Validity and reliability of the Swedish version of the Self-Efficacy for Managing Chronic Disease scale for individuals with systemic sclerosis.

OBJECTIVE: To investigate aspects of validity and reliability of the Swedish version of the Self-Efficacy for Managing Chronic Disease (SEMCD-Swe) scale in systemic sclerosis (SSc). METHOD: A forward-backward translation procedure was used. Content validity was assessed through interviews with 11 people with SSc and 10 healthcare professionals. Construct validity, internal consistency, test-retest reliability, and floor and ceiling effects were evaluated in 104 SSc patients. RESULTS: The content validity of the SEMCD-Swe was interpreted as satisfactory, but some adjustments were made to increase the understanding. Confirmatory factor analysis supported a single-factor structure. Moderate to strong correlations between the SEMCD-Swe and Scleroderma Health Assessment Questionnaire; Multidimensional Assessment of Fatigue; Patient Health Questionnaire-8 (rs = -0.4 to -0.7), and RAND-36 subscales (rs = 0.5 to 0.7) were found. Weak correlations were found between SEMCD-Swe and modified Rodnan skin score; and disease severity of peripheral vascular and lung (rs = -0.1 to -0.2) and kidney (rs = 0.1) systems (Medsger severity scale). Cronbach's alpha was sufficient (0.85) and corrected item-to-total correlations were good (≥ 0.50). The intraclass correlation coefficient for the total score was sufficient (0.82). No floor or ceiling effects were found. CONCLUSION: Support for construct validity was indicated, as the SEMCD-Swe in SSc show a single-factor structure and is more strongly associated with pain, fatigue, depressive symptoms, interferences with daily activities, disability, and quality of life than with disease severity. Our results also indicate support for content validity and reliability. However, the responsiveness of the SEMCD-Swe needs to be tested.

Differences associated with age at onset in early systemic sclerosis patients: a report from the EULAR Scleroderma Trials and Research Group (EUSTAR) database.

OBJECTIVE: The aim of this study was to analyse differences in clinical presentation in patients with early (< 3 years' duration) systemic sclerosis (SSc), comparing three age groups according to disease subsets. METHOD: Cross-sectional analysis of the prospective EULAR Scleroderma Trials and Research database (EUSTAR) was performed. Patients fulfilling preliminary American College of Rheumatology 1980 classification criteria for SSc, with < 3 years from the first non-Raynaud's SSc symptom at first entry, were selected. Patients with < 3 years from the first SSc symptom, including Raynaud's phenomenon, were also analysed. SSc-related variables, including antibodies, SSc subsets, and organ involvement, were examined. Age was categorized into ≤ 30, 31-59, and ≥ 60 years. We performed descriptive and bivariate analyses. RESULTS: The study included 1027 patients: 90% Caucasian, 80% women, and 40% with diffuse disease. In early stages of SSc, younger patients had significantly more anti-Scl-70 antibodies and diffuse disease. With increasing age, we observed more elevation of estimated pulmonary systolic pressure on echocardiography (5%, 13%, and 30%, respectively, in the three age groups), cardiac conduction blocks (6%, 6%, and 15%), and left ventricular diastolic dysfunction (4%, 12%, and 27%). The results were similar for 650 patients with < 3 years from first SSc symptom, including Raynaud's. CONCLUSION: In early stages of SSc, older patients showed data indicating more severe disease with greater cardiac involvement. The diffuse subset was more frequent in the younger subgroup. The identification of such differences may help in selecting appropriate management for individual patients in clinical practice.

Increased B-cell activating factor, interleukin-6, and interleukin-8 in induced sputum from primary Sjögren's syndrome patients.

OBJECTIVE: Small airway disease and chronic obstructive pulmonary disease are common in primary Sjögren's syndrome (pSS). However, the underlying inflammatory mechanisms behind pSS-associated airway disease have not been studied in detail. We therefore wanted to study cytokine and leucocyte levels in induced sputum in never-smoking patients with pSS. METHOD: Induced sputum cytokines and leucocytes were assessed in 20 never-smoking patients with pSS and 19 age- and gender-matched population-based controls. In addition, pulmonary function, disease activity, respiratory symptoms, and inflammatory and serological features of pSS were assessed. RESULTS: B-cell activating factor (BAFF), interleukin-6 (IL-6) and IL-8 were significantly increased in induced sputum in pSS patients compared to population-based controls, while IL-1ß, interferon-α, and tumour necrosis factor-α levels and leucocytes were not. The proportion of lymphocytes and BAFF levels in induced sputum correlated significantly in pSS patients. However, cytokine levels in induced sputum were not associated with pulmonary function tests, disease activity, respiratory symptoms, or serological features of pSS. CONCLUSION: The increase in BAFF, IL-6, and IL-8 in induced sputum suggests a specific ongoing inflammatory disease process in the airways in pSS patients. Its association with pSS-associated airway disease needs to be further examined in future larger studies.

Angiogenic and inflammatory biomarkers for screening and follow-up in patients with pulmonary arterial hypertension.

OBJECTIVE: To identify circulating angiogenic and inflammatory biomarkers with potential in screening for pulmonary arterial hypertension (PAH) in systemic sclerosis (SSc), and in early diagnosis and determination of treatment response in PAH. METHOD: Plasma samples were taken at the time of PAH diagnosis and at treatment follow-up after a median (interquartile range) of 4 months (3-9.8 months) in idiopathic (n = 9) and SSc-associated PAH (n = 11). In patients with SSc-associated PAH, plasma samples had also been gathered a median of 2 years (0.8-3 years) before PAH diagnosis (n = 10). Additional plasma samples were retrieved at two time-points separated by a median of 12 years (10-13 years) from SSc patients who did not develop PAH (n = 10) and from controls (n = 8). Angiogenic and inflammatory biomarkers were analysed by multiplex immunoassays. RESULTS: Plasma levels of placenta growth factor (PlGF), soluble vascular endothelial growth factor receptor-1 (sVEGFR-1), and tumour necrosis factor-α (TNF-α) were higher (p < 0.05) in SSc patients who later developed PAH than in those who did not. Plasma vascular endothelial growth factor (VEGF)-D increased (p < 0.05) in SSc patients as PAH developed. Plasma levels of PlGF, VEGF-A, VEGF-D, sVEGFR-1, interleukin-6, and TNF-α were higher (p < 0.05) in PAH than controls. There were no significant differences in circulating biomarkers between idiopathic and SSc-associated PAH. Plasma sVEGFR-1 decreased (p < 0.05) after initiating PAH-targeted treatments. CONCLUSIONS: Plasma levels of PlGF, sVEGFR-1, TNF-α, and VEGF-D have potential in screening for SSc-associated PAH. Plasma sVEGFR-1 may be a biomarker of treatment response.

Raynaud's phenomenon and its impact on activities in daily life during one year of follow-up in early systemic sclerosis.

OBJECTIVE: To investigate Raynaud's phenomenon (RP) and its impact on daily life activities during 1 year of follow-up in early systemic sclerosis (SSc). METHOD: Fourteen SSc patients with a median disease duration of 2 years were enrolled in the study. Every 7 weeks the patients completed a 7 day diary documenting the frequency and duration of RP attacks, the activity causing the attack, and how they handled the attack. The patients also recorded in the diary daily self-assessments of the difficulties with RP, using a 0-10 ordinal scale according to the Raynaud's Condition Score. RESULTS: Ninety-eight RP weekly diaries were analysed. The median number of RP attacks varied between six and nine per week, and the median score reflecting the difficulty associated with the attacks varied between 2.0 and 2.9. No difference was found in the number of attacks or the difficulties associated with them between winter, spring, and autumn. Fewer attacks and less difficulty were reported in August than in any of the other documented weeks (p < 0.05). In all diaries, all patients reported RP attacks associated with domestic activities. The use of heating devices varied during the follow-up. In February, all patients except one used such devices, while about half of the group used devices during the rest of the year. CONCLUSIONS: Difficulties resulting from RP are present and disabling all year round, which underscore the importance of intense vasoactive therapy and non-pharmacological strategies throughout the year.

CD81 and CD48 show different expression on blood eosinophils in systemic sclerosis: new markers for disease and pulmonary inflammation?

OBJECTIVES: In systemic sclerosis (SSc)-related interstitial lung disease (ILD), elevated eosinophil counts in bronchoalveolar lavage are associated with a worse outcome. We hypothesized that eosinophils may be activated in the peripheral circulation, thereby increasing their recruitment to affected tissues and contributing to inflammation and fibrosis. The aim of this study was to characterize the blood eosinophils in SSc patients. METHOD: Expression levels of surface markers CD11b, CD44, CD48, CD54, CD69, CD81, and HLA-DR on CD16(low)CD9(high)-expressing eosinophils were measured by flow cytometry in whole blood from SSc patients (n = 32) and controls (n = 11). RESULTS: Expression levels of CD54, CD69, and HLA-DR were undetectable in all groups. CD44 and CD11b expression levels were similar between groups. CD81 expression was lower in patients compared to controls independent of disease duration (p = 0.001). CD48 expression was increased in patients with a short disease duration (< 2 years) compared to both controls (p = 0.042) and patients with longer disease duration (≥ 2 years; p = 0.027). In patients with short disease duration, increased CD48 expression was associated with alveolar inflammation as measured by an increased concentration of alveolar nitric oxide (r = 0.76, p = 0.003). CONCLUSIONS: Blood eosinophils change phenotype during disease evolution in SSc, and CD48 expression may be used as a biomarker for pulmonary inflammation.

Personal factors in systemic sclerosis and their coverage by patient-reported outcome measures. A multicentre European qualitative study and literature review.

BACKGROUND: Systemic sclerosis (SSc) is an autoimmune disease where thickening of the skin can lead to reduced body function and limitations in activities. Severe forms can also affect and seriously damage inner organs. Patient-centred rehabilitation emphasises considerations of patients' background, experience and behavior which highlights the need to know if patient-reported outcome measures (PROMs) include such personal factors. AIM: To identify and describe personal factors in the experiences of functioning and health of persons with SSc and to examine if and to what extent PROMs in SSc research cover these factors. DESIGN: Data from a qualitative study with focus group interviews were analysed. PROMs in SSc research were identified in a literature review between 2008-2013. SETTING: Participants were recruited from outpatient clinics at rheumatology department. POPULATION: Sixty-three patients with SSc from four European countries participated. METHODS: Data from interviews were analysed using a structure of personal factors developed by Geyh et al. Identified PROMs were analysed and linked to main concepts, related to the personal factors, found in the interview data. RESULTS: Nineteen main concepts were related to the area "patterns of experience and behaviour" in the personal factor structure, 16 to "thoughts and beliefs", nine to "feelings", one to "motives" and one to "personal history and biography", respectively. Among the 35 PROMs identified, 15 did not cover any of the identified concepts. Concepts within the area "feelings" were mostly covered by the PROMs. Five of the PROMs covered "patterns of experience and behaviour", while "motives" and "personal history and biography" were not covered at all. Four of the identified PROMs covered concepts within the areas "feelings", "thoughts and beliefs" and "patterns of experience and behaviour" in the same instrument. The Illness Cognition Questionnaire and Illness Behaviour Questionnaire were such PROMs. CONCLUSION: Patterns of experience and behaviour had the highest number of concepts related to personal factors, but few of the PROMs in SSc research covered these factors. Only a few PROMs covered several personal factors areas in the same instrument. CLINICAL REHABILITATION IMPACT: The results would be of value when developing core sets for outcome measurements in SSc.

Vascular events are risk factors for anal incontinence in systemic sclerosis: a study of morphology and functional properties measured by anal endosonography and manometry.

OBJECTIVES: To study anal sphincter morphology, anal sphincter pressure, and rectoanal inhibitory reflex (RAIR) in patients with systemic sclerosis (SSc) complicated by anal incontinence (AI) and to investigate possible risk factors for AI in SSc. METHOD: Nineteen SSc patients with severe AI were investigated using anal endosonography, anal manometry, and rectal manovolumetry. To determine risk factors for AI, disease characteristics of SSc patients with AI were compared with those of 95 SSc patients without AI; there were five matched SSc patients without AI for each SSc patient with AI. RESULTS: The mean (SD) internal sphincter thickness was 1.3 (0.46) mm in patients with AI, which was thinner (p < 0.001) than reference data from healthy individuals whose internal sphincter measured 2.2 (0.45) mm, whereas the external sphincter thickness did not differ. The mean (SD) resting pressure in AI patients was lower than the reference data from healthy individuals [60 (22) vs. 94 (29) mmHg, p < 0.002] whereas the squeeze pressure did not differ. Centromeric antibodies and features of vascular disease [i.e. the presence of pulmonary arterial hypertension (PAH), digital ulcers, pitting scars, or the need for iloprost infusions] were associated with AI whereas fibrotic manifestations [i.e. modified Rodnan skin score (mRss), the diffuse cutaneous SSc (dcSSc) subset, or low vital capacity (VC)] were not. CONCLUSIONS: SSc patients with AI have a thin internal anal sphincter and a low resting pressure. Risk factors for AI among SSc patients are centromeric antibodies and vascular disease, which supports the hypothesis that gastrointestinal involvement in SSc is in part a vascular manifestation of the disease.

The forced oscillation technique is a sensitive method for detecting obstructive airway disease in patients with primary Sjögren's syndrome.

OBJECTIVES: To study signs of obstructive airway disease (OAD) in patients with primary Sjögren's syndrome (pSS) using the forced oscillation technique (FOT). METHOD: Thirty-seven female pSS patients (median age 64, range 38-77 years) without previous physician-diagnosed OAD, participating in a longitudinal follow-up study of pulmonary function, and 74 female population-based controls (median age 64, range 47-77 years), also without physician-diagnosed OAD, and matched with regard to age, height, weight, and tobacco consumption, were included in the study. The pSS patients and controls were studied by the FOT, evaluating resistance and reactance of the respiratory system. RESULTS: pSS patients had significantly increased resistances at 5-25 Hz, decreased reactance at 10-35 Hz, and an increased resonant frequency (Fres) in comparison with controls. Resistance was correlated negatively and reactance positively to the vital capacity (VC), the forced expiratory volume in 1 s (FEV1), and the diffusing capacity for carbon monoxide (DLCO). Compared with controls, pSS patients with (n = 14) and without OAD (n = 21), as determined by spirometry, had significantly increased resistances at 5-25 Hz and decreased reactances at 10-35 Hz. In never-smoking subjects, identical FOT signs were found. CONCLUSIONS: pSS patients showed FOT signs of obstruction affecting both peripheral and central airways. pSS patients without spirometric signs of OAD and never-smoking pSS patients also showed clear FOT signs of obstruction. FOT therefore seems to be a sensitive method for detecting obstruction in pSS patients.

Prevalence and incidence of systemic sclerosis in southern Sweden: population-based data with case ascertainment using the 1980 ARA criteria and the proposed ACR-EULAR classification criteria.

OBJECTIVES: To estimate the prevalence and incidence of systemic sclerosis (SSc) in southern Sweden. METHODS: In Skåne, the southernmost region of Sweden (total population 1.2 million), healthcare provided is registered in the Skåne Healthcare Register. We identified all Skåne residents who had received an International Classification of Diseases 10 diagnosis of SSc (M34) or Raynaud's phenomenon (I73.0) between 1998 and 2010. Every single case was ascertained by review of medical records in reference to the 1980 American Rheumatism Association preliminary classification criteria for SSc and the proposed American College of Rheumatology (ACR)-European League Against Rheumatism (EULAR) classification criteria presented at the ACR/Association of Rheumatology Health Professionals Annual Meeting 2012. We calculated the point prevalence by the end of 2010 by linkage with the population register to exclude deceased persons and we also estimated the mean annual cumulative incidence for 2006-2010. RESULTS: Using the 1980 ARA criteria, the adult prevalence and annual incidence of SSc in the Skåne region were 235 and 14 per 1 million inhabitants respectively. Applying the proposed ACR-EULAR criteria, the corresponding figures were 305 and 19 per 1 million inhabitants. A majority (82%) of the prevalent cases had the limited cutaneous SSc subtype. CONCLUSIONS: The prevalence and incidence of SSc in southern Sweden, based on the 1980 ARA criteria, are higher than previously reported in northern Europe and do not support the concept of a north-south gradient of SSc occurrence in Europe. Application of the proposed ACR-EULAR classification criteria in this population results in about 30-40% higher estimates of SSc prevalence and incidence compared to the 1980 ARA criteria.

Increased serum type I interferon activity in early systemic sclerosis patients is associated with antibodies against Sjögren's syndrome antigens and nuclear ribonucleoprotein antigens.

OBJECTIVE: To study serum type I interferon (IFN) activity in patients with early systemic sclerosis (SSc). METHOD: Serum type I IFN activity was measured in 33 consecutive patients with SSc and a disease duration of < 2 years and in 13 healthy individuals by calculating a type I IFN score according to the induction of six IFN-α regulated genes in a reporter cell line. RESULTS: Twenty-seven per cent of the SSc patients had an increased type I IFN score compared to none of the healthy individuals (p < 0.05). The clinical SSc phenotype associated with high serum type I IFN activity did not differ from patients with low serum type I IFN activity regarding the presence of skin or lung fibrosis, pulmonary hypertension, or digital complications. Patients with high serum type I IFN activity were younger (p < 0.01) and had a lower frequency of cardiac involvement (p = 0.053), lower leucocyte count (p < 0.001), higher immunoglobulin (Ig)G levels (p < 0.05), and a higher amount of antibodies against extractable nuclear antigens (p < 0.01) than patients with low serum type I IFN activity. The presence of antibodies against topoisomerase I, Sjögren's syndrome antigen, and nuclear ribonucleoprotein antigens was associated with higher type I IFN activity (p < 0.05 for all comparisons). CONCLUSIONS: Our study indicates that increased serum type I IFN activity in early SSc patients is associated with an antibody and laboratory profile that may reflect a subclinical overlap of SSc with other type I IFN-driven connective tissue diseases (CTDs).

Psychometric properties of the Swedish version of the Scleroderma Health Assessment Questionnaire and the Cochin Hand Function Scale in patients with systemic sclerosis.

OBJECTIVES: To translate the visual analogue scales (VAS) in the Scleroderma Health Assessment Questionnaire (SSc HAQ) and the Cochin Hand Function Scale (CHFS) and to examine the reliability and validity of the Swedish versions of the instruments. METHOD: The reproducibility, internal consistency, acceptability, and validity of the instruments were evaluated. Eighty-three consecutive patients participated in the evaluation of the SSc HAQ and 56 in the CHFS. Sixty-six per cent fulfilled the criteria for limited systemic sclerosis (lcSSc) and 29% for diffuse systemic sclerosis (dcSSc). The patients were assessed regarding disease parameters, hand involvement, and quality of life, the latter using the 36-item short form health survey (SF-36). RESULTS: The reproducibility in the HAQ Disability Index (HAQ-DI), the VAS of pulmonary, digital ulcer, and overall disease severity, and in the CHFS was good (intra-class correlation coefficients, ICCs ≥ 0.75). The internal consistency was high in the HAQ-DI and the CHFS but lower in the VAS. The HAQ-DI showed higher correlations coefficients with physical-related scores in the SF-36 (rs = -0.600) than with mental-related dimensions (rs = -0.235). All VAS showed significant correlation with the item for general health (p < 0.05). The CHFS showed high correlation to hand-related items in the HAQ (rs = 0.858) and moderate correlation to the physical summary score in SF-36 (rs = -0.521). The instruments could not discriminate between lcSSc and dcSSc, although significant correlations between the CHFS and hand involvement (p < 0.05) indicate the ability of the CHFS to discriminate between mild and severe hand involvement. CONCLUSIONS: The Swedish version of the SSc HAQ and the CHFS meet the requirements of reproducibility and concurrent validity. More studies are needed to examine the capacity of these instruments to discriminate between disease severities.

Evidence that deletion at FCGR3B is a risk factor for systemic sclerosis.

There is increasing evidence that gene copy number (CN) variation influences clinical phenotype. The low-affinity Fc receptor 3B (FCGR3B) located in the FCGR gene cluster is a CN polymorphic gene involved in the recruitment of polymorphonuclear neutrophils to sites of inflammation and their activation. Given the genetic overlap between systemic lupus erythematosus and systemic sclerosis (SSc) and the strong evidence for FCGR3B CN in the pathology of SLE, we hypothesised that FCGR3B gene dosage influences susceptibility to SSc. We obtained FCGR3B deletion status in 777 European Caucasian cases and 1000 controls. There was an inverse relationship between FCGR3B CN and disease susceptibility. CN of ≤ 1 was a significant risk factor for SSc (OR=1.55 (1.13-2.14), P=0.007) relative to CN ≥ 2. Although requiring replication, these results suggest that impaired immune complex clearance arising from FCGR3B deficiency contributes to the pathology of SSc, and FCGR3B CN variation is a common risk factor for systemic autoimmunity.

A rare polymorphism in the gene for Toll-like receptor 2 is associated with systemic sclerosis phenotype and increases the production of inflammatory mediators.

OBJECTIVE: To investigate whether polymorphisms in Toll-like receptor (TLR) genes, previously reported to be associated with immune-mediated diseases, are involved in systemic sclerosis (SSc). METHODS: We genotyped 14 polymorphisms in the genes for TLRs 2, 4, 7, 8, and 9 in a discovery cohort comprising 452 SSc patients and 537 controls and a replication cohort consisting of 1,170 SSc patients and 925 controls. In addition, we analyzed 15-year followup data on 964 patients to assess the potential association of TLR variants with the development of disease complications. We analyzed the functional impact of the associated polymorphism on monocyte-derived dendritic cells. RESULTS: In the discovery cohort, we observed that a rare functional polymorphism in TLR2 (Pro631His) was associated with antitopoisomerase (antitopo) positivity (odds ratio 2.24 [95% confidence interval 1.24-4.04], P=0.003). This observation was validated in the replication cohort (odds ratio 2.73 [95% confidence interval 1.85-4.04], P=0.0001). In addition, in the replication cohort the TLR2 variant was associated with the diffuse subtype of the disease (P=0.02) and with the development of pulmonary arterial hypertension (PAH) (Cox proportional hazards ratio 5.61 [95% confidence interval 1.53-20.58], P=0.003 by log rank test). Functional analysis revealed that monocyte-derived dendritic cells carrying the Pro63His variant produced increased levels of inflammatory mediators (tumor necrosis factor α and interleukin-6) upon TLR-2-mediated stimulation (both P<0.0001). CONCLUSION: Among patients with SSc, the rare TLR2 Pro631His variant is robustly associated with antitopoisomerase positivity, the diffuse form of the disease, and the development of PAH. In addition, this variant influences TLR-2-mediated cell responses. Further research is needed to elucidate the precise role of TLR-2 in the pathogenesis of SSc.

Scleroderma renal crisis in a Swedish systemic sclerosis cohort: survival, renal outcome, and RNA polymerase III antibodies as a risk factor.

OBJECTIVES: To study survival, renal outcome, and RNA polymerase III antibodies (RNAP Abs) as a risk factor for scleroderma renal crisis (SRC) in a Swedish cohort of systemic sclerosis (SSc) patients. METHODS: SRC was diagnosed in 16 SSc patients during the period from 1982 to 2010. For comparison, 112 (seven for each SRC patient) SSc patients without SRC were included. RNAP Abs were detected by a fully automated fluoroenzyme immunoassay (EliA). Values greater than 15 µg/L were considered positive. Frozen serum samples from the time of diagnosis of SSc were used. RESULTS: The 5- and 10-year survival rates were, respectively, 58% and 40% for SRC patients and 90% and 76% for patients without SRC (p < 0.001). The odds ratio (OR) for mortality was 4.39 [95% confidence interval (CI) 2.10-9.16, p < 0.001] in patients with SRC compared to those without SRC. Renal outcome was good in three patients. Haemodialysis was started in 10 patients and peritoneal dialysis in three. Renal function improved in three patients and dialysis was terminated. Four patients underwent renal transplantation. Seven SRC patients and nine without SRC were positive for RNAP Abs. Anti-RNAP Abs was a strong predictor of SRC. The sensitivity and specificity for development of SRC were 0.44 and 0.92, respectively. The OR for development of SRC was 8.90 (95% CI 2.68-29.6, p = 0.001) in RNAP-positive patients. CONCLUSIONS: RNAP positivity is a strong risk factor for SRC. Renal outcome was variable and survival is still notably decreased.

Progressive capillary loss over a decade in patients with systemic sclerosis, in particular in patients with early digital ischaemic manifestations.

OBJECTIVE: Characteristic capillary abnormalities occur early in systemic sclerosis (SSc). Our aim was to study the longitudinal development of capillary density in SSc patients. METHODS: Forty-eight consecutive patients with SSc fulfilling a follow-up of at least 8 years were retrospectively analysed for capillary loss over the observation period. Eleven had diffuse cutaneous SSc (dcSSc) and 37 limited cutaneous SSc (lcSSc). The median disease duration at first assessment was 2.5 years. Capillary density was determined by direct counting of capillaries in the distal row on eight fingers in a stereo-zoom microscope at 20× magnification. RESULTS: Capillary density decreased over the observation period in dcSSc (from median 5.1 to 4.4 loops/mm, p < 0.05) and in lcSSc (from 5.1 to 4.2 loops/mm, p < 0.001). No significant difference was found between the two forms at start or at follow-up. Digital ischaemic manifestations had already been found at the first assessment in 19 patients. They did not differ in capillary density from those without ischaemic manifestations at the first assessment (5.0 and 5.3 loops/mm), but did differ at follow-up (3.6 and 4.7 loops/mm, p < 0.001). Capillary loss was more pronounced in patients who already had digital ischaemic manifestations at the first assessment compared to those without (p < 0.02). CONCLUSION: In SSc, early digital ischaemic manifestations may precede a subsequent progressive capillary loss. The association between capillary loss and serious internal vascular complications remains to be studied.

Clinical prediction of 5-year survival in systemic sclerosis: validation of a simple prognostic model in EUSTAR centres.

OBJECTIVE: Systemic sclerosis (SSc) is associated with a significant reduction in life expectancy. A simple prognostic model to predict 5-year survival in SSc was developed in 1999 in 280 patients, but it has not been validated in other patients. The predictions of a prognostic model are usually less accurate in other patients, especially from other centres or countries. A study was undertaken to validate the prognostic model to predict 5-year survival in SSc in other centres throughout Europe. METHODS: A European multicentre cohort of patients with SSc diagnosed before 2002 was established. Patients with SSc according to the preliminary American College of Rheumatology classification criteria were eligible for the study when they were followed for at least 5 years or shorter if they died. The primary outcome was 5-year survival after diagnosis of SSc. The predefined prognostic model uses the following baseline variables: age, gender, presence of urine protein, erythrocyte sedimentation rate (ESR) and carbon monoxide diffusing capacity (DLCO). RESULTS: Data were available for 1049 patients, 119 (11%) of whom died within 5 years after diagnosis. Of the patients, 85% were female, the mean (SD) age at diagnosis was 50 (14) years and 30% were classified as having diffuse cutaneous SSc. The prognostic model with age (OR 1.03), male gender (OR 1.93), urine protein (OR 2.29), elevated ESR (1.89) and low DLCO (OR 1.94) had an area under the receiver operating characteristic curve of 0.78. Death occurred in 12 (2.2%) of 509 patients with no risk factors, 45 (13%) of 349 patients with one risk factor, 55 (33%) of 168 patients with two risk factors and 7 (30%) of 23 patients with three risk factors. CONCLUSION: A simple prognostic model using three disease factors to predict 5-year survival at diagnosis in SSc showed reasonable performance upon validation in a European multicentre study.

Faecal calprotectin: a biomarker of gastrointestinal disease in systemic sclerosis.

BACKGROUND: Assessment of gastrointestinal (GI) involvement in systemic sclerosis (SSc) is difficult. Measurement of calprotectin in faeces is a valuable tool for the assessment of inflammatory bowel diseases. Calprotectin is an intracellular protein found in leucocytes and is a potent activator of the innate immune system. OBJECTIVE: To determine whether faecal calprotectin (F-calprotectin) could serve as a biomarker of GI disease in SSc. DESIGN: In a cross-sectional study, F-calprotectin and plasma calprotectin were measured in patients with SSc using an enzyme-linked immunosorbent assay. F-calprotectin concentrations were evaluated in relation to cineradiography, medical records, laboratory measurements and patients' subjective GI symptoms. SETTING: The study was conducted at a tertiary referral centre for SSc. SUBJECTS: The study comprised 81 consecutive patients with SSc. RESULTS: A majority of the patients had pathological levels of F-calprotectin when compared to accepted clinical reference values for healthy adults. F-calprotectin did not correlate with calprotectin levels in plasma. F-calprotectin was associated with the following patient characteristics: pathological cineradiography, history of referral to another clinic because of GI disease, treatment of vitamin or mineral deficiency and use of proton pump inhibitors. We did not find any significant correlation between F-calprotectin and patient-reported GI symptoms. CONCLUSION: Faecal calprotectin is increased in a majority of patients with SSc. It correlates with objective and clinically important features of GI disease, and faecal concentrations do not vary with plasma concentrations. We suggest that F-calprotectin is a promising objective non-invasive biomarker of GI involvement in SSc.