ImmunoTargets and Therapy (Jul 2023)
Towards Early Diagnosis of Mixed Connective Tissue Disease: Updated Perspectives
Abstract
Chiara Alfia Ferrara,1 Gaetano La Rocca,2 Giuseppe Ielo,1 Alessandro Libra,1 Gianluca Sambataro1 1Department of Clinical and Experimental Medicine, Regional Referral Centre for Rare Lung Diseases, A.O.U. “Policlinico-San Marco”, University of Catania, Catania, Italy; 2Department of Rheumatology, University of Pisa, Pisa, ItalyCorrespondence: Gianluca Sambataro, Regional Referral Center for Rare Lung Disease, University of Catania, via S. Sofia 68, Catania, 95123, Italy, Email [email protected]: 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.Keywords: mixed connective tissue disease, diagnosis, Raynaud’s phenomenon, nailfold videocapillaroscopy, anti-RNP, inflammatory arthritis
