Background:As a rare, complex, and heterogeneous disease, mixed connective tissue disease (MCTD) represents a challenge for clinical practice.Objectives:We aimed to unravel potential pitfalls including correct referral diagnosis, fulfilment of diagnostic criteria, distinction from other CTDs, disease course and activity, and treatment modalities.Methods:We analysed the prospectively collected MCTD cohort at our tertiary referral centre. The patients’ medical histories were investigated for fulfilment of Sharp’s (1), Kasukawa’s (2), and Alarcón-Segovia’s (3) diagnostic MCTD criteria. We defined overlap syndromes as simultaneous fulfilment of clinical as well as immunological criteria of two defined rheumatic diseases. Disease conversion was defined as emergence of new symptoms and autoantibodies consistent with another rheumatic disease. Remission was defined by simultaneous systemic lupus erythematosus disease activity index 2000 (SLEDAI-2 K) of 0 and European League Against Rheumatism scleroderma trial and research (EUSTAR) activity index <2.5. Disease phenotype and disease activity were monitored over time and all patients were evaluated for fulfilment of classification criteria of various connective tissue diseases.Results:Out of 85 patients initially referred as MCTD, only one third fulfilled the diagnostic MCTD criteria. Most of the remaining patients had undifferentiated CTD (29%) or overlap syndromes (20%). In our final cohort of 33 MCTD patients, 6 (48%) also met the classification criteria of systemic sclerosis, 13 (39%) those of systemic lupus erythematosus (SLE), 6 (18%) those of rheumatoid arthritis, and 3 (9%) those of primary myositis. Over the median observation period of 4.6 (1.6, 9.9) years, only two patients (6%) underwent disease conversion from MCTD to SLE and no patient converted towards other diseases. The number of patients in remission increased from 6 (18%) to 15 (45%) due to introduction of immune modulatory treatment. Combination therapy was favoured in most cases (17 patients, 52%), whereas monotherapy was less frequent (12 patients, 36%), and only 4 (12%) patients remained without immune modulators until the end of the follow-up period. Hydroxychloroquine, prednisone, and methotrexate were the most frequently used medications in our cohort.Conclusion:Our study showed a high risk for misdiagnosis for patients with MCTD. Phenotype conversion was a very rare event. As a multi-organ disease, MCTD required prolonged (combined) immunosuppressive therapy to achieve remission. The establishment of an international registry with longitudinal data from observational multi-centre cohorts might represent a first step to address the many unmet needs of MCTD.References:[1]Sharp GC. Diagnostic criteria for classification of MCTD. In: Kasukawa R, Sharp GC, editors. Mixed connective tissue disease and anti-nuclear antibodies: proceedings of the International Symposium on Mixed Connective Tissue Disease and Anti-nuclear Antibodies, Tokyo, 29-30 August 1986. no. 719. Amsterdam: Elsevier Science Publishers B.V. (Biomedical Division); 1987. p. 23-30.[2]Kasukawa R, Tojo T, Miyawaki S, Yoshida H, Tanimoto K, Nobunaga M, et al. Preliminary diagnostic criteria for classification of mixed connective tissue disease. In: Kasukawa R, Sharp GC, editors. Mixed connective tissue disease and anti-nuclear antibodies: proceedings of the International Symposium on Mixed Connective Tissue Disease and Anti-nuclear Antibodies, Tokyo, 29-30 August 1986. no. 719. Amsterdam: Elsevier Science Publishers B.V. (Biomedical Division); 1987. p. 41-7.[3]Alarcón-Segovia D, Villarreal M. Classification and diagnostic criteria for mixed connective tissue disease. In: Kasukawa R, Sharp GC, editors. Mixed connective tissue disease and anti-nuclear antibodies: proceedings of the International Symposium on Mixed Connective Tissue Disease and Anti-nuclear Antibodies, Tokyo, 29-30 August 1986. no. 719. Amsterdam: Elsevier Science Publishers B.V. (Biomedical Division); 1987. p. 33-40.Disclosure of Interests:Adrian Wanzenried: None declared, Alexandru Garaiman: None declared, Suzana Jordan: None declared, Oliver Distler Consultant of: O.D. had consultancy relationship and/or has received research funding from Abbvie, Actelion, Acceleron Pharma, Amgen, AnaMar, Baecon Discovery, Blade Therapeutics, Bayer, Boehringer Ingelheim, Catenion, Competitive Drug Development International Ltd, CSL Behring, ChemomAb, Curzion Pharmaceuticals, Ergonex, Ga-lapagos NV, Glenmark Pharmaceuticals, GSK, Inventiva, Italfarmaco, iQone, iQvia, Lilly, medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Novartis, Pfizer, Roche, Sanofi, Target Bio Science and UCB in the area of potential treatments of scleroderma and its complications., Britta Maurer Consultant of: Boehringer-Ingelheim, Grant/research support from: AbbVie, Protagen, and Novartis Biomedical Research as well as congress support from Pfizer, Roche, Actelion, mepha, and MSD.
Clinical and Immunological Profile of Mixed Connective Tissue Disease and a Comparison of Four Diagnostic Criteria
