Mixed Connective Tissue Disease

IntroductionBoth experimental and clinical data provide evidence that vitamin D is one of those important environmental factors that can increase the prevalence of certain autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, insulin-dependent diabetes mellitus, and inflammatory bowel disease. The aim of the present study was to investigate the prevalence of vitamin D insufficiency in patients with undifferentiated connective tissue disease (UCTD).MethodsPlasma 25(OH)D3 levels in 161 UCTD patients were measured in both summer and winter periods. Autoantibody profiles (antinuclear antibody, anti-U1-ribonucleoprotein, anti-SSA, anti-SSB, anti-Jo1, anti-Scl70, anti-double-stranded DNA, anti-centromere, anti-cardiolipin, rheumatoid factor, and anti-cyclic citrullinated peptide) and clinical symptoms of the patients were assessed.ResultsPlasma levels of 25(OH)D3 in UCTD patients were significantly lower compared with controls in both summer and winter periods (UCTD summer: 33 +/- 13.4 ng/mL versus control: 39.9 +/- 11.7 ng/mL, P = 0.01; UCTD winter: 27.8 +/- 12.48 ng/mL versus control: 37.8 +/- 12.3 ng/mL, P = 0.0001). The presence of dermatological symptoms (photosensitivity, erythema, and chronic discoid rash) and pleuritis was associated with low levels of vitamin D. During the average follow-up period of 2.3 years, 35 out of 161 patients (21.7%) with UCTD further developed into well-established connective tissue disease (CTD). Patients who progressed into CTDs had lower vitamin D levels than those who remained in the UCTD stage (vitamin D levels: CTD: 14.7 +/- 6.45 ng/mL versus UCTD: 33.0 +/- 13.4 ng/mL, P = 0.0001).ConclusionsIn patients with UCTD, a seasonal variance in levels of 25(OH)D3 was identified and showed that these levels were significantly lower than in controls during the corresponding seasons. Our results suggest that vitamin D deficiency in UCTD patients may play a role in the subsequent progression into well-defined CTDs.

BackgroundDepression and anxiety adversely affects outcomes in systemic lupus erythematosus (SLE) and healthcare utilization is high for pediatric SLE. We aimed to characterize the prevalence of depression and anxiety in pediatric SLE, and their association with healthcare utilization.MethodsWe conducted a cross-sectional analysis of pediatric SLE and mixed connective tissue disease (MCTD) subjects and healthy controls aged 8 years and above. We used the Patient Health Questionnaire 9 (PHQ-9) and the Screen for Childhood Anxiety Related Disorders (SCARED) to identify depression, suicidal ideation and anxiety symptoms, respectively. We compared symptom prevalence in SLE/MCTD and healthy subjects using logistic regression. For SLE/MCTD subjects, we calculated the rate of annual outpatient visits [rheumatology/nephrology, primary care provider (PCP) and emergency department], hospitalizations and rheumatology/nephrology telephone consultations in the preceding year. We compared these outcomes in those with and without depression and anxiety using negative binomial regression.ResultsWe identified depression symptoms in 10 (20%) SLE/MCTD and 4 (8%) healthy subjects, representing a trend towards increased prevalence in unadjusted analysis (OR = 2.9, 95% CI 0.8-9.9, p = 0.09). Adjusted analysis did not show a significant difference; however, non-white race was a statistically significant independent risk factor for depression symptoms compared to white race (OR = 5.4, 95% CI 1.1-27.2, p = 0.04). We identified anxiety symptoms in 11 (22%) SLE/MCTD and 13 (26%) healthy subjects, which was not statistically different. Suicidal ideation was present in 7 (14%) SLE/MCTD and 2 (4%) healthy subjects, which was a statistically significant difference (OR = 5.4, 95% CI 1.02-28.3, p = 0.047). Of the 34% of SLE/MCTD subjects with any symptoms, only 24% had previous mental health care. Those with depression symptoms had a statistically significant lower rate of visits to the PCP (IRR = 0.38, 95% CI 0.19-0.76, p ConclusionsDepression and anxiety symptoms were prevalent, and suicidal ideation significantly more common in SLE/MCTD than in healthy subjects. Non-white race was an independent risk factor for depression. Despite prevalent symptoms, there were poor rates of prior mental health treatment, and less frequent PCP visits among those with depression symptoms. Further investigation of barriers to mental health care and interventional strategies for symptomatic youth with SLE/MCTD is needed.

Modifications occurring on autoantigens during cell death have been proposed to have a role in the initiation of autoimmune diseases. Patients suffering from mixed connective tissue disease (MCTD) produce autoantibodies directed to U1 small nuclear ribonucleoprotein (snRNP), and antibodies against a 70 kDa protein component, the U1-70K (70K) protein, are the most prominent. During apoptosis, 70K is cleaved by caspase-3 to a 40 kDa product, which remains associated with the complex. Autoantibodies preferentially recognizing the apoptotic form of 70K have been described previously, and an apoptosis-specific epitope on 70K has been identified. This study shows that 29 of 53 (54%) MCTD sera preferentially recognize the apoptotic form of 70K over intact 70K. Moreover, we show that antibodies directed to an apoptosis-specific epitope on 70K are more specifically associated with MCTD than other anti-70K antibodies, suggesting that apoptotic 70K is a better antigen for the detection of these antibodies in MCTD patients. Longitudinal analysis of 12 MCTD patients showed in several patients that early sera are relatively enriched with antibodies recognizing an apoptosis-specific epitope, and that the levels of these apoptosis-specific antibodies decrease in time. These findings indicate that the early detection of apoptotic 70K is of considerable interest for anti-U1 snRNP-positive patients.

BackgroundMixed connective tissue disease (MCTD) is a systemic autoimmune disease with overlapping features with systemic lupus erythematosus, systemic sclerosis, and inflammatory idiopathic myopathies, characterized by anti-U1-RNP antibodies. Although subclinical retinal microvascular changes have been described in other connective tissue diseases, such data are lacking in patients with MCTD.MethodsWe performed a cross-sectional exploratory pilot study including patients with a defined diagnosis of MCTD according to one of the sets of classification criteria and age- and sex-matched healthy controls (HC), with elderly individuals equally distributed. Data on disease duration, renal function (creatinine and eGFR), and complement levels (C3 and C4) were recorded. All participants underwent optical coherence tomography angiography (OCT-A) to evaluate retinal vessel density (VD) using parafoveal, perifoveal, and foveal scans, whole images, and foveal avascular zones (FAZs). Nailfold videocapillaroscopy (NVC) was performed in patients with MCTD on four fingers of both hands to assess microangiopathy patterns.ResultsPatients with MCTD (n = 20, mean age 60.6 ± 11.4 years, 85% females) showed a significant reduction in both superficial and deep retinal VD across all evaluated regions compared with 20 HC. In patients with MCTD, deep retinal VD was inversely correlated with disease duration (r = -0.6, P = 0.0003) and directly correlated with eGFR (r = 0.4, P = 0.05). In patients with MCTD, C3 levels were positively correlated with age (r = 0.4, P = 0.03) and superficial parafoveal VD (r = 0.5, P = 0.008). In MCTD, NVC abnormalities, including non-specific microangiopathy and scleroderma patterns, occurred in 60% (n = 12) of cases and did not correlated with OCT-A findings.ConclusionPatients with MCTD present subclinical retinal microvascular abnormalities detectable by OCT-A. Our hypothesis-generating study suggests that retinal vascular changes may be linked to disease duration, renal function, and complement levels. OCT-A may be a useful tool for assessing MCTD.