Ismail Dina, Ezzy Fatema, Ayesha Bibi
Jacobi Medical Center, Albert Einstein College of Medicine, 400 Pelham Parkway S, 10461, Bronx, NY, USA.
Montefiore Medical Center, Albert Einstein College of Medicine, 1250 Waters place, Bronx, NY, 10461-2720, USA.
Respir Med Case Rep. 2025 Apr 18;55:102224. doi: 10.1016/j.rmcr.2025.102224. eCollection 2025.
Rapidly progressive interstitial lung disease (RP-ILD) poses a critical challenge in clinical practice, characterized by nonspecific symptoms that rapidly progress to respiratory failure despite intensive management. Anti-melanoma differentiation-associated gene 5 antibody (anti-MDA5), associated with dermatomyositis-related ILD, is a key biomarker in such cases. This report highlights two fatal cases of anti-MDA5-positive RP-ILD, emphasizing diagnostic and management challenges.
The first case involved a 56-year-old male without prior autoimmune disease who developed acute respiratory distress syndrome (ARDS) and multiorgan failure. The second case concerned a 49-year-old female with systemic lupus erythematosus (SLE), whose condition similarly culminated in multiorgan failure despite aggressive treatment. Both patients faced delayed diagnoses and suboptimal responses to immunosuppressive therapy, underscoring the complexity of managing RP-ILD.
Prolonged testing turnaround for MDA5 and reliance on nonspecific clinical indicators remain significant barriers to early diagnosis. Dermatological signs such as Gottron's papules, while indicative of RP-ILD, are associated with poorer prognoses. Current serum biomarkers under investigation lack the sensitivity and specificity of MDA5, complicating early detection efforts. Aggressive immunosuppression in deteriorating patients frequently leads to infectious complications, further compromising outcomes.
To address these challenges, early recognition of dermatological indicators, prompt immunosuppressive therapy, and tailored patient management are critical. Additionally, timely referral for extracorporeal membrane oxygenation (ECMO) as a bridge to lung transplantation may improve survival. Advancing research into serum biomarkers holds promise for enhancing diagnostic precision and therapeutic decision-making in RP-ILD.
快速进展性间质性肺病（RP-ILD）在临床实践中构成了严峻挑战，其特征是非特异性症状，尽管进行了强化治疗仍迅速进展为呼吸衰竭。与皮肌炎相关的ILD相关的抗黑色素瘤分化相关基因5抗体（抗MDA5）是此类病例的关键生物标志物。本报告重点介绍了两例抗MDA5阳性RP-ILD的致命病例，强调了诊断和管理方面的挑战。
第一例患者为一名56岁男性，既往无自身免疫性疾病，出现急性呼吸窘迫综合征（ARDS）和多器官功能衰竭。第二例患者为一名49岁女性，患有系统性红斑狼疮（SLE），尽管积极治疗，其病情同样最终发展为多器官功能衰竭。两名患者均面临诊断延迟和免疫抑制治疗反应不佳的问题，凸显了管理RP-ILD的复杂性。
MDA5检测周转时间长以及依赖非特异性临床指标仍然是早期诊断的重大障碍。Gottron丘疹等皮肤体征虽然提示RP-ILD，但与较差的预后相关。目前正在研究的血清生物标志物缺乏MDA5的敏感性和特异性，使早期检测工作复杂化。对病情恶化的患者进行积极的免疫抑制治疗常常导致感染并发症，进一步影响治疗结果。
为应对这些挑战，早期识别皮肤指标、及时进行免疫抑制治疗以及个性化的患者管理至关重要。此外，及时转诊进行体外膜肺氧合（ECMO）作为肺移植的桥梁可能会提高生存率。推进血清生物标志物的研究有望提高RP-ILD的诊断准确性和治疗决策水平。
