Holly Ennis

Incidence of childhood linear scleroderma and systemic sclerosis in the UK and Ireland.

Childhood scleroderma encompasses a rare, poorly understood spectrum of conditions. Our aim was to ascertain the incidence of childhood scleroderma in its different forms in the UK and Ireland, and to describe the age, sex, and ethnicity of the cases.

Observational Study of Treatment Outcome in Early Diffuse Cutaneous Systemic Sclerosis

Objective. Randomized clinical trials in early diffuse cutaneous systemic sclerosis (dcSSc) are challenging. We used an observational approach to estimate the relative effectiveness of different current treatment approaches, capturing entry and outcome data in a standardized way. Methods. Patients with dcSSc within 3 years of the onset of skin thickening were included. Standardized entry and followup data were collected in relation to the first disease-modifying treatment at baseline and 4–6 weeks, then 3, 6, 12, 18, 24, 30, and 36 months. The 5 different protocols were (1) intravenous cyclophosphamide followed by mycophenolate mofetil (MMF); (2) antithymocyte globulin followed by MMF; (3) MMF alone; (4) no disease-modifying treatment; (5) other immunosuppressant treatment. The primary outcome measure was the modified Rodnan skin score (mRSS). Inverse probability of treatment weights were used to allow for differing patient characteristics between groups. Results. The study included 147 patients from 12 centers. Numbers of patients starting on Protocols 1 to 5 were 29, 25, 61, 19, and 13, respectively. mRSS decreased over time from 24 (IQ 19–32) at baseline to 15.5 (IQ 9–24.5) at 3 years. Although there were differences in the magnitude of the change for different protocols, there were no significant differences between protocols in the rate of change of mRSS over time (p = 0.43). When inverse probability weights were applied, the results remained nonsignificant (p = 0.41). Conclusion. Using this observational approach, there were no obvious differences in outcome between groups after allowing as far as possible for baseline differences in treatment allocations.

A prospective study of systemic sclerosis-related digital ulcers: prevalence, location, and functional impact.

Objectives: Although digital ulcers (DUs) are common in patients with systemic sclerosis (SSc), prevalence estimates vary, and functional impact and pathophysiology have been relatively little studied. We investigated the point prevalence of all DUs (both digital-tip and extensor) in a cohort of patients with SSc, testing the hypothesis that both digital-tip and extensor ulcers are associated with functional impairment. Method: Over a 12-month period, patients attending an SSc clinic for annual review were assessed by specialist nurses: active DUs were documented and the Hand Mobility in Scleroderma (HAMIS) test performed. Patients also completed the Scleroderma Health Assessment Questionnaire (SHAQ), the Scleroderma Functional Index (SFI), and the Cochin Hand Function Scale (CHFS). Results: A total of 25 active DUs (nine digital-tip and 16 extensor surface) were found in 15 of the 148 patients recruited, giving a prevalence for each ulcer type of 6% and an overall point prevalence of 10%. HAMIS scores were higher (indicating greater impairment) in those with active DUs than in those without: left hand difference 8.8 points [95% confidence interval (CI) 3.2–14.5], p = 0.002; difference significant for extensor as well as digital-tip ulcers. Active DUs were associated with higher visual analogue scale (VAS) scores for pain (p = 0.04), DUs (p < 0.001), and ‘overall’ assessment (p = 0.03). Conclusions: Extensor surface ulcers have the same prevalence as digital-tip ulcers in patients with SSc, and are equally disabling. Clinical trials should therefore include both categories of DUs.

Influence of childhood scleroderma on physical function and quality of life

Objective. There have been few studies of quality of life in childhood scleroderma and these focused predominantly on self-perception and the influence of skin lesions. Our cross-sectional study aimed to describe the influence of childhood scleroderma on physical function and quality of life in relation to clinical and demographic measures. Methods. Children with either localized scleroderma or systemic sclerosis (SSc) attending pediatric rheumatology clinics, together with their parents or guardians, were asked to complete a set of 4 validated measures. Clinical and demographic data were provided by consultant pediatric rheumatologists. Results. In total, 28 children and their parents/guardians participated in the study (68% female, median age 13 yrs; 86% localized scleroderma, 14% SSc). The median Child Health Assessment Questionnaire (CHAQ) score was 0.1 (range 0–3, 0 indicating no impairment), the median Child Dermatology Life Quality Index (CDLQI) score was 5 (range 0–30, 0 indicating no impairment), and the median Child Quality of Life Questionnaire (CQOL) function score was 26 (range 0–105, 0 indicating no impairment). Family activity, measured by the Child Health Questionnaire (CHQ-PF50), was also moderately impaired by scleroderma, with a median score of 83 (0–100, 100 indicating no impairment). Conclusion. Scleroderma had only a moderate effect on quality of life and physical function as measured by the 4 validated instruments. Although a small number of children reported greater impairment, this is an encouraging finding, given its potential disfiguring and debilitating effects.

A study comparing videocapillaroscopy and dermoscopy in the assessment of nailfold capillaries in patients with systemic sclerosis–spectrum disorders

OBJECTIVES Nailfold videocapillaroscopy (NVC), the current gold standard for detection of capillary abnormalities suggestive of an SSc-spectrum disorder, is not widely available: a key question is whether lower-magnification, easy-to-use dermoscopy compares favourably. This is especially relevant given the inclusion of capillaroscopic abnormality within the 2013 classification criteria for SSc. Our objectives were to examine the ability to classify capillaries and to evaluate abnormality (severity), by both NVC and dermoscopy, to determine whether these differ between general and specialist rheumatologists, and to compare intra- and interrater reliability of both techniques. METHODS NVC and dermoscopy images were acquired from all 10 nailbeds of 32 subjects with a range of capillary abnormalities. Images were graded (using a web-based interface) on a 0-3 scale of severity: normal (0), mildly (1), definitely (2) and grossly abnormal (3), and an unclassifiable category. Raters graded images from four subjects (40 nailbeds) using each technique, with five repeated images to estimate intrarater reliability. RESULTS Forty-eight rheumatologists from 12 countries participated in the study (22 generalists, 26 specialists). While most images could be graded by both techniques, more were graded by NVC (84% vs 70%) and were systematically scored higher by NVC (mean difference 0.43 between the ratings). Agreement between the techniques was moderate. Intra- and interrater reliability were comparable for the two techniques in the classifiability of images and the grading of severity. CONCLUSION Our results suggest that dermoscopy is comparable to NVC, although NVC images were more likely to be classifiable and were graded more severely.

Mercaptopurine versus placebo to prevent recurrence of Crohn's disease after surgical resection (TOPPIC): a multicentre, double-blind, randomised controlled trial

Summary Background Up to 60% of patients with Crohns disease need intestinal resection within the first 10 years of diagnosis, and postoperative recurrence is common. We investigated whether mercaptopurine can prevent or delay postoperative clinical recurrence of Crohns disease. Methods We did a randomised, placebo-controlled, double-blind trial at 29 UK secondary and tertiary hospitals of patients (aged >16 years in Scotland or >18 years in England and Wales) who had a confirmed diagnosis of Crohns disease and had undergone intestinal resection. Patients were randomly assigned (1:1) by a computer-generated web-based randomisation system to oral daily mercaptopurine at a dose of 1 mg/kg bodyweight rounded to the nearest 25 mg or placebo; patients with low thiopurine methyltransferase activity received half the normal dose. Patients and their carers and physicians were masked to the treatment allocation. Patients were followed up for 3 years. The primary endpoint was clinical recurrence of Crohns disease (Crohns Disease Activity Index >150 plus 100-point increase in score) and the need for anti-inflammatory rescue treatment or primary surgical intervention. Primary and safety analyses were by intention to treat. Subgroup analyses by smoking status, previous thiopurines, previous infliximab or methotrexate, previous surgery, duration of disease, or age at diagnosis were also done. This trial is registered with the International Standard Randomised Controlled Trial Register (ISRCTN89489788) and the European Clinical Trials Database (EudraCT number 2006-005800-15). Findings Between June 6, 2008, and April 23, 2012, 240 patients with Crohns disease were randomly assigned: 128 to mercaptopurine and 112 to placebo. All patients received at least one dose of study drug, and no randomly assigned patients were excluded from the analysis. 16 (13%) of patients in the mercaptopurine group versus 26 (23%) patients in the placebo group had a clinical recurrence of Crohns disease and needed anti-inflammatory rescue treatment or primary surgical intervention (adjusted hazard ratio [HR] 0·54, 95% CI 0·27–1·06; p=0·07; unadjusted HR 0·53, 95% CI 0·28–0·99; p=0·046). In a subgroup analysis, three (10%) of 29 smokers in the mercaptopurine group and 12 (46%) of 26 in the placebo group had a clinical recurrence that needed treatment (HR 0·13, 95% CI 0·04–0·46), compared with 13 (13%) of 99 non-smokers in the mercaptopurine group and 14 (16%) of 86 in the placebo group (0·90, 0·42–1·94; pinteraction=0·018). The effect of mercaptopurine did not significantly differ from placebo for any of the other planned subgroup analyses (previous thiopurines, previous infliximab or methotrexate, previous surgery, duration of disease, or age at diagnosis). The incidence and types of adverse events were similar in the mercaptopurine and placebo groups. One patient on placebo died of ischaemic heart disease. Adverse events caused discontinuation of treatment in 39 (30%) of 128 patients in the mercaptopurine group versus 41 (37%) of 112 in the placebo group. Interpretation Mercaptopurine is effective in preventing postoperative clinical recurrence of Crohns disease, but only in patients who are smokers. Thus, in smokers, thiopurine treatment seems to be justified in the postoperative period, although smoking cessation should be strongly encouraged given that smoking increases the risk of recurrence. Funding Medical Research Council.

Clinical features of childhood localized scleroderma in an incidence cohort

OBJECTIVES Our aim was to describe clinical features and pattern of care in children with localized scleroderma presenting to secondary care during a 25-month incidence study. METHODS Eighty-seven patients were identified, and clinical features, serum autoantibodies, current treatment and outcome at 12 months were documented. RESULTS Fifty-eight (67%) had linear scleroderma, 25 (29%) non-linear morphoea and 4 (4%) a mixed pattern. Of the 58 patients with linear scleroderma, 29 (50%) presented with lesions of the trunk and/or limbs only, 26 (45%) with face-head localization only and 3 (5%) with both. Thirteen (15%) had extracutaneous features and 16 (43%) out of 37 were ANA positive. At 12 months, 59% were on MTX. At 12 months, 51 (65%) were improved/resolved, 14 (18%) were unchanged and 13 (17%) had deteriorated. CONCLUSION Key findings included the high prevalence of face-head involvement in those with linear disease, and the high prevalence of extracutaneous disease and of ANA positivity. After 12 months, most patients improved according to clinicians opinion.

Further confirmation that digital ulcers are associated with the severity of abnormality on nailfold capillaroscopy in patients with systemic sclerosis

Sofia Ramiro, Astrid van Tubergen, Désirée van der Heijde, Filip van den Bosch, Maxime Dougados and Robert Landewé Department of Clinical Immunology and Rheumatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands, Department of Rheumatology, Hospital Garcia de Orta, Almada, Portugal, Department of Medicine, Division of Rheumatology, Maastricht University Medical Center, School for Public Health and Primary Care (CAPHRI), University of Maastricht, Maastricht, Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands, Department of Rheumatology, Ghent University Hospital, Ghent, Belgium, Rheumatology B Department, Cochin Hospital, Paris-Descartes University, Paris, France and Department of Rheumatology, Atrium Medical Center, Heerlen, The Netherlands. Accepted 18 October 2013. Correspondence to: Sofia Ramiro, Department of Clinical Immunology and Rheumatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. E-mail: sofiaramiro@gmail.com

Pilot study of intense pulsed light for the treatment of systemic sclerosis-related telangiectases.

Background  Telangiectases represent microvascular changes inherent in the systemic sclerosis (SSc) disease process. Intense pulsed light (IPL) is an effective treatment for non‐SSc‐related cutaneous telangiectases.

HLA-DRB1 associations with rheumatoid arthritis-related pulmonary fibrosis

The aetiology of rheumatoid arthritis (RA)-related pulmonary fibrosis (PF), one of the major extraarticular manifestations of RA (1), remains unknown and is likely to be multifactorial (2). However, to date only a few studies have examined its genetic basis (3). The association between RA and a number of human leucocyte antigen (HLA)-DRB1 alleles that share a common sequence (4), known as the shared epitope (SE), is well known. Our objective was to perform a pilot study to determine whether there is a difference between HLA-DRB1 alleles associated with susceptibility to RA-related PF compared with RA alone. Fifty-two Caucasian patients (33 males, median age at onset of RA 54 years, median disease duration 11 years) with RA-related PF were recruited from hospitals across North West England. The study was approved by the North West Research Ethics Committee and all patients signed an informed consent form. PF was confirmed by high-resolution computed tomography in 48 (92%) cases: in the other four, diagnosis was on the basis of bilateral basal shadowing on chest X-ray with a restrictive defect on pulmonary function testing. DNA samples from 537 healthy Caucasian controls and 3397 Caucasian RA patients recruited by the UK Rheumatoid Arthritis Genetics (UKRAG) Consortium were available for comparison. HLA-DRB1 genotyping was performed using Dynal RELI sequence-specific oligonucleotide (SSO) HLA-DRB1 kits. HLA-DRB1 allele frequencies in patients with RA-related PF were compared with those in healthy controls, and with RA patients from the UKRAG Consortium (Table 1). A two-stage statistical analysis was used to account for the multi-allelic nature of HLA-DRB1 and the small sample size. An overall Pearson χ test of broad-type HLA-DRB1 allele frequencies was performed, and allele frequencies were compared with a reference allele using multinomial logistic regression. Allele and phenotype frequencies for the broad-type HLA-DRB1 alleles in RA-related PF cases, RA cases, and healthy controls are shown in Table 1. HLA-DRB1 SE analysis: The frequency of SE carriage was 70, 75, and 46% in RA-related PF, RA, and healthy controls, respectively. Carriage of SE was significantly higher in RA-related PF cases compared with healthy controls [odds ratio (OR) 2.80, 95%