Limited Form Of Systemic Sclerosis Research Articles

Causes and predictors of death among Finnish patients with systemic sclerosis

Objective The aim of this study was to assess causes and predictors of death among Finnish patients with systemic sclerosis (SSc). Method Medical records of patients registered with the ICD-10 code M34 from 1996 to 2018 in two university hospitals were reviewed retrospectively. Clinical data were collected until the end of 2020. Death certificates were obtained from Statistics Finland up to August 2021. Using death certificates and patient records, the cause of death for each patient was determined. The mean age at death, median time from SSc diagnosis, and factors predicting death were analysed. Results Among 313 SSc patients, 91 deaths occurred between April 2000 and September 2020. Overall 5 and 10 year survival rates were 88.4% and 80.2%, respectively. SSc was the most common primary cause of death (n = 35) and interstitial lung disease (ILD) was the most common SSc-related cause of death (n = 13). Moreover, 52% of the patients with diffuse SSc and 33% of those with limited cutaneous SSc died as a result of SSc itself. Patients who died because of SSc were significantly younger [mean ± sd age 65.6 ± 12.7 years, 95% confidence interval (CI) 61.2–70.1] than those who died from other causes (74.2 ± 9.6 years, 95% CI 71.5–76.9) (p = 0.0006). ILD, pulmonary arterial hypertension, gastrointestinal involvement, male gender, and older age at disease onset predicted death. Conclusion The disease itself was the major cause of death among Finnish SSc patients, in both diffuse and limited forms of SSc.

Insights into the Relationship between Periodontitis and Systemic Sclerosis Based on the New Periodontitis Classification (2018): A Cross-Sectional Study.

(1) Background: This study aimed to assess the periodontitis burden in systemic sclerosis patients and the possible association between them, and the degree to which some potential risk factors and two potential diagnostic biomarkers may account for this association. (2) Methods: This cross-sectional study included a test group (systemic sclerosis patients) and a control group (non-systemic sclerosis patients). Both groups benefited from medical, periodontal examination and saliva sampling to determine the salivary flow rate and two inflammatory biomarkers (calprotectin, psoriasin). A systemic sclerosis severity scale was established. (3) Results: In the studied groups, comparable periodontitis rates of 88.68% and 85.85%, respectively, were identified. There were no significant differences in the severity of periodontitis among different systemic sclerosis severity, or in the positivity for anti-centromere and anti-SCL70 antibodies. Musculoskeletal lesions were significantly more common in stage III/IV periodontitis (n = 33, 86.84%) than in those in stage I/II (n = 1, 100%, and n = 3, 37.5%, respectively) (p = 0.007). Comparable levels of the inflammatory mediators were displayed by the two groups. There were no significant differences in calprotectin and psoriasin levels between diffuse and limited forms of systemic sclerosis. (4) Conclusions: Within the limitations of the current study, no associations between systemic sclerosis and periodontitis, or between their risk factors, could be proven.

Myocardial Involvement in CREST Syndrome: A Case Report of a Rare Myocarditis’ Etiology

Limited cutaneous systemic sclerosis also known as CREST syndrome - represents a limited form of systemic sclerosis, and although cardiac involvement is common in systemic sclerosis, it is extremely rare in the limited form [1].

The relationship between Sjogren's syndrome, systemic sclerosis and lymphoproliferative diseases

To study demographic, clinical, laboratory and immunological characteristics of patients with a combination of primary Sjogrens syndrome (pSS) and SSc and diagnosed lymphoproliferative diseases (LPDs); to characterize morphological/immunomorphological variants and course of non-Hodgkins lymphomas (NHL), developing in patients with these rheumatic diseases (RDs). In 19982018 at the Nasonova Research Institute of Rheumatology, 13 patients with clinical and laboratory manifestations of pSS (12) and SSc (13) were diagnosed with various lymphoproliferative diseases (LPDs). In 3 cases, an induced RD was observed: 1 case of a diffuse, rapidly progressive form of SSc, 2 cases of pSS in combination with a limited form of SSc after chemotherapy and radiation therapy of Hodgkins lymphoma (1), B-cell NHL (1) and CR of the breast (1) respectively. The first 2 cases were excluded from the analysis, since the development of lymphomas is not pathogenetically associated with RD. Of 11 patients with LPDs, 10 after a long course of RDs were diagnosed with NHL [MALT lymphoma of the parotid salivary glands 7, disseminated MALT lymphoma 2, disseminated MALT lymphoma with transformation into diffuse large B-cell lymphoma (DLBCL) 1]. RDs debuted with Raynauds phenomenon (RP) in 64.5% and pSS manifestations in 45.5% of patients. Stomatological manifestations of pSS were characterized by recurrent parotitis in 36%, significant parotid gland enlargement with massive infiltration of labial salivary glands (focus score 4) in 100%, severe xerostomia in 70%, extraglandular manifestations and lymphadenopathy in 50% of patients. The course of the SSc was characterized by mild RP with various types of capillaroscopic changes and mild lung changes and non-significant progression during long-term follow-up (median 22 years). The entire spectrum of SSс specific antibodies (anticentromere antibodies 60%, antibodies to ribonucleoprotease III 30%, Pm/Scl 10%), excepting antibodies to topoisomerase I, as well as pSS specific autoantibodies (antiRo/La 70%, RF (rheumatoid factor) 90%), were detected in patients with a combination of these RDs. pSS is often combined with a limited form of SSc regardless of the type of autoantibodies detected. The presence of pSS, rather than SSc, is a high-risk factor for the development of NHL in this group of patients. The patients with pSS and SSc are characterized by a steady progression of pSS with a slow and mild course of SSc throughout the observation period. The development of severe stomatological manifestations and high immunological activity of pSS contribute to the development of localized MALT lymphomas (70%) and disseminated MALT lymphomas (30%) with primary lesions of the salivary glands and transformation into DLBCL in case of their late diagnosis. The optimal method for preventing the development of NHL in this group of patients is the early diagnosis of pSS, the appointment of alkylating cytotoxic agents and/or anti-B-cell therapy in the early stages of pSS. Given the possibility of transformation of localized NHL into DLBCL, for early diagnosis, minimally invasive surgical biopsies of significantly enlarged parotid salivary glands should be performed before glucocorticoids are prescribed. Detection of positive B-cell clonality and lymphoepithelial lesions in the parotid salivary gland is considered a predictor of MALT lymphoma development during follow-up. Localized and disseminated MALT lymphomas in patients with pSS and SSc respond well to therapy, in contrast to MALT lymphomas transformed into DLBCL.

Evaluation of quality of life, functionality and disability in patients with systemic sclerosis in a University Hospital

Introduction: Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by progressive fibrosis of the skin and internal organs that promotes high morbidity and mortality. Objective: To evaluate the functionality, disability and quality of life of patients with systemic sclerosis and to compare the clinical forms of the disease. Methods: Cross-sectional, descriptive and analytical study performed at the Rheumatology Clinic of the Hospital das Clínicas of the Federal University of Pernambuco (HC-UFPE) from August 2018 to April 2019. The non-probabilistic, convenience sample consisted of 60 patients diagnosed with systemic sclerosis (SSc), followed at the Rheumatology outpatient clinic of the Hospital das Clínicas, Federal University of Pernambuco. To evaluate the outcomes, the following instruments were used: Cochin Hand Functional Scale (CHFS) for hand function; 12-Item Short-Form Health Survey (SF-12) for quality of life; and Scleroderma Health Assessment Questionnaire (SHAQ) for functionality and disability. Results: The mean results for CHFS, SHAQ, SF-12 Physical Component Summary and SF-12 Mental Component Summary were 14.5 (6.0-29.75), 1.01±0.56, 35.04±8.09, 40.94±10.56, respectively. There were no significant differences in CHFS outcomes between patients with diffuse and limited forms of SSc, SHAQ and the mental component of SF-12. However, in the physical component of SF-12, a better score was found in patients with the diffuse form of the disease (p=0.04). Conclusion: Patients with SSc present an important impairment of hand function, quality of life and functional capacity, and those with limited cutaneous form present worse scores of the physical component in the evaluation of quality of life.

AB0606 SYSTEMIC SCLEROSIS – ARE PATIENTS WITH CALCINOSIS DIFFERENT FROM THOSE WHO DO NOT HAVE IT?

Background:Systemic Sclerosis (SS) is a heterogenous disease with a broad range of organ involvement. Calcinosis is a common problem and although it may affect almost any body tissue, it is typically seen in the limbs.1Its presence relates with higher risk of digital ulcers and infection.2It is still unknown whether patients with calcinosis also have other clinical features that differentiate them from the remaining.Objectives:To determine the prevalence of calcinosis in a SS cohort and to evaluate if its presence relates with specific clinical features.Methods:A cross-sectional study was conducted evaluating a cohort of SS patients. Plain radiographs were taken to assess calcinosis at elbows, hands, knees and feet. Clinical data was obtained and analyzed using IBM SPSS Statistics 26®.Results:We included 25 patients, 21 females [n= 21 (84%)], median (min, max) age was 58 (27, 75) years-old. Regarding disease classification, 16 (64%) had limited SS, 4 (16%) had diffuse SS, 3 (12%) had overlap syndrome and 2 (8%) had early SS. Ten (40%) patients had radiological calcinosis in at least one site, seven of which (70%) were subclinical. The most affected areas were knees and hands [n=6 (24%)]. Table 1 summarizes the clinical characteristics of patients with and without calcinosis. Limited SS was significantly more prevalent in the calcinosis group [n=9 (90%) vs. n=7 (46.7%), p=0.04]. All patients had Raynaud phenomenon [n=10 (100%) vs. 15 (100%)]. Current or past digital ulcers [n=5 (50%) vs. n=6 (40%), p=0.697], telangiectasias [n=9 (90%) vs. n=11 (73.3%), p=0.615], pulmonary hypertension [n=2 (20%) vs. n=1 (6.7%), p=0.550] and esophageal involvement [n=6 (60%) vs. n=6 (40%), p=0.428] were more frequent in the calcinosis group but with no statistical significance. Although late capillaroscopic pattern was more frequent in the calcinosis group, there was no statistical significance difference [n=4 (40%) vs. n=1 (6.7%), p=0.121]. Seropositivity for centromere-B antibodies was more frequent in the calcinosis group but with no statistical significance [n=7 (70%) vs. n=8 (53.3%), p=0.678].Table 1.Demographic and clinical data of patients with and without calcinosis.Demographic and clinical dataCalcinosis (n=10)No calcinosis (n=15)p-valueFemale gender, n (%)9 (90)12 (80)0.626Age (years), median [min,max]68.5 [27, 75]52 [36, 73]0.129Cutaneous classificationLimited, n (%)9 (90)7 (46.7)0.04Diffuse, n (%)1 (10)3 (20)0.626Early, n (%)0 (0)2 (13.3)0.500Overlap, n (%)0 (0)3 (20)0.250Clinical manifestationsCurrent or previous digital ulcers, n (%)5 (50)6 (40)0.697Interstitial lung disease, n (%)2 (20)4 (26.7)1.000Pulmonary hypertension, n (%)2 (20)1 (6.7)0.550Arthritis, n (%)2 (20)3 (20)1.000Calcinosis, n (%)3 (30)0 (0)0.052Esophageal involvement, n (%)6 (60)6 (40)0.428NFC patternsNon specific abnormalities, n (%)1 (10)3 (20)0.626Early scleroderma, n (%)1 (10)1 (6.7)1.000Active scleroderma, n (%)3 (30)10 (58.8)0.111Late scleroderma, n (%)4 (40)1 (6.7)0.121AutoantibodiesCentromere B, n (%)7 (70)8 (53.3)0.678Scl-70, n (%)1 (10)4 (26.7)0.615Conclusion:The prevalence of calcinosis was similar to that reported in literature (18-49%). This study confirmed the association, already found in previous studies, between calcinosis and the limited form of SS and raises attention for the importance of calcinosis radiographic screening since there was a high prevalence of subclinical calcinosis.1Although there were some clinical differences between patients with and without calcinosis, given the small cohort, statistical significance was not obtained. Larger studies are needed to increase statistical power.

CLINICAL AND LABORATORY FEATURES OF ANTICENTROMERE ANTIBODY-POSITIVE SJö GREN’S SYNDROME

Objective: to study the clinical and laboratory features of patients with anticentromere antibody (ACA) positive Sjö gren’s syndrome (SjS); to assess the spectrum of autoantibodies in patients of this group; to determine the frequency with which the SjS patients who are highly positive for ACA, meet the international classification criteria for SjS and systemic sclerosis (SS); to reveal the incidence of MALT lymphomas in this patient group; to estimate the incidence of primary biliary cirrhosis (PBC)/biliary lesions as part of autoimmune epithelitis in SjS in this patient group.Material and methods. A total of 83 patients with ACA positive SjS were comprehensively examined at the V.A. Nasonova Research Institute of Rheumatology during the period 2012 to 2018. The inclusion criteria were con formity to the 2001 Russian SjS criteria and a high ACA level. MALT lymphomas were diagnosed on the basis of histological and immunohistochemical studies and polymerase chain reaction-based determination of B-cell clonality in the biopsy samples of affected organs according to the World Health Organization classification of Hematopoietic Tumors. The diagnosis of PBC/biliary lesions was made on the basis of histological and immunohistochemical studies of liver biopsy specimens.Results and discussion. The investigation revealed low detection rates for anti-Ro antibodies (32.5%), anti-La antibodies (7.2%) and rheumatoid factor (RF) (21.7%), which were typical for the classical SjS immunophenotype), increased ESR (14%), leukopenia (7%), hypergammaglobulinemia (17.6%), elevated levels of IgG (9.5%) and IgA (18.7%), and hypocomplementemia (16.1%) in the ACA positive SjS patients. Despite the low detection rate of RF, 15 (18%) patients in this group developed MALT lymphomas: 14 patients had salivary gland MALT lymphoma and one patient had tonsil MALT lymphoma with peripheral lymph node involvement (generalized marginal zone lymphoma). Also, the patients of this group showed high detection rates for AMA antibodies (34.6%), increased IgM level (29.7%) and a higher risk for PBC/biliary lesions as a manifestation of autoimmune epithelitis in SjS (14.5%). AMA-antibodies were absent in only two patients who were diagnosed with liver disease according to biopsy specimens. Nervous system and renal lesions, antiphospholipid syndrome, rheumatoid arthritis, hypergammaglobulinemic purpura, and cryoglobulinemic vasculitis were much less common and sporadic. Also ACA-positive SjS patients often have Raynaud’s phenomenon (54.9%) with scleroderma-type capillaroscopic changes (68%) and a limited form of SS (24%) according to the 2013 ACR criteria.Conclusion. ACA-positive SjS is a subtype of the disease, which is significantly different from the classic one in a number of clinical and laboratory signs and characterized by an increased risk for SS, MALT lymphomas, and PBC/biliary lesions as a manifestation of autoimmune epithelitis in SjS which in some cases leads to the underdiagnosis of SjS. ACA should be considered as pathogenetically related to SjS autoantibodies; and all patients who are seropositive for ACA should be examined for SjS and PBC/biliary lesions as a manifestation of autoimmune epithelitis in SjS regardless of whether they have SS or not, as well as complaints of dry mouth and eyes. Patients with significantly enlarged salivary glands should undergo biopsy to rule out or confirm MALT lymphoma before initiating hormonal, antilymphoproliferative, and anti-B-cell therapy.

КЛІНІКО-ПАТОГЕНЕТИЧНА ЗНАЧУЩІСТЬ СИНДРОМУ ЕНДОГЕННОЇ ІНТОКСИКАЦІЇ ПРИ СИСТЕМНІЙ СКЛЕРОДЕРМІЇ.

Системні аутоімунні ревматичні захворювання супроводжуються синдромом ендогенної інтоксикації (СЕІ), але його клініко-патогенетична значущість при системній склеродермії (ССД) залишається невідомою.Мета дослідження. Оцінка ролі СЕІ в частоті розвитку і тяжкості перебігу окремих клінічних ознак ССД, значущості у патогенетичних побудовах захворювання, виділення найбільш інформативних прогностичних критеріїв.Матеріали і методи. Під спостереженням перебували 63 хворих у віці від 16 до 67 років (у середньому 42 роки), серед яких було 11 % чоловіків і 89 % жінок. У 43 % випадків мала місце лімітована форма ССД, в 57 % – дифузна, тривалість захворювання склала в середньому 11 років, І ступінь активності патологічного процесу встановлено у 41% від числа хворих, ІІ – у 38 %, ІІІ – в 21 %. Позитивність ССД за наявністю в сироватці антитопоізомеразних-1 антитіл (aScl70) встановлена у 78 % випадків, антитіл до нативної дезоксирибонуклеїнової кислоти (aDNA) – в 64 %, а до кардіоліпіну – в 18 %.Результати досліджень та їх обговорення. Було вивчено 12 показників крові (дієнові кон’югати, малоновий діальдегід, ксантиноксидаза, аміак, сечовина, креатинін, сечова кислота, нітрити, молекули середньої маси різних фракцій). Усі показники були оцінені в 1 бал, у випадках їх параметрів >M+SD (де М – медіана, SD – стандартне відхилення) оцінювали в 2 бали, а при > M + 2SD – в 3 бали. Суму балів ділили на число досліджених показників, отримуючи тим самим індекс ендогенної інтоксикації, а коли той перевищував 1, говорили про наявність СЕІ. Крім того, додатково визначали інтегральний сурфактантний індекс з урахуванням рівня рівноважного (статичного) поверхневого натягу крові. СЕІ розвивається у 70 % від числа хворих на ССД, що був зумовлений підвищенням у крові рівнів середньомолекулярних сполук, небілкових азотистих і продуктів пероксидного окиснення ліпідів, бере участь у патогенезі склеродермічної кардіоміопатії і дисциркуляторної енцефалопатії. У свою чергу, СЕІ при ССД може викликати ураження шкіри, легень, серця, печінки, нирок і нервової системи. Вміст азотистих з’єднань, як компонентів СЕІ, має достовірні прямі співвідношення з рівнем у крові aScl70, а показник тяжкості перебігу СЕІ – з aDNA.Висновки. СЕІ розвивається у більшості хворих на ССД і бере участь в її патогенезі, при цьому гіперазотемія є фактором ризику ураження центральної нервової системи, накопичення в організмі молекул середньої маси – печінки і серця, а сурфактантний індекс більше 4 у. о. є прогнозонегативним критерієм щодо шкірного синдрому.

FRI0536 Content of Tumor Necrosis Factor Alpha in Children with Juvenile Sleroderma

ObjectivesTo determine the content of TNF in the serum of children with juvenile scleroderma.MethodsBaseline demographics, clinical characteristics and disease activity parameters have been documented. Determination of the concentration of tumor...

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.

AB0507 Frequency and evolution of digital ulcers in systemic sclerosis

BackgroundDigital ulcers are frequent and recurrent complication in systemic sclerosis (SSc) and are the main cause of pain, impaired function of the hand and disability in SSc.ObjectivesTo evaluate the frequency...

Tissue Doppler assessment of right ventricular function in female patients with limited form of systemic sclerosis

Abstract Background Cardiac involvement in systemic sclerosis (SSc) is often clinically occult. The aim of this study was the evaluation of early subclinical right ventricular (RV) involvement in patients with limited form of systemic sclerosis by tissue Doppler. Methods Twenty female patients with limited cutaneous SSc and 20 control female subjects, matched for age were studied with transthoracic echocardiography and tissue Doppler imaging (TDI) to assess RV function. Patients with pulmonary hypertension, chronic renal failure, diabetes mellitus, hypertension, heart failure, left ventricular hypertrophy, ischemic or rheumatic heart disease were excluded. Results Patients with limited form SSc had significant lower tricuspid annulus peak systolic velocities (ST) (9.95 ± 1.78 vs. 11.05 ± 1.53 cm/s, p Conclusions Patients with limited form of SSc present with pulsed-tissue Doppler imaging indices indicative of right ventricle dysfunction, which had significant correlations with disease duration. Tissue Doppler is a valuable non-invasive tool for detecting RV myocardial involvement in patients with limited SSc.

Perfil de autoanticorpos e correlação clínica em um grupo de pacientes com esclerose sistêmica na região sul do Brasil

To assess the manifestations of systemic sclerosis (SSc), with an emphasis on the analysis of autoantibodies and their clinical correlations, in a population of patients followed up at the SSc Outpatient Clinics of the Hospital de Clínicas of the Universidade Federal do Paraná. Cross-sectional study with 96 patients followed up at the SSc Outpatient Clinics of the hospital between September 2007 and September 2009. Most patients were of the female sex, in their forties or fifties, and the median time of disease was ten years. The limited cutaneous form of SSc was more prevalent. The analysis of the autoantibodies showed the association of anticentromere antibody (ACA) with the following: the limited form of SSc; more advanced age at the time of diagnosis; longer disease time; longer interval between the appearance of the Raynaud's phenomenon (RyP) and the first non-RyP symptom; systemic arterial hypertension (SAH); and cardiac conduction blocks. The antitopoisomerase-1 antibody (ATA-1, previously called anti-Scl-70) was more common in the presence of the diffuse form of SSc, active disease, and digital ulcers. The anti-RNA polymerase III antibody (anti-Pol III) correlated with the diffuse form of SSc, disease activity, and synovitis. This study emphasizes and confirms the important role of autoantibodies in assessing patients with SSc, allowing the correlation between the autoimmune profile of patients with SSc and specific manifestations of the disease.

Reactivity of pulmonary circulation and right ventricle function to inhaled nitric oxide in systemic sclerosis patients.

Systemic sclerosis (SSc) is complicated by pulmonary hypertension and right ventricle (RV) failure in approximately 10% of the patients. Factors influencing the reactivity of pulmonary circulation to vasodilators are not established, while the examination of vasoreactivity is important in determining the treatment, because systemic administration of oral vasodilators can induce severe adverse events in nonresponders. The mechanism of RV failure in SSc is unclear and may result either from increased RV afterload or intrinsic myocardial disease. The aim of the study was to assess the reactivity of pulmonary circulation to inhaled nitric oxide (iNO) and to evaluate its influence on RV function in SSc patients with elevated right ventricle systolic pressure (RVSP). In 60 SSc patients aged 24–73 (58 females, two males; 33 patients with limited SSc and 27 with diffuse SSc), echocardiographic examination with tissue Doppler echocardiography (TDE) was performed. RV function was measured by systolic (S) and early diastolic (E) velocity of tricuspid annulus by TDE. In patients with RVSP >45 mmHg, the reactivity of pulmonary circulation was assessed by iNO test. High-resolution computerized tomography (HRCT) was performed to assess the extent of pulmonary fibrosis. Of 14 SSc subjects with elevated RVSP (13 females, one male; RVSP 47–62 mmHg), positive reaction to iNO was observed in five (RVSP decreased from 51.6 ± 3.7 to 32.24 ± 2.3 mmHg); nine patients were not reactive (RVSP 53.5 ± 5.7 mmHg before iNO vs. 49.6 ± 6.7 mmHg). RV systolic function was decreased in patients with elevated RVSP as compared to the patients with normal pulmonary pressure (S velocity 13.2 ± 1.3 vs. 14.4 ± 1.6 cm/s, respectively, p < 0.05). Significant increase of RV systolic function during iNO test was found in reactive patients only (S velocity before iNO 12.8 ± 1.2 cm/s, during iNO 14.5 ± 1.5 cm/s, p < 0.01). RVSP decrease strongly correlated with S velocity increase (r = 0.95, p < 0.0001). Response to iNO was found only in limited form of SSc; diffuse SSc patients showed no response. Pulmonary fibrosis on HRCT was more frequent in subjects nonreactive to iNO (67% of patients) than in the reactive group (40% of patients). The reactivity of pulmonary circulation to iNO in SSc patients with elevated RVSP was found predominantly in limited form of the disease. Pulmonary fibrosis typical for diffuse SSc was more frequent in nonreactive subjects. Elevated pulmonary pressure plays an important role in RV systolic dysfunction. Pulmonary pressure decrease during iNO test leads to the improvement of RV systolic function. Therapy for right-heart failure in reactive SSc patients should be directed, if possible, at the decrease in pulmonary resistance.

Les manifestations buccofaciales de la sclérodermie systémique : étude de 30 patients consécutifs

The face is frequently involved in systemic sclerosis. The main stomatologic manifestations include limited mouth opening, xerostomia, skin atrophy, trigeminal neuralgia. The objective of this study was to describe oral and facial manifestations observed in scleroderma patients from our cohort. Between March and October 2006, a stomatologic consultation was included in the follow-up of scleroderma patients seen during consultation or daily hospital in internal medicine or dermatology units. Demographic, clinical and biological data were collected. Stomatologic examination comprised measure of the mouth opening, sugar's and Schirmer's tests, orthopantomogram analysis, and evaluation of the repercussion of symptoms on quality of life using a visual analogical scale (VAS between 0 and 10). This study included 30 patients (women 87 %, mean age 58.6 + or - 13.6 years). Mean duration of systemic sclerosis (n=20 limited cutaneous form, n=10 diffuse form) was eight years. Stomatologic manifestations were: skin atrophy (n=28), peribuccal rhagades (n=25), telangiectasia (n=21), decreased mouth opening (n=20), xerostomia (n=20), xerophtalmia (n=16), periodontal ligament space widening (n=10), bone resorptions (n=2), trigeminal neuralgia (n=1). Xerostomia was considered more discomforting (mean VAS=3.8) than decreased mouth opening (mean VAS=2.6). Xerostomia was the second more discomforting sign of scleroderma and was significantly associated to the limited cutaneous form (p=0.045) and to anticentromeres antibodies expression (p=0.002). Decreased mouth opening was correlated to oesophageal involvement (p=0.025). Oral and facial manifestations are frequently observed in scleroderma patients. These manifestations lead to major functional discomfort, mainly due to decreased mouth opening that seems to be frequently associated to oesophageal involvement. Xerostomia is also frequent and is commonly observed in anticentromere antibodies positive cutaneous limited forms of systemic sclerosis. Evolution of radiographic abnormalities like periodontal ligament space widening (33 % of cases), or osteolytic lesions (7 %) is poorly known.

Prevalence of sicca symptoms in a South Australian cohort with systemic sclerosis

The presence of sicca symptoms is a frequent finding in patients with systemic sclerosis (SSc). The aim of this study was to examine the prevalence of sicca symptoms in a South Australian cohort of SSc patients and correlate this to a number of parameters, including autoantibody status, use of anticholinergic medication, age and the presence of functional anti-muscarinic-3 receptor (M3R)-blocking antibodies. A screening questionnaire was sent out to all patients on the South Australian Scleroderma Register from the years 1998-2006 to determine the prevalence of sicca symptoms. A subset of patients on the register had ocular sicca symptoms tested by use of Schirmer's strips to validate the accuracy of the questionnaire. Eight patients were tested for anti-M3R-blocking antibodies using a functional physiological assay. One hundred and ninety-three SSc patients took part in this study. Sicca symptoms were present in 59% of patients with the limited form of SSc, compared with 49% of patients with the diffuse form and 40% of patients with the overlap syndrome. The use of anticholinergic medication or thyroxine was associated with higher sicca scores in SSc patients. SS-A and SS-B autoantibodies (seen in Sjögren's syndrome) were detected in eight patients in this study. The detection of anti-M3R-blocking antibodies correlated well to presence of sicca. This study confirmed that sicca symptoms are found in a high proportion of patients with SSc, especially those with the limited variant. Further testing of larger numbers of SSc patients with sicca for anti-M3R-blocking antibodies will be needed before more definitive conclusions can be drawn. Physicians should be made aware that sicca symptoms are a frequent cause of morbidity for SSc patients*.

Les manifestations buccofaciales de la sclérodermie systémique : étude de 30 patients consécutifs

The face is frequently involved in systemic sclerosis. The main stomatologic manifestations include limited mouth opening, xerostomia, skin atrophy, trigeminal neuralgia. The objective of this study was to describe oral and facial manifestations observed in scleroderma patients from our cohort. Between March and October 2006, a stomatologic consultation was included in the follow-up of scleroderma patients seen during consultation or daily hospital in internal medicine or dermatology units. Demographic, clinical and biological data were collected. Stomatologic examination comprised measure of the mouth opening, sugar's and Schirmer's tests, orthopantomogram analysis, and evaluation of the repercussion of symptoms on quality of life using a visual analogical scale (VAS between 0 and 10). This study included 30 patients (women 87%, mean age 58.6+/-13.6 years). Mean duration of systemic sclerosis (n=20 limited cutaneous form, n=10 diffuse form) was eight years. Stomatologic manifestations were: skin atrophy (n=28), peribuccal rhagades (n=25), telangiectasia (n=21), decreased mouth opening (n=20), xerostomia (n=20), xerophtalmia (n=16), periodontal ligament space widening (n=10), bone resorptions (n=2), trigeminal neuralgia (n=1). Xerostomia was considered more discomforting (mean VAS=3.8) than decreased mouth opening (mean VAS=2.6). Xerostomia was the second more discomforting sign of scleroderma and was significantly associated to the limited cutaneous form (p=0.045) and to anticentromeres antibodies expression (p=0.002). Decreased mouth opening was correlated to oesophageal involvement (p=0.025). Oral and facial manifestations are frequently observed in scleroderma patients. These manifestations lead to major functional discomfort, mainly due to decreased mouth opening that seems to be frequently associated to oesophageal involvement. Xerostomia is also frequent and is commonly observed in anticentromere antibodies positive cutaneous limited forms of systemic sclerosis. Evolution of radiographic abnormalities like periodontal ligament space widening (33% of cases), or osteolytic lesions (7%) is poorly known.

Associations of breast cancer development in patients with systemic sclerosis: an exploratory study

The goal of this study was to describe the clinical characteristics of patients with a diagnosis of systemic sclerosis who develop breast cancer and to identify associations for this relationship. From 769 patients followed at the scleroderma center of our institution over the past 16 years, 24 patients developed a diagnosis of breast cancer. The demographics and clinical characteristics of these patients will be compared to those of a randomly selected group of scleroderma patients without a diagnosis of cancer. A further analysis will compare the patients who developed their breast cancer before the diagnosis of systemic sclerosis to those diagnosed after. Twenty-four patients developed 25 breast cancers with 13 patients diagnosed before the diagnosis of systemic sclerosis and 11 after. Compared to 48 randomly selected systemic sclerosis patients without a diagnosis of cancer, the patients with breast cancer were diagnosed with systemic sclerosis at an older age (53.5 +/- 15.2) as compared to those without (42.4 +/- 12.5) (p = 0.002). A relatively equal amount of patients had the diffuse and limited form of systemic sclerosis, while pulmonary fibrosis (p = 0.015) and the lack of antinuclear antibody (ANA) positivity (p = 0.02) were more commonly seen in patients with breast cancer. Patients who developed breast cancer before the diagnosis of systemic sclerosis were older at systemic sclerosis diagnosis (61.6 +/- 11.3) compared to those after (43.9 +/- 13.5) (p = 0.03). An older age at diagnosis of systemic sclerosis, a lack of ANA positivity, and the presence of pulmonary fibrosis were more commonly seen in patients with systemic sclerosis who have a diagnosis of breast cancer.

Primary biliary cirrhosis (PBC)–CREST overlap syndrome with coexistence of Sjögren's syndrome and thyroid dysfunction

Calcinosis, Raynaud's phenomenon, oesophageal dysmotility, sclerodactyly, telangiectasia (CREST) syndrome, a limited form of systemic sclerosis, is sometimes complicated by primary biliary cirrhosis (PBC). A 52- and 61-year-old Japanese woman with PBC-CREST overlap syndrome accompanied by Sjögren's syndrome, and Hashimoto's thyroiditis, and Graves' disease, respectively, are reported. They had suffered from Raynaud's phenomena, sclerodactyly, morning stiffness, arthralgia, and sicca symptoms during these several years. They exhibited an increased level of alkaline phosphatase, gamma-glutamyl transpeptidase, positive antibodies against mitochondria and centromere, and hyperglobulinemia without any cholestatic symptoms. Histological findings from liver biopsy specimens were consistent with those of PBC. Clinically, they were diagnosed as both asymptomatic PBC and incomplete CREST syndrome. Their human leukocyte antigen typing showed both DR4 and DR8 positive. The association of the four autoimmune conditions is clinically and etiologically important. Although a combination of these diseases is rare, it is of importance to keep in mind that various autoimmune diseases could occur simultaneously. Of critical importance is that an active diagnostic attitude towards them is admirable, and that early diagnosis and therapy are needed.

Pulmonary arterial hypertension associated to connective tissue diseases

Pulmonary arterial hypertension is a well-known complication of connective tissue diseases such as systemic sclerosis, systemic lupus erythematosus, mixed connective tissue diseases, and to a lesser extent, rheumatoid arthritis, dermatopolymyositis and primary Sjögren's syndrome. In these patients, pulmonary hypertension may occur in association with left heart disease, interstitial fibrosis or as a result of a isolated pulmonary arteriopathy. The incidence of pulmonary arterial hypertension in the limited form of systemic sclerosis is about 10%. The pathophysiologic mechanisms leading to pulmonary arterial hypertension remain unknown. Symptoms and clinical presentation are very similar to idiopathic pulmonary arterial hypertension but mortality was confirmed to be higher. Echocardiography is the reference investigation for the detection of pulmonary arterial hypertension but the results should be confirmed by right heart catheterization. Treatment appears more complex as compared to idiopathic pulmonary arterial hypertension. Intravenous epoprostenol therapy has been shown to be effective in a special trail. Also, the endothelin receptor antagonists bosentan and sitaxentan, the phosphodyesterase-type-5 sildenafil and subcutaneous treprostinil have shown favourable results.