Orthotopic heart transplant in a pediatric patient with mixed connective tissue disease.

BACKGROUND: Patients with autoimmune inflammatory syndromes such as mixed connective tissue disease (MCTD) and systemic lupus erythematosus have previously been considered marginal candidates for orthotopic heart transplant (OHT). METHODS: A retrospective chart review was completed for this case report. RESULTS: We present the case of an 11-year-old girl with known MCTD who developed congestive heart failure refractory to medical therapy and underwent OHT. CONCLUSIONS: Despite her autoimmune condition, this patient has not experienced antibody-mediated rejection post-transplant and her inflammatory symptoms have greatly improved.

Salivary gland ultrasound in the diagnostic workup of juvenile Sjögren's syndrome and mixed connective tissue disease.

BACKGROUND: Juvenile 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. METHODS: We 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. RESULTS: Twenty 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). CONCLUSION: SGUS 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.

Spectrum of paediatric rheumatic disorders at a tertiary hospital in Tanzania.

BACKGROUND: Paediatric rheumatic disorders are common in children and result in significant impairment in quality of life, morbidity and mortality. There is limited information on the burden of these disorders in lower income countries especially in sub-Saharan Africa. Few case reports have documented presence of paediatric rheumatic disorders in Tanzania. This study was conducted to determine the spectrum of rheumatic disorders among children at Muhimbili National Hospital (MNH). METHODS: This was a retrospective study conducted among children who were attended at MNH between January 2012 and August 2019. Paediatric patients seen in the out-patient clinics and those admitted in the wards were eligible. All patients with diagnosis of rheumatic disorders were identified from admission books and outpatient clinic logbooks, and later data were collected from their case notes and were recorded in clinical research forms. Collected information included age, sex, clinical features and laboratory tests results. RESULTS: A total of 52 children with mean age of 9.5 ± 4.3 years, 12 (40.4%) participants were aged above 10 years and 32 (61.5%) were females. Frequently reported clinical presentations were joint pain 44 (84.6%), joint swelling 34 (65.4%), fever 24 (46.2%) and skin rashes 21(40.4%). Juvenile idiopathic arthritis (JIA) was the predominant diagnosis reported in 28 (53.8%) participants followed by juvenile systemic lupus erythematosus 8 (15.4%), mixed connective tissue diseases 4 (7.7%) and juvenile dermatomyositis 4 (7.7%). Antinuclear antibody test was performed in 16 participants it was positive in 9 (56.2%). Nine participants were tested for anti-double stranded DNA test and 5 (55.6%) were positive for this test. C-reactive protein was tested in 46 participants out of which 32 (69.6%) had elevated levels. HIV was tested in 24 (46.2%) participants and results were negative. Thirty-five out of 52 (67.3%) participants had anaemia. Predominant drugs used for treatment of JIA include prednisolone and methotrexate. CONCLUSIONS: Paediatric rheumatic disorders are not uncommon in Tanzania-and were noted to affect more female children in this study. Predominant conditions included juvenile idiopathic arthritis (JIA), juvenile systemic lupus erythematosus (JSLE) and juvenile dermatomyositis (JDM).

Nailfold capillaroscopy and autoimmune connective tissue diseases in patients from a Portuguese nailfold capillaroscopy clinic.

Raynaud's phenomenon (RP) is frequent in autoimmune connective tissue diseases (AICTD) and its approach includes nailfold capillaroscopy (NFC), as it is a non-invasive technique that permits direct visualization of the microcirculation. The aim of this study is to analyze and establish clinical correlations between NFC findings and particular aspects of autoimmune disorders. This is a retrospective study. Clinical data from patients attending our NFC clinic were reviewed. Inclusion criteria included AICTD previous diagnosis, which included systemic sclerosis (SSc), mixed connective tissue disease (MCTD), systemic lupus erythematosus (SLE), Sjögren syndrome, inflammatory idiopathic myopathies (IIM), rheumatoid arthritis, undifferentiated connective tissue disease and antiphospholipid syndrome (APS). Videocap® version 3.0 biomicroscope was used. NFC score was determined. For statistics, SPSS software was utilized. 384 patients were included; most of them were women, with mean age of 47 years. RP was present in 91% of the patients, with greater prevalence in SSc and MCTD. Scleroderma pattern was the most prevalent NFC pattern, mainly in SSc, MCTD and IIM. Mean capillary density was reduced in IIM, SSc and MCTD. NFC score was worse in SSc, IIM and MCTD. In patients with AICTD, RP is related to microvascular damage and worse NFC score. NFC scleroderma pattern correlates with SSc classification criteria score. In MCTD, scleroderma pattern relates to myositis. SLE and APS reveal significant hemorrhages, but not related to APS antibodies. This study highlights the possible role of NFC as biomarker of AICTD, particularly in SSc and IIM.

Pulmonary Manifestations and Progression of Lung Disease in Juvenile-onset Mixed Connective Tissue Disease.

OBJECTIVE: To assess the occurrence and extent of interstitial lung disease (ILD) in patients with juvenile mixed connective tissue disease (JMCTD), compare pulmonary function in patients and matched controls, study associations between ILD and disease-related variables, and examine progression of pulmonary manifestations over time. METHODS: A cohort of 52 patients with JMCTD were examined in a cross-sectional study after a mean 16.2 (SD 10.3) years of disease duration with high-resolution computed tomography (HRCT) and pulmonary function tests (PFT) comprising spirometry, DLCO, and total lung capacity (TLC). Matched controls were examined with PFT. Previous HRCT and PFT were available in 37 and 38 patients (mean 8.8 and 10.3 yrs before study inclusion), respectively. RESULTS: Compared to controls, patients with JMCTD had lower forced vital capacity (FVC), DLCO, and TLC (p < 0.01). The most frequent abnormal PFT was DLCO in 67% of patients versus 17% of controls (p < 0.001). Fourteen patients (27%) had ILD on HRCT. Most had ILD in < 10% of their lungs. ILD was associated with low values for FVC and TLC, but not with DLCO. HRCT findings did not progress significantly over time, but FVC declined (p < 0.01). CONCLUSION: Compared to controls, patients with JMCTD had impaired pulmonary function. ILD was present in 27% of patients after a mean 16 years of disease duration, mostly as mild disease, and did not progress. ILD seems to be less common in juvenile-onset than in adult-onset MCTD, and ILD in JMCTD seems mostly mild and stable over time.

Clinical and immunological profile in patients with mixed connective tissue disease.

Mixed connective tissue disease (MCTD) is a rare disease and presents with varied overlapping symptoms of different connective tissue disorders. Many patients evolve into other connective tissue disorders with the passage of time. The case series included 20 patients with the diagnosis of MCTD, registered at the Rheumatology Clinic of Jinnah Postgraduate Medical Centre (JPMC), Karachi, from June 2010 to May 2015. Of these, 16 (80.0%) were female and 4 (20.0%) patients were male. The mean age was 30.5±8.9 years and the mean duration of illness was 4.5±2 years. Commonest presenting symptom was arthralgia in 17 (85%) patients. All the patients had positive ANA and anti-RNP antibodies. Over the disease course of 6 years, 2 (10%) patients evolved into Systemic lupus erythematosus (SLE); One each (5%) into Sjogren's syndrome, Scleroderma and Rheumatoid arthritis.

Comparison of articular manifestations of mixed connective tissue disease and systemic lupus erythematosus on clinical examination and musculoskeletal ultrasound.

BACKGROUND: Polyarthritis is common to both mixed connective tissue disease (MCTD) and systemic lupus erythematosus (SLE). Apart from being erosive and deforming in the former, we speculated that it was more common and the extent of joints involved would be higher in MCTD. METHODS: This was a cross-sectional study that included patients with MCTD aged 18-75 years fulfilling the Kasukawa criteria. An equal number of patients with SLE matched for disease duration and gender were included. Clinical manifestations were compared between patients with MCTD and with SLE. Examination of joints was done for the presence of tenderness or swelling and deformity. Musculoskeletal ultrasound was done on the non-dominant hand for detection of synovitis and tenosynovitis and radiographs of the hands were obtained. The use of methotrexate and non-steroidal anti-inflammatory drugs (NSAIDs) for arthritis was noted. Statistical tests used were non-parametric. RESULTS: Forty patients with MCTD and forty patients with SLE were included in this study, with patients being slightly older in MCTD than SLE (36 ± 10.2, 31.8 ± 13.3 years, p = 0.01). There were no significant differences in disease duration (4.7 ± 3.1, 3.7 ± 2.3, p = 0.1) or gender (females = 38, 38). Nearly one-half of patients with MCTD had at least one swollen joint compared with only 15% of patients with SLE. Median (95% confidence interval) tender joint count (5 (4.8-10.4), 0 (1.3-7.2), p = 0.01) and swollen joint count (0 (0.9-2.6), 0 (0-1.2), p = 0.002) was significantly higher in patients with MCTD compared with SLE. More patients with MCTD than SLE had tender or swollen proximal interphalangeal joints (12, 4, p = 0.025). More patients with MCTD than SLE had received methotrexate (8,2, p = 0.04) and NSAIDs (39, 32, p = 0.03) for arthritis. There was no difference in the number of patients with MCTD or SLE who had evidence of synovitis or tenosynovitis on ultrasound. There was no difference in erosive disease on hand radiographs, but acro-osteolysis was higher among MCTD patients. CONCLUSIONS: A higher proportion of patients with MCTD had at least one swollen and tender joint as compared with patients with SLE, as well as higher use of methotrexate and NSAIDs. However, there was no difference in ultrasound detected synovitis or tenosynovitis.

Musculoskeletal Manifestations of Non-RA Connective Tissue Diseases: Scleroderma, Systemic Lupus Erythematosus, Still's Disease, Dermatomyositis/Polymyositis, Sjögren's Syndrome, and Mixed Connective Tissue Disease.

The most common systemic rheumatologic conditions are connective tissue diseases (including rheumatoid arthritis [RA]) followed by spondyloarthropathy. With the advent of biotherapies and imaging biomarkers, development in the imaging of RA and spondyloarthropathies has received substantial attention in the literature. This article details the various musculoskeletal imaging features of the other connective tissue diseases such as scleroderma and progressive systemic sclerosis, systemic lupus erythematosus, Still's disease, dermatomyositis and polymyositis, Sjögren's syndrome, and mixed connective tissue disease.

Hechos y controversias en la enfermedad mixta del tejido conectivo / Facts and controversies in mixed connective tissue disease

La enfermedad mixta del tejido conectivo (EMTC) es una enfermedad reumática autoinmunitaria sistémica (ERAS) caracterizada por la asociación de manifestaciones clínicas de lupus eritematoso sistémico (LES), esclerosis sistémica cutánea (ESC) y polimiositis-dermatomiositis en presencia de títulos elevados de anticuerpos anti-U1-RNP en el suero de los pacientes. Sus principales síntomas son la poliartritis, el edema de manos, el fenómeno de Raynaud, la esclerodactilia, la miositis y la hipomotilidad esofágica. Actualmente, la mayoría de los autores acepta que la EMTC es una entidad independiente, pero algunos mantienen que estos pacientes podrían presentar una ERAS, definida en su fase precoz como LES o ESC, o ser, en realidad, un síndrome de solapamiento de la ERAS (AU)

Mixed connective tissue disease (MCTD) is a systemic autoimmune rheumatic disease (SARD) characterised by the combination of clinical manifestations of systemic lupus erythematosus (SLE), cutaneous systemic sclerosis (SSc) and polymyositis-dermatomyositis, in the presence of elevated titers of anti-U1-RNP antibodies. Main symptoms of the disease are polyarthritis, hand oedema, Raynaud's phenomenon, sclerodactyly, myositis and oesophageal hypomobility. Although widely discussed, most authors today accept MCTD as an independent entity. Others, however, suggest that these patients may belong to subgroups or early stages of certain definite connective diseases, such as SLE or SSc, or are, in fact, SARD overlap syndromes (AU)

[Mixed connective tissue disease: prevalence and clinical characteristics in African black, study of 7 cases in Gabon and review of the literature]. / La connectivite mixte: prévalence et caractéristiques cliniques chez le noir africain, étude de 7 cas au Gabon et revue de la littérature.

The literature reports that mixed connective tissue disease seems more frequent in the black population and among Asians. This study aims to determine the prevalence of mixed connective tissue disease (MCTD) among connective tissue disorders and all rheumatologic pathologies in a hospital population in Gabon as well as to describe the clinical features of this disease. We conducted a retrospective study by reviewing the medical records of patients treated for mixed connective tissue disease (Kasukawa criteria) and other entities of connective tissue disorders (ACR criteria) in the Division of Rheumatology at the University Hospital in Libreville between January 2010 and December 2015. For each case of MCTD the parameters studied were articular and extra-articular manifestations, anti-U1RNP antibodies levels, patient's evolution. Over a period of 6 years, data were collected by medical records of 7 patients out of 6050 patients and 67 cases of connective tissue disorders, reflecting a prevalence of 0.11% and 10.44% respectively. the 7 patients were women (100%), with an average age of 39.5 years. Articular manifestations included: polyarthritis, myalgias, chubby fingers and Raynaud's phenomenon in 87.5%, 87.5%, 28.6% and 14% respectively. The 7 patients had high anti-U1RNP antibodies levels, ranging between 5 and 35N (N≤ 7 IU). A case of death due to pulmonary arterial hypertension (PAH) was certified. This is the largest case series of MCTD reported in Black Africa. The disease seems to be rare among the black Africans; the reason could be genetic. The demographic and clinical aspects appear similar to those in Caucasians, Asians and Blacks except for a low frequency of Raynaud?s phenomenon among Blacks.

Mixed Connective Tissue Disease and Epitope Spreading: An Historical Cohort Study.

OBJECTIVES: Mixed connective tissue disease (MCTD) is characterized by the presence of anti-U1-snRNP autoantibodies and a variable set of associated clinical features. Some MCTD patients test positive over time to autoantibodies against Sm, proteins spatially related with U1-snRNP. This situation has been attributed to expanding of the autoimmune response by a phenomenon known as epitope spreading. Our aim was to study the frequency of this phenomenon in MCTD patients and the specific clinical features of those with epitope spreading. METHODS: All anti-U1-RNP-positive patients (2010-2015) were retrospectively reviewed, and those meeting the MCTD criteria were included in the study. Patients showing epitope spreading were compared with the remainder of the MCTD cohort. In addition, the clinical features of patients with epitope spreading were compared before and after the phenomenon occurred. RESULTS: Among 72 anti-U1-RNP-positive patients, 40 (37 women) were diagnosed with MCTD. Thirteen MCTD patients (43%) presented epitope spreading, mainly during the first 2 years after the diagnosis of the disease (median, 1.4 years). Patients with epitope spreading had a significantly lower prevalence of skin sclerosis (0% vs. 44%, P = 0.004) and a greater prevalence of interstitial lung disease (46% vs. 15%, P = 0.05) than those without. Arthritis (92% vs. 25%, P = 0.02) and muscle involvement (67% vs. 17%, P = 0.02) were less frequent after epitope spreading had occurred. CONCLUSION: Epitope spreading is common in MCTD, occurring early after the diagnosis. The clinical manifestations in patients with this phenomenon differ from those without, and their clinical features change after the immunological phenomenon has occurred.

Calcinosis tumoral asociada a enfermedad mixta del tejido conectivo / Tumoral calcinosis associated with mixed connective tissue disease

No disponible

Imaging Patterns of Cardiovascular Involvement in Mixed Connective Tissue Disease Evaluated by Cardiovascular Magnetic Resonance.

BACKGROUND: To clarify the imaging patterns of cardiovascular lesions in patients with mixed connective tissue disease (MCTD) and cardiovascular symptoms with or/ without abnormal routine non-invasive evaluation. PATIENTS-METHODS: Twenty-two MCTD patients (19F/3M), aged 38±4 yrs with cardiovascular symptoms were evaluated using a 1.5 T scanner. Of them, 8/22 had systemic lupus erythematosus (SLE), 5/22 rheumatoid arthritis (RA), 5/22 scleroderma (SSc) and 4/22 myositis (MY) overlap syndromes; 10/22 patients with MCTD presented with Raynaud phenomenon (RP) and all were positive for Anti-RNP antibodies. The cardiovascular magnetic resonance study (CMR) included evaluation of function, inflammation and fibrosis. Myocardial stress perfusion-fibrosis evaluation was performed only in MCTD patients with RP. RESULTS: A positive CMR study was identified in 4/8 with SLE, 1/5 with RA, 4/5 with SSc and in 1/4 with MY like MCTD. The CMR lesions were subendocardial or transmural LGE following the distribution of coronary arteries, intramyocardial LGE and diffuse subendocardial LGE in SLE-RA, MY and SSc like MCTD, respectively. Although no evidence of fibrosis was identified in patients with RP, adenosine stress myocardial perfusion revealed diffuse subendocardial perfusion defects. No correlation between disease duration and/or inflammatory indices and cardiac lesions was identified. CONCLUSION: CMR can reveal myocardial lesions in MCTD patients with cardiac symptoms including myocardial infarction, inflammation, diffuse subendocardial fibrosis and diffuse perfusion defects, necessitating further cardiac investigation and/or treatment.

Impaired endothelial function in patients with undifferentiated connective tissue disease: a follow-up study.

OBJECTIVE: In this study the alteration of endothelial function, arterial stiffness and autoantibodies was investigated in patients with UCTD. METHODS: Thirty-one patients with UCTD were included in this prospective study. All the patients remained in the UCTD stage during the average 3.8 years follow-up period. The onset of UCTD was denoted as UCTD1, while the end of the follow-up period was called UCTD2. Flow-mediated vasodilation (FMD), carotid intima-media thickness (IMT), autoantibodies [such as anti-SSA, anti-SSB, anti-DNA, anti-RNP, anti-CCP, aCL, anti-oxidized low-density lipoprotein (oxLDL) and AECA], von Willebrand factor antigen, thrombomodulin (TM), endothelin 1 (ET-1) and lipid parameters were measured. RESULTS: In the UCTD1 stage, high-sensitivity CRP (hsCRP) and endothelial cell activation and/or damage markers such as TM, ET-1 and AECA levels were significantly higher compared with controls (controls vs UCTD1: hsCRP, P < 0.0001; TM, P = 0.001; ET-1, P < 0.0001). In the UCTD2 stage, the carotid IMT increased (UCTD1 vs UCTD2, P = 0.01) and FMD further deteriorated (UCTD1 and UCTD2, P = 0.001). In UCTD2 there was a close correlation between the carotid IMT, and duration of the disease (r = 0.612, P < 0.001), the level of TM (r = 0.673, P < 0.001) and anti-oxLDL (r = 0.800, P < 0.001). CONCLUSION: Our data suggest that the presence of inflammation and autoantibodies provoke endothelial cell activation and/or injury in UCTD patients. The persistent endothelial dysfunction may provoke the development of atherosclerosis. FMD was found to be the most sensitive marker for arterial stiffness, and the increase of IMT clearly indicated the existence of preclinical atherosclerosis in UCTD patients.