Risk of coronary artery disease in patients with idiopathic inflammatory myopathies: A systematic review and meta-analysis of observational studies

Objectives

To investigate the risk of coronary artery disease in patients with idiopathic inflammatory myopathies (IIM).

Methods

We conducted a systematic review and meta-analysis of observational studies that reported odds ratios, relative risks, hazard ratios, or standardized incidence ratios comparing the risk of coronary artery disease in patients with IIM versus non-IIM participants. We searched published studies indexed in MEDLINE, EMBASE, and the Cochrane database from inception to December 2013 using the terms “coronary artery disease” OR “coronary heart disease” OR “myocardial infarction” OR “atherosclerosis” combined with the terms “dermatomyositis” OR “polymyositis” OR “Idiopathic inflammatory myopathy.” Pooled risk ratio and 95% confidence interval were calculated using a random-effect, generic inverse variance method.

Result

Overall, four studies were identified and included for data analysis. The pooled risk ratio of CAD in patients with IIM was 2.24 (95% CI: 1.02–4.92). The statistical heterogeneity of this meta-analysis was high with an I² of 97%.

Conclusion

Our study demonstrated a statistically significant increased risk of CAD among patients with IIM.     

Response to cyclophosphamide and rituximab therapy in idiopathic inflammatory myopathies: A single center experience

Aim of the workTo evaluate the clinical response to cyclophosphamide (CYC), and rituximab (RTX) following CYC regarding muscle power and creatine kinase (CK) level changes, and the ability to manage cardiac and bulbar affection in dermatomyositis (DM) and polymyositis (PM) patients.Patients and methodsTwenty two idiopathic inflammatory myopathies (IIM) patients: 14 (63.6%) DM and 8 (36.4%) PM were categorized into CYC group (n = 17) received only CYC, and RTX group received RTX following refractory CYC (n = 5). History taking and clinical examination were done, and Medical Research Council Sum Score (MRC-SS) and CK were evaluated at baseline visit, by end of monthly CYC, and 18 months after CYC or RTX. Improvement of cardiac affection or bulbar manifestations was checked.ResultsPatients were 16 females and 6 males (F:M 2.7:1) and mean age was 34.9 ± 14.9 years. The patients were followed up for 7.7 ± 4.3 years. MRC–SS increased in (CYC group) and in (RTX group) (p < 0.001, and p = 0.018 respectively). CK levels decreased significantly in CYC group (p < 0.001) but not in RTX group. MRC-SS changes in males, females, DM, PM patients were (p = 0.007, p < 0.001, p < 0.001, p = 0.006 respectively), and CK changes (p = 0.17, p < 0.001, p < 0.001, p = 0.006 respectively). The two DM cardiac patients and the three PM patients with bulbar manifestations in (RTX group) showed improvement in their extra-muscular manifestations.ConclusionCYC can be an effective drug in the treatment of IIM muscle affection. RTX may be promising for refractory myositis, cardiac and bulbar manifestations, so these patients should be a target for its early administration.     

Characterization of relapses in adult idiopathic inflammatory myopathies

The objective of the current report was to determine the relapse rates and characterize the nature of relapses during the disease course of adult patients with idiopathic inflammatory myopathies (IIM). A retrospective cohort study of 53 medical records of patients with polymyositis (PM), dermatomyositis (DM), connective tissue disease (CTD)-associated myositis, and malignancy-associated myositis at an academic rheumatology center was performed. Medical records were reviewed to determine clinical presentation, initial treatment, and clinical follow-up, with an emphasis on relapses. Relapses were defined as a sustained elevation in serum creatine kinase (CK) levels in the absence of an alternative etiology. Patients were followed for an average of 65±43 months. All patients received corticosteroids, and 35 patients received additional immunosuppressive medications as part of their initial treatment. Serum CK levels normalized in 51 patients, and muscle strength normalized in 43 patients. Biochemical relapse was observed in 33 patients (65%). Patients with PM and CTD-associated myositis had a higher relapse rate compared to DM and malignancy-associated myositis patients. Multiple relapses were observed in 17 patients. Relapses tended to occur within the first 2 years after treatment initiation and during the tapering phase of treatment. No risk factors were unequivocally identified, although advanced age and increased duration of symptoms prior to treatment initiation had nonsignificant associations with increased risk of relapse. In conclusion, initial treatment of IIM results in a high rate of normalization of serum CK and muscle weakness. However, physicians should be aware of the high rate of relapse in patients with IIM.     

“Pregnancy in adult-onset idiopathic inflammatory myopathy”: Report from a cohort of myositis patients from a single center

Background and purpose

Idiopathic inflammatory myopathies (IIM) are systemic diseases, characterized by the presence of an inflammatory muscle infiltrate. Although more frequent in women, its relationship with pregnancy has not been extensively studied. Our goal was to analyze the interaction between pregnancy and myositis in a cohort of IIM women from a single center.

Methods

A total of 51 patients from a historical cohort of IIM diagnosed between 1983 and 2013 were interviewed with a specific questionnaire. Comparisons between pregnancies occurring before and after the onset of the disease were performed using generalized mixed-effect models with normal and binomial distributions adjusted for confounding factors and clustering.

Results

A total of 102 pregnancies from 51 patients (41 with dermatomyositis and 10 with polymyositis) were analyzed. A total of 14 pregnancies from 8 patients occurred after disease onset; statistically significant (p = 0.02) clinical improvement during gestation was evident in 7 pregnancies (4 patients), 5 of them (from 2 patients) experienced a relapse of IIM symptoms afterwards, while in the rest, there was no influence of pregnancy on the disease. No disease flare associated with pregnancy was observed. Two patients were diagnosed within the first 6 months after delivery and none during pregnancy. No evidence was found to support pregnancy as a trigger for myopathy (p = 0.71).

Conclusions

Pregnancy does not seem to carry a worse prognosis for the mother nor for the fetus in patients with IIM; on the contrary, nearly half of the patients in our series improved clinically when they became pregnant, a relapse of IIM symptoms being common afterwards. Pregnancy does not appear to be a trigger for IIM.     

主要组织相容性复合物在特发性炎性肌病中的表达及临床应用价值

目的 研究多发性肌炎(PM)和皮肌炎(DM)患者骨骼肌组织中的主要组织相容性复合物(MHC)的表达,探讨它们在特发性炎性肌病(IIM)发病机制中的作用及临床应用价值.方法 选取我院1986-2007年风湿免疫科收住的IIM患者骨骼肌组织标本45例(PM 19例,DM 26例),以性别、年龄相匹配的外伤患者骨骼肌标本30例作为对照.用免疫组织化学方法检测人类白细胞抗原(HIA)-A/B/C(即MHC-Ⅰ分子)和HLA-DR(即MHC-Ⅱ分子)在PM/DM患者及对照组肌组织中的表达.结果 HLA-A/B/C在18例PM、24例DM和3例对照组肌组织中有表达,阳性率分别为95%、92%和10%;HLA-DR在PM组、DM组和对照组肌组织中的阳性表达率分别为84%、81%和13%.HLA-A/B/C和HLA-DR在PM/DM患者肌组织中的表达量均较正常对照组明显升高(P均<0.05),但在PM组和DM组间差异无统计学意义(P均>0.05).根据组织病理学特点把PM/DM患者分为病变程度不同的3组,HLA-A/B/C和HLA-DR在PM/DM患者肌组织中的表达量与肌纤维变性、坏死、炎症浸润的程度和各项临床及实验室指标无明显关联(P均>0.05).结论 MHC-Ⅰ和Ⅱ类分子在PM/DM患者肌肉组织中表达增高,在无明显炎症浸润和肌纤维坏死的患者中也可见到这种表达的上调,检测肌组织中MHC-Ⅰ和Ⅱ类分子的表达可用于PM/DM的诊断.     

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.     

Myositis in clinical practice—relevance of new antibodies

Novel classification schemes for idiopathic inflammatory myopathy are based on serologic and histopathologic features. The presence of specific myositis autoantibodies may correspond to particular clinical phenotypes. Patients with a known diagnosis of inflammatory myopathy require a prompt clinical evaluation and the assessment of myositis-associated autoantibodies. Patients possessing autoantibodies associated with ILD or those with any pulmonary symptoms should undergo pulmonary functions tests and high-resolution computed tomography scanning of their lungs. Despite the lack of placebo-controlled trials, systemic glucocorticoids are considered the mainstay of initial treatment of myositis-associated ILD. Glucocorticoid-sparing agents are often started concomitantly with glucocorticoids, particularly in patients with moderate or severe disease. The first-line conventional immunosuppressive drugs include either mycophenolate mofetil or azathioprine, and when they fail or if the features are rapidly progressive, more aggressive therapy includes tacrolimus or cyclosporine, rituximab, intravenous immunoglobulin, or cyclophosphamide used either alone or in various combinations.     

Idiopathic inflammatory myositis

Knowledge on idiopathic inflammatory myopathy (IIM) has evolved with the identification of myositis-associated and myositis-specific antibodies, development of histopathological classification and the recognition of how these correlate with clinical phenotype and response to therapy. In this paper, we outline key advances in diagnosis and histopathology, including the more recent identification of antibodies associated with immune-mediated necrotising myopathy (IMNM) and inclusion body myositis (IBM). Ongoing longitudinal observational cohorts allow further classification of these patients with IIM, their predicted clinical course and response to specific therapies. Registries have been developed worldwide for this purpose.A challenging aspect in IIM, a multisystem disease with multiple clinical subtypes, has been defining disease status and clinically relevant improvement. Tools for assessing activity and damage are now recognised to be important in determining disease activity and guiding therapeutic decision-making. The International Myositis Assessment and Clinical Studies (IMACS) group has developed such tools for use in research and clinical settings.There is limited evidence for specific treatment strategies in IIM. With significant development in the understanding of IIM and improved classification, longitudinal observational cohorts and trials using validated outcome measures are necessary, to provide important information for evidence-based care in the clinical setting.     

Myo-Spain: Registro de pacientes con miopatía inflamatoria idiopática de España. Metodología

ObjectivesTo describe the methods of the Spanish Registry of patients with idiopathic inflammatory myopathy (IIM) (Myo-Spain), as well as its strengths and limitations. The main objective of the project is to analyse the evolution and clinical management of a cohort of patients with IIM.MethodsObservational, longitudinal, ambispective and multicentre study of a cohort of patients with IIM seen in rheumatology units in Spain. All patients with a diagnosis of IMM will be included in the regular follow-up of the participating centres, regardless of age on initiation of the process. Incident cases will be all patients who at the beginning of the study have been diagnosed for less than 12 months and prevalent cases for more than 12 months. The registry will include data from the visit at baseline, one year and two years. Socio-demographic, clinical, analytical variables, complications, comorbidities, association with other rheumatic diseases, hospital admissions, mortality and treatments will be collected. In addition, indices, scales and questionnaires of activity, muscle involvement, damage, disability, and quality of life will be determined. The recruitment period will be 23 months. The purpose is to obtain a cohort of 400 patients with IMM.ConclusionsMyo-Spain registry provides the opportunity to develop a cohort of incident and prevalent patients with IMM in Spain. Myo-Spain will be able to assess in detail the clinical characteristics of the disease at different times. The comprehensive information collected during the visits is expected to provide a broad source of data for future analysis.     

Coxsackievirus infection and the development of polymyositis/dermatomyositis

Recently, it has been suggested that coxsackievirus plays an etiologic role in juvenile dermatomyositis (DM). Neutralizing antibodies to 12 coxsackievirus antigens were measured in the sera of four clinical subsets of patients with adult polymyositis (PM)/DM. Elevated antibody titers to coxsackievirus A7, B3, and B4 were detected in patients with adult PM, adult DM, and adult PM/DM with malignancy, respectively. The development of these three subsets of idiopathic inflammatory myopathies may be related to infection with specific coxsackievirus serotypes.     

Cancer and myositis: Who,when, and how to screen

Cancer screening in idiopathic inflammatory myopathies (IIMs) is essential because an increased risk of cancer in IIMs has been well demonstrated. However, a consensus regarding cancer screening approaches is lacking. Therefore, the approach presented in this review reflects available evidence and our clinical experiences. Patients with IIMs should be evaluated for 3 distinct types of risk categories: (a) clinical with their history, physical examination, and laboratory parameters; (b) based on IIMs subtypes; and (c) based on serology – myositis specific and associated autoantibodies. Further, according to these characteristics, patients should be classified as low risk, moderate risk, and high risk for cancer. In our approach, all patients with IIM within 3 years of disease onset should undertake cancer screening according to their risk stratification. First, irrespective of risk, all patients should undergo age and gender-appropriate screening as per local guidelines. Patients at low-risk stratification should undertake basic cancer screening with routine blood counts, labs, and imaging; at moderate-risk stratification, patients should undertake enhanced cancer screening including CT chest; and at high-risk stratification, patients should undertake comprehensive cancer screening including PET/CT at baseline. Consensus guidelines among all major stakeholders, including rheumatologists, neurologists, dermatologists, and oncologists representing different parts of the world, establishing uniform cancer screening approaches in patients with IIM, are the need of the hour.     

特发性炎性肌病分型诊断标准的比较分析

目的 评价Bohan/Peter标准(B/P标准)与欧洲神经肌肉疾病中心(ENMC)标准对特发性炎性肌病分型诊断皮肌炎和多发性肌炎的准确性.方法 回顾性收集86例初诊为特发性炎性肌病患者的临床、实验室及骨骼肌病理资料,分别用B/P标准与ENMC标准进行分型诊断,比较两个标准诊断皮肌炎和多发性肌炎的异同性.数据分析采用SPSS 13.0软件系统进行非参数检验(Mann Whitney U检验)和一致性检验(Kappa分析)方法.结果 B/P标准诊断皮肌炎37例,多发性肌炎49例;ENMC标准诊断皮肌炎46例,多发性肌炎仅14例,其余为嗜酸细胞性肌炎1例、疑诊散发性包涵体肌炎9例,未能分型者5例,肢带型肌营养不良2B型11例.Kappa分析检验两个标准诊断皮肌炎一致性较好(κ=0.79),诊断多发性肌炎一致性差(κ=0.26).结论 B/P标准对多发性肌炎存在过度诊断、误诊风险.ENMC标准纳入免疫病理,增加了临床与病理诊断的排除标准,其分型诊断准确性优于B/P标准.     

Selective expression of MHC class I in the affected muscle of a patient with idiopathic inflammatory myopathy

The dominant clinical feature of polymyositis/dermatomyositis is weakness in proximal, rather than distal, musculature. Although rare, cases of focal/localized myositis in which polymyositis-like muscle inflammation is present in only one muscle or extremity have also been reported. The underlying mechanisms dictating involvement of specific muscle groups in polymyositis/dermatomyositis and focal/localized myositis have not been identified. Here, we describe a rare case of dropped-head syndrome due to localized idiopathic inflammatory myopathy (IIM) in the splenius capitis (neck extensor) muscle where major histocompatibility complex (MHC) class I expression was up-regulated in involved muscle fibers. Interestingly, the adjacent trapezius muscle was not affected, corresponding to muscle biopsy findings that did not show any sign of inflammation or MHC class I expression. Our case report therefore suggests that selection of affected muscle in IIM might be influenced by the MHC class I expression of the muscle.     

Idiopathic inflammatory myopathies: diagnostic criteria,classification and epidemiological features

Idiopathic inflammatory myopathies (IIM) are a group of rare autoimmune disorders characterized by muscle inflammation and progressive weakness. The cause of IIM is unclear but it is believed that disease expression may be triggered by unknown factors in genetically predisposed individuals. Diagnosis is based on a combination of clinical, laboratory and electromyography findings. Muscle biopsy is the definitive diagnostic test. Research into IIM has been limited by the rarity of the disease, a somewhat insidious onset, difficulties with classification and diagnostic methods and heterogeneous study populations making cross‐study evaluations difficult. This paper reviews the diagnostic and classification criteria of the IIM and examines epidemiological studies that have been performed, focusing on demographics.     

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.

     

A killer revealed: 10-year experience with beta-thalassemia intermedia

Objectives

Patients with beta-thalassemia intermedia tend to present later in life with milder anemia than beta-thalassemia major patients. The incidence of mortality and its causes in this patient population remains unknown. We aim to reveal the incidence and most common causes of death in this population.

Methods and results

We reviewed the charts of all of the beta-thalassemia intermedia patients who had been followed at the Chronic Care Center in Hazmieh, Lebanon during a 10-year period. A total of 18 patients out of 127 had died during the follow-up period giving a cumulative 10-year mortality incidence of 14%. The most common causes of cardiac deaths were due to renal and cardiac causes.

Discussion

Most causes of death have been linked to the high levels of iron coupled with anemia present in this patient population. Many of deaths could be prevented by adequate treatment.

Conclusion

Larger studies with more comprehensive data capture on risk factors of mortality in this patient population are called for.     

Tumor necrosis factor-alpha in inflammatory myopathies: pathophysiology and therapeutic implications

OBJECTIVES: To present, in an organized fashion, data from the medical literature on the possible role of tumor necrosis factor (TNF)-alpha in the pathogenesis of dermatomyositis (DM) and polymyositis (PM), as well as recent clinical studies where TNF-inhibition was used as a treatment for myositis. METHODS: PUBMED was searched from 1966 to the present using the terms: TNF-alpha, TNF-inhibitors, dermatomyositis, polymyositis, myositis, and inflammatory myopathy. In addition, relevant abstracts from major recent rheumatology meetings were retrieved. RESULTS: Several studies that employed immunostaining and polymerase chain reaction analysis in muscle biopsy specimens from patients with inflammatory myopathies showed increased presence of TNF-alpha and its soluble receptors in inflamed muscle. One genetic study proposed an association between DM and the -308A TNF polymorphism. Abnormally high levels of TNF-alpha in the muscle may be directly toxic to myofibers, while preventing muscle regeneration. Furthermore, TNF-alpha may induce, or augment, the production of other pro-inflammatory cytokines such as interleukin (IL)-1, monocyte chemotactic protein-1, IL-6, and IL-8. These findings have prompted some investigators to use off-label, TNF-inhibitors in DM/PM patients, especially if they had failed corticosteroids, immune gamma-globulin, and traditional immunosuppressive agents. The results from these early, uncontrolled, studies have been promising. CONCLUSION: TNF-alpha may have a role in the pathogenesis of the myositis and has emerged as a possible therapeutic target. Larger, carefully controlled studies are needed to confirm the results from early studies and clearly define the efficacy and safety of anti-TNF agents in the treatment of inflammatory myopathies.     

Treatment of early and refractory dermatomyositis with infliximab: a report of two cases

The idiopathic inflammatory myopathies embody the largest group of acquired and potentially treatable causes of skeletal muscle weakness. The three major groups of this disorder are polymyositis (PM), dermatomyositis (DM), and inclusion body myositis. Corticosteroids continue to be the mainstay of initial treatment in the majority of cases of PM/DM. The treatment of refractory disease can be challenging despite the utilization of the medications currently available. We report two patients with refractory DM who were treated with infliximab. We describe their presentation, clinical course, treatment, and outcomes.