Rare Connective Tissue Disease Research Articles

Клинический случай длительной дифференциальной диагностики диссеминированного процесса в легких как проявление смешанного заболевания соединительной ткани

Connective tissue diseases (CTD) are common causes of disseminated small – focal lung damage. The complexity of diagnostic approach in such cases occur due to intolerance of many symptoms and syndromes, that can also relate to diseases of other different etiologies. It is often not possible to identify the pathognomonic syndrome in CTD, as well as to establish an accurate diagnosis after a long time. This complicates the selection of effective treatment and, accordingly, the inability to predict the course and development of the disease. Sometimes, due to the intersection of symptoms, the diagnosis sounds like «MCTD» (mixed connective tissue diseases) – a rare systemic connective tissue disease, characterized by a combination of individual signs of systemic lupus erythematosus, systemic scleroderma, rheumatoid arthritis, polymyositis. This publication presents a clinical case of a long-term course of mixed MCTD in a patient who has been observed for more than 10 years in different hospitals, and by outpatient observation, and within this year’s differential diagnosis with other CTD and infectious diseases was held, including rheumatic fever.

RarERN Path: a methodology towards the optimisation of patients\u2019 care pathways in rare and complex diseases developed within the European Reference Networks

BackgroundIn 2017, the European Commission has launched the European Reference Networks (ERNs), virtual networks involving healthcare providers across Europe. The aim of the ERNs is to tackle complex and rare diseases and conditions that require highly specialized treatment and a concentration of knowledge and resources. The ERN on rare and complex connective tissue and musculoskeletal diseases (ERN ReCONNET) is one of the 24 ERNs approved that aims to improve the management of Rare and Complex Connective Tissue and Musculoskeletal Diseases.ObjectiveThe RarERN Path methodology aims to create a single reference organisational model for patients’ care pathways which, if applied in different contexts, helps to ensure an improved, cost-effective and patient-centred equal care to rare and complex diseases.MethodsStarting from existing standard methods for the creation and elaboration of patients’ care pathways, a specific methodology was created in order to take advantage of the distinctive and peculiar characteristics of the ERNs. Specifically, the development of the RarERN Path methodology involved different stakeholders: health economists, clinicians and researchers expert in rare and complex diseases, communication experts, experts in patients’ involvement and narrative medicine and policy-makers.ResultsThe RarERN Path methodology foresees six consecutive phases, each with different and specific aims. Specifically, the six phases are represented by: Phase 1—mapping of existing patients’ care pathways and patients’ stories; Phase 2—design of an optimised common patients’ care pathway; Phase 3—consensus on an optimised common patients’ care pathway; Phase 4—key performance indicators definition; Phase 5—refinement; Phase 6—pilot phase (optional).ConclusionThe application of RarERN Path to the different disease-specific and geographical contexts would help to ensure an improved, cost-effective and patient-centred equal care to rare and complex diseases across Europe as well as a possible tangible action towards the integration of ERNs into the different European healthcare systems.

Exploring patient education unmet needs for rare and complex connective tissue and musculoskeletal diseases: A survey of health care providers' and patients' expectations in Europe.

The European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases involves health care providers (HCPs) from 8 European countries and 7 patients' representatives of European Patient Advocacy Groups. The objective was to evaluate current practice and unmet needs for patient education (PE) in Europe. A questionnaire was sent to HCP members asking about the PE practices and another, to enquire about their needs, was sent to patients' associations in the different countries. The questionnaire was completed by 33 HCPs. Half had no specific staff members dedicated to PE. For HCPs with dedicated staff, 83.3% (n = 11) considered that care providers were insufficient to meet patients' needs. Most of HCPs would like to see the practice of PE standardized. Sixty eight percent (n = 1093) of patients suffering from connective tissue diseases completed the questionnaire had never heard about PE. Most of them were interested in taking part in a PE program. Our survey revealed a strong interest in PE among patients and HCP and heterogeneity of practice. PE appeared important for both HCPs and patients. An online course for medical students in Europe will be developed in partnership with EULAR to respond to these unmet needs.

O22 An inflammatory journey from brain to skin: a case of En Coupe De Sabre scleroderma presenting with raised intracranial pressure, seizures, and uveitis

O22 An inflammatory journey from brain to skin: a case of En Coupe De Sabre scleroderma presenting with raised intracranial pressure, seizures, and uveitis

A case of eosinophilic fasciitis without skin manifestations: a case report in a patient with lupus and literature review

Eosinophilic fasciitis (EF) is a rare connective tissue disease that causes inflammation and fibrosis of the fascia, inducing pain and motor dysfunction. Characteristic skin manifestations, such as edema, erythema, induration, peau d'orange appearance, and the groove sign, are of diagnostic significance and observed in the majority of patients with EF. We herein report a case of EF without these characteristic skin manifestations. A 66-year-old Japanese woman developed progressive limb pain and motor dysfunction. No skin changes were observed. We diagnosed the patient with EF based on the clinical course, magnetic resonance imaging, and en bloc biopsy containing fascia and muscle. Oral prednisolone therapy markedly attenuated limb pain and motor dysfunctions. Through a systemic search of the medical literature, we retrieved 4 juvenile cases and 8 adult cases of EF without characteristic skin manifestations during the clinical course. We herein present a systemic review on EF without skin manifestations and discuss differences between the two proposed sets of diagnostic criteria of EF.

Clinical presentation, sonographic features and treatment options of segmental stiff skin syndrome.

Segmental stiff skin syndrome is a rare genetic connective tissue disease, which is often misdiagnosed. High-frequency ultrasonography can represent a useful clinical adjunct in the differential diagnosis of this condition, in conjunction with the clinical and histopathological findings. Treatment options are limited and evidence is scarce. We present the clinical, sonographic and histological features of five paediatric patients diagnosed at our institution and discuss their response to treatment.

A new nucleosomic-based model to identify and diagnose SSc-ILD

BackgroundSystemic sclerosis (SSc) is a rare connective tissue disease associated with rapid evolving interstitial lung disease (SSc-ILD), driving its mortality. Specific biomarkers associated with the evolution of the lung disease are highly needed. We aimed to identify specific biomarkers of SSc-ILD to predict the evolution of the disease. Nucleosomes are stable DNA/protein complexes that are shed into the blood stream making them ideal candidates for biomarkers.MethodsWe studied circulating cell-free nucleosomes (cf-nucleosomes) in SSc patients, 31 with ILD (SSc-ILD) and 67 without ILD. We analyzed plasma levels for cf-nucleosomes and investigated whether global circulating nucleosome levels in association with or without other biomarkers of interest for systemic sclerosis or lung fibrosis (e.g., serum growth factors: IGFBP-1 and the MMP enzyme: MMP-9), could be suitable potential biomarkers for the correct identification of SSc-ILD disease.ResultsWe found that H3.1 nucleosome levels were significantly higher in patients with SSc-ILD compared SSc patients without ILD (p < 0.05) and levels of MMP-9 were significantly increased in patients with SSc-ILD compared to SSc patients without ILD (p < 0.05). Conversely, IGFBP-1 was significantly reduced in patients with SSc-ILD compared to SSc without ILD (p < 0.001). The combination of cf-nucleosomes H3.1 coupled to MMP-9 and IGFBP-1 increased the sensitivity for the differential detection of SSc-ILD. High levels of accuracy were reached with this combined model: its performances are strong with 68.4% of positive predictive value and 77.2% of negative predictive value for 90% of specificity. With our model, we identified a significant negative correlation with FVC % pred (r = −0.22) and TLC % pred (r = −0.31). The value of our model at T1 (baseline) has a predictive power over the Rodnan score at T2 (after 6-18 months), showed by a significant linear regression with R2 = 19% (p = 0.013). We identified in the sole group of SSc-ILD patients a significant linear regression with a R2 = 54.4% with the variation of DLCO between T1 and T2 (p < 0.05).ConclusionIn our study, we identified a new blood-based model with nucleosomic biomarker in order to diagnose SSc-ILD in a SSc cohort. This model is correlated with TLC and FVC at baseline and predictive of the skin evolution and the DLCO. Further longitudinal exploration studies should be performed in order to evaluate the potential of such diagnostic and predictive model.

Clinical practice guidelines adherence, knowledge and awareness in rare and complex connective tissue diseases across Europe: results from the first ERN ReCONNET survey

IntroductionThe European Reference Network (ERN) ReCONNET is the ERN aimed at improving the management of rare and complex connective tissue and musculoskeletal diseases (rCTDs) across the European Union (EU). In...

Psychosocial effects of systemic sclerosis: A case report

“…Sit down. Look at the TV. Move slowly. Wait for death.” Background &amp; Aim: Systemic sclerosis or scleroderma is a rare chronic connective tissue disease included among autoimmune rheumatic diseases. The disease affects many organs and the organ system. It also has multiple effects on the patient’s individual life. In care management, in addition to the physical effects of the disease, its emotional, psychological, and social influences must also be considered and managed. The present study aimed to touch the psychosocial aspect of scleroderma and the unseen effects of the disease are presented over a case study. Case Report: 52-year-old, female patient, married with two children. Her self-evaluation after the diagnosis of the disease, she explained that her physical state, social relationships, economic condition, domestic relations, and mood were affected by the disease negatively. Conclusion: In managing psychosocial problems in nursing care, it is necessary to consider that each patient has different needs, perspectives on life, future expectations, and coping mechanisms. The present study reveals the unknown face scleroderma, its psychosocial effects, from a patient’s point of view.

AB0611 STRAIN ANALYSIS OF THE RIGHT VENTRICLE USING 2D-SPECKLE TRACKING ECHOCARDIOGRAPHY IN A COHORT OF PATIENTS WITH SYSTEMIC SCLEROSIS

Background:Systemic Sclerosis (SSc) is a rare and life-threatening connective tissue disease with multiple organ impairment. Cardio-pulmonary involvement is common: pulmonary fibrosis, pulmonary hypertension (PH), and electrical disorders are the most serious complications and causes of increased mortality.Objectives:We evaluated features related with the onset and development of PH in a cohort of SSc patients. We further studied ecocardiographic abnormalities, by means of 2D-speckle tracking echocardiography (STE) with specific reference to the right ventricular strain measure (RV-strain).Methods:We analyzed data from 50 SSc patients (pts) referred to our University-based Rheumatology Centre and SSc Unit from January 2007 to June 2019 (F/M 45/5; lc/dcSSc 45/5; mean age 59.20±14.357 years; mean disease duration 12.08±8.75 years). All pts underwent general and cardio-pulmonary assessment in our Cardio-Rheumatology Clinic. The following parameters were considered: blood exams, in particular inflammation indexes, uric acid test and serum autoantibodies; pulmonary function tests; high resolution scan of the lungs (HRCT); standard electrocardiogram (ECG) and RV-strain measured by 2D-STE. These examinations were performed according to clinical picture and current methodologies. We compared SSc subjects with (10/50) and without (40/50) PH diagnosis during follow-up regardless of treatments.Results:SSc pts with PH didn’t show significant alterations concerning RV-strain if compared with pts without PH (p=0.707). Nevertheless, RV-strain value was modified in relation to TAPSE alterations in all pts but this data correlated with right ventricular dilatation only in PH subjects. Furthermore, interesting significant values about dilatation of right and left atria (p=0.007, p=0.048), dilatation of inferior vena cava (p=0.037) and right ventricle (p=0.023) were observed. Left ventricular hypertrophy (p=0.012) as well as valvular insufficiencies (mitral and aortic) were more frequent in PH group too (p=0.016). These pts showed higher incidence of skin ulcers (p=0.0001), higher values of blood pressure (p=0.004), elevated uric acid levels (p=0,027) and anti-centromere antibodies positivity (p=0.0001).Conclusion:Our research provides further evidence of the prognostic value of echocardiographic findings in SSc subjects, with focus on PH. Population enlargement is ongoing in order to identify more accurate results about RV-strain, considering the efficacy of PH treatments on cardiac contractility. Speckle tracking echocardiography proves to be a sensitive, low-cost, non-invasive and reliable tool to detect early cardiac impairment in Ssc, full of potential future prospects.Disclosure of Interests:None declared

Successful treatment of systemic sclerosis complicated by ventricular tachycardia with a cardiac resynchronization therapy-defibrillator: A case report

BACKGROUNDSystemic sclerosis is a rare connective tissue disease characterized by localized or diffuse skin thickening and fibrosis, which usually accumulates in various organs throughout the body. Tachyarrhythmia is a common clinical manifestation of cardiovascular damage in systemic sclerosis patients. However, few studies have reported the use of catheter ablation and an implantable cardioverter defibrillator in patients with systemic sclerosis complicated by ventricular tachycardia.CASE SUMMARYA 39-year woman with an 11-year history of systemic sclerosis was referred to our hospital due to three syncopal episodes in the past 6 mo. The results of an electrocardiogram and a transthoracic echocardiogram revealed ventricular tachycardia and left ventricular systolic and ventricular septum segmental motion abnormalities, respectively. The results of an electrocardiogram showed a sinus rhythm with complete blockage of the left bundle branch. In light of the progressive nature of systemic sclerosis, the presence of a left bundle branch block, and the decreased ejection fraction, a cardiac resynchronization therapy-defibrillator was implanted. The patient’s clinical conditions improved, and at the 3-mo follow-up, the patient was free of ventricular tachycardia and all cardiac symptoms.CONCLUSIONWe report the first case of systemic sclerosis complicated by ventricular tachycardia that was successfully treated with a cardiac resynchronization therapy-defibrillator.

Effectiveness of Tocilizumab in the Treatment of Fasciitis with Eosinophilia: Two Case Reports.

Fasciitis with eosinophilia (FE) is a rare connective tissue disease. Due to its rarity, large-scale studies are lacking, which makes its treatment challenging. Systemic corticosteroids (SCSs) are the cornerstone of treatment; however, additional immunosuppressive drugs (ISDs) are frequently necessary (usually methotrexate). We report 2 patients, for whom an SCS and methotrexate were not a viable long-term option. In the first case, we were unable to taper the SCS dose without symptom relapse, the patient showed only a partial response to methotrexate and presented side effects. The second case never fully responded to the SCS and methotrexate and demonstrated serious SCS adverse effects. Both patients were started on tocilizumab with extremely favourable results, making this drug a potential therapeutic weapon for these patients.LEARNING POINTSThe treatment of FE is challenging and mainly based on retrospective reviews, open-label trials and case reports, all of which included a small number of patients.Currently, systemic corticosteroids are the mainstay of treatment; however, other ISDs are frequently necessary.Cases showing a favourable clinical response to tocilizumab have recently been described in patients with corticosteroid-refractory disease, suggesting that this drug may potentially become a therapeutic weapon for these patients.

Management of Pulmonary Arterial Hypertension in Patients with Systemic Sclerosis.

Systemic sclerosis (SSc) is a rare and complex immune-mediated connective tissue disease characterized by multi-organ fibrosis and dysfunction. Systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH) is a leading cause of death in this population. Pulmonary arterial hypertension (PAH) can coexist with other forms of pulmonary hypertension in SSc, including pulmonary hypertension related to left heart disease, interstitial lung disease, chronic thromboembolism and pulmonary venous occlusive disease, which further complicates diagnosis and management. Available pulmonary arterial hypertension therapies target the nitric oxide, endothelin and prostacyclin pathways. These therapies have been studied in SSc-PAH in addition to idiopathic PAH, often with different treatment responses. In this article, we discuss the management as well as the treatment options for patients with SSc-PAH.

Congenital cutis laxa with multi-system involvement

&lt;p class="abstract"&gt;Cutis laxa is a heterogeneous group of inherited and acquired rare connective tissue disease characterized by loose, wrinkled, and inelastic skin. It clinically presents as loose skin with folds giving a premature aged appearance. Cutis laxa is very rare, with an estimated incidence of one in 4 million. There are many case reports on acquired cutis laxa but very few on “congenital” cutis laxa. Authors report a 15 years old female presenting with a history of recurrent respiratory tract infections since the age of 2 years associated with flaccid skin all over her body and extensive loose folds of skin over face, neck, abdomen, arms and thighs since birth. Cutis laxa has been diagnosed based on the clinical picture and histopathological appearance. No medical treatment is available for correction of the pathology of disease. Plastic surgery remains the only modality of treatment to improve the cosmetic appearance. Systemic abnormalities need specific treatment depending upon the condition. The purpose of this report is due to its rarity and involvement of skin, hairs, respiratory, cardiovascular and genitourinary system in a single patient.&lt;/p&gt;

A case report of capillary leak syndrome with recurrent pericardial and pleural effusions.

BackgroundCapillary leak syndrome (CLS) is a rare connective tissue disease, triggered by the leak of serous fluid into the interstitial spaces, characterized by a hallmark of oedema and effusions in confined spaces. The limiting factor in CLS management appears to be its diagnosis rather than treatment, which is usually to contain the disease progression rather than a cure.Case summaryWe report a case of a 51-year-old woman with recurrent life-threatening presentations of pericardial effusions, pleural effusions, and generalized swelling of face and extremities. The only notable past medical history was of Type 1 diabetes. Numerous investigations did not lead to specific disease accounting for pericardial effusions and pleural effusions. Eventually, the diagnosis of CLS was made based on hypovolaemic shock, hypoalbuminaemia, and haemoconcentration without the presence of albuminuria. She was managed with steroids to reduce system inflammation and later with immunoglobulins and tumour necrosis factor to contain the disease process. Since her diagnosis and subsequent appropriate management, she has not had further admissions with cardiac tamponade 16 months of follow-up.DiscussionThe diagnosis of CLS is difficult to make unless there is a high degree of suspicion and until other causes have been ruled out. It remains a challenging condition to manage as the treatment options are limited and patients recurrently present with emergencies until the correct diagnosis is made and the optimal treatment is provided.

Decreased CCN3 in Systemic Sclerosis Endothelial Cells Contributes to Impaired Angiogenesis

Systemic sclerosis (SSc) is a rare and severe connective tissue disease combining autoimmune and vasculopathy features, ultimately leading to organ fibrosis. Impaired angiogenesis is an often silent and life-threatening complication of the disease. We hypothesize that CCN3, a member of the CCN family of extracellular matrix proteins, which is an antagonist of the profibrotic protein CCN2 as well as a proangiogenic factor, is implicated in SSc pathophysiology. We performed skin biopsies on 26 patients with SSc, both in fibrotic and nonfibrotic areas for 17 patients, and collected 18 healthy control skin specimens for immunohistochemistry and cell culture. Histological analysis of nonfibrotic and fibrotic SSc skin shows a systemic decrease of papillary dermis surface as well as disappearance of capillaries. CCN3 expression is systematically decreased in the dermis of patients with SSc compared with healthy controls, particularly in dermal blood vessels. Moreover, CCN3 is decreased invitro in endothelial cells from patients with SSc. We show that CCN3 is essential for endothelial cell migration and angiogenesis invitro. In conclusion, CCN3 may represent a promising therapeutic target for patients with SSc presenting with vascular involvement.

Rupture of a Median Sacral Artery Aneurysm in a Patient with Vascular Ehlers Danlos Syndrome

IntroductionVascular Ehlers Danlos syndrome is a rare connective tissue disease that is associated with various arterial complications.ReportA 25 year old man with vascular Ehlers Danlos syndrome presented with acute lower back pain as a result of a ruptured aneurysm of the median sacral artery (MSA). Prior medical history included several vascular events resulting in a right iliac occlusion. The unusual location of aneurysmal disease of the MSA might be explained by extensive collateral flow recruitment due to this occlusion.ConclusionPrevious vascular events inducing collateral recruitment might justify a more frequent follow up in patients with connective tissue disorders.

Clinical features and outcome of mixed connective tissue disease in developmental age - observational study from one center.

ObjectivesMixed connective tissue disease is a rare systemic connective tissue disease of developmental age and it includes the features of arthritis, polymyositis/dermatomyositis, systemic lupus erythematosus and systemic sclerosis, with presence of anti-ribonucleoprotein antibodies (anti-RNP) in serum. Early diagnosis of the disease is difficult but essential in preventing development of systemic complications, which are often irreversible. International literature does not report many studies on large cohorts of children with this disease. The aim of this retrospective study was to define clinical characteristics and long-term results of treatment of the disease in 60 children with mixed connective tissue disease hospitalized in the period between 1978 and 2018. The diagnosis was established on the basis of Kasukawa’s criteria.Material and methodsIt was a group of 60 children (46 girls and 16 boys) aged 10.5 on average (4–16.5). When assessing general symptoms at the onset of the disease according to Kasukawa’s criteria, the highest number, over 80% of children, demonstrated symptoms suggesting SLE, about 40% suggesting DM and about 25% suggesting SSC. In the period of observation the number of children with clinical symptoms suggesting SSC increased. The most common clinical symptoms included Raynaud syndrome, arthritis and myositis and the most common irregularities in the test results included presence of anti-RNP antibodies and rheumatoid factor and hematological symptoms such as leukopenia/thrombocytopenia. Restrictive lung function impairment was demonstrated by 20% of children. Treatment most often included combined therapy (glucocorticosteroids + methotrexate/azathioprine).ResultsIn 70% of the patients stable improvement was observed. Remission concerned 7% of the patients, frequent exacerbations were found in almost 20% of patients, and 2 children (3.5%) died.ConclusionsThe long term observations of patients in developementeal age with mixed connective tissue disease revealed that the majority of them had domination of SLE symptoms, only in 7% achieved remission and 70% remained in stable improvement. Serious infections with septic state were the cause of death in two cases.

Protocol for a partially nested randomized controlled trial to evaluate the effectiveness of the Scleroderma Patient-centered Intervention Network Support Group Leader EDucation (SPIN-SSLED) Program

BackgroundSome people with rare diseases rely on peer-led support groups for disease-specific education and emotional and practical support. Systemic sclerosis (SSc), or scleroderma, is a rare autoimmune connective tissue disease. Many people with SSc cannot access support groups, and, when support groups exist, they may not be sustained due to challenges that could be addressed via leader training. The Scleroderma Patient-centered Intervention Network (SPIN), along with SSc patient organization partners, developed a training program for SSc patient support group leaders, the Scleroderma Support group Leader EDucation (SPIN-SSLED) Program. We recently completed a feasibility trial in which we successfully delivered the program to two groups of support group leaders who reported a high level of satisfaction with the program and its delivery. The primary objective of the full-scale SPIN-SSLED trial is to evaluate the effect of the program on support group leaders’ self-efficacy for carrying out their leadership role. Secondary objectives include evaluating effects on leader burnout, leader satisfaction (participation efficacy), and emotional distress.Methods/designThe SPIN-SSLED trial is a pragmatic randomized controlled trial (RCT) in which 180 support group leaders will be randomly allocated to training groups of 6 participants each or to a waitlist control. We will use a partially nested RCT design to reflect dependence between individuals in training groups, but not in the waitlist control. Participants allocated to the training program will receive the 13-module SPIN-SSLED Program, delivered via webinar over the course of 3 months in weekly 60–90-min sessions. The primary outcome is leader self-efficacy, measured by the Scleroderma Support Group Leader Self-efficacy Scale post-intervention. Secondary outcomes are leader self-efficacy at 3 months post-intervention, and leader burnout, volunteer job satisfaction (participation efficacy), and emotional distress post-intervention and at 3 months post-intervention.DiscussionThe SPIN-SSLED trial will test whether a training program for SSc patient support group leaders increases the self-efficacy of group leaders to carry out leadership tasks. The program has the potential to significantly improve the effectiveness and sustainability of existing SSc support groups, to increase the number of available support groups, and to be adapted for other chronic diseases.Trial registrationClinicalTrials.gov, NCT03965780. Registered on 29 May 2019.

The nosology of systemic sclerosis: how lessons from the past offer new challenges in reframing an idiopathic rheumatological disorder.

Systemic sclerosis is a rare connective tissue disease characterised by a wide range of clinical manifestations. Compared with previous sets of criteria, the 2013 American College of Rheumatology and European League Against Rheumatism (ACR/EULAR) classification of systemic sclerosis encompasses a broader and more relevant spectrum of the condition. Nonetheless, clinical and prognostic heterogeneity persists among patients fulfilling these criteria. The next task in the classification of systemic sclerosis is the development of new subset criteria that can successfully identify subgroups of patients with distinct prognostic or pathophysiological features. In this Viewpoint we describe the history of systemic sclerosis over the past century with the objective of highlighting the effect of previous nosological debates on efforts to understand and manage this disorder. Rather than seeking to present a systematic review of possible subgrouping for systemic sclerosis in relation to prognosis, we aim to clarify how nosological considerations have influenced our understanding of the cause and prognosis of this so-called idiopathic rheumatological disorder and how aetiological, prognostic, and pathophysiological hypotheses have helped to describe clusters within the disease. By reflecting on past nosological debates and endeavours, we identify challenges for the current initiative to develop a new subgrouping of systemic sclerosis.