Development of classification criteria for discoid lupus erythematosus: Results of a Delphi exercise.

BACKGROUND: No classification criteria currently exist for discoid lupus erythematosus (DLE), which has led to problematic heterogeneity in both observational and interventional research efforts. OBJECTIVES: We sought to develop DLE classification criteria based on consensus of international expert opinion of relevant stakeholders in the field. METHODS: Using a Delphi consensus process and nominal group techniques, potential items for classification criteria were generated. Experts ranked items in terms of their appropriateness and ability to discriminate DLE from other diagnoses, and items were subsequently eliminated using consensus exercises. RESULTS: A final list of 12 clinical and histopathologic items was generated for potential inclusion into a set of DLE classification criteria through a formal ongoing validation process. LIMITATIONS: The participants are predominantly composed of DLE experts in North America and Europe. CONCLUSION: This work represents a key step toward the development of formal DLE classification criteria.

The link between enthesitis and arthritis in psoriatic arthritis: a switch to a vascular phenotype at insertions may play a role in arthritis development.

OBJECTIVE: Subclinical enthesopathy is recognised in both psoriasis and psoriatic arthritis (PsA). This study used ultrasonography with power Doppler (PD) to test the hypothesis that subclinical enthesopathy in PsA was associated with an 'inflammatory' or vascular phenotype compared to that seen in psoriasis. METHODS: 100 patients with a mean age of 46.3 years (SD 15) (42 with psoriasis and 58 with PsA) and 23 matched healthy controls (HC) from two centres were included. 1230 lower limb entheses were scanned by ultrasonographers blinded to clinical details. Both inflammatory and chronic features of enthesopathy were scored. RESULTS: Psoriasis patients (with or without arthritis) were more likely to express a vascular phenotype, with higher inflammation-related enthesopathy scores than HC (for inflammation p<0.0001, for chronicity p=0.02, for total ultrasound scores p<0.0001). The PsA patients had higher ultrasound enthesopathy scores than psoriasis patients (inflammation p=0.04, chronicity p=0.02) and HC (inflammation p<0.0001, chronicity p=0.003). When symptomatic entheses were excluded, PsA patients still had higher PD scores than psoriasis patients (p=0.003). Doppler positivity in at least one entheseal site was observed more frequently in PsA (21/58, 36.2%) versus psoriasis (4/42, 9.5%; p=0.002). CONCLUSIONS: This study shows that the ultrasound appearances of subclinical enthesitis in psoriasis differ from the subclinical enthesitis in PsA, with PsA patients having more PD. This is suggestive of a more inflammatory or vascular process in PsA, and offers potentially novel insights into the progression from skin to joint disease in psoriasis.

Psoriasis patients with nail disease have a greater magnitude of underlying systemic subclinical enthesopathy than those with normal nails.

OBJECTIVE: Enthesopathy is a major feature of psoriatic arthritis (PsA), which is supported by imaging studies. Given that nail disease often predates PsA and that the nail is directly anchored to entheses, the authors asked whether nail involvement in psoriasis equates with a systemic enthesopathy. METHODS: Forty-six patients with psoriasis (31 with nail disease) and 21 matched healthy controls (HC) were recruited. 804 entheses of upper and lower limbs were scanned by an ultrasonographer blinded to clinical details. RESULTS: Psoriasis patients had higher enthesitis scores than HC (median (range) 21 (0-65) vs 11 (3-39), p=0.005). Enthesopathy scores were higher in patients with nail disease (23 (0-65)) than in patients without nail disease (15 (5-26), p=0.02) and HC (11 (3-39), p=0.003). Inflammation scores of patients with nail disease (13 (0-34)) were higher than patients without nail disease (8 (2-15), p=0.02) and HC (5 (0-19), p<0.001). Modified nail psoriasis severity index scores were correlated to both inflammation (r(2)=0.45, p=0.005) and chronicity scores (r(2)=0.35, p=0.04). No link between the psoriasis area and severity index and enthesitis was evident. CONCLUSION: The link between nail disease and contemporaneous subclinical enthesopathy offers a novel anatomical basis for the predictive value of nail psoriasis for PsA evolution.

Comparison of ALitretinoin with PUVA as the first-line treatment in patients with severe chronic HAnd eczema (ALPHA): study protocol for a randomised controlled trial.

INTRODUCTION: Hand eczema (HE) is one of the most common skin disorders and an important cause for morbidity and occupational disability. The 1-year prevalence of HE is estimated to be up to 10% and it is estimated that 5%-7% of those develop severe chronic HE. However, current clinical evidence is not compelling enough to guide clinical practice. In a survey among 194 UK dermatologists the most frequent first choice approaches were psoralen combined with ultraviolet A (UVA) treatment (PUVA), oral steroids and alitretinoin (AL). When asked which strategy was most efficient for long-term outcome 20% of clinicians indicated they did not know; 43% of clinicians reported AL and 30% reported PUVA. METHODS AND ANALYSIS: ALPHA is a multicentre, open, prospective, two-arm parallel group, randomised controlled trial comparing PUVA and AL with a planned sample size re-estimation. Between 500 and 780 participants will be randomised on a 1:1 basis. The physician's global assessment (PGA) will direct treatment after randomisation, non-responders will be treated according to usual clinical practice; providing valuable pilot data on second line therapeutic approaches to inform future trials.Assessments will be conducted up to 52 weeks post randomisation. The primary outcome measure is the Hand Eczema Severity Index at 12 weeks. Secondary outcome measures include modified Total Lesion Symptom Score, PGA, time to relapse, patient reported outcome measures and DNA extraction and assessment of genetic variants. A substudy on molecular inflammatory mediators will provide information on subgroup specific treatment responses. Photographs will be taken and HE severity assessed by a central review panel. ETHICS AND DISSEMINATION: Ethics approval was obtained from Leeds West Research Ethics Committee (14/YH/1259).Trial results will be disseminated at relevant clinical conferences and societies, published in peer-reviewed journals and through relevant patient groups. TRIAL REGISTRATION NUMBER: ISRCTN80206075.

Linear pitting and splinter haemorrhages are more commonly seen in the nails of patients with established psoriasis in comparison to psoriatic arthritis.

BACKGROUND: Recently the role of several ligament and tendon insertions around the nail matrix and nail plate have been identified as possible contributory factors that explain the higher prevalence of nail involvement in psoriatic arthritis (PsA). The purpose of this study was to determine whether such anatomical factors might also be associated with different patterns of nail involvement in skin psoriasis and PsA. METHODS: A total of 173 patients were recruited: 121 PsA cases and 52 psoriasis cases. All patients had a standardised assessment of the nails for lesions including pitting, splinter haemorrhages and onycholysis. RESULTS: The overall modified Nail Psoriasis Severity Index scores did not differ between the two groups (psoriasis mean 8.5, SD 7.1; PsA mean 8.3, SD 9.4). In the nail matrix, linear pitting appeared to be more common in skin psoriasis (OR 0.27, 95% CI 0.18-0.41). There were no significant differences in the distribution of nail plate abnormalities other than splinter haemorrhages which were more commonly seen in psoriasis cases (OR 0.23, 95% CI 0.14-0.39). CONCLUSION: The pattern of nail disease in psoriasis and PsA differed with respect to the frequency of linear pitting and splinter haemorrhages, with both features occurring more often in psoriasis.

Liver fibrosis in patients with psoriasis and psoriatic arthritis on long-term, high cumulative dose methotrexate therapy.

OBJECTIVES: Dermatologists and rheumatologists have differed in their use of serial liver biopsy and liver function tests (LFT) to monitor the risk of hepatic fibrosis in long-term MTX therapy. It is judged safe to monitor LFT only in RA. Whilst there are few studies in PsA to justify this approach, it is widely used in rheumatology practice. The study aimed to assess prevalence of hepatic fibrosis in both psoriasis and PsA patients on long-term MTX therapy. METHODS: A prospective study of 54 patients with psoriatic disease had a liver biopsy according to dermatology guidelines on long-term MTX treatment with full assessment of risk factors. Previously, monitoring these patients was in accordance with ACR guidelines with 3-monthly LFT. RESULTS: MTX treatment duration was a mean of 6.9 years, with a mean cumulative dose of 4396 mg. There were no cases of advanced fibrosis or of cirrhosis and mild early fibrosis in 11 (22%) patients. The presence of early mild changes was related to the number of risk factors that the patient had for hepatic fibrosis [also the risk factors for non-alcoholic steatohepatitis (NASH)]. Pro-collagen 3 N-terminal peptide (PIIINP) was unhelpful in PsA and frequently elevated despite normal liver biopsy. CONCLUSIONS: Despite other risk factors for NASH, monitoring for hepatic fibrosis using serial liver function and ACR guidelines tests alone as in RA appears safe in psoriasis and PsA. Liver biopsy ought to be considered to assess the liver if LFT are persistently elevated. PIIINP is misleading in active PsA.

Low-dose UVA1 phototherapy for proximal and acral scleroderma in systemic sclerosis.

Previous studies report the benefit of UVA1 phototherapy in treating acrosclerosis in patients with systemic sclerosis. We carried out a retrospective study to examine the effectiveness of UVA1 phototherapy in scleroderma affecting acral and proximal sites in patients with this disease. Patients with systemic sclerosis (diffuse type, n=5; limited type, n=3) underwent low-dose UVA1 radiation (30-40 J/cm(2)) thrice weekly. In all patients skin lesions improved, demonstrated by a fall in the modified Rodnan skin score ranging from 8 to 18 points in diffuse systemic sclerosis and 6 to 10 points in limited disease. This study would suggest that UVA1 phototherapy is effective for scleroderma affecting proximal and acral sites in patients with systemic sclerosis.

Regression of Peripheral Subclinical Enthesopathy in Therapy-Naive Patients Treated With Ustekinumab for Moderate-to-Severe Chronic Plaque Psoriasis: A Fifty-Two-Week, Prospective, Open-Label Feasibility Study.

OBJECTIVE: To investigate whether sonographically determined subclinical enthesopathy in patients with moderate-to-severe psoriasis regresses with the use of ustekinumab therapy for skin disease. METHODS: Seventy-three patients with moderate-to-severe psoriasis, who were not treated with systemic therapy and did not have symptoms of psoriatic arthritis (PsA), and 23 healthy volunteers were screened by ultrasound for subclinical enthesitis. Subsequently, 23 patients with psoriasis whose ultrasound results showed inflammatory changes were treated with ustekinumab for 52 weeks. The evolution of sonographic abnormalities of the upper and lower limb entheses was assessed using an extensive gray-scale and power Doppler (PD) ultrasound protocol at weeks 0, 12, 24, and 52. For each parameter, a gray-scale or PD ultrasound score of >0 was determined to be abnormal, and a summative score based on the Glasgow Ultrasound Enthesitis Scoring System was calculated. RESULTS: Of all the patients with psoriasis screened using ultrasound, 49.3% had at least 1 inflammatory entheseal abnormality. Mean ± SD inflammation scores were higher in the patients with psoriasis compared with the healthy volunteers (9.9 ± 6.6 versus 1.0 ± 1.4). With treatment, the mean inflammation scores decreased significantly by 42.2% from week 0 to week 24 (-4.2 [95% confidence interval -6.3, -2.1]; P < 0.001) and by 47.5% by week 42 (-4.7 [95% confidence interval -7.1, -2.3]; P = 0.001). Entheseal structural abnormalities did not change significantly during treatment. CONCLUSION: Within 12 weeks of treatment, interleukin-12 (IL-12)/IL-23 inhibition for psoriasis appears to suppress subclinical enthesopathy, and the suppression is maintained through week 52. Further longitudinal studies are needed to determine whether therapy initiated for skin disease may prevent the development of PsA.

Plucked hair follicles from patients with chronic discoid lupus erythematosus show a disease-specific molecular signature.

OBJECTIVE: When faced with clinical symptoms of scarring alopecia-the standard diagnostic pathway involves a scalp biopsy which is an invasive and expensive procedure. This project aimed to assess if plucked hair follicles (HFs) containing living epithelial cells can offer a non-invasive approach to diagnosing inflammatory scalp lesions. METHODS: Lesional and non-lesional HFs were extracted from the scalp of patients with chronic discoid lupus erythematosus (CDLE), psoriasis and healthy controls. RNA was isolated from plucked anagen HFs and microarray, as well as quantitative real-time PCR was performed. RESULTS: Here, we report that gene expression analysis of only a small number of HF plucked from lesional areas of the scalp is sufficient to differentiate CDLE from psoriasis lesions or healthy HF. The expression profile from CDLE HFs coincides with published profiles of CDLE from skin biopsy. Genes that were highly expressed in lesional CDLE corresponded to well-known histopathological diagnostic features of CDLE and included those related to apoptotic cell death, the interferon signature, complement components and CD8+ T-cell immune responses. CONCLUSIONS: We therefore propose that information obtained from this non-invasive approach are sufficient to diagnose scalp lupus erythematosus. Once validated in routine clinical settings and compared with other scarring alopecias, this rapid and non-invasive approach will have great potential for paving the way for future diagnosis of inflammatory scalp lesions.

Efalizumab in the treatment of discoid lupus erythematosus.

BACKGROUND: Discoid lupus erythematosus is a chronic inflammatory condition in which the pathogenesis and the role of cell-mediated immunity remains unclear. Currently, the most effective treatments for severe disease are thalidomide, methotrexate, and cyclosporin, although the evidence for this is limited. Efalizumab is a monoclonal antibody directed against CD11a, the alpha-subunit of the leukocyte-functioning antigen 1, with a current license for use in psoriasis. Because discoid lupus erythematosus is known to be predominantly T-cell mediated, our aim was to use efalizumab as a T-cell modulator in patients with recalcitrant disease. OBSERVATIONS: Thirteen patients received efalizumab, with treatment responses varying from good to excellent in 12 of 13 patients. There was a significant reduction in the cutaneous lupus activity and severity score (CLASS) score after therapy with efalizumab (P = .002). CONCLUSIONS: We have presented efalizumab as a novel alternative treatment for patients with difficult discoid lupus erythematosus. The response to treatment in 12 patients was very encouraging, with the mean time to response being 5.5 weeks. However, patient numbers were small, and many remain in the early stages of therapy. A prospective randomized study with a long-term follow-up is required, especially in light of recent findings to evaluate both the effectiveness and safety profile of this monoclonal antibody.

Treatment of refractory subacute cutaneous lupus erythematosus with efalizumab.

We report the case of a 47-year-old woman who first presented with erythematous plaques on the upper portion of her right arm, which developed into an annular eruption involving the face, upper portion of the trunk, and limbs in a predominantly photosensitive distribution. Findings from histopathologic evaluation of a lesion from her arm were consistent with the clinical diagnosis of SCLE. After years of unsuccessful treatment with conventional medications for SCLE, she began therapy with efalizumab and experienced dramatic improvement in her cutaneous lesions after 6 weeks.

Halo naevi, vitiligo and diffuse alopecia areata associated with tocilizumab therapy.

We present a follow-up case report of a 33-year-old lady with juvenile onset arthritis who developed halo naevi while on treatment with tocilizumab. This case report describes the development of halo naevi, vitiligo and diffuse alopecia areata associated with tocilizumab therapy following infection with Methicillin-resistant Staphylococcus aureus (MRSA) and Panton-Valentine leukocidin positivity. This is the first case that describes these events and supports previous theories on cellular and humoral immunity as causative factors. The regression of melanocytes during treatment with tocilizumab could also implicate IL-6 and sIL-6R as future targets in the treatment of melanoma through its direct effect of melanocytic cytotoxicity, which supports previous studies.

Developing classification criteria for discoid lupus erythematosus: an update from the World Congress of Dermatology 2015 meeting.

Currently, no standardized classification criteria exist for cutaneous lupus erythematosus. With increased interest in studying cutaneous lupus erythematosus, specifically discoid lupus erythematosus, it is our aim to apply previously adopted methods from rheumatology to dermatologic diseases to develop feasible, validated, and standardized classification criteria useful in both academic and community practice. Here we report the progress to date to define discoid lupus erythematosus using clinical, histopathologic, and serologic features by means of a Delphi method-using a series of iterative questionnaires sent to expert stakeholders. We present specific updates from the World Congress of Dermatology 2015 meeting, at which a nominal group of expert stakeholders met to discuss the results of round 1 of the Delphi process to further clarify and harmonize specific classification items for inclusion into round 2.

A randomised, controlled trial of a 4% cutaneous emulsion of sodium cromoglicate in treatment of atopic dermatitis in children.

INTRODUCTION: Atopic dermatitis (AD) is a chronic inflammatory skin disease. Sodium cromoglicate (SCG) is a chromone with anti-inflammatory, anti-itch and anti-allergic activity. This trial is a 12-week comparison (RCT) of a 4% SCG cutaneous emulsion with its vehicle in AD. MATERIALS AND METHODS: 208 children aged 2-12 years participated, 104 in each group. The primary endpoint was change in SCORAD score. Secondary endpoints included SASSAD score, topical steroid usage and global assessments. RESULTS: SCORAD was reduced by 28% (SCG group) and by 19% (vehicle): difference was statistically significant (p = 0.03) after 8 weeks and nearly significant (p = 0.09) after 12. A similar result occurred in SASSAD (p = 0.001 at 8 weeks). In subjects without major protocol deviations (SCG-64, vehicle-63), difference in SCORAD remained significant at 12 weeks (p = 0.04). Weight of topical steroids reduced in both groups: -0.60 ± 1.3 g/day (35%), SCG and -0.05 ± 1.1 g/day vehicle (p = 0.04). Treatment success, defined as investigator global opinion graded very or moderately effective, was significantly more frequent in SCG group (p = 0.025). Application site discomfort reported by 12.5% of subjects in SCG group and 16.5% in vehicle group. CONCLUSIONS: SCG 4% cutaneous emulsion provides an effective, well-tolerated, steroid-sparing treatment for AD in children.

Objective assessment of compliance with psoriasis treatment.

OBJECTIVE: To assess patient compliance with psoriasis treatment. DESIGN: Open prospective study. Patients with psoriasis were examined and completed a brief medical and social history, a compliance assessment sheet, and the Dermatology Life Quality Index (DLQI). Patients were reexamined at 3 months, and their actual treatment use was assessed and compared with the expected use. Medication adherence was assessed by direct questioning. SETTING: Dermatology outpatient clinic. PATIENTS: Two hundred ninety-four patients fulfilled the inclusion criteria, and 201 completed the study. MAIN OUTCOME MEASURE: Adherence with topical and oral therapies, using objective and self-reporting methods and description of factors affecting compliance. RESULTS: The overall mean +/- SD medication adherence was 60.6% +/- 33.0% (range, 0%-169%). The mean +/- SD DLQI in the study was 17.4 +/- 8.9 (range, 0-30). There was a highly significant negative correlation (r = -0.92) between these variables. Being female, married, employed, and not paying for prescriptions were characteristics associated with increased medication adherence and a lower DLQI. Medication adherence was greater for topical or combined therapy, for once-daily treatment, and for first-time use of treatment. Adverse effects reduced compliance. The major reasons for missing treatment were drinking alcohol, being fed up, forgetfulness, and being too busy. Patients with facial disease and with more extensive disease had lower medication adherence. CONCLUSIONS: A range of disease-related and social factors may affect compliance with psoriasis treatment. The inversely proportional relationship between DLQI and medication adherence reflects the interaction of physical and psychological factors, as well as perceived treatment failure.