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1.
J Scleroderma Relat Disord ; 3(2): 170-174, 2018 Jun 01.
Article in English | MEDLINE | ID: mdl-29876526

ABSTRACT

INTRODUCTION: The reliability of clinician grading of systemic sclerosis-related digital ulcers has been reported to be poor to moderate at best, which has important implications for clinical trial design. The aim of this study was to examine the reliability of new proposed UK Scleroderma Study Group digital ulcer definitions among UK clinicians with an interest in systemic sclerosis. METHODS: Raters graded (through a custom-built interface) 90 images (80 unique and 10 repeat) of a range of digital lesions collected from patients with systemic sclerosis. Lesions were graded on an ordinal scale of severity: 'no ulcer', 'healed ulcer' or 'digital ulcer'. RESULTS: A total of 23 clinicians - 18 rheumatologists, 3 dermatologists, 1 hand surgeon and 1 specialist rheumatology nurse - completed the study. A total of 2070 (1840 unique + 230 repeat) image gradings were obtained. For intra-rater reliability, across all images, the overall weighted kappa coefficient was high (0.71) and was moderate (0.55) when averaged across individual raters. Overall inter-rater reliability was poor (0.15). CONCLUSION: Although our proposed digital ulcer definitions had high intra-rater reliability, the overall inter-rater reliability was poor. Our study highlights the challenges of digital ulcer assessment by clinicians with an interest in systemic sclerosis and provides a number of useful insights for future clinical trial design. Further research is warranted to improve the reliability of digital ulcer definition/rating as an outcome measure in clinical trials, including examining the role for objective measurement techniques, and the development of digital ulcer patient-reported outcome measures.

2.
Acta Derm Venereol ; 96(5): 641-4, 2016 Jun 15.
Article in English | MEDLINE | ID: mdl-26695444

ABSTRACT

Extensive morphoea causes major morbidity, disability and disfigurement; pathophysiology is poorly understood. The aim of this study was to investigate, with non-invasive imaging, the relationship between localised abnormalities of skin structure and perfusion, which characterise morphoea. Thirty-two patients with morphoea underwent imaging at affected and unaffected sites. Skin thickness was imaged with optical coherence tomography (OCT) and high-frequency ultrasound (HFUS). Perfusion was imaged with dual-wavelength laser Doppler imaging (LDI) and thermography. Epidermal thickness showed a small increase from affected to unaffected site (OCT, active and inactive plaques [p = 0.005 and p = 0.004], HFUS active plaques only [p = 0.03]). Deeper perfusion was higher within affected than unaffected sites (LDI p < 0.001, thermography p < 0.0001, active and inactive plaques). Epidermal thickness was inversely related to superficial (but not deeper) perfusion. This novel study of OCT, HFUS, LDI and thermography confirms loss of epidermal thickness and increased deeper perfusion in morphea plaques.


Subject(s)
Scleroderma, Localized/diagnostic imaging , Skin/blood supply , Adult , Female , Humans , Laser-Doppler Flowmetry , Male , Regional Blood Flow , Scleroderma, Localized/pathology , Skin/pathology , Thermography , Tomography, Optical Coherence , Ultrasonography
3.
Rheumatology (Oxford) ; 50(10): 1865-8, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21729934

ABSTRACT

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 clinician's opinion.


Subject(s)
Scleroderma, Localized/diagnosis , Back , Child , Cohort Studies , Extremities , Face , Female , Humans , Immunosuppressive Agents/therapeutic use , Male , Methotrexate/therapeutic use , Scleroderma, Localized/drug therapy , Scleroderma, Localized/epidemiology , Severity of Illness Index , Skin/pathology , Surveys and Questionnaires
4.
Rheumatology (Oxford) ; 49(9): 1776-82, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20538680

ABSTRACT

OBJECTIVES: Advances in nail-fold capillaroscopy allow capillary abnormalities to be quantified. Our aim was to investigate, in patients with SSc, the relationships between the degree of nail-fold capillary abnormality and disease subtypes (lcSSc and dcSSc), duration of RP and the presence of (i) severe digital ischaemia (as defined by previous i.v. vasodilators, debridements or amputations), (ii) a positive ACA, (iii) clinically evident calcinosis, (iv) pulmonary arterial hypertension and (v) telangiectases. METHODS: This was a retrospective study of 176 patients. Six capillary measurements (four semi-automated and two manual) were calculated (automated width, distance between capillaries, tortuosity and derangement, and manual distance and density). Relationships between these measurements and the different clinical features of SSc were examined using multiple linear regressions (adjusted for age, sex and smoking status). RESULTS: One hundred and forty-two patients had lcSSc and 34 had dcSSc. Sixty-eight (39%) had a history of severe digital ischaemia, 66 (38%) were anti-centromere positive, 53 (30%) had clinically evident calcinosis and 26 (15%) had an estimated pulmonary artery pressure of >30 mmHg. Positive associations were found between both automated and manually measured distance between capillaries and (i) presence of severe digital ischaemia and (ii) positive ACA, and reduced density was also associated with positive anti-centromere. Patients with moderate/severe telangiectases had wider capillaries compared with those with 'mild' lesions. CONCLUSIONS: Both severe digital ischaemia and positive ACA are associated with measurable nail-fold capillaroscopic change, which has the potential of being an outcome measure for the structural microvascular disease associated with SSc-spectrum disorders.


Subject(s)
Centromere/immunology , Fingers/blood supply , Ischemia/physiopathology , Microscopic Angioscopy/methods , Nails/blood supply , Telangiectasis/physiopathology , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies , Female , Humans , Ischemia/immunology , Male , Middle Aged , Retrospective Studies , Severity of Illness Index , Statistics as Topic , Telangiectasis/immunology , Young Adult
5.
Arthritis Care Res (Hoboken) ; 62(2): 213-8, 2010 Feb.
Article in English | MEDLINE | ID: mdl-20191520

ABSTRACT

OBJECTIVE: 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. METHODS: The members of 5 specialist medical associations including pediatricians, dermatologists, and rheumatologists were asked to report all cases of abnormal skin thickening suspected to be localized (including linear) scleroderma or systemic sclerosis (SSc) in children <16 years of age first seen between July 2005 and July 2007. RESULTS: We received notification of 185 potential cases, and 94 valid cases were confirmed: 87 (93%) with localized scleroderma and 7 (7%) with SSc. This gave an incidence rate per million children per year of 3.4 (95% confidence interval [95% CI] 2.7-4.1) for localized scleroderma, including an incidence rate of 2.5 (95% CI 1.8-3.1) for linear scleroderma, and 0.27 (95% CI 0.1-0.5) for SSc. Of the 87 localized cases, 62 (71%) had linear disease. Of localized disease cases, 55 (63%) were female, 71 (82%) were classified as white British, and the patients' mean age when first seen in secondary care was 10.4 years. Of the 7 SSc cases, all were female, 6 (86%) were white British, and the mean age when first seen was 12.1 years. The median delay between onset and being first seen was 13.1 months for localized scleroderma and 7.2 months for SSc. CONCLUSION: These data provide additional estimates of the incidence of this rare disorder and its subforms.


Subject(s)
Scleroderma, Localized/epidemiology , Scleroderma, Systemic/epidemiology , Adolescent , Child , Female , Humans , Incidence , Ireland/epidemiology , Male , Prospective Studies , Scleroderma, Localized/ethnology , Scleroderma, Systemic/ethnology , Sex Distribution , United Kingdom/epidemiology , White People/statistics & numerical data
6.
Exp Dermatol ; 13(7): 452-60, 2004 Jul.
Article in English | MEDLINE | ID: mdl-15217366

ABSTRACT

Contact allergen-induced migration of epidermal Langerhans cells (LCs) to draining lymph nodes is dependent upon receipt by LCs of at least two cytokine signals provided by tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-1beta. It has been reported previously that intradermal injection of healthy human volunteers with homologous TNF-alpha or IL-1beta each induces a significant reduction in LC frequency, as measured in epidermal sheets prepared from 6-mm punch biopsies. In the current experiments, we have compared the frequency of LCs in punch biopsies with those obtained concurrently in epidermal sheets from the roofs of suction blisters isolated from the sun-protected buttock skin of healthy adult volunteers. There was a significant, approximately 30%, reduction in CD1a(+) LC numbers in suction blister roofs compared with punch biopsies. Injection of homologous recombinant IL-1beta, a stimulus that provokes measurable epidermal LC mobilization in punch biopsy sites, failed to provoke further LC migration in suction blister sites. These data suggest that the mechanical trauma to the skin caused by the creation of suction blisters provokes the degree of cutaneous inflammation necessary for LC mobilization. The responsive cells (only a proportion of resident LCs, approximately 30%) have already migrated, thus addition of an exogenous cytokine signal (IL-1beta) is without further effect. It is not possible therefore to measure the regulation of LC mobilization by exogenous cytokines in suction blister roofs. However, this technique provides an opportunity to profile induced changes in the cutaneous cytokine environment, with cytokine expression measured by a multiple cytokine array system. Using this technique, intradermal injection of IL-1beta was found to cause a marked upregulation of proinflammatory cytokines including TNF-alpha, IL-6, IL-8, monocyte chemotactic protein-1 (MCP-1) and the anti-inflammatory cytokine IL-10 in fluid from suction blisters raised at the site of injection. In conclusion, the suction blister technique appears to be a powerful tool for measurement of induced changes in cutaneous cytokines.


Subject(s)
Blister/pathology , Cytokines/biosynthesis , Langerhans Cells/pathology , Skin/metabolism , Skin/pathology , Adult , Biopsy , Cell Movement , Chemokine CCL2/metabolism , Cytokines/metabolism , Dermatitis, Contact/pathology , Enzyme-Linked Immunosorbent Assay , Female , Humans , Interleukin-1/metabolism , Interleukin-10/metabolism , Interleukin-6/metabolism , Interleukin-8/metabolism , Lymph Nodes/pathology , Male , Middle Aged , Recombinant Proteins/metabolism , Signal Transduction , Time Factors , Tumor Necrosis Factor-alpha/metabolism
7.
J Invest Dermatol ; 122(1): 209-15, 2004 Jan.
Article in English | MEDLINE | ID: mdl-14962110

ABSTRACT

Vascular endothelial growth factor (VEGF)--a stimulus of angiogenesis--is produced by epidermal keratinocytes, and elevated levels have been found in plaques of psoriasis. Polymorphisms in the VEGF gene regulate production of VEGF. We postulated that patients with psoriasis may have altered systemic expression of VEGF consequent upon programming at the genomic level. We investigated the genetic basis of VEGF expression in patients with type 1 (onset before age 40 y) chronic plaque psoriasis compared to healthy controls and also measured plasma levels of VEGF and its receptors flt-1 and KDR. Patients with severe disease, and those with onset of psoriasis between the ages of 20 and 40 y showed significantly increased frequency of the +405 CC genotype (p=0.04 and p=0.02) and the C allele (p=0.03 and p=0.02), respectively, compared to healthy controls. Plasma levels of VEGF and flt-1 were significantly detectable in patients with psoriasis compared with controls (p<0.001); by contrast, mean plasma levels of KDR in psoriatic patients were comparable with controls. These results suggest that alterations in the biology of VEGF may be involved in the pathogenesis of psoriasis. VEGF, flt-1, and KDR could provide attractive targets for future psoriasis therapy.


Subject(s)
Polymorphism, Single Nucleotide , Psoriasis/genetics , Vascular Endothelial Growth Factor A/genetics , Adolescent , Adult , Age of Onset , Aged , Aged, 80 and over , Extracellular Matrix Proteins/blood , Female , Genotype , Humans , Male , Middle Aged , Psoriasis/blood , Vascular Endothelial Growth Factor A/blood , Vascular Endothelial Growth Factor Receptor-1 , Vascular Endothelial Growth Factor Receptor-2/blood
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