Ferrara Chiara Alfia, La Rocca Gaetano, Ielo Giuseppe, Libra Alessandro, Sambataro Gianluca
Department of Clinical and Experimental Medicine, Regional Referral Centre for Rare Lung Diseases, A.O.U. "Policlinico-San Marco", University of Catania, Catania, Italy.
Department of Rheumatology, University of Pisa, Pisa, Italy.
Immunotargets Ther. 2023 Jul 26;12:79-89. doi: 10.2147/ITT.S390023. eCollection 2023.
Mixed Connective Tissue Disease (MCTD) is an autoimmune disease first described by Sharp et al in 1972, characterized by the presence of anti-Ribonucleoprotein antibodies directed against the U1 complex (anti-U1RNP). The condition shares clinical characteristics with Systemic Lupus Erythematosus, Rheumatoid Arthritis, and Systemic Sclerosis. Diagnosis is quite difficult due to its rarity, the lack of validated classification criteria, and its heterogeneous clinical presentation. While in the early stages its nuanced clinical features might lead to it being incorrectly classified as other Connective Tissue Diseases (CTDs) or even not recognized, in cases of longstanding disease its classification as a CTD is clear but challenging to discriminate from overlap syndromes. MCTD should be considered a distinct entity due to the presence of a specific genetic substrate and the presence of the high titer of a specific autoantibody, anti-U1RNP, present in all the commercial kits for Extractable Nuclear Antigens, and almost always associated with Antinuclear Antibody positivity with a coarse speckled pattern. Except for anti-U1RNP, no specific biomarkers are available to guide clinicians to a correct classification of MCTD, which is arrived at by the association of clinical, serological and instrumental evaluation. In the first stages, the disease is mainly characterized by Raynaud's phenomenon, inflammatory arthritis, puffy fingers, myalgia and/or myositis, and rarely, trigeminal neuropathy. Longstanding disease is generally associated with the development of Pulmonary Hypertension and Interstitial Lung Disease, which are the two main causes of mortality in MCTD. The aim of this review is to summarize current knowledge on the early recognition of MCTD.
混合性结缔组织病（MCTD）是一种自身免疫性疾病，1972年由夏普等人首次描述，其特征是存在针对U1复合物的抗核糖核蛋白抗体（抗U1RNP）。该病症与系统性红斑狼疮、类风湿性关节炎和系统性硬化症具有共同的临床特征。由于其罕见性、缺乏经过验证的分类标准以及临床表现的异质性，诊断相当困难。在疾病早期，其细微的临床特征可能导致被错误地归类为其他结缔组织病（CTD），甚至未被识别；而在病程较长的病例中，其作为CTD的分类是明确的，但难以与重叠综合征相区分。由于存在特定的遗传底物，以及在所有可提取核抗原的商业试剂盒中均存在高滴度的特定自身抗体抗U1RNP，且几乎总是与核抗体阳性及粗颗粒状模式相关，MCTD应被视为一种独特的疾病实体。除抗U1RNP外，没有特定的生物标志物可指导临床医生对MCTD进行正确分类，MCTD的分类是通过临床、血清学和仪器评估相结合得出的。在疾病初期，主要表现为雷诺现象、炎性关节炎、手指肿胀、肌痛和/或肌炎，很少出现三叉神经病变。病程较长的疾病通常与肺动脉高压和间质性肺病的发展相关，这是MCTD的两个主要死亡原因。本综述的目的是总结目前关于MCTD早期识别的知识。
