 patients were studied for MSAs and MAAs by RNA and protein immunoprecipitation. HLA typing was performed by sequence‐specific primer– and sequence‐specific oligonucleotide–polymerase chain reaction and serology. Statistical analyses were performed with Student's t‐test and Fisher's exact test. Cumulative survival probabilities were estimated by the Kaplan‐Meier method and Cox regression analysis.

Results

Twenty‐eight patients (30%) had MSAs, most commonly antisynthetase antibodies (23.9%). Six patients (7.5%) had anti–Mi‐2 antibodies. No anti–signal recognition particles were found. Arthritis, mechanic's hands, interstitial lung disease, and sicca syndrome were more prevalent in patients with antisynthetase antibodies. Dysphagia and the need for more treatment courses were more frequent in patients who were anti–Mi‐2 positive. Forty‐three patients (48%) had MAAs, 20 (22%) with anti–Ro 60 and 18 (20.4%) with anti–Ro 52. Ten patients (11.4%) were positive for anti–PM‐Scl, 6 (6.8%) for anti‐RNP, and 1 for anti‐Ku antibodies. Patients with PM‐Scl, RNP, or Ro antibodies were more often classified as having overlap syndrome. Immunogenetic studies found a significant association between HLA–DR3 and the presence of antisynthetase antibodies (P = 0.049), anti–PM‐Scl antibodies (P = 0.017), and interstitial lung disease (P = 0.03). No statistically significant differences in mortality, survival, or clinical course were observed between patients positive for MSAs or MAAs and the remaining patients.

Conclusion

These results are consistent with those from other published series, although some differences warrant consideration. Autoantibody studies may be useful for defining more homogeneous groups of patients with idiopathic inflammatory myopathies.

     

Diagnosis and classification of idiopathic inflammatory myopathies

The idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of diseases, collectively termed myositis, sharing symptoms of muscle weakness, fatigue and inflammation. Other organs are frequently involved, supporting the notion that these are systemic inflammatory diseases. The IIMs can be subgrouped into dermatomyositis, polymyositis and inclusion body myositis. The myositis‐specific autoantibodies (MSAs) identify other and often more distinct clinical phenotypes, such as the antisynthetase syndrome with antisynthetase autoantibodies and frequent interstitial lung disease and anti‐SRP and anti‐HMGCR autoantibodies that identify necrotizing myopathy. The MSAs are important both to support myositis diagnosis and to identify subgroups with different patterns of extramuscular organ involvement such as interstitial lung disease. Another cornerstone in the diagnostic procedure is muscle biopsy to identify inflammation and to exclude noninflammatory myopathies. Treatment effect and prognosis vary by subgroup. To develop new and better therapies, validated classification criteria that identify distinct subgroups of myositis are critical. The lack of such criteria was the main rationale for the development of new classification criteria for IIMs, which are summarized in this review; the historical background regarding previous diagnostic and classification criteria is also reviewed. As the IIMs are rare diseases with a prevalence of 10 in 100 000 individuals, an international collaboration was essential, as was the interdisciplinary effort including experts in adult and paediatric rheumatology, neurology, dermatology and epidemiology. The new criteria have been developed based on data from more than 1500 patients from 47 centres worldwide and are based on clinically easily available variables.     

Coexistence of two antisynthetases in a patient with the antisynthetase syndrome

We describe the immunologic findings in a patient with the antisynthetase syndrome characterized by prominent arthritis, lung fibrosis, and subclinical myositis. At disease onset and during the followup, this patient's serum showed 2 different subsets of antisynthetase autoantibodies: anti–Jo-1, which reacted with histidyl–transfer RNA (tRNA) synthetase by immunoblot and inhibited its enzymatic function; and anti-OJ, which immunoprecipitated the multi-enzyme complex of synthetases, and reacted with lysyl-tRNA synthetase by immunoblot. This is the first report of anti–Jo-1 and another antisynthetase antibody being found together in the same patient.     

Idiopathic inflammatory myopathies

The idiopathic inflammatory myopathies are a group of systemic autoimmune syndromes characterized by striated muscle inflammation. Here, we discuss the clinical features of this group of cond2itions and review the recent developments in the understanding of the pathogenesis and immunogenetics of the idiopathic inflammatory myopathies. The role of myositis-specific autoantibodies and their clinical significance and an overview of management are also provided.     

Myositis-specific and myositis-associated antibodies in a series of eighty-eight Mediterranean patients with idiopathic inflammatory myopathy

OBJECTIVE: To determine the prevalence of myositis-specific autoantibodies (MSAs) and myositis-associated autoantibodies (MAAs) and their clinical and immunogenetic correlations in Mediterranean patients with idiopathic inflammatory myopathies. METHODS: Sera from 88 patients were studied for MSAs and MAAs by RNA and protein immunoprecipitation. HLA typing was performed by sequence-specific primer- and sequence-specific oligonucleotide-polymerase chain reaction and serology. Statistical analyses were performed with Student's t-test and Fisher's exact test. Cumulative survival probabilities were estimated by the Kaplan-Meier method and Cox regression analysis. RESULTS: Twenty-eight patients (30%) had MSAs, most commonly antisynthetase antibodies (23.9%). Six patients (7.5%) had anti-Mi-2 antibodies. No anti-signal recognition particles were found. Arthritis, mechanic's hands, interstitial lung disease, and sicca syndrome were more prevalent in patients with antisynthetase antibodies. Dysphagia and the need for more treatment courses were more frequent in patients who were anti-Mi-2 positive. Forty-three patients (48%) had MAAs, 20 (22%) with anti-Ro 60 and 18 (20.4%) with anti-Ro 52. Ten patients (11.4%) were positive for anti-PM-Scl, 6 (6.8%) for anti-RNP, and 1 for anti-Ku antibodies. Patients with PM-Scl, RNP, or Ro antibodies were more often classified as having overlap syndrome. Immunogenetic studies found a significant association between HLA-DR3 and the presence of antisynthetase antibodies (P = 0.049), anti-PM-Scl antibodies (P = 0.017), and interstitial lung disease (P = 0.03). No statistically significant differences in mortality, survival, or clinical course were observed between patients positive for MSAs or MAAs and the remaining patients. CONCLUSION: These results are consistent with those from other published series, although some differences warrant consideration. Autoantibody studies may be useful for defining more homogeneous groups of patients with idiopathic inflammatory myopathies.     

Antisynthetase syndrome and interstitial lung involvement. Report of 6 cases

The cases of 6 patients (4 men, 2 women) with antisynthetase syndrome are reported. The mean age was 60 years and the most frequent symptom was increasing dyspnea (4 patients). One of the remaining 2 patients had hemoptysis and the last was asymptomatic. Systemic symptoms included Raynaud's phenomenon (2 patients), arthritis in hands (3) and muscle impairment (4). Chest films showed linear interstitial infiltrates of varying severity in 5 patients; the patient without such infiltrates also suffered silicosis. Functional assessment showed restrictive impairment in 4 patients; of the remaining 2 patients, 1 had chronic obstructive pulmonary disease and 1 had normal function. The antisynthetase antibody (ASAB) detected was anti-Jo-1 in 4 cases, anti-PL-12 in 1 case, and unidentified in 1 case. The course of disease was satisfactory for 5 patients. ASAB analysis is useful for studying idiopathic interstitial lung disease.     

Jusqu’où explorer une hyperéosinophilie associée à des manifestations pulmonaires ?

An eosinophilic inflammatory response is associated with various lung diseases. Progress in the pathophysiology of certain diseases with hypereosinophilia, called idiopathic, has led to their being clarified, for example, the so-called idiopathic hypereosinophilic syndromes. In children, after eliminating parasitic infection, the diagnosis is guided by the patient's clinical status (association with asthma, changes in the general state of health, extrarespiratory symptoms, drugs). Bronchoscopy with broncho-alveoalar lavage and biopsy that show alveolar and parenchymal eosinophilia and a thoracic CT can narrow the diagnosis and determine the subsequent laboratory studies to be done. Whatever the cause, prolonged hypereosinophilia carries with it a risk of systemic pathology, especially cardiac, especially if the eosinophils are activated.     

Joint and muscle inflammatory disease: A scoping review of the published evidence

ObjectivesPolyarthritis is commonly reported in idiopathic inflammatory myositis patients, but few studies have focused on the overlap of myositis with rheumatoid arthritis which is a difficult diagnosis in the absence of well-defined diagnostic criteria. The primary objective of this scoping review was to map the field of research to explore the potential diagnoses in patients presenting with both myositis and polyarthritis.MethodsTwo electronic databases (MEDLINE/PubMed® and Web of Science®) were systematically searched using the terms (myositis OR ‘inflammatory idiopathic myopathies’) AND (polyarthritis OR ‘rheumatoid arthritis’) without any publication date limit.ResultsAmong individual records, 280 reports met inclusion criteria after full-text review. There was heterogeneity in the definition of overlap myositis as well as the characteristics of rheumatoid arthritis. In many studies, key data were lacking; rheumatoid factor status was reported in 56.8% (n=151), anti-citrullinated proteins antibodies status in 18.8% (n=50), and presence or absence of bone erosions in 45.1% (n=120) of the studies. Thirteen different diagnoses were found to associate myositis with polyarthritis: antisynthetase syndrome (29.6%, n=83), overlap myositis with rheumatoid arthritis (16.1%, n=45), drug-induced myositis (20.0%, n=56), rheumatoid myositis (7.5%, n=21), inclusion body myositis (1.8%, n=5), overlap with connective tissue disease (20.0%, n=56), and others (5.0%, n=14).ConclusionThe spectrum of joint and muscle inflammatory diseases encompasses many diagnoses including primitive and secondary myositis associated with RA or arthritis mimicking RA. This review highlights the need for a consensual definition of OM with RA to better individualise this entity from the numerous differential diagnoses.     

Antisynthetase syndrome without muscle involvement

Antisynthetase syndrome is a well defined syndrome characterized by the presence of interstitial lung disease in association with arthritis, miositis, mechanic's hands and Ruynaud's phenomenon in the presence of antisynthetase antibodies, especially Ac anti-Jo1. We described the case of a 68-year-old man with this syndrome in the absence of inflammatory muscle disease.     

Antisynthetase syndrome – much more than just a myopathy

The aim of the study was to summarize current knowledge on antisynthetase syndrome (ASS), including its epidemiology, pathogenesis, proposed so far diagnostic criteria, heterogeneity of clinical manifestations, prognostic factors and therapeutic possibilities. PubMed database was screened for “antisynthetase syndrome” OR “antisynthetase antibodies” between February and April 2020. Aminoacyl-tRNA synthetases participate in the immune system activation as antigens, but also serve chemoattractive and cytokine-resembling roles, initiating innate and adaptive pathways. Exposure to various inhaled antigens may induce the autoimmune cascade leading to ASS. NK cells with its impaired INF-y production as well as formation of NETs by neutrophils contribute to pathogenesis. The prevalence of symptoms vary significantly depending on the study with muscular, articular and pulmonary involvement being the most frequently observed. Although classified as subtype of idiopathic inflammatory myopathies, myositis may not necessarily be the prominent manifestation. Since clinical presentation is heterogeneous and symptoms can emerge gradually, ASS could be considered as a heterogeneous spectrum rather than a homogenous disease entity. The currently available classification criteria do not fully correspond with the clinical patterns of the disease. Therapy is based on glucocorticosteroids and other immunosuppressive agents. Randomized controlled trials, dedicated for patients with ASS, are needed to form treatment algorithms.     

Seasonal influence on the onset of idiopathic inflammatory myopathies in serologically defined groups

OBJECTIVE: To assess possible seasonal patterns in the onset of polymyositis (PM) and dermatomyositis (DM). METHODS: The study group comprised 503 patients who met the criteria for probable or definite PM or DM and for whom detailed data on the time of myositis onset were available. Statistical analyses were performed using a Poisson model that assessed associations of ethnicity, sex, autoantibody presence, and month of onset of muscle weakness. RESULTS: There were no significant seasonal patterns of disease onset in myositis patients as a whole or in the total PM or DM populations. Significant seasonal associations were present, however, in the serologically defined groups. In the 131 patients with antisynthetase autoantibodies who were categorized as non-black, myositis onset peaked in March-April (P = 0.03). Among the antisynthetase-positive patients, the association was predominantly in those with PM (n = 85; P = 0.05) and in men (n = 51; P = 0.042). Patients with anti-signal recognition particle autoantibodies, however, did not have a significant seasonal onset, which is in contrast to previous findings. Patients without myositis-specific autoantibodies showed a significant peak in summer, with myositis onset in June-July (n = 252; P = 0.03); this seasonal association was significant in women (n = 182; P = 0.005), whereas there was no seasonal pattern in men (P = 0.9). CONCLUSION: These findings, in conjunction with other data, suggest that diverse environmental agents, acting upon different immunogenetic backgrounds, result in distinct immune responses and clinical syndromes in the idiopathic inflammatory myopathies. Our results emphasize the importance of considering more homogeneous disease groups, based on clinicopathologic features, immune responses, ethnicity, and sex, when attempting to decipher the pathogeneses of autoimmune disorders.     

“Hiker’s feet”: a novel cutaneous finding in the inflammatory myopathies

Clinical Rheumatology - Mechanic’s hands is a well-characterized manifestation of select idiopathic inflammatory myopathy (IIM) syndromes. Less well characterized is the hyperkeratosis of the...     

Beneficial effect of treatment with cyclosporin A in a case of refractory antisynthetase syndrome

We report a case of idiopathic inflammatory myopathy accompanied with the presence of anti-Jo1 antibodies and complicated by diffuse parenchymal lung disease (antisynthetase syndrome). Efficacy of different therapeutic agents, including corticosteroids, cyclophosphamide and cyclosporin A, is described. We present beneficial effect of cyclosporin A and corticosteroids regimen, and confirm no benefits of plasmapheresis. An interesting association of the disease onset with toxoplasmosis infection is discussed and difficulties regarding diagnosis of cardiac involvement are addressed. We also review other case reports of this rare disorder of poor prognosis.     

Rare association of antisynthetase syndrome and Kennedy’s disease

Antisynthetase syndrome is a type of Idiopathic Inflammatory Myopathy (IIM) associated with anti-Jo1 antibody. Kennedy's disease or X-linked spinal and bulbar muscular atrophy (SBMA) is a rare neuromuscular disease. We describe the case report of a 53-year-old man who presented with proximal muscle weakness and a history of bilateral hand tremor. Initial physical examination demonstrated "mechanic's hands", Raynaud's phenomenon, having elevated creatine kinase and lactate dehydrogenase levels and anti-Jo1 antibody positivity. His muscle biopsy demonstrated inflammatory infiltrate characteristic of IIM. Considering these findings, we reached the diagnosis of antisynthetase syndrome and commenced immunosuppressive therapy. On follow-up examination, he had developed dysphagia, and his tremor had worsened. His electroneurogram result was characteristic of Kennedy's disease, and the genetic test result showed an allele with 44 CAG repeat expansion in the androgen receptor gene of the X chromosome. This confirmed that in addition to antisynthetase syndrome, he also had Kennedy's disease. This patient now receives immunology and neurology follow-up. His symptoms have improved with low dose corticosteroids, propranolol for tremor, vitamin B supplementation, and physiotherapy. This article presents a rare case report of a patient with concurrent antisynthetase syndrome and Kennedy's disease, both of which lead to elevated creatine kinase levels and muscle weakness, thus, underpinning the importance of careful follow-up of patients with IIM and maintaining an open mind to other diagnoses when faced with refractory and/or new symptoms.