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

Development and testing of new candidate psoriatic arthritis screening questionnaires combining optimal questions from existing tools

Objective: Several questionnaires have been developed to screen for psoriatic arthritis (PsA), but head-to-head studies have found limitations. This study aimed to develop new questionnaires encompassing the most discriminative questions from existing instruments.<p></p> Methods: Data from the CONTEST study, a head-to-head comparison of 3 existing questionnaires, were used to identify items with a Youden index score of ≥0.1. These were combined using 4 approaches: CONTEST (simple additions of questions), CONTESTw (weighting using logistic regression), CONTESTjt (addition of a joint manikin), and CONTESTtree (additional questions identified by classification and regression tree [CART] analysis). These candidate questionnaires were tested in independent data sets.<p></p> Results: Twelve individual questions with a Youden index score of ≥0.1 were identified, but 4 of these were excluded due to duplication and redundancy. Weighting for 2 of these questions was included in CONTESTw. Receiver operating characteristic (ROC) curve analysis showed that involvement in 6 joint areas on the manikin was predictive of PsA for inclusion in CONTESTjt. CART analysis identified a further 5 questions for inclusion in CONTESTtree. CONTESTtree was not significant on ROC curve analysis and discarded. The other 3 questionnaires were significant in all data sets, although CONTESTw was slightly inferior to the others in the validation data sets. Potential cut points for referral were also discussed.<p></p> Conclusion: Of 4 candidate questionnaires combining existing discriminatory items to identify PsA in people with psoriasis, 3 were found to be significant on ROC curve analysis. Testing in independent data sets identified 2 questionnaires (CONTEST and CONTESTjt) that should be pursued for further prospective testing

Report from the Annual Conference of the British Society of Echocardiography, November 2017, Edinburgh International Conference Centre, Edinburgh

No abstract available

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

I-123 MIBG cardiac uptake measurements: limitations of collimator choice and scatter correction in the clinical context

OBJECTIVE: Low uptake of metaiodobenzylguanidine (MIBG) in patients with heart failure generally indicates poor prognosis. Our objective was to determine the best method for calculating I-123 MIBG uptake. MIBG uptake as a percentage of the injected dose is presented as an alternative method for serial assessment. METHODS: Patients with chronic heart failure were imaged with I-123 MIBG with both a medium-energy (ME) collimator and a low-energy high-sensitivity (LEHS) collimator. Scatter correction was used to correct the LEHS images. Heart-to-mediastinal (H/M) ratio and the percentage of myocardial uptake of MIBG were obtained. RESULTS: Mean H/M ratios for the ME images, LEHS images and scatter-corrected LEHS images were 2.45+/-0.61, 2.22+/-0.47 and 2.51+/-0.62, respectively. Mean H/M ratio was significantly different among all the three sets (P<0.001) of images. The average difference in H/M ratios between the ME images and LEHS images was lower when scatter correction was applied (4.95% vs. 9.79%). The error in calculating the myocardial uptake as a percentage of the injected dose was significantly lower than the error in calculating H/M ratio (0.2 vs.10.2% LEHS; 0.3 vs.16.0% ME; 0.2 vs.11.8% LEHS scatter corrected). CONCLUSION: For quantitative assessment of H/M ratio in I-123 MIBG imaging a LEHS collimator can be used in place of a ME collimator to achieve better counting statistics, but scatter correction must be used. The calculation of the myocardial uptake as a percentage of the injected dose has potential as an alternative method of measurement, particularly for serial assessment

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

Efficacy and safety of pimecrolimus cream in the long-term management of atopic dermatitis in children

OBJECTIVE: Pimecrolimus cream (SDZ ASM 981), a nonsteroid inhibitor of inflammatory cytokines, is effective in atopic dermatitis (AD). We assessed whether early treatment of AD signs/symptoms with pimecrolimus could influence long-term outcome by preventing disease flares. METHODS: Early intervention with pimecrolimus was compared with a conventional AD treatment strategy (ie, emollients and topical corticosteroids). In this 1-year, controlled, double-blind study, 713 AD patients (2-17 years) were randomized 2:1 to a pimecrolimus-based or conventional regimen. Both groups used emollients for dry skin. Early AD signs/symptoms were treated with pimecrolimus cream or, in the conventional treatment group, vehicle to prevent progression to flares. If flares occurred, moderately potent topical corticosteroids were mandated. The primary efficacy endpoint was ranked flares at 6 months. Safety was monitored clinically, and a skin recall-antigen test was performed at study completion. RESULTS: BASELINE CHARACTERISTICS OF THE PATIENTS: The mean age for both groups was approximately 8 years, and the majority of patients had moderate disease at baseline. PATIENT FOLLOW-UP AND EXPOSURE TO STUDY MEDICATION: The mean duration of follow-up (+/-standard error) was 303.7 (+/-5.30) days in the pimecrolimus group and 235.2 (+/-9.40) days in the control group. The discontinuation rate was significantly higher in the control group than in the pimecrolimus group (51.5% vs 31.6% at 12 months), and proportionately more patients with severe or very severe disease discontinued in the control group. The main reason for the higher discontinuation rate in the control group was unsatisfactory therapeutic effect (30.4% vs 12.4%). This resulted in a substantially higher mean number of study medication treatment days in the pimecrolimus group compared with the control group: 211.9 (69.8% of study days) versus 156.0 (66.3% of study days). Of those patients who completed 12 months on study, 14.2% and 7.0% of patients in the pimecrolimus and vehicle groups, respectively, used study medication continuously. EFFICACY: Patients in the pimecrolimus group experienced significantly fewer AD flares than those in the control group, according to the primary efficacy analysis on ranked flares of AD (Van Elteren test). The proportion of patients who completed 6 or 12 months with no flares was approximately twice as high in the pimecrolimus group compared with control (61.0% vs 34.2% at 6 months; 50.8% vs 28.3% at 12 months). Fewer flares were observed in the pimecrolimus group regardless of baseline disease severity, so even severe patients derived benefit from the treatment. The analysis of time to first flare showed that treatment with pimecrolimus was associated with a significantly longer flare-free period (log- rank test). Covariate analysis indicated a statistically significant effect on time to first flare of baseline Eczema Area and Severity Index score, and whether patients had "severe" or "very severe" disease at baseline according to the Investigators' Global Assessment, although patients in all baseline disease severity subgroups benefited from treatment. Age had no significant effect. Fewer patients in the pimecrolimus group required topical corticosteroid therapy compared with control (35.0% vs 62.9% at 6 months; 42.6% vs 68.4% at 12 months), and patients in the pimecrolimus group spent fewer days on topical corticosteroid therapy (57.4% vs 31.6% [pimecrolimus vs control, respectively] spent 0 days on topical corticosteroid therapy, 17.1% vs 27.5% 1-14 days, and 25.5% vs 41.0% >14 days over the 12 months of the study). This steroid-sparing effect of pimecrolimus was evident despite pimecrolimus-treated patients being on study longer than patients in the control group. The average proportion of study days spent on second-line corticosteroids was 4.08% in the pimecrolimus group and 9.10% in the control group. Analysis of Eczema Area and Severity Index over time showed significantly lower median scores, thus indicating better disease control in the pimecrolimus group compared with the control group. Similar results were obtained from analysis of the Investigators' Global Assessment (not shown). The treatment groups were well balanced with respect to the number of patients using antihistamines during the study (57.2% vs 62.9%, pimecrolimus vs control, respectively). SAFETY: There were no appreciable differences between treatment groups in the overall incidence of adverse events. The most frequent adverse events were common childhood infections and ailments, including nasopharyngitis, headache, and cough. The incidence of suspected drug-related adverse events was not significantly different in the pimecrolimus group (24.7% vs 18.7%--pimecrolimus vs control), and the incidence of serious adverse events was low (8.3% vs 5.2%--pimecrolimus vs control). Life-table analysis of incidence of adverse events revealed no significant differences between the treatment groups, except for cough. Local tolerability was good in both treatment groups. The most common application site reaction reported was sensation of burning (10.5% vs 9.3%--pimecrolimus vs control). There were no major differences between treatment groups in the duration or severity of application site reactions, most of which were mild-to-moderate and transient, occurring within the first week of treatment. Skin infections were reported in both groups. There were no between-group differences in the life-table analysis of time to first occurrence of bacterial skin infections nor in the adjusted incidence of bacterial skin infections. Although there were no significant differences between treatment groups in the incidence of individual viral skin infections, the incidence of grouped viral skin infections (12.4% vs 6.3%--pimecrolimus vs control) showed a slightly higher incidence in the pimecrolimus group. Laboratory values and vital signs showed no significant between-group differences. There were no significant differences between treatment groups in response to recall antigens in those patients who remained on study for 12 months. CONCLUSIONS: Treatment of early AD signs/symptoms with pimecrolimus was effective in preventing progression to flares in more than half the patients, reducing or eliminating the need for topical corticosteroids. The benefits were consistently seen at 6 months across important disease severity subgroups and with respect to the various predefined efficacy endpoints. Furthermore, these benefits were sustained for 12 months, providing evidence that long-term treatment with pimecrolimus leads to better control of AD. Treatment with pimecrolimus was well tolerated and was not associated with clinically relevant adverse events compared with the conventional treatment group. The results reported here offer the prospect of effective long-term management of AD with reduced need for topical corticosteroid