Course Of Connective Tissue Diseases Research Articles

Dense fine speckled nuclear immunofluorescence: A mildly reassuring antinuclear antibody pattern meriting consideration.

Antinuclear antibodies (ANAs) are regarded as a hallmark of connective tissue diseases (CTDs) and play a key role in their diagnosis, but the value of some particular antibodies in management of patients and the disease prognosis is controversial. The mechanism underlying the production of ANAs in CTDs, other chronic inflammatory conditions and even in healthy people, is not completely elucidated. Anti-DFS70 antibodies connected with the dense fine speckled autoantigen of 70 kD, known as the lens epithelium-derived growth factor p75, are a subgroup of ANAs. Their presence and coexistence with other antibodies and their clinical significance are the matter of debate. Based on literature data, the authors focused on current knowledge explaining the role of anti-DFS70 antibodies in selected CTDs. However, the literature data is ambiguous and does not fully support the validity of the anti-DFS70 assay for a specific CTD diagnosis. Most researchers claim that the presence of anti-DFS70 as the only one usually exclude the diagnosis of CTD. Nevertheless, its coexistence with other ANAs is not an excluding factor but has predictive value due to more favorable course of CTD. Such situations may also suggest an enhanced risk of the development of a CTD in the future. Although more studies are needed in this field, it seems reasonable to ascertain the presence of anti-DFS70 in routine clinical practice.

Особенности поражения почек при системных заболеваниях соединительной ткани

Системные заболевания соединительной ткани (СЗСТ) — достаточно большая гетерогенная группа заболеваний, имеющих определенные характерные клинические проявления и нарушения иммунорегуляции, приводящие к образованию аутоантител. Субклинические или явные признаки вовлечения почек имеют значительное усугубляющее влияние на клиническое течение СЗСТ. Нарушение функции почек характерно для таких СЗСТ, как системная красная волчанка (СКВ), ревматоидный артрит (РА), системная склеродермия, синдром Шегрена, аутоиммунные миопатии (дерматомиозит и полимиозит). На современном этапе, учитывая доступность многих диагностических манипуляций и возможности этиопатогенетического лечения, терапевтам, ревматологам и нефрологам необходимо своевременно заподозрить наличие заболевания почек у пациентов с СЗСТ и принять необходимые меры по диагностике и лечению. Современные стратегии классификации и лечения СКВ скорректированы с учетом результатов биопсии почек, что значительно улучшило прогноз поражения почек при этом заболевании. Одно из наиболее тяжелых поражений почек у пациентов с СЗСТ — это почечный склеродермический криз (ПСК), характеризующийся тяжелой гипертонией, прогрессирующим снижением функции почек и тромботической микроангиопатией, своевременное назначение ингибиторов ангиотензинпревращающего фермента таким пациентам показывает значительный эффект в борьбе с ПСК. Контроль активности основного заболевания улучшает функцию почек у большинства пациентов с синдромом Шегрена, аутоиммунными миопатиями и РA. С другой стороны, хроническое использование иммунодепрессантов и нестероидных противовоспалительных препаратов, а также сопутствующие заболевания, такие как диабет, гипертония и сердечно-сосудистые осложнения, могут являться основными причинами поражения почек у пациентов с ревматическими заболеваниями. Кроме того, первичные заболевания почек с длительным анамнезом могут привести к проявлениям, имитирующим первичные ревматологические расстройства. В этом обзоре мы фокусируемся на диагностике нарушений функции почек вследствие основного заболевания, побочных эффектах препаратов и принятии решений о своевременном соответствующем лечении.

An expert opinion of the Polish Cardiac Society Working Group on Pulmonary Circulation and the Polish Society for Rheumatology on the diagnosis and treatment of pulmonary hypertension in patients with connective tissue disease.

Systemic connective tissue diseases (CTDs) comprise a large group of diseases that are auto-immune in nature and characterized by the involvement of multiple systems and organs. Pul-monary hypertension (PH) of various etiologies may develop in the course of CTD, including pulmonary arterial hypertension (PAH), PH secondary to the lung disease, postcapillary PH in the course of left heart disease, and chronic thromboembolic pulmonary hypertension (CTEPH). In addition, the different forms of PH may coexist with each other. Among patients with CTD, PAH occurs most commonly in those with systemic sclerosis, where it affects ap-proximately 8%-12% of patients. The prognosis in patients with untreated PAH is very poor. It is particularly important to identify the high-risk CTD-PAH population and to perform effi-cient and accurate diagnostics so that targeted therapy of the pulmonary arteries can be intro-duced. Echocardiography is used to screen for PH, but clinical and echocardiographic suspicion of PH always requires confirmation by right heart catheterization. Confirmation of PAH ena-bles the initiation of life-prolonging pharmacological treatment in this group of patients, which should be administered in referral centers. Drugs available for pharmacological management include endothelin receptor antagonists, phosphodiesterase-5 inhibitors, and prostacyclins.

Structure of the vasculitides observed in the Clinic of Rheumatology

Systemic vasculitides are a heterogenic group of disorders characterized by destructive inflammation and fibrinoid necrosis of the vascular wall, vessel occlusion and tissue ischemia. Vasculitides presenting with necrosis are included in neither of the contemporary classifications, even though this type of vascular pathology is the one with the most dramatic manifestations in rheumatology. There have been no analyses of the nosological association, clinical features and therapeutic management of the vasculitides with necrosis in the pertinent literature. The aim of the present study was to analyze vasculitides in the Bulgarian population in terms of their nosological association; to examine the portion that ANCA-associated vasculitides represent out of all vasculitic syndromes on the one hand, and to make an analysis of the vasculitides with necrosis according to their nosological association on the other. In the present study, we included 388 patients with vasculitis, 251 of whom were female and 137 male. We conducted a prospective and retrospective analysis which covered the patients with vasculitis who were admitted to the Clinic of Rheumatology over the period 2009-2018. ANCA-associated vasculitides were the most often diagnosed vasculitides in the Clinic of Rheumatology. Vasculitic manifestations over the course of connective tissue diseases (most often systemic lupus erythematosus and systemic sclerosis) were the second most common group. Life-threatening cases of vasculitis with necrosis were mainly the result of flares of different connective tissue diseases. The major necrotizing vasculitides (Wegener’s granulomatosis and microscopic polyangiitis) were responsible for 12.6% of the cases of vasculitis with necrosis. In order to establish the correct diagnosis and start the suitable treatment, it is of vital importance to recognize the different vasculitic syndromes and their wide differential diagnosis. Most of them respond well to the currently available therapeutic options, especially if the correct diagnosis has been established early.

Pathological lesions in the oral cavity in the course of connective tissue diseases

Abstract Dentistry, is one of the intensively and rapidly growing branches of medicine. This prompts dentists to take an interdisciplinary approach to their patients. Thus, the dentist, being a general practitioner, can make significant contributions to the early diagnosis of systemic disease and the faster implementation of appropriate treatment. In view of the aforementioned, we undertook research on the relationship of pathological changes observed in the oral cavity with diseases of the connective tissue system. Collagenosis is a chronic autoimmune disease initiated by many factors, among which the genetic factor and viral infections are mentioned. The changes observed in the oral cavity may be a picture of the disease, a complication of the disease or a side effect of the treatment. The aim of the study is, thus, too present the pathological changes in the oral cavity which often accompany collagenosis, and to discuss the risk factors of connective tissue system diseases and methods of dental treatment.

Analysis of peripheral nerve and autonomic nervous system function and the stage of microangiopathy in patients with secondary Raynaud's phenomenon in the course of connective tissue diseases.

The pathogenesis of secondary Raynaud's phenomenon (SRP) associated with connective tissue diseases (CTD) is not entirely understood. Nervous system dysfunction and microangiopathy are considered to be causes of this pathology. Peripheral and autonomic nervous system function, the stage of microangiopathy, and the relationships between these in patients with SRP were analyzed. In the study, 20 patients with CTD-related SRP and 30 healthy controls were subject to capillaroscopy, standard conduction velocity tests and conduction velocity distribution (CVD) tests in ulnar and peroneal nerves, heart rate variability (HRV), and sympathetic skin response (SSR) tests. There were no significant differences in the standard motor and sensory conduction velocity tests, or in CVD tests in the ulnar and peroneal nerves in SRP patients compared with the controls. The patients with SRP had a significantly lower SSR amplitude and longer latency in hands and feet. The patients with CTD-related SRP had a significantly lower mean HRV with higher low frequency (LF) values in the spectral analysis and expiration/inspiration ratio (E/I) during deep breathing. There was no correlation between the stage of microangiopathy and neurophysiological test results. Correct standard conduction velocity and CVD testing in patients with SPR suggest that vasomotor disturbances may occur in CTD regardless of peripheral neuropathy. The lack of relationship between SSR and microangiopathy could confirm that these 2 processes occur independently in patients with CTD-related SRP. Autonomic nervous system impairment together with normal peripheral nerve function suggest the central origin of CTD-related SRP.

Nailfold capillaroscopy assessment of microcirculation abnormalities and endothelial dysfunction in children with primary or secondary Raynaud syndrome.

Raynaud syndrome (RS) manifests as episodes of transient spasms of peripheral blood vessels, most often in response to cold. The reason of that symptom (primary RS (pRS)) usually cannot be found but may be accompanied by some autoimmune diseases (secondary RS (sRS)). In this study, we assessed microcapillary status and serum concentrations of chosen cytokines, adhesive molecules, and nitric oxide (NO) in patients with pRS and sRS in comparison with healthy children. Eighty-six patients with RS were enrolled into the study, including 52 with pRS and 34 with sRS. The control group consisted of 29 healthy children. A decrease in myorelaxative and anticoagulant abilities was observed, with simultaneous prevalence of vasopressor substances and procoagulative activity. Therefore, several important factors such as endothelin-1 (ET-1), E-selectin (E-sel), interleukin-18 (IL-18), and nitrogen oxide (NO) were also analyzed. Two types of capillaroscopy status were determined: normal and microangiopathic. There was a significant relationship between presence of microangiopathy and higher serum ET-1 (p = 0.018) and E-sel (p = 0.021) levels. Similarly, we have found a correlation between presence of ANA and higher ET-1 (p = 0.005), but not E-sel (p = 0.241). In patients with pRS, we found significant relationship between ANA and higher ET-1 (p = 0.008). No such relations were observed in sRS patients. Our data indicates that external factor-induced vasoconstrictive effects dominated in pRS, whereas in sRS in the course of connective tissue diseases, it was accompanied by coexistent vasodilation due to endothelial dysfunction. The latter phenomenon is at least partially dependent on insufficient NO release.

AB0998 The Severity of Pulmonary Fibrosis in Transthoracic Ultrasonography (TUS)

BackgroundThe aim of this study was to determine the scale of severity of pulmonary fibrosis in the transthoracic ultrasonography (TUS).ObjectivesThis study propose an estimation of severity of pulmonary fibrosis in...

Traitement des calcinoses sous-cutanées des connectivites

Calcinosis cutis constitutes a heterogeneous group of chronic disorder. It can be associated with disturbance of calcium and/or phosphate metabolism (metastatic, tumor calcinosis, calciphylaxis) but may also develop without any metabolic disorder, in particular during the course of connective tissue diseases. Among these, the most common are dermatomyositis and the limited form of systemic sclerosis. The physiopathology of calcinosis cutis is poorly known. It can cause pain, chronic ulcerations, infections, which are sources of sometimes major disability. Treatment of calcinosis is challenging because no drug has been shown to be reliably effective in stopping the progression or decreasing dystrophic calcifications in controlled trials. Calcium blocker and colchicine are generally prescribed as the first line systemic therapy. In the localized forms of small lesions, surgical excision is often effective and sometimes preceded by local treatments (laser therapy, extracorporeal shock wave lithotripsy, topical sodium thiosulfate, etc.) or systemic treatment (minocycline, warfarine). When calcinosis is disseminated, it may require additional treatments (aluminium hydroxyde, bisphosphonates) possibly associated with surgery in case of large lesions. Time to response may be prolonged from weeks to months. The calcinosis cutis can lead to secondary infection, pain and functional disability that have to be prevented.

Zmiany śródmiąższowe w Płucach u Chorych na Zapalenie Wielomięśniowe i Skórno-Mięśniowe—Prezentacja Trzech Przypadków

Polymyositis (PM) and dermatomyositis (DM) are connective tissue diseases (CTD) characterized by proximal muscle weakness along with changes in various internal organs, with the lungs most frequently involved. Presentation of the disease in the lungs comprises diffuse alveolar haemorrhage due to vasculitis and interstitial lung disease (ILD), which is the most frequent manifestation of CTD in the lungs and worsens the outcome and prognosis. The mechanisms involved in the ILD are not fully known, but the role of autoimmune response is unquestioned. No relationship between the severity of CTD and the changes in the lungs was observed. ILD may present at any time in the course of CTD, sometimes before the signs and symptoms of myositis occur. The more accurate imaging methods are, the more frequently changes in the lungs are detected. High resolution computed tomography (HRCT) is a gold standard in ILD imaging. Treatment of PM/DM-related ILD relays on systemic glucocorticosteroids as the first choice drugs. We present three cases of PM/DM-related ILD in middle-aged men, with a different clinical and radiological presentation. In all cases, apart from imaging (plain X-ray and HRCT of the chest) and pulmonary function tests, histological evaluation of lung changes was performed. In two cases non-specific interstitial pneumonitis (NSIP) was diagnosed, and in the third--organizing pneumonia along with sarcoid changes in the lymph nodes. Because of decreased pulmonary function all patients were treated with systemic corticosteroids and two of them additionally with azathioprine or cyclophosphamide, and the outcome was good in all of them.

THU0373 Retrospective Analysis of the Safety of Zoledronic Acid in Patients with Osteoporosis in the Course of Connective Tissue Diseases Compared to Patients with Postmenopausal Osteoporosis.

BackgroundCauses of osteoporosis in patients with connective tissue diseases (CTD) are more complex than in patients with postmenopausal osteoporosis (PO). None of the studies published so far examined the safety...

AB0689 Interstitial lung disease in severe connective tissue diseases (CTD)

BackgroundWe here report the incidence, the clinical features and treatment response of interstitial lung disease (ILD) associated to idiopathic inflammatory myopathies (IIM), Sjogren’s Syndrome (SS) and systemic lupus erythematosus (SLE).MethodsWe...

FRI0099 Pulmonary fibrosis and connective tissue diseases: Follow-up of lung involvement in rheumatoid arthritis and systemic sclerosis

BackgroundLung involvement in connective tissue diseases (CTDs) is a significant cause of morbidity and mortality. The most frequent pulmonary component affected is the interstistium. The most common histopathologic pattern of...

Renal involvement in autoimmune connective tissue diseases

Connective tissue diseases (CTDs) are a heterogeneous group of disorders that share certain clinical presentations and a disturbed immunoregulation, leading to autoantibody production. Subclinical or overt renal manifestations are frequently observed and complicate the clinical course of CTDs. Alterations of kidney function in Sjögren syndrome, systemic scleroderma (SSc), auto-immune myopathies (dermatomyositis and polymyositis), systemic lupus erythematosus (SLE), antiphospholipid syndrome nephropathy (APSN) as well as rheumatoid arthritis (RA) are frequently present and physicians should be aware of that.In SLE, renal prognosis significantly improved based on specific classification and treatment strategies adjusted to kidney biopsy findings. Patients with scleroderma renal crisis (SRC), which is usually characterized by severe hypertension, progressive decline of renal function and thrombotic microangiopathy, show a significant benefit of early angiotensin-converting-enzyme (ACE) inhibitor use in particular and strict blood pressure control in general. Treatment of the underlying autoimmune disorder or discontinuation of specific therapeutic agents improves kidney function in most patients with Sjögren syndrome, auto-immune myopathies, APSN and RA.In this review we focus on impairment of renal function in relation to underlying disease or adverse drug effects and implications on treatment decisions.

Pneumatosis Cystoides Intestinalis: A Rare Benign Cause of Pneumoperitoneum

Pneumatosis cystoides intestinalis is a rare gastrointestinal complication in the course of connective tissue diseases, especially in scleroderma, that can lead to pneumoperitoneum or obstruction. Findings on plain radiography may reveal radiolucent linear or bubbly circular air bubbles in the bowel wall, with or without free gas accumulation in the peritoneal cavity. Treatment of pneumatosis cystoides intestinalis ranges from supportive care to laparotomy.

Survival and Extrapulmonary Course of Connective Tissue Disease After Lung Transplantation

Connective tissue disease (CTD)-related lung dysfunction is a common cause of morbidity and mortality; however, few lung transplantations (LTs) are performed in this population secondary to uncertainty regarding the posttransplant survival, outcome, and management. The objectives were to evaluate the survival and the pulmonary and extrapulmonary courses of CTD after LT. Survival outcomes of patients documented within the Organ Procurement and Transplantation Network who had undergone a LT for CTD were compared with those who underwent LT for chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). In addition, the pulmonary and extrapulmonary courses of the CTD were evaluated after LT. From 1991 to 2009, there were 284 documented LT in patients with CTD. Post-LT cumulative survival of patients with CTD was less than that for COPD through 5 years, with a difference that peaked at 1 year (72.7% vs. 83.1%, P < 0.001). When patients with CTD were compared with those with IPF, a difference was only noted at 1 year (72.7% vs. 77.7%, P = 0.049). There were no documented post-LT pulmonary recurrences of the CTD, and extrapulmonary flares of the CTD were rare (1 possible flare per 20.3 patient-years and 1 probable flare per 81.0 patient-years). Cumulative survival of patients with CTD who underwent LT is similar to those with IPF and slightly less than those with COPD, with an increased risk of mortality that was most prominent at 6 months after transplant followed by subsequent narrowing of the survival differences over time. Lung transplantation may be a viable therapeutic option for patients with end-stage lung dysfunction resulting from a CTD.

Pneumatosis cystoides intestinalis in scleroderma‐related conditions

Pneumatosis cystoides intestinalis (PCI) is a rare life-threatening gastrointestinal complication in the course of connective tissue disease (CTD). PCI is characterised by the appearance of intramural clusters of gas in the small and large bowel wall on X-ray or computed tomography and often is accompanied by free air in the peritoneal cavity. We present three cases of PCI in patients with scleroderma-related conditions. A review of the English language literature published on MEDLINE from 1973 to 2008 was conducted using the terms: 'systemic sclerosis', 'connective tissue disease' and 'pneumatosis cystoides intestinalis'. This review focused on clinical features, diagnostic and treatment strategies of PCI in the context of CTD. Symptoms of PCI are non-specific: abdominal pain, vomiting, constipation, bloating and weight loss. Coexistence of PCI with other manifestations of CTD, such as intestinal pseudo-obstruction and/or bacterial overgrowth, complicates the clinical diagnosis. Treatment approach to PCI is mostly conservative: intestinal 'rest', parenteral nutrition, antibiotics, fluids and electrolyte supplementation, and inhaled oxygen. Surgical intervention should be performed only in cases of bowel perforation, ischaemia or necrosis. Patients with PCI have high mortality rates due to PCI itself but also to the severity and variety of basic CTD complications. Recognition of PCI, particularly in the context of underlying CTD, is necessary for proper therapeutic application. In patients with underlying CTD and symptoms of abdominal emergency, recruitment of multidisciplinary teams, including rheumatologist, gastroenterologist, imaging specialist and surgeons familiar with intestinal complications of CTD-related conditions, is warranted.

Effect of race/ethnicity on risk, presentation and course of connective tissue diseases and primary systemic vasculitides

Understanding the effects of race/ethnicity on the risk and expression of systemic rheumatic diseases has potential clinical implications and provides insight into their etiopathogeneses. This review summarizes knowledge of the effects of race/ethnicity on the following nine conditions: antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV), Behçet's disease, dermatomyositis/polymyositis, Henoch-Schönlein purpura, Kawasaki disease, large-vessel vasculitis (LVV), primary Sjögren's syndrome (pSS), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). Distinct racial/ethnic patterns have emerged for most of the conditions considered here. Areas of progress include the finding that the two AAVs, granulomatosis with polyangiitis (Wegener's) (GPA) and microscopic polyangiitis, exhibit distinct racial/ethnic susceptibilities in disease risk. In addition, nonwhites, with known high risk of SLE and SSc, may also be at a high risk for pSS and have more severe disease. Evidence is accumulating that nonwhites are rarely affected by the LVV giant-cell arteritis. Race/ethnicity-specific genetic risk factors were recently detected for GPA. Epidemiologic data have allowed discerning the racial/ethnic profiles for many of the considered systemic rheumatic conditions. Future challenges will be to unravel the genetic, environmental and/or socio-econonomic determinants of the observed racial/ethnic disparities. More research is needed to clarify the impact of race/ethnicity on the AAV Churg-Strauss syndrome, dermatomyositis/polymyositis and Takayasu arteritis.

The kidneys and antiphospholipid syndrome

There are clinical observations and data from literature showing that kidney involvement is frequently found in antiphospholipid syndrome (APS). The clinical pictures of renal involvement in APS can be different: from modest to severe hypertension, nephritic or nephrotic syndrome and chronic kidney disease at all stages. There is no clear connection between the presence of a significant level of antiphospholipid antibodies (aPL) and advancing of nephropathy especially occurring in course of connective tissue diseases. In the paper the relations between APS, the presence of aPL and nephropathy have been discussed.

Therapy resistance antiphosholipid syndrome in the course of systemic lupus erythematosus: case report

Antiphospholipid syndrome (APS) is one of the most common reasons of thromboembolic complications in the course of connective tissue diseases. There is a strong relationship between presence of antiphospholipid antibodies and the risk of thrombosis. APS related thromboembolic complications range from superficial vein thrombosis up to rapidly developing, life threatening, multi-organ embolism. We present a case of a 21-year old female who presented with myocardial infarction as the first symptom of systemic lupus erythematosus and APS. Afterwards she was consequently treated with antithrombotic and anti-aggregation agents but it did not prevent her from reoccurrence of middle retinal vein. During the 10-year follow up she presented with reoccurring neurological symptoms i.e.: headache, memory deficits, concentration loss and impairment of the cognitive functions. She was found many times to be positive for IgG and IgM anticardiolipin antibodies, anti-beta2glicoprotein-I antibodies and lupus anticoagulant.