“Give me strength” – inflammatory muscle disease in children

Juvenile dermatomyositis is the most common idiopathic inflammatory myopathy of childhood. Management focuses on early aggressive suppression of inflammation to induce sustained remission and prevent complications such as muscle contractures or calcinosis. Advances in diagnostic modalities and treatment have led to improved mortality and morbidity, but long-term risks remain significant. Early disease recognition with appropriate referral and management by a specialist multidisciplinary team is crucial. This review focuses on juvenile dermatomyositis including differential diagnosis from other conditions causing muscle weakness in children.     

多发性肌炎与甲状腺功能减退性肌病的鉴别诊断

目的探讨多发性肌炎与甲状腺功能减退性肌病的异同点以减少误诊。方法回顾分析4例多发性肌炎和4例甲状腺功能减退性肌病患者的临床表现、实验室检查资料及治疗转归。结果多发性肌炎与甲状腺功能减退性肌病的丙氨酸转氨酶、肌酸激酶、肌肉病理有明显统计学差异,甲状腺功能检查结果、治疗转归明显不同。结论对于肌肉无力和肌酶升高的患者需常规检测甲状腺功能,肌肉病理、诊断性甲状腺素替代治疗对鉴别多发性肌炎和甲状腺功能减退症肌病所致肌肉病变有重要意义。     

Impairment of respiratory function in late‐onset distal myopathy due to MATR3 Mutation

Introduction: Recently, mutations in the MATR3 gene were found to cause late‐onset distal myopathy. The frequency and impact of respiratory involvement are not clear. Methods: Respiratory parameters [maximum vital capacity (VCmax); forced expiratory volume (FEV₁); peak expiratory flow (PEF), postural drop of VCmax from sitting to supine, maximum inspiratory muscle pressure (PImax), mouth occlusion pressure after 100 ms (P 0.1), peak cough flow, and blood‐gas analysis] were monitored prospectively at baseline, and then 6 months and 12 months later in 8 patients with genetically confirmed MATR3 myopathy. Results: All patients showed involvement of respiratory function. Six of 8 reported exertional dyspnea. At the end of follow‐up, 5 of 8 had decreased VC, 7 of 8 had reduced PImax, and 5 of 7 had decreased partial pressure of oxygen (PO ₂). Within 12 months, respiratory parameters deteriorated non‐significantly. No patient required non‐invasive ventilation. Conclusions: There is a high risk of abnormal respiratory function with progressive worsening in MATR3 myopathy. Muscle Nerve 51 : 916–918, 2015     

Sporadic late‐onset nemaline myopathy as a rare cause of slowly progressive muscle weakness with young adult onset

Introduction: Sporadic late‐onset nemaline myopathy (SLONM) is a rare intractable acquired myopathy characterized by progressive muscle weakness and atrophy, usually with middle to late adult onset. Autologous peripheral blood stem cell transplantation (auto‐PBSCT) has been reported to be a promising treatment for SLONM. Methods: In this study we performed clinical characterization, muscle histopathological analysis, and muscle power monitoring after auto‐PBSCT in a 27‐year‐old HIV‐negative man with monoclonal gammopathy. Results: He showed improved muscle strength after treatment with high‐dose melphalan and auto‐PBSCT. Conclusions: Considering the recent reports of successful treatment of SLONM, early and correct diagnosis of this condition in association with monoclonal gammopathy is important. SLONM should be added to the list of diseases to consider in the differential diagnosis of progressive muscle weakness with young adult onset. Muscle Nerve 51 :772–774, 2015     

Myopathy in older people receiving statin therapy: a systematic review and meta-analysis

Objective

The aim of the present study was to determine the risk of myopathy in older people receiving statin therapy.

Methods

Eligible studies were identified searching Ovid Medline, EMBASE, Scopus, CINAHL, Cochrane and PSYCHINFO databases (1987 to July 2014). The selection criteria comprised randomized controlled studies that compared the effects of statin monotherapy and placebo on muscle adverse events in the older adult (65+ years). Data were extracted and assessed for validity by the authors. Odds ratios and 95% confidence intervals (CIs) were used to calculate binary outcomes. Evidence from included studies were pooled in a meta-analysis using Revman 5.3.

Results

The trials assessed in the systematic review showed little or no evidence of a difference in risks between treatment and placebo groups, with myalgia [odds ratio (OR) 1.03, 95% CI 0.90, 1.17; I² = 0%; P = 0.66] and combined muscle adverse events (OR 1.03, 95% CI 0.91, 1.18; I² = 0%; P = 0.61) (myopathy). No evidence was found for an increased risk of rhabdomyolysis (OR 2.93, 95% CI 0.30, 28.18; I² = 0%; P = 0.35) in the seven trials that reported this. No trials reported mortality due to a muscle-related event. Discontinuations due to an adverse effect were reduced in the treatment group compared with placebo (OR 0.74, 95% CI 0.50, 1.09; I² = 0%; P = 0.13).

Conclusion

The results obtained from the present review suggest that statins are relatively safe, even in older people. There was no evidence to suggest an increased risk of myopathy in older adults receiving statin therapy. There is slightly increased seen with rhabdomyolysis when compared with the general population, although the event is relatively rare. Statins should be prescribed to elderly people who need it, and not withheld, as its myopathy safety profile is tolerable.     

成人发病的肌原纤维肌病的临床和病理学特征(附2例报告)

目的 探讨成人发病的肌原纤维肌病的临床和病理学特征.方法 回顾性分析2例成年发病的肌原纤维肌病患者的临床资料.结果 2例患者表现为近端或远近端肌肉无力,进行性加重.光镜下可见肌纤维内和肌膜下颗粒样或团块样物质沉积,免疫组化为结蛋白.电镜发现1例肌膜下及肌原纤维间存在大小不一的包涵体,另1例肌原纤维排列紊乱,Z线不规则样增粗.常见突变基因检测未见异常.结论 成人发病的肌原纤维肌病临床无特异性表现,其病理学特征为肌纤维内可见异常物质沉积,电镜发现肌原纤维间包涵体结构或Z线异常.     

A novel MYH7 mutation with prominent paraspinal and proximal muscle involvement

Laing distal myopathy (LDM) is caused by mutations in the MYH7 gene, and known to have muscle weakness of distal limbs and neck flexors. Through whole exome sequencing, we identified a novel p.Ala1439Pro MYH7 mutation in a Korean LDM family. This missense mutation is located in more N-terminal than any reported rod domain LDM mutations. In the early stage of disease, the present patients showed similar clinical patterns to the previously described patients of LDM. However, in the later stage, fatty replacement and atrophy of paraspinal or proximal leg muscles was more severely marked than lower leg muscles, and asymmetric atrophies were observed in trapezius, subscapularis and adductor magnus muscles. Distal myopathy like LDM showed marked and predominant fatty infiltrations in paraspinal or proximal leg muscles with marked asymmetry. These observations expand the clinical spectrum of LDM with the MYH7 mutation.     

Elevated urinary β2 microglobulin in the first identified Japanese family afflicted by X-linked myopathy with excessive autophagy

Here we report what is to our knowledge the first identified Japanese family afflicted by X-linked myopathy with excessive autophagy. The index case is a 52-year-old man with almost 40 years of progressive proximal muscle weakness. High urinary β2 microglobulin, normal serum β2 microglobulin, autophagic vacuoles with sarcolemmal features, and a hemizygous c.164–7T>G mutation in the VMA21 gene were found. His two maternal uncles had similar clinicopathological findings. High urinary β2 microglobulin without obvious renal dysfunction might result from decreased urine acidification in the distal convoluted tubules caused by the VMA21 gene mutation. These findings might prove to be useful as a preliminary marker suggestive of X-linked myopathy with excessive autophagy.