Naifold capillaroscopy in mixed connective tissue disease patients.

INTRODUCTION: 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. OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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).

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.

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.

Increased Endothelial Activation in Patients with Mixed Connective Tissue Disease.

OBJECTIVE: Juvenile-onset mixed connective tissue disease (JMCTD) is a chronic inflammatory disease. We have previously demonstrated preclinical atherosclerosis in these patients, now exploring this further by assessing markers of endothelial dysfunction. METHODS: Thirty-three patients with JMCTD and 33 age-and sex-matched controls were included. Soluble intercellular adhesion molecule-1 (sICAM-1), Il-6 and, von Willenbrand factor (vWF) were assayed from blood taken at the time of carotid ultrasound. RESULTS: Our major findings were: (1) Levels of sICAM-1 (P < .001), IL-6 (P = .004), and vWF (P = .001) were higher, whereas (2) high density lipoprotein cholesterol (<.01) and apolipoprotein A1 (P < .01) were lower in the patient group compared to controls. CONCLUSIONS: Patients with JMCTD had significantly increased levels of markers of endothelial dysfunction.

Long-term follow-up of nailfold videocapillaroscopic microvascular parameters in mixed connective tissue disease versus systemic sclerosis patients: a retrospective cohort study.

OBJECTIVES: To retrospectively study nailfold videocapillaroscopy (NVC) changes in mixed connective tissue disease (MCTD) patients and to compare the capillary morphological abnormalities between patients affected by MCTD and systemic sclerosis (SSc) over time. METHODS: Ten MCTD patients on whom NVC had been performed, with a follow-up of three years, were selected. In addition, ten patients affected by SSc with similar age and disease duration of MCTD patients were enrolled to compare NVC abnormalities at baseline (T0). RESULTS: Seven out of ten patients with MCTD showed a "scleroderma-like pattern" at first NVC. No statistically significant variation of the detected NVC parameters was observed during the 3-year follow-up, and no statistically significant correlation was observed between capillary parameters and MCTD clinical aspects at first visit and during the follow-up. The scores of enlarged capillaries, giant capillaries and microhaemorrhages were significantly lower (p<0.05) in MCTD versus SSc patients at T0, moreover, the absolute number of total capillaries and normal capillaries was found significantly higher (p<0.05) in MCTD versus SSc patients. CONCLUSIONS: This study suggests that nailfold microvascular damage does not seem to be significantly progressive in MCTD patients during a three-year follow-up. MCTD patients show significantly lower number of enlarged/giant capillaries, but higher number of total and normal capillaries than SSc patients at first nailfold capillaroscopy. The identification of a specific NVC pattern in MCTD patients is not yet possible.

Nail fold dermoscopy in collagen vascular disorders: A cross-sectional study.

BACKGROUND: The collagen vascular disorders, particularly systemic sclerosis, dermatomyositis, systemic lupus erythematosus and mixed connective tissue disorder, are often characterized by microangiopathic abnormalities of the nail folds. Nail fold dermoscopy is a well-established technique to assess these vascular changes. AIMS: To evaluate finger nail capillary vascular abnormalities by dermoscopy and their correlation with cutaneous and systemic involvement in the patients of collagen vascular disorders. METHODS: This was a cross-sectional study involving patients of collagen vascular disorders presenting to Government Medical College, Amritsar over a period of 2 years. Nail fold dermoscopy was done in these patients and correlated with cutaneous and systemic involvement. Statistical analysis was done using SPSS 17.0 version. RESULTS: A total of 30 patients were enrolled in the study. Sixteen (53.3%), 11 (36.7%) and 3 (10%) patients of systemic sclerosis, systemic lupus erythematosus and mixed connective tissue disorder, respectively were included for nail fold dermoscopy. The commonest change recorded in our study was dilated capillaries in 21 (70%) patients, followed by capillary dropouts in 17 (56.7%) patients and avascular areas in 16 (53.3%) patients. Of 17 patients presenting with sclerodactyly, active, early and late patterns were seen in 7 (41.2%), 2 (11.8%) and 7 (41.2%) patients, respectively. Out of 13 patients with respiratory involvement, active, early and late patterns were seen in 1, 1 and 7 (53.8%) patients, respectively (P value = 0.004). LIMITATIONS: Owing to lesser number of patients in our study, it is difficult to draw conclusive recommendations, and more studies with a larger sample size are required. CONCLUSION: Dermoscopy is a valuable tool not only to diagnose collagen vascular disorders but also for prognostication by correlating with systemic involvement.

Imaging findings of mixed connective tissue disease in children and adolescents: a case series.

Mixed connective tissue disease (MCTD) is a rare disease in children and adolescents which overlaps features of juvenile idiopathic arthritis, polymyositis/dermatomyositis, systemic lupus erythematosus, and systemic sclerosis. We have provided an image-based approach for evaluation of MCTD in children and adolescents, outlying the most frequent imaging findings. This approach would aid imagers and clinicians to consider the diagnosis of this rare entity and be able to make an accurate list of differential diagnosis for complex rheumatologic diseases such as MCTD, thus facilitating the ultimate goal of early diagnosis and optimal management of affected children.

Connective Tissue Disorders in Childhood: Are They All the Same?

Systemic connective tissue disorders are characterized by the presence of autoantibodies and multiorgan system involvement. Juvenile systemic lupus erythematosus with or without associated antiphospholipid syndrome; juvenile dermatomyositis; sclerodermiform syndromes, including systemic and localized sclerodermas and eosinophilic fasciitis; mixed connective tissue disease; and Sjögren syndrome are the disorders that affect children most frequently. Diagnosis is difficult, because the clinical presentation of patients is diverse, from mild to severe disease. In addition, all organs may be affected. However, a variety of imaging techniques are now available to investigate rheumatic disease in children. These imaging modalities offer the potential for earlier diagnosis and improved assessment of therapeutic response. This article reviews the main connective tissue disorders that affect children, highlighting their key imaging features on images acquired with different diagnostic imaging modalities and correlating these features with clinical and pathologic findings, when available. ©RSNA, 2019.

Position article and guidelines 2018 recommendations of the Brazilian Society of Rheumatology for the indication, interpretation and performance of nailfold capillaroscopy.

Nailfold capillaroscopy (NFC) is a reproducible, simple, low-cost, and safe imaging technique used for morphological analysis of nail bed capillaries. It is considered to be extremely useful for the investigation of Raynaud's phenomenon and for the early diagnosis of systemic sclerosis (SSc). The capillaroscopic pattern typically associated with SSc, scleroderma ("SD") pattern, is characterized by dilated capillaries, microhemorrhages, avascular areas and/or capillary loss, and distortion of the capillary architecture. The aim of these recommendations is to provide orientation regarding the relevance of NFC, and to establish a consensus on the indications, nomenclature, the interpretation of NFC findings and the technical equipments that should be used. These recommendations were formulated based on a systematic literature review of studies included in the database MEDLINE (PubMed) without any time restriction.

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.

Radiological images of interstitial pneumonia in mixed connective tissue disease compared with scleroderma and polymyositis/dermatomyositis.

OBJECTIVE: Little has been reported on the radiological and pathological findings of interstitial pneumonia in mixed connective tissue disease (MCTD). There may be possible difference in treatment response and prognosis between the imaging patterns of systemic sclerosis (SSc)-like and polymyositis/dermatomyositis (PM/DM)-like. The purpose of this study was to examine whether the radiological images of interstitial pneumonia in MCTD presented SSc-like or PM/DM-like pattern, and to assess whether the imaging patterns corresponded to clinical and pathological features. MATERIALS AND METHODS: This retrospective study included 29 patients with interstitial pneumonia who underwent surgical lung biopsy; 10 with SSc, 10 with PM/DM, and 9 with MCTD. High resolution computed tomography (HRCT) images were classified as SSc, PM/DM, or the other pattern by two radiologists independently without clinical information. The pathology of the lung specimens from MCTD patients were evaluated and compared with the imaging pattern. RESULTS: The concordance rate between clinical diagnosis and radiological pattern was 100% in SSc patients, and 80% in PM/DM patients. Among patients with MCTD, imaging patterns were classified as SSc pattern in 4 (MCTD-SSc), PM/DM pattern in 4 (MCTD-PM/DM) and other in one. The imaging patterns did not always correlate with the clinical findings in MCTD patients. Pathologically, plasma cell infiltration and organizing pneumonia were relatively more frequent in MCTD-PM/DM, and smooth muscle hyperplasia was relatively more frequent in MCTD-SSc. CONCLUSION: HRCT images in MCTD patients can be classified as SSc pattern or PM/DM pattern. MCTD-SSc and MCTD-PM/DM were corresponded to similar pathological findings of SSc and PM/DM.

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.

Spectrum of interstitial lung disease from a tertiary care hospital in Karachi.

OBJECTIVE: To determine the clinical features and patterns of interstitial lung disease. METHODS: This retrospective study was conducted at the Aga Khan University Hospital, Karachi, and comprised record of patients diagnosed with interstitial lung disease from January 2005 to December 2015. All patients aged 16 years and above diagnosed with interstitial lung disease on the basis of clinical features, radiological features on high-resolution computed tomography of the chest, and lung biopsies were included. SPSS 19 was used for data analysis. RESULTS: Of the 537 patients, 324(60.3%) of the participants were females. The overall mean age was 60.5±14.9 years. The most common co-morbid condition was diabetes mellitus in 72(13.4%) patients, followed by hypertension in 48(8.9%) and ischaemic heart disease in 21(3.9%). The most common interstitial lung disease was idiopathic pulmonary fibrosis in 217(40.4%) patients, followed by non-specific interstitial pneumonia in 106(19.7%), sarcoidosis in 82(15.3%) and connective tissue disease-related interstitial lung disease in 56(10.4%) patients. CONCLUSIONS: Idiopathic pulmonary fibrosis was found to be the most common interstitial lung disease subtype followed by non-specific interstitial pneumonia, sarcoidosis and connective tissue disease-related-interstitial lung disease.

Protein-losing Gastroenteropathy Related to Mixed Connective Tissue Disease: A Case Report of a Successful Outcome and Literature Review.

We herein report the case of a 44-year-old woman who developed protein-losing gastroenteropathy (PLGE) with hypoalbuminemia as the first manifestation of mixed connective tissue disease (MCTD). Albumin leakage from the stomach and intestinal tract was demonstrated by 99mTc-labeled human serum albumin scintigraphy. The patient's response to prednisolone therapy was insufficient; therefore, additional cyclosporin A (CsA) treatment was administered, and clinical remission was achieved. We concluded that although PLGE is a rare complication of MCTD, it may manifest as an initial clinical episode of MCTD. Furthermore, CsA can be a useful treatment option for refractory PLGE related to MCTD.

Pulmonary-Limited Granulomatosis with Polyangiitis Coexisting with Mixed Connective Tissue Disease.

Granulomatosis with polyangiitis (GPA) is a systemic disease characterized by necrotizing, granulomatous vasculitis of the upper and lower respiratory tracts and glomerulonephritis, and is classified as a classical or limited form. The classical form of GPA demonstrates the involvement of the upper respiratory tract, sinuses, lungs and kidneys, whereas the limited form is characterized by the lack of the renal involvement with female predominance. On the other hand, mixed connective tissue disease (MCTD) shows the clinical and laboratorial features of systemic lupus erythematosus, systemic sclerosis and polymyositis, along with high titers of anti-ribonucleoprotein antibodies and is characterized by good response to corticosteroid therapy and favorable prognosis. We herein report a patient with a history of MCTD that developed into a limited form of GPA (pulmonary-limited GPA). A 39-year-old woman suffered from persistent cough, left back pain and appetite loss. At 21 years of age she was diagnosed with MCTD, but the persistent administration of prednisolone or immunosuppressants was not needed. On admission, high-resolution chest computed tomography showed bilateral, multiple, poorly circumscribed nodules and masses, some of which showed cavitation. A surgical lung biopsy demonstrated granulomas with vasculitis surrounding the necrotic lesions. She was diagnosed with pulmonary-limited GPA. In conclusion, we should recognize that GPA may develop during the disease course of MCTD even after prolonged disease remission. To prevent progression to an irreversible state, physicians should consider a surgical lung biopsy for the diagnosis in patients suspected of having pulmonary-limited GPA.

THORACIC INVOLVEMENT IN CONNECTIVE TISSUE DISEASES: RADIOLOGICAL PATTERNS AND FOLLOW-UP.

Connective tissue diseases (CTDs) are a heterogeneous group of idiopathic inflammatory diseases involving various organs. A thoracic involvement is frequent, and chest-CT represents the imaging technique of reference in its assessment. Pulmonary abnormalities related to CTDs are various; although several disease-specific aspects have been described, the two most clinically relevant complications are represented by interstitial lung disease and pulmonary arterial hypertension. The early identification of a thoracic involvement, with the adoption of specific therapies, can significantly change patient's prognosis. The aim of this article is to review the most common typical and atypical CT features of thoracic involvement occurring in CT, especially focusing on interstitial lung disease.

A case of catastrophic antiphospholipid syndrome, which presented an acute interstitial pneumonia-like image on chest CT scan.

We report the case of catastrophic antiphospholipid syndrome (CAPS) complicated with mixed connective tissue disease (MCTD). A female patient was diagnosed with acute interstitial pneumonia (AIP) with MCTD by chest CT scan. Corticosteroid therapy was refractory for lung involvement, and she died due to acute respiratory failure. The autopsy revealed that AIP was compatible with lung involvement of CAPS. We therefore suggest that chest CT might reveal AIP-like findings in CAPS patients whose condition is complicated with pulmonary manifestations.

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.