Diagnosis Of Mixed Connective Tissue Disease Research Articles

Naifold capillaroscopy in mixed connective tissue disease patients.

Mixed connective tissue disease (MCTD) is a rare systemic disease characterized by overlapping features of systemic lupus erythematosus (SLE), systemic sclerosis (SSc), dermato-/polymyositis (DM/PM), and rheumatoid arthritis (RA). Naifold capillaroscopy (NFC) is a non-invasive test for evaluating the capillaries of the nail shaft used in the diagnosis of rheumatic diseases. To determine whether there are characteristic abnormalities in NFC in MCTD patients, and whether the type of NFC lesions correlates with organ involvement in these patients. Clinical picture and NFC patterns were analyzed in 43 patients with MCTD. Capillaroscopic images were divided into scleroderma-like pattern (SD-like pattern) according to the Cutolo classification, non-specific lesions, and normal images. Relationships between the clinical aspects considered in the MCTD classification criteria and the changes in the capillaroscopic images were evaluated. SD-like pattern was present in 20 MCTD patients (46.51%) with a predominance of the "early" pattern. Giant, branched, dilated capillaries and reduced capillary density were found more frequently in MCTD patients compared to the control group (p-values 0.0005, 0.005, 0.02, < 0.0001 respectively). There were associations found between the presence of a reduced number of vessels, avascular areas, and SD-like pattern with the presence of sclerodactyly in MCTD patients (p = 0.002, p = 0.006, p = 0.02, respectively), alongside an association between the presence of branched vessels and the subpapillary plexus with pulmonary arterial hypertension (PAH) (p = 0.04 and p = 0.005, respectively). MCTD patients are significantly more likely to have abnormalities upon NFC. It is worthwhile to perform capillaroscopic examination in MCTD patients. Key Points • Scleroderma-like pattern was found in more than half of the MCTD patients. • Reduced capillary density was found to be a significant predictor of the diagnosis of MCTD. • There were relationships between the presence of reduced capillary density, avascular areas, and SD-like with the presence of sclerodactyly in the MCTD patients. • There was an association between the presence of branched vessels and the visibility of the subpapillary plexus and pulmonary arterial hypertension (PAH).

A 63-year-old Chinese female with mixed connective tissue disease who suffered from renal crisis

Mixed connective tissue disease (MCTD) is a rare autoimmune disorder. We present a case of a Chinese female who has been admitted to our hospital on eight separate occasions. Her initial symptoms involved internal organs including the lung and heart. Due to the presence of anti-U1RNP antibodies and other clinical features, a diagnosis of MCTD was considered. Throughout her first to seventh admissions, her serum creatinine levels remained normal. During her eighth hospitalization, her renal function deteriorated rapidly, culminating in renal crisis. Chest computed tomography (CT) confirmed pulmonary edema, necessitating hemodialysis. Her interleukin (IL)-6 level increased significantly during throughout hospitalizations. The patient responded well to treatment with an IL-6 receptor antagonist (IL-6RA). This case raises the question of whether IL-6 could serve as a potential biomarker for predicting renal crisis incidence in MCTD patients, a topic warranting further investigation in the future.

The diagnostic challenge of patients with anti-U1-RNP antibodies.

Anti-U1-RNP antibodies are necessary for the diagnosis of mixed connective tissue disease (MCTD), but they are also prevalent in other connective tissue diseases, especially systemic lupus erythematosus (SLE), from which distinction remains challenging. We aimed to describe the presentation and outcome of patients with anti-U1-RNP antibodies and to identify factors to distinguish MCTD from SLE. We retrospectively applied the criteria sets for MCTD, SLE, systemic sclerosis (SSc) and rheumatoid arthritis (RA) to all patients displaying anti-U1-RNP antibodies in the hospital of Caen from 2000 to 2020. Thirty-six patients were included in the analysis. Eighteen patients (50%) satisfied at least one of the MCTD classifications, 11 of whom (61%) also met 2019 ACR/EULAR criteria for SLE. Twelve other patients only met SLE without MCTD criteria, and a total of 23 patients (64%) met SLE criteria. The most frequent manifestations included Raynaud's phenomenon (RP, 91%) and arthralgia (67%). We compared the characteristics of patients meeting only the MCTD (n = 7), SLE (n = 12), or both (n = 11) criteria. Patients meeting the MCTD criteria were more likely to display SSc features, including sclerodactyly (p < 0.01), swollen hands (p < 0.01), RP (p = 0.04) and esophageal reflux (p < 0.01). The presence of scleroderma features (swollen hands, sclerodactyly, gastro-oesophageal reflux), was significantly associated with the diagnosis of MCTD. Conversely, the absence of those manifestations suggested the diagnosis of another definite connective tissue disease, especially SLE.

AB0655 Clinical and immunological features of a Portuguese cohort of Mixed Connective Tissue Disease

BackgroundVarious nationwide studies have been already published to better understand Mixed Connective Tissue Disease (MCTD) (1,2). However, Portuguese data is not available.ObjectivesTo characterize clinical and immunological features of a Portuguese cohort of patients with MCTD.MethodsRetrospective, multicenter study including adult-onset patients with clinical diagnosis of MCTD and fulfilling at least one of the following classification criteria: Sharp, Kasukawa, Alarcón-Segovia or the Kahn’s criteria. Positivity to other autoantibodies besides anti-U1-RNP were allowed. SPSS was used for statistical analysis and significance level was defined as 2-sided p&lt;.05.ResultsA total of 98 patients were included, with a mean age at diagnosis and disease duration of 40.5±13.7 and 7.0±6.5 years, respectively. Most patients were female (87.8%) and Caucasian (70.4%). Raynaud’s phenomenon (96.9%), arthralgia/arthritis (94.9/74.5%) and puffy fingers (60.2%) were the most common and early manifestations. Gastroesophageal (GE), respiratory and muscular involvement were also prevalent, mostly during the follow up, affecting 30.6%, 34.7% and 43.9% of the patients, respectively. Clinical and immunological characteristics are described in Table 1. Males were older at symptom’s onset (65.0 VS 46.7, p=.035), having more respiratory involvement (OR=4.5, 95% CI 1.3-16.4), and positivity to anti-ACPA (OR=20.0, 95% CI: 3.1-129.4). GE involvement occurred more often in Caucasian patients (OR=3.8; 95% CI: 1.0-14.1), while anemia of chronic diseases (OR=2.7; 95% CI: 1.0-7.2), myositis (OR=3.6; 95% CI: 1.3-9.9) and constitutional symptoms (OR=3.2; 95% CI: 1.2-8.3) were more frequent in Afro-American patients, whose were also younger at disease (34.1 VS 50.6, p=.01). After a median follow-up time of 4 (IQR 8) years, 4 deaths occurred (4.1%), mostly (75%) due to infectious complications.Table 1.Clinical and immunological characteristicsClinical ManifestationsAt presentationFollow-upMucocutaneous systemRaynaud’s phenomenon, n (%)85 (86.7)95 (96.9)Puffy hands, n (%)48 (49.0)59 (60.2)SSc-like, n (%)43 (44.8)59 (60.8)SLE-like, n (%)28 (28.9)35 (35.7)Musculoskeletal systemArthralgia/Arthritis, n (%)/n (%)81 (82.7) / 56 (57.1)93 (94.9) / 73 (74.5)Myositis, n (%)26 (25.6)43 (43.9)Hematological system, n (%)46 (46.9)70 (71.4)Respiratory system, n (%)14 (14.3)34 (34.7)Cardiovascular system3 (3.1)4 (4.1)Pulmonary hypertension*2 (2.0)15 (15.3)Gastroesophageal involvement, n (%)11 (11.2)30 (30.6)Renal involvement, n (%)2 (2.0)10 (10.2)Neurological involvement, n (%)6 (6.3)14 (14.3)Constitutional symptoms, n (%)26 (26.5)30 (30.6)Immunological characteristicsAnti-dsDNA, n (%)21 (21.4)Anti-smith antibody, n (%)21 (21.4)Anti-Ro/SSA, n (%)31 (31.6)Anti-La/SSB, n (%)7 (7.1)Anti-centromere, n (%)3 (4.1)Rheumatoid Factor, n (%)39 (39.8)Anti- anti-citrullinated protein antibodies, n (%)6 (6.1)Antiphospholipid antibodies, n (%)7 (7.1)Myositis antibodies, n (%)9 (9.2)Complement activation, n (%)27 (27.6)Hypergammaglobulinemia, n (%)51 (52.0)Legend: Anti-dsDNA: anti-double stranded deoxyribonucleic acid antibody; SLE: systemic lupus erythematosus, SSc: systemic sclerosis. *No information regarding cardiac catheterism, then compatible alterations in the echocardiogram.ConclusionRaynaud’s phenomenon, puffy fingers and arthritis were the most common manifestations in Portuguese patients, with similar proportions found in literature (1,2). However, we reported some differences in mucocutaneous, renal and serosa involvement and higher prevalence of probable pulmonary hypertension (1,2), which may be explained by the heterogeneity of the inclusion criteria. Except for respiratory, myositis, GE and constitutional symptoms, there were no differences regarding gender and ethnicity.Here, we characterize the largest cohort of MCTD in Portugal.

COVID-19 Induced Mixed Connective Tissue Disease (MCTD)—Case Report

Mixed connective tissue disease (MCTD) is a rare systemic autoimmune disorder that damages multiple organs simultaneously and is associated with chronic inflammation, in which the signs of systemic sclerosis, systemic lupus erythematosus, and polymyositis can co-occur. Its distinctive feature and the basis for the diagnosis of MCTD is the presence of an antibody against the uridine-rich RNP of the cell nucleus (Anti-U1-RNP). It has been observed that intercurrent infections can trigger autoimmune diseases, however, the fact that viral infections—such as SARS-CoV-2—induce them is currently poorly understood. The present study raises the etiological role of the SARS-CoV-2 virus in the development of the disease. Authors describe the case of a 38-year-old patient in good general condition, who was diagnosed with mixed connective tissue disease three months after COVID-19 infection.

Urinary abnormality in mixed connective tissue disease predicts development of other connective tissue diseases and decrease in renal function.

To clarify the clinical significance of development of urinary abnormality in mixed connective tissue disease (MCTD). Forty-one patients with an initial diagnosis of MCTD, followed at five hospitals between April 1, 2000 and December 31, 2013, were included. The relationship between urinary abnormality and various clinical parameters were retrospectively analyzed. Urinary abnormality was defined as proteinuria and/or hematuria detected by urinalysis. Development of other connective tissue diseases (CTDs) was defined as satisfaction of the criteria of each respective disease. Of 41 patients (34 females, 7 males, mean age at diagnosis 42.2 ± 15.2 years), 16 developed urinary abnormality (UrA(+) patients). The total incidences of development of other CTDs were higher in the UrA(+) patients than UrA(-) (62.5% versus 16.0%, p = .01). In the comparison between UrA(+) and UrA(-) patients, there were no significant differences in follow-up duration or last determined estimated glomerular filtration rate (eGFR), although eGFR decreased more significantly in the UrA(+) patients than UrA(-). (-20.2 ± 17.2 vs -6.1 ± 13.8 ml/min/1.73m2, p = .01; -21.0 ± 18.9 vs -6.7 ± 14.1%, p = .03). Urinary abnormality during the clinical course in MCTD is predictive of a higher incidence of developing other CTDs. Furthermore, it might also predict long-term renal prognosis in patients with an initial diagnosis of MCTD.

O18 The Rollercoaster Reality of Mixed Connective Tissue disease

O18 The Rollercoaster Reality of Mixed Connective Tissue disease

De Novo Pulmonary Arterial Hypertension After Heart Transplantation

Background Orthotopic heart transplantation (OHT) recipients undergo scheduled right heart catheterizations (RHC) and biopsies. Some of these patients who have mixed connective tissue disease (MCTD) are at increased risk of developing pulmonary artery hypertension (PAH). The natural history and impact of immunosuppression on new-onset PAH is unknown. Case A 43 year old male required OHT after the development of lupus cardiomyopathy. Post-transplant he was treated with tacrolimus and mycophenolate. Three years later, he developed significant dyspnea on exertion. His serology was anti-nuclear antibody positive (1:2560, speckled). Over eight months, RHCs performed in the setting of endomyocardial biopsies for surveillance of rejection showed a dramatic change, from normal shortly after transplantation, to a markedly elevated PA pressure of 81/34 (mean 52) mmHg, pulmonary capillary wedge pressure of 7 mmHg, transpulmonary gradient of 45 mmHg, and pulmonary vascular resistance of 9.36 Wood units (Figure 1). The patient's constellation of symptoms and RHC findings supported a diagnosis of MCTD - PAH, despite ongoing immunotherapy. Severe PAH occurred incidentally while being monitored with RHC for another indication. He was treated with tadalafil, ambrisentan, and amlodipine with an improvement in functional class. Conclusions This case describes de novo development of PAH after OHT in a patient with MCTD, despite anti-rejection immunotherapy. This suggests a lack of efficacy of immunosuppression in preventing scleroderma-PAH and highlights the rapidity of onset of this disease. Figure 1. Results of serial right heart catheterizations

Salivary gland ultrasound in the diagnostic workup of juvenile Sj\xf6gren\u2019s syndrome and mixed connective tissue disease

BackgroundJuvenile Sjögren’s Syndrome (jSS) is a rare phenomenon that may appear as primary jSS or associated with mixed connective tissue disease (MCTD) and other autoimmune diseases as secondary jSS. With currently no standard diagnostic procedures available, jSS in MCTD seems to be underdiagnosed. We intended to describe and identify similar distinct salivary gland ultrasound (SGUS) findings in a cohort of primary and secondary jSS patients, focusing on sicca like symptoms and glandular pain/swelling in the patients‘history.MethodsWe present a single-center study with chart data collection. B-mode examinations of salivary glands were obtained with a linear high-frequency transducer and evaluated using the scoring-system of Hocevar. Inclusion criteria were: (i) primary or secondary jSS and/or (ii) diagnosis of MCTD and additionally (iii) any presence of sicca like symptoms or glandular pain/swelling.ResultsTwenty five patients with primary (pjSS) and secondary jSS (sjSS) were included in the study (n = 25, 21 female, 4 male), with a median age of 15.3 years at the time of first visit and a mean disease duration of 4.9 years. Pathologic SGUS findings were observed in 24 of 25 patients, with inhomogeneous parenchymal appearances with hypoechoic lesions present in 96% of patients. At least one submandibular gland was affected in 88.5% of the whole group, and all patients in the MCTD-group. Twenty of twenty five patients were scanned and scored on a second visit. Pre-malignancies or mucosa-associated lymphoid tissue (MALT) were detected in biopsies of three patients (Hocevar scoring of 40, 33, and 28).ConclusionSGUS in patients with pjSS and sjSS is a helpful first-line tool to detect and score salivary gland involvement, in particular when keratoconjunctivitis sicca, xerostomia, or glandular swelling occurs. Juvenile MCTD patients have a significant risk of developing secondary jSS. We propose SGUS as a method in the diagnostic workup and screening for inflammatory changes. Further studies have to determine the predictive value of SGUS for follow up.

AB0593 DOES REALLY EXIST MIXED CONNECTIVE TISSUE DISEASE?

Background:Currently, most authors accept that mixed connective tissue disease (MCTD) is an independent entity, although there are those who argue that it is actually an overlap syndrome or an undifferentiated early phase of another systemic autoimmune disease (SAD).Objectives:To analyze the long term evolution of a serie of patients with MCTD.Methods:Observational, retrospective and multicenter study in patients with MCTD (diagnostic criteria of Alarcón-Segovia et al),followed for a minimun of 2 years.Results:Fifty-five patients (49 women) with a median age at diagnosis of 38±14 years and with a follow up time (median) of 101 months (range, 24-237 months with a total of 501.2 pacients-year) were identified.At the end of the follow-up period, only 27% (15/55) of the patients kept on fulfilling MCTD criteria. In the remaining 73% (40), 40% (22) had been differentiated to systemic lupus erythematosus (SLE), 13% (7) to systemic sclerosis (SSc) and 20% (11) developed an overlap syndrome [SSc+SLE in 8 cases and SSc+rheumatoid arthritis (AR) in 3]. In 8% of these patients, a secondary Sjögren’s syndrome was diagnosed during the follow-up period. The average score in patients who met the EULAR/ACR 2013 criteria for SSc was 11 (minimum 9 - maximum 16) and the average time elapsed from the diagnosis of MCTD to meet SSc criteria was 64.4 months (interquartile range [IQR] 25-75%: 10-127 months).Applying the 2012 SLICC criteria, only 24 patients of those initially diagnosed as MCTD ended up meeting SLE criteria. The average score in these patients was 5.6 (4-9) and the average time elapsed from the diagnosis of MCTD unltil fulfilling the SLICC criteria was 39 months (IQR 25-75%: 6-28). When we apply the new ACR/EULAR 2019 criteria, the percentage of patients who meet SLE criteria increased to 30%, with an average score of 17.3 (10-38). The average time elapsed since the diagnosis of MCTD until meeting the new SLE criteria was reduced to 17 months (IQR 25-75: 0-10).In the multivariate study, the presence of sclerodactyly (OR: 2.91; IC 95% 1.90 - 4.1, p= 0.001) and esophageal involvement (OR: 2.05; IC 95% 1.14–3.66, p=0.016) were associated with the evolution to SSc. Any predictor of evolution to SLE was identified.Conclusion:Only slightly more than a quarter of patients initially diagnosed as MCTD maintain this diagnosis during the follow-up. The majority, ended up evolving towards to another SAD, fundamentally SLE and SSc. The new ACR/EULAR 2019 criteria seems to be more sensitive than the SLICC 2012 criteria for diagnose SLE in these patients.Disclosure of Interests:L Montolio-Chiva: None declared, J. Narváez: None declared, Maria Pascual: None declared, Hye Sang Park: None declared, Ana V Orenes Vera: None declared, Eduardo Flores: None declared, Juanjo J Alegre-Sancho Consultant of: UCB, Roche, Sanofi, Boehringer, Celltrion, Paid instructor for: GSK, Speakers bureau: MSD, GSK, Lilly, Sanofi, Roche, UCB, Actelion, Pfizer, Abbvie, Novartis, Iván Castellví: None declared, Joan Miquel Nolla: None declared

Clinical and Immunological Profile of Mixed Connective Tissue Disease and a Comparison of Four Diagnostic Criteria.

Mixed connective tissue disease (MCTD) was initially described as a chronic immune-mediated disease with overlapping features of systemic lupus erythematosus, scleroderma, and polymyositis. We conducted a cross-sectional study to describe the clinical and immunological profile of patients with MCTD and to compare the four diagnostic criteria, namely, Sharp, Kasukawa, Alarcón-Segovia, and Khan criteria. A total of 291 patients who were admitted from June 2007 to June 2017 and fulfilled the inclusion criteria were included in the study. A clinical diagnosis of MCTD was made in 111 patients, of whom 103 (92.8%) were women. The mean age at presentation was 39.3 years (SD ± 11.6). The most common organ systems that were involved were musculoskeletal system (95.5%), skin and mucosa (78.4%), and the gastrointestinal and hepatobiliary systems (56%). The maximum sensitivity was for the Kasukawa criteria with a sensitivity of 77.5% (95% CI 68.4-84.6) and specificity of 92.2% (95% CI 87-95.5). The Kahn criteria and Alarcón-Segovia criteria had the maximum specificity; the Alarcón-Segovia criteria had a sensitivity of 69.4% (95% CI 59.8-77.6) and a specificity of 99.4% (95% CI 96.5-99.9), while the Kahn criteria had a sensitivity of 52.3% (95% CI 42.6-61.7) and a specificity of 99.4% (95% CI 96.5-99.9). The sensitivity and specificity of Sharp criteria were 57.7% (95% CI 47.9-66.87) and 90% (95% CI 84.4-93.8), respectively.

3241 An Unusual Case of Mixed Connective Tissue Disease Presenting as Abdominal Pain

INTRODUCTION: Mixed Connective Tissue Disease (MCTD) is a rare systemic autoimmune condition with clinical features similar to systemic lupus erythematous, dermatomyositis, sarcoidosis and rheumatoid arthritis. The diagnosis of MCTD consists of high antibody titers to U1 small nuclear ribonucleoprotein (RNP) in peripheral blood and the presence of clinical manifestations. The most common manifestations are Raynaud phenomenon, joint and muscle pain. Gastrointestinal manifestations of MCTD are less common and are usually gastroesophageal reflux disease or dysphagia. This case describes MCTD presenting as epigastric abdominal pain in a healthy woman. CASE DESCRIPTION/METHODS: The patient is a 50-year-old female with no past medical history who was referred to gastroenterology for evaluation of two months of epigastric pain that failed to improve after a thirty-day course of esomeprazole. The pain was described as “squeezing and strangling” in character. A subsequent EGD was unremarkable. The patient was noted to have a mild elevation in her ALT (38) and underwent an ultrasound that demonstrated hepatomegaly and hepatic steatosis. A serological chronic liver disease work-up was negative with the exception of ANA, which was 1:80 in a homogenous pattern. The rest of the patient's laboratory work-up was unremarkable. ANA nine months later was again positive. Anti-RNP antibody was also positive. In the setting of persistent unexplained pain, a repeat ultrasound was performed and was normal. A HIDA scan was done, which demonstrated a borderline ejection fraction of 27%. Biliary dyskinesia was not felt to be cause of the patient's pain given its character and timing. The patient was advised to see a rheumatologist regarding her positive anti-RNP antibody but failed to do so. She presented to a new PCP with continued epigastric pain and new onset arthralgia and edema. The patient was started on methylprednisolone rapid taper which resolved all of the patient's symptoms. The patient was advised to start hydroxychloroquine but she declined due to resolution of her symptoms. DISCUSSION: MCTD is a rare systemic autoimmune condition with clinical manifestations affecting multiple organ systems. Gastrointestinal involvement of MCTD is less common. In this case a previously healthy woman presented with epigastric pain and was found to have MCTD as a cause of her symptoms. This case is an unusual presentation of MCTD and is clinically important as early treatment of MCTD decreases the risk of progression to other organ systems.

Mixed connective tissue disease

Mixed connective tissue disease (MCTD), also known as Sharp's syndrome, is a rare systemic connective tissue disorder that characterized by a combination of some features of systemic lupus erythematosus, systemic sclerosis, rheumatoid arthritis, polymyositis with the presence of antibodies to soluble nuclear ribonucleoprotein (anti-U1-RNP) in high titers. The most common clinical manifestations of MCTD include Raynaud's phenomenon, hand edema, muscle weakness, arthralgia/arthritis, and esophageal hypotonia. The course of the disease is mostly benign; however, there are severe cases with damage to the lung, kidneys, cardiovascular system and central nervous system. Poor prognosis and the highest mortality rate are associated with pulmonary hypertension. The diagnosis of MCTD is difficult due to the absence of unified diagnostic criteria and lack of specific manifestations at the onset of the disease. Furthermore, there are no generally accepted guidelines for MCTD treatment. The paper considers the modern concepts of MCTD, its current diagnostic criteria, clinical and immunological features, and treatment.

Associations between nailfold capillaroscopy findings and interstitial lung disease in patients with mixed connective tissue disease.

IntroductionMixed connective tissue disease (MCTD) is a chronic immune-mediated disorder defined by the combined presence of serum anti-RNP antibodies and distinct clinical features including progressive lung fibrosis. The aim of this study was to evaluate potential associations between lung fibrosis in MCTD and specific clinical and laboratory findings including results of nailfold capillaroscopy (NFC) examination.Material and methodsPatients with MCTD who were admitted to the Departments of Allergy and Immunology or Dermatology at the University Hospital of Krakow (Poland) in 2015–2018 were identified based on comprehensive individual record review. Diagnosis of MCTD required fulfilment of at least one of the four widely accepted sets of diagnostic criteria. Clinical and laboratory data were collected, and statistical analysis was performed to identify potential predictors of interstitial lung disease (ILD).ResultsThirty patients (90% females) aged 22–81 years met the study inclusion criteria. The mean duration of symptoms associated with MCTD was 7.3 months. Photosensitivity and Raynaud’s phenomenon were the most common clinical manifestations (90% and 70%, respectively). Hand oedema, sclerodactyly and the presence of giant capillaries in NFC correlated significantly with the risk of lung involvement. In multivariate analysis, the presence of enlarged loops in NFC (giant capillaries) was identified as an independent factor for ILD (R 2 = 0.82, p < 0.0000001).ConclusionsThe NFC examination should be considered in all patients with a diagnosis of MCTD. The presence of giant capillaries may be a promising marker for interstitial lung disease in these patients, especially among those with a short duration of disease (i.e. < 1 year).

Mixed connective tissue disease: state of the art on clinical practice guidelines

Mixed connective tissue disease (MCTD) is a complex overlap disease with features of different autoimmune connective tissue diseases (CTDs) namely systemic sclerosis, poly/dermatomyositis and systemic lupus erythematous in patients with...

Prevalence of Mixed Connective Tissue Disease in a Population-Based Registry of American Indian/Alaska Native People in 2007.

To determine the prevalence of mixed connective tissue disease (MCTD) in 2007 in the Indian Health Service (IHS) active clinical population from 3 regions of the US. The IHS Lupus Registry was designed to identify possible MCTD cases in addition to systemic lupus erythematosus cases. The population denominator for this report includes American Indian or Alaska Native adults within the IHS active clinical population in 2007, residing in select communities in 3 regions of the US. Potential MCTD cases were identified using a broad range of diagnostic codes and were confirmed by detailed medical record abstraction. Classification as MCTD for this analysis required both rheumatologist diagnosis of MCTD without diagnosis of other CTD, and documentation of the Alarcón-Segovia MCTD criteria in the medical record. Prevalence was also calculated using 2 alternate definitions of MCTD. The age-adjusted prevalence of MCTD using our primary definition was 6.4 per 100,000 (95% confidence interval 2.8-12.8). The prevalence was higher in women than in men using all 3 definitions of MCTD, and no men met the criteria for the primary definition of MCTD. The first population-based estimates of the prevalence of MCTD in the US American Indian/Alaska Native population show that the prevalence appears to be higher than in other populations. Additional population-based estimates are needed to better understand the epidemiology of MCTD.

Epidemiology of Mixed Connective Tissue Disease, 1985-2014: A Population-Based Study.

To characterize the epidemiology of mixed connective tissue disease (MCTD) from 1983 to 2014. An inception cohort of patients with incident MCTD in 1985-2014 in Olmsted County, Minnesota was identified based on comprehensive individual medical record review. Diagnosis of MCTD required fulfillment of at least 1 of the 4 widely accepted diagnostic criteria without fulfillment of classification criteria for other connective tissue diseases. Data were collected on demographic characteristics, clinical presentation, laboratory investigations, and mortality. A total of 50 incident cases of MCTD were identified (mean age 48.1 years and 84% were female). The annual incidence of MCTD was 1.9 per 100,000 population. Raynaud's phenomenon was the most common initial symptoms (50%), followed by arthralgia (30%) and swollen hands (16%). The diagnosis was frequently delayed with the median time from first symptom to fulfillment of criteria of 3.6 years. At fulfillment of criteria, arthralgia was the most prevalent manifestation (86%), followed by Raynaud's phenomenon (80%), swollen hands (64%), leukopenia/lymphopenia (44%), and heartburn (38%). Evolution to other connective tissue occurred infrequently with a 10-year rate of evolution of 8.5% and 6.3% for systemic lupus erythematosus and systemic sclerosis, respectively. The overall mortality was not different from the general population with a standardized mortality ratio of 1.1 (95% confidence interval 0.4-2.6). This study was the first population-based study of MCTD to provide a complete picture of epidemiology and clinical characteristics of MCTD. MCTD occurred in about 2 persons per 100,000 per year. Evolution to other connective diseases occurred infrequently and the mortality was not affected.

Mixed connective tissue disease.

The concept of mixed connective tissue disease (MCTD) as a separate connective tissue disease (CTD) has persisted for more than four decades. High titers of antibodies targeting the U1 small nuclear ribonucleoprotein particle (U1 snRNP) in peripheral blood are a sine qua non for the diagnosis of MCTD, in addition to distinct clinical features including Raynaud's phenomenon (RP), "puffy hands," arthritis, myositis, pleuritis, pericarditis, interstitial lung disease (ILD), and pulmonary hypertension (PH). Recently, population-based epidemiology data from Norway estimated the point prevalence of adult-onset MCTD to be 3.8 per 100,000 and the mean annual incidence to be 2.1 per million per year, supporting the notion that MCTD is the least common CTD. Little is known about the etiology of MCTD, but recent genetic studies have confirmed that MCTD is a strongly HLA (​human leukocyte antigen)-linked disease, as the HLA profiles of MCTD differ distinctly from the corresponding profiles of ethnically matched healthy controls and other CTDs. In the first section of this review, we provide an update on the clinical, immunological, and genetic features of MCTD and discuss the relationship between MCTD and the other CTDs. Then we proceed to discuss the recent advances in therapy and our current understanding of prognosis and prognostic factors, especially those that are associated with the more serious pulmonary and cardiovascular complications of the disease. In the final section, we discuss some of the key, unresolved questions related to anti-RNP-associated diseases and indicate how these questions may be approached in future studies.

Clinical Course, Prognosis, and Causes of Death in Mixed Connective Tissue Disease

To study the survival rate and prognostic indicators of mixed connective tissue disease (MCTD) in a Hungarian population. Two hundred eighty patients with MCTD diagnosed between 1979 and 2011 were followed prospectively. Clinical features, autoantibodies, and mortality data were assessed. Prognostic factors for survival were investigated and survival was calculated from the time of the diagnosis by Kaplan-Meier method. A total of 22 of 280 patients died: the causes of death were pulmonary arterial hypertension (PAH) in 9 patients, thrombotic thrombocytopenic purpura in 3, infections in 3, and cardiovascular events in 7. The 5, 10, and 15-year survival rates after the diagnosis was established were 98%, 96%, and 88%, respectively. The deceased patients were younger at the diagnosis of MCTD compared to patients who survived (35.5 ± 10.4 vs 41.8 ± 10.7 yrs; p < 0.03), while there was no difference in the duration of the disease (p = 0.835). Our cohort study showed that the presence of cardiovascular events (p < 0.0001), esophageal hypomotility (p = 0.04), serositis (p < 0.001), secondary antiphospholipid syndrome (p = 0.039), and malignancy (p < 0.001) was significantly higher in the deceased patients with MCTD. The presence of anticardiolipin (p = 0.019), anti-β2-glycoprotein I (p = 0.002), and antiendothelial cell antibodies (p = 0.002) increased the risk of mortality. Overall, PAH remained the leading cause of death in patients with MCTD. The prevalence of cardiovascular morbidity and mortality, malignancy, and thrombotic events increased during the disease course of MCTD. The presence of antiphospholipid antibodies raised the risk of mortality.

Mixed connective tissue disease presenting with progressive scleroderma symptoms in a 10-year-old girl

Mixed connective tissue disease (MCTD) is a systemic inflammatory disease affecting connective tissue with the underlying autoimmunological mechanism. The core of MCTD is an appearance of symptoms of several other inflammatory diseases of connective tissue – systemic lupus erythematosus, systemic scleroderma, poly- or dermatomyositis, rheumatoid arthritis at the same time, accompanied by a high level of anti-ribonucleoprotein antibodies (anti-U1RNP). The disease was described more than 40 years ago by Sharp et al. During recent years, many efforts to better understand clinical and serological features of MCTD have been made. Diagnosis of MCTD can be difficult. Obligatory international diagnostic criteria are required to be fulfilled. Several versions of such criteria have been proposed, but the most widely used one was described by Kasukawa. There is no consensus about treatment – a choice of drugs depends on symptoms. We present a case of a 10-year-old girl with sclerodactyly and trophic damages of fingers accompanied by symptoms of Raynaud's phenomenon. After an almost 2-year course of the disease, a diagnosis of MCTD has been established.