Background The mixed connective tissue disease (MCTD) is an infrequent and possibly underdiagnosed connective tissue disease, which is characterized by the presence of high titres of anti-U1 ribonucleoprotein antibodies (anti-RNP). Although, the anti-RNP antibodies are always present in patients with MCTD because its positivity is part of the definition of this disorder, they lack specificity and may be detected in other autoimmune conditions.
Objectives To know the prevalence of MCTD in patients with high titres of persistently positive anti-RNP. Also, we attempt to identify which other autoimmune diseases may be associated with anti-RNP and describe its clinical characteristics.
Methods The study was performed in the Complexo Hospitalario Universitario of Vigo(Hospital Xeral), which has 700 beds and attends a population of 400,000 inhabitants. The clinical record of patients with at least 1 positive anti-RNP determinations from January 2006 until December 2012, were reviewed. Only those patients with enough clinical and laboratory information were included. Anti-RNP was defined as persistently positive when tested positive (by ELISA) in two or more occasions, without any negative result and with ANA>1/640 speckled pattern. Clinical, demographic, immunologic and follow up variables were recorded. Specifically, it was checked whether the patients had been diagnosed with MCTD or not and whether met the classification criteria for MCTD of Alarcón-Segovia and Kahn.
Results During the 7 years of the study period 15,173 anti-RNP assays were performed. Of them, 235 determinations(1.55%)in 84 patients were positive. Due to lack of information or insufficient follow up, 23 patients were excluded. Additionally, 18 patients, all of them with connective tissue diseases, anti-RNP tested positive in only 1 occasion with other anti-RNP assays negative. Finally, 47 patients met the inclusion criteria and were studied, 39 of them were women(Ratio women/men 5:1). The mean age was 51 years(range 12-86 years). The average of positive anti-RNP determination per patient was 4.4 and the mean follow up was 59 months(DS). MCTD was correctly diagnosed in 9 patients(19%). Patients in the group of anti-RNP+ No-MCTD(n= 38)have arthritis(20/38; 53%), Raynaud(18/38;47%), Lupus nephritis 3/19(16%) all of them anti-Sm positive. Anti-Sm was detected in 18/38 patients (48%) and anti-Ro in 13/38(34). In this group 19 patients were diagnosed with Lupus, Sjögren Syndrome(4), Rheumatoid arthritis(3), Systemic Sclerosis(1), and 7 patients have undifferentiated connective tissue disease. When charts were reviewed, 4 patients(31% of the total of MCTD)of the anti-RNP+ No-MCTD group were reclassified as MCTD because they have fulfilled clinical criteria from the beginning. Eventually, 13 patients(28%)with anti-RNP persistently positive have a MCTD.
Conclusions Most patients with high titres persistently positive anti RNP will have other autoimmune diseases different of MCTD. Near a third of patients with MCTD are not correctly diagnosed.
Cappelli S, Randone SB, Martinovic, et al.“To Be or Not To Be,”Ten YearsAfter:Evidence for Mixed Connective Tissue Disease as a DistinctEntity. SeminArthritisRheum 2012;41:589-98.
Alarcón-Segovia D, Cardiel MH. Comparison between 3 diagnostic criteria for mixed connective tissue disease. Study of 593 patients. J. Rheumatol 1989;16:328-34
Disclosure of Interest None Declared
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