Fujisawa Tomoyuki
Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama Higashi-ku, Hamamatsu 431-3192, Japan.
Medicina (Kaunas). 2021 Apr 3;57(4):347. doi: 10.3390/medicina57040347.
Idiopathic inflammatory myopathies, including polymyositis (PM), dermatomyositis (DM), and clinically amyopathic DM (CADM), are a diverse group of autoimmune diseases characterized by muscular involvement and extramuscular manifestations. Interstitial lung disease (ILD) has major pulmonary involvement and is associated with increased mortality in PM/DM/CADM. The management of PM-/DM-/CADM-associated ILD (PM/DM/CADM-ILD) requires careful evaluation of the disease severity and clinical subtype, including the ILD forms (acute/subacute or chronic), because of the substantial heterogeneity of their clinical courses. Recent studies have highlighted the importance of myositis-specific autoantibodies' status, especially anti-melanoma differentiation-associated gene 5 (MDA5) and anti-aminoacyl tRNA synthetase (ARS) antibodies, in order to evaluate the clinical phenotypes and treatment of choice for PM/DM/CADM-ILD. Because the presence of the anti-MDA5 antibody is a strong predictor of a worse prognosis, combination treatment with glucocorticoids (GCs) and calcineurin inhibitors (CNIs; tacrolimus (TAC) or cyclosporin A (CsA)) is recommended for patients with anti-MDA5 antibody-positive DM/CADM-ILD. Rapidly progressive DM/CADM-ILD with the anti-MDA5 antibody is the most intractable condition, which requires immediate combined immunosuppressive therapy with GCs, CNIs, and intravenous cyclophosphamide. Additional salvage therapies (rituximab, tofacitinib, and plasma exchange) should be considered for patients with refractory ILD. Patients with anti-ARS antibody-positive ILD respond better to GC treatment, but with frequent recurrence; thus, GCs plus immunosuppressants (TAC, CsA, azathioprine, and mycophenolate mofetil) are often needed in order to achieve favorable long-term disease control. PM/DM/CADM-ILD management is still a therapeutic challenge for clinicians, as evidence-based guidelines do not exist to help with management decisions. A few prospective clinical trials have been recently reported regarding the treatment of PM/DM/CADM-ILD. Here, the current knowledge on the pharmacologic managements of PM/DM/CADM-ILD was mainly reviewed.
特发性炎性肌病，包括多发性肌炎（PM）、皮肌炎（DM）和临床无肌病性皮肌炎（CADM），是一组多样的自身免疫性疾病，其特征为肌肉受累及肌肉外表现。间质性肺疾病（ILD）主要累及肺部，与PM/DM/CADM患者死亡率增加相关。由于PM/DM/CADM相关ILD（PM/DM/CADM-ILD）临床病程存在显著异质性，其管理需要仔细评估疾病严重程度和临床亚型，包括ILD类型（急性/亚急性或慢性）。最近的研究强调了肌炎特异性自身抗体状态的重要性，尤其是抗黑色素瘤分化相关基因5（MDA5）和抗氨酰tRNA合成酶（ARS）抗体，以便评估PM/DM/CADM-ILD的临床表型和治疗选择。由于抗MDA5抗体的存在是预后较差的有力预测指标，对于抗MDA5抗体阳性的DM/CADM-ILD患者，建议联合使用糖皮质激素（GCs）和钙调神经磷酸酶抑制剂（CNIs；他克莫司（TAC）或环孢素A（CsA））进行治疗。抗MDA5抗体阳性的快速进展性DM/CADM-ILD是最难治疗的情况，需要立即联合使用GCs、CNIs和静脉注射环磷酰胺进行免疫抑制治疗。对于难治性ILD患者，应考虑额外的挽救治疗（利妥昔单抗、托法替布和血浆置换）。抗ARS抗体阳性的ILD患者对GC治疗反应较好，但易复发；因此，通常需要GCs加免疫抑制剂（TAC、CsA、硫唑嘌呤和霉酚酸酯）以实现良好的长期疾病控制。PM/DM/CADM-ILD的管理对临床医生来说仍然是一个治疗挑战，因为目前尚无基于证据的指南来帮助做出管理决策。最近有一些关于PM/DM/CADM-ILD治疗的前瞻性临床试验报告。在此，主要综述了目前关于PM/DM/CADM-ILD药物治疗的知识。
