Current prescribing for pyoderma gangrenosum in the UK and access to biologic medications: Results from a UK Dermatology Clinical Trials Network (UKDCTN) survey of UK Dermatologists.

Pyoderma gangrenosum (PG) is an ulcerative inflammatory disorder affecting the lower legs in 80% of cases. The use of biologic medications to treat PG is increasing although there is a limited evidence base to guide treatment choices. In some health systems, such as the UK NHS, limitations are placed on biologic prescribing for PG leading to wide variations in prescribing. A survey of mainly UK clinicians showed that prednisolone remains the first line treatment for PG (90%). Biologics have been used by 66% of clinicians as second line therapy but 19% have had prescribing requests declined. Further research is needed to determine optimal treatment strategies for PG.

TGFß2 Induces the Soluble Isoform of CTLA-4 - Implications for CTLA-4 Based Checkpoint Inhibitor Antibodies in Malignant Melanoma.

Malignant melanoma is an aggressive form of cancer, which can be treated with anti-CTLA-4 and anti-PD-1 checkpoint inhibitor antibodies but while anti-CTLA-4 antibodies have clear benefits for some patients with melanoma, productive responses are difficult to predict and often associated with serious immune related adverse events. Antibodies specific to CTLA-4 bind two major isoforms of CTLA-4 in humans, the receptor isoform and a second naturally secretable, soluble isoform - sCTLA-4. The primary aim here was to examine the effect of selectively blocking the function of sCTLA-4 on in vitro immune responses from volunteer healthy or melanoma patient PBMC samples. Addition of recombinant sCTLA-4 to healthy PBMC samples demonstrated sCTLA-4 to have immunosuppressive capacity comparable to recombinant CTLA4-Ig, partially reversible upon antibody blockade. Further, we identified a mechanistic relationship where melanoma patient TGFß2 serum levels correlated with sCTLA-4 levels and provided the basis for a novel protocol to enhance sCTLA-4 production and secretion by T cells with TGFß2. Finally, a comparison of selective antibody blockade of sCTLA-4 demonstrated that both healthy and melanoma patient effector cytokine responses can be significantly increased. Overall, the data support the notion that sCTLA-4 is a contributory factor in cancer immune evasion.

Risk of Serious Infection in Patients with Psoriasis Receiving Biologic Therapies: A Prospective Cohort Study from the British Association of Dermatologists Biologic Interventions Register (BADBIR).

Serious infection is a concern for patients with psoriasis receiving biologic therapies. We assessed the risk of serious infections for biologics used to treat psoriasis by comparison with a cohort receiving non-biologic systemic therapies in a propensity score-weighted Cox proportional hazards model using data from the British Association of Dermatologists Biologic Interventions Register. Overall, 1,352; 3,271; and 994 participants were included in the etanercept, adalimumab, ustekinumab cohorts, respectively, and 3,421 participants were in the non-biologic cohort. A total of 283 patients had a serious infection; the incidence rates with 95% confidence intervals (CI) per 1,000 person-years were as follows: non-biologic, 14.2 (11.5-17.4); etanercept, 15.3 (11.6-20.1); adalimumab, 13.9 (11.4-16.6); and ustekinumab, 15.1 (10.8-21.1). No significant increases in the risk of serious infection were observed for etanercept (hazard ratio [HR] = 1.10, 95% CI = 0.75-1.60), adalimumab (HR = 0.93, 95% CI = 0.69-1.26), or ustekinumab (HR = 0.92, 95% CI = 0.60-1.41) compared with non-biologic systemic therapies or methotrexate-only (etanercept: HR = 1.47, 95% CI = 0.95-2.28; adalimumab: HR = 1.26, 95% CI = 0.86-1.84; ustekinumab: HR = 1.22, 95% CI = 0.75-1.99). The risk of serious infection should not be a key discriminator for patients and clinicians when choosing between non-biologic systemic therapies, etanercept, adalimumab, and ustekinumab for the treatment of psoriasis.

Is speed of healing a good predictor of eventual healing of pyoderma gangrenosum?

BACKGROUND: Pyoderma gangrenosum is a rare inflammatory skin condition. Two prospective studies have evaluated treatments for pyoderma gangrenosum using a primary outcome of healing speed at 6 weeks. OBJECTIVE: Using data from both studies we assessed the predictive value of 3 early predictors for healing at 6 months: speed of healing, Investigator Global Assessment (IGA), and resolution of inflammation, recorded at 2 and 6 weeks. METHODS: Logistic regression models were applied and the effectiveness of the 3 measures was assessed through estimating the positive and negative predictive values and the area under the receiver operating characteristic curve. RESULTS: The positive and negative predictive value at 6 weeks were, respectively, 63.5% (95% confidence interval [CI] 52.4%-73.7%) and 74.6% (95% CI 62.5%-84.5%) for speed of healing; 80% (95% CI 68.7%-88.6%) and 74.2% (95% CI 64.1%-82.7%) for IGA; and 72.1% (95% CI 59.9%-82.3%) and 68.1% (95% CI 57.7%-77.3%) for resolution of inflammation. IGA had the best combined positive predictive value, negative predictive value, and area under the receiver operating characteristic curve at 2 and 6 weeks. LIMITATIONS: We were limited by data available from existing datasets. CONCLUSION: Speed of healing, IGA, and resolution of inflammation were all shown to be good predictors of eventual healing of pyoderma gangrenosum.

Clinical outcomes and response of patients applying topical therapy for pyoderma gangrenosum: A prospective cohort study.

BACKGROUND: Pyoderma gangrenosum (PG) is an uncommon dermatosis with a limited evidence base for treatment. OBJECTIVE: We sought to estimate the effectiveness of topical therapies in the treatment of patients with PG. METHODS: This was a prospective cohort study of UK secondary care patients with a clinical diagnosis of PG that was suitable for topical treatment (recruited between July 2009 and June 2012). Participants received topical therapy after normal clinical practice (primarily topical corticosteroids [classes I-III] and tacrolimus 0.03% or 0.1%). The primary outcome was speed of healing at 6 weeks. Secondary outcomes included the following: proportion healed by 6 months; time to healing; global assessment; inflammation; pain; quality of life; treatment failure; and recurrence. RESULTS: Sixty-six patients (22-85 years of age) were enrolled. Clobetasol propionate 0.05% was the most commonly prescribed therapy. Overall, 28 of 66 (43.8%) ulcers healed by 6 months. The median time to healing was 145 days (95% confidence interval, 96 days to ∞). Initial ulcer size was a significant predictor of time to healing (hazard ratio, 0.94 [95% confidence interval, 0.88-1.00); P = .043). Four patients (15%) had a recurrence. LIMITATIONS: Our study did not include a randomized comparator. CONCLUSION: Topical therapy is potentially an effective first-line treatment for PG that avoids the possible side effects associated with systemic therapy. It remains unclear whether more severe disease will respond adequately to topical therapy alone.

Interventions for hidradenitis suppurativa.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition characterised by recurrent painful boils in flexural sites, such as the axillae and groin, that affects about 1% of the population, with onset in early adulthood. OBJECTIVES: To assess the effects of interventions for HS in people of all ages. SEARCH METHODS: We searched the following databases up to 13 August 2015: the Cochrane Skin Group Specialised Register, CENTRAL in the Cochrane Library (Issue 7, 2015), MEDLINE (from 1946), EMBASE (from 1974), and LILACS (from 1982). We also searched five trials registers and handsearched the conference proceedings of eight dermatology meetings. We checked the reference lists of included and excluded studies for further references to relevant trials. SELECTION CRITERIA: Randomised controlled trials (RCTs) of all interventions for hidradenitis suppurativa. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study eligibility and methodological quality and performed data extraction. Our primary outcomes were quality of life, measured by a validated dermatology-specific scale, and adverse effects of the interventions. MAIN RESULTS: Twelve trials, with 615 participants, met our inclusion criteria. The median number of participants in each trial was 27, and median trial duration was 16 weeks. The included studies were conducted over a 32-year time period, from 1983 to 2015. A single RCT that was underpowered to detect clinically meaningful differences investigated most interventions.There were four trials of anti-TNF-α (tumour necrosis factor-alpha) therapies, which included etanercept, infliximab, and adalimumab. Adalimumab 40 mg weekly improved the Dermatology Life Quality Index (DLQI) score in participants with moderate to severe HS by 4.0 points relative to placebo (95% confidence interval (CI) -6.5 to -1.5 points), an effect size approximately equal to the DLQI minimal clinically important difference. We reduced the evidence quality to 'moderate' because the effect size was based on the results of only one study. In a meta-analysis of two studies with 124 participants, standard dose adalimumab 40 mg every other week was ineffective compared with placebo (moderate quality evidence). In a smaller study of 38 participants, of whom only 33 provided efficacy data, infliximab 5 mg/kg treatment improved DLQI by 8.4 DLQI points after eight weeks. Etanercept 50 mg twice weekly was well tolerated but ineffective.In a RCT of 200 participants, no difference was found in surgical complications (week one: risk ratio (RR) 0.78, 95% CI 0.58 to 1.05, moderate quality evidence) or risk of recurrence (after three months: RR 0.96, 95% CI 0.68 to 1.34, moderate quality evidence) in those randomised to receive a gentamicin-collagen sponge prior to primary closure compared with primary closure alone.RCTs of other interventions, including topical clindamycin 1% solution; oral tetracycline; oral ethinylestradiol 50 mcg with either cyproterone acetate 50 mg or norgestrel 500 mcg; intense pulsed light; neodymium-doped yttrium aluminium garnet (Nd:YAG) laser; methylene blue gel photodynamic therapy; and staphage lysate, were relatively small studies, preventing firm conclusions due to imprecision. AUTHORS' CONCLUSIONS: Many knowledge gaps exist in RCT evidence for HS. Moderate quality evidence exists for adalimumab, which improves DLQI score when 40 mg is given weekly, twice the standard psoriasis dose. However, the 95% confidence interval includes an effect size of only 1.5 DLQI points, which may not be clinically relevant, and the safety profile of weekly dosing has not been fully established. Infliximab also improves quality of life, based on moderate quality evidence.More RCTs are needed in most areas of HS care, particularly oral treatments and the type and timing of surgical procedures. Outcomes should be validated, ideally, including a minimal clinically important difference for HS.

Comparison of the two most commonly used treatments for pyoderma gangrenosum: results of the STOP GAP randomised controlled trial.

OBJECTIVE: To determine whether ciclosporin is superior to prednisolone for the treatment of pyoderma gangrenosum, a painful, ulcerating skin disease with a poor evidence base for management. DESIGN: Multicentre, parallel group, observer blind, randomised controlled trial. SETTING: 39 UK hospitals, recruiting from June 2009 to November 2012. PARTICIPANTS: 121 patients (73 women, mean age 54 years) with clinician diagnosed pyoderma gangrenosum. Clinical diagnosis was revised in nine participants after randomisation, leaving 112 participants in the analysis set (59 ciclosporin; 53 prednisolone). INTERVENTION: Oral prednisolone 0.75 mg/kg/day compared with ciclosporin 4 mg/kg/day, to a maximum dose of 75 and 400 mg/day, respectively. MAIN OUTCOME MEASURES: The primary outcome was speed of healing over six weeks, captured using digital images and assessed by blinded investigators. Secondary outcomes were time to healing, global treatment response, resolution of inflammation, self reported pain, quality of life, number of treatment failures, adverse reactions, and time to recurrence. Outcomes were assessed at baseline and six weeks and when the ulcer had healed (to a maximum of six months). RESULTS: Of the 112 participants, 108 had complete primary outcome data at baseline and six weeks (57 ciclosporin; 51 prednisolone). Groups were balanced at baseline. The mean (SD) speed of healing at six weeks was -0.21 (1.00) cm(2)/day in the ciclosporin group compared with -0.14 (0.42) cm(2)/day in the prednisolone group. The adjusted mean difference showed no between group difference (0.003 cm(2)/day, 95% confidence interval -0.20 to 0.21; P=0.97). By six months, ulcers had healed in 28/59 (47%) participants in the ciclosporin group compared with 25/53 (47%) in the prednisolone group. In those with healed ulcers, eight (30%) receiving ciclosporin and seven (28%) receiving prednisolone had a recurrence. Adverse reactions were similar for the two groups (68% ciclosporin and 66% prednisolone), but serious adverse reactions, especially infections, were more common in the prednisolone group. CONCLUSION: Prednisolone and ciclosporin did not differ across a range of objective and patient reported outcomes. Treatment decisions for individual patients may be guided by the different side effect profiles of the two drugs and patient preference. Trial registration Current Controlled Trials ISRCTN35898459.

Differential Drug Survival of Biologic Therapies for the Treatment of Psoriasis: A Prospective Observational Cohort Study from the British Association of Dermatologists Biologic Interventions Register (BADBIR).

Drug survival reflects a drug's effectiveness, safety, and tolerability. We assessed the drug survival of biologics used to treat psoriasis in a prospective national pharmacovigilance cohort (British Association of Dermatologists Biologic Interventions Register (BADBIR)). The survival rates of the first course of biologics for 3,523 biologic-naive patients with chronic plaque psoriasis were compared using survival analysis techniques and predictors of discontinuation analyzed using a multivariate Cox proportional hazards model. Data for patients on adalimumab (n=1,879), etanercept (n=1,098), infliximab (n=96), and ustekinumab (n=450) were available. The overall survival rate in the first year was 77%, falling to 53% in the third year. Multivariate analysis showed that female gender (hazard ratio (HR) 1.22; 95% confidence interval (CI): 1.09-1.37), being a current smoker (HR 1.19; 95% CI: 1.03-1.38), and a higher baseline dermatology life quality index (HR 1.01; 95% CI: 1.00-1.02) were predictors of discontinuation. Presence of psoriatic arthritis (HR 0.82; 95% CI: 0.71-0.96) was a predictor for drug survival. As compared with adalimumab, patients on etanercept (HR 1.63; 95% CI: 1.45-1.84) or infliximab (HR 1.56; 95% CI: 1.16-2.09) were more likely to discontinue therapy, whereas patients on ustekinumab were more likely to persist (HR 0.48; 95% CI: 0.37-0.62). After accounting for relevant covariates, ustekinumab had the highest first-course drug survival. The results of this study will aid clinical decision making when choosing biologic therapy for psoriasis patients.

Evaluation of the Efficacy, Safety, and Tolerability of 3 Dose Regimens of Topical Sodium Nitrite With Citric Acid in Patients With Anogenital Warts: A Randomized Clinical Trial.

IMPORTANCE: Anogenital warts are a common disorder associated with significant physical and mental distress and a substantial cause of health care costs. OBJECTIVE: To assess the efficacy of the topical application of nitric oxide delivered using acidified nitrite. DESIGN, SETTING, AND PARTICIPANTS: A multicenter, randomized, controlled, dose-ranging clinical trial was conducted in European genitourinary medicine clinics between December 20, 2001, and January 14, 2003. Analysis was by intent to treat for all individuals initiating therapy. Participants included male and female volunteers older than 18 years with between 2 and 50 external anogenital warts. A total of 299 individuals from 40 centers were randomized to a control arm and a treatment arm that received 3 doses of acidified nitrite applied topically for 12 weeks with an additional 12 weeks of follow-up, with the final follow-up visit on January 14, 2003. INTERVENTIONS: Placebo nitrite cream and placebo citric acid cream were applied twice daily. Active treatment was divided as low dose (sodium nitrite, 3%, with citric acid, 4.5%, creams applied twice daily), middle dose (sodium nitrite, 6%, with citric acid, 9%, creams applied once daily at night, with placebo applied in the morning), and high dose (sodium nitrite, 6%, with citric acid, 9%, creams applied twice daily). MAIN OUTCOMES AND MEASURES: The primary outcome was proportion of patients with complete clinical clearance of target warts; secondary outcomes were reduction in target wart area and safety. RESULTS: Complete clinical clearance at 12 weeks occurred in 10 of 74 patients (14%; 95% CI, 6%-21%) with placebo; 11 of 72 (15%; 95% CI, 7%-24%) with low-dose treatment; 17 of 74 (23%; 95% CI, 13%-33%) with middle-dose treatment; and 22 of 70 (31%; 95% CI, 21%-42%) with high-dose treatment (P = .01). Reduction in target wart area, time to clearance, and patient and investigator assessments supported the superiority of the high-dose therapy vs placebo. There were no systemic or serious adverse events associated with treatment. However, there was a dose-related increase in itching, pain, edema, and staining of the anogenital skin associated with the active treatment. Overall, 21 patients withdrew from active treatment because of adverse events compared with none using placebo. CONCLUSIONS AND RELEVANCE: Use of sodium nitrite, 6%, with citric acid, 9%, twice daily is more effective than placebo in the treatment of anogenital warts. Treatment was associated with local irritant adverse effects. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02015260.

Treatment of acne in children.

Acne is a common skin condition in adolescents. It is not uncommon in childhood and it persists into adulthood. A broad range of acne treatments are available and have been shown to be safe and effective in adolescents and adults. However, there is limited literature regarding acne treatment in childhood and its available therapeutic options. It seems reasonable to extrapolate findings of the various studies reported on treatment of acne in the adolescent and adult age group, with the exclusion of the use of tetracycline derivatives. As clinicians, we must be more familiar with the clinical presentation of acne and available treatment options in our younger patients. Early recognition of acne with prompt and appropriate initiation of therapy in childhood will help prevent severe scarring in children.

The management of acne vulgaris in pregnancy.

Acne vulgaris is a common condition in adolescence and also for many women of childbearing age. The management of acne in pregnancy is complicated by the lack of clinical studies and pharmacokinetic data in this patient population and safety concerns regarding retinoid use in pregnancy. Of primary concern to both patients and clinicians is the safety profile of medications used during pregnancy. This review seeks to clarify what management options are available to treat acne during pregnancy and what data are available to guide decision making. Topical treatments are considered the safest option during pregnancy. They have the best safety profile and minimize the levels of systemic absorption, and therefore the least risk of fetal exposure. If these are applied properly with a strong emphasis on adherence, excellent results can be achieved.

Topical tacrolimus 0.1% ointment for treatment of cutaneous Crohn's Disease.

BACKGROUND: Cutaneous Crohn's Disease is a notoriously difficult condition to treat and causes significant morbidity, impacting heavily on quality of life. This is the first study in adults examining the effect of topical tacrolimus on the different cutaneous manifestations of Crohn's Disease. METHODS: This open label observational study of 20 patients with heterogeneous forms of cutaneous Crohn's disease used topical tacrolimus 0.1% ointment once daily to affected areas for 12 weeks with a maximal total dose of 90g. Therapy was stopped at 12 weeks to assess whether the condition relapsed. Thereafter relapsing patients optionally continued an open label extension of topical tacrolimus therapy and were observed for a total of 12 months. RESULTS: Of seventeen patients completing the twelve-week study, fifteen improved using a specifically designed physicians' global severity scale. One patient cleared, four showed a pronounced improvement (51-75%) and ten demonstrated a mild (1-25%) or moderate improvement (25-50%) in twelve weeks. Over twelve months eleven patients remained in the study, nine of which improved, one cleared and one showed no change. Perineal disease responded better with two out of twelve clearing, four showing pronounced benefit and four mild to moderate improvement. Long-term application of 0.1% tacrolimus applied to broken skin and mucosa was safe and serum levels of tacrolimus were undetectable in all subjects throughout the study. CONCLUSION: 0.1% tacrolimus ointment was safe and effective in treating cutaneous manifestations of Crohn's disease, particularly perineal disease and pyoderma gangrenosum, yet it seldom cleared the condition. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Protocol Registration System ID: 33000332.

Factors affecting adherence to treatment of psoriasis: comparing biologic therapy to other modalities.

OBJECTIVES: This study evaluated self-reported patient adherence to different types of treatment in psoriasis and factors that affect adherence. PATIENTS AND METHODS: Patients attending a Dermatology Department for treatments of psoriasis completed a questionnaire about adherence to each of their therapies, Self-assessed Psoriasis Area and Severity Index (SAPASI) and Dermatology Life Quality Index (DLQI). RESULTS: Hundred and six patients participated, 98 on topical treatments, 43 on oral systemic therapies, 39 on phototherapy and 29 were on biologic therapies. The overall rate of self-reported treatment adherence was 85.8%. There was a significant relationship between the types of treatment (topical, oral systemic, phototherapy and biologic therapy) and the number of combinations of treatments and adherence. Adherence ranked significantly better on biologic therapies 100%, followed by oral therapy 96%, phototherapy 93% and then topical therapy 75%. Being too busy, being fed up and cigarette smoking were associated with reduced adherence. About 56.8% of patients reported that messiness of treatment prevented them from adhering. Patients with mild psoriasis and those with DLQI of 5 or less adhered less to topical therapy. CONCLUSIONS: There is a significant relationship between the types of treatment (topical, oral systemic, phototherapy and biologic therapy) and the number of combinations of treatments and adherence.

UK Dermatology Clinical Trials Network's STOP GAP trial (a multicentre trial of prednisolone versus ciclosporin for pyoderma gangrenosum): protocol for a randomised controlled trial.

BACKGROUND: Pyoderma gangrenosum (PG) is a rare inflammatory skin disorder characterised by painful and rapidly progressing skin ulceration. PG can be extremely difficult to treat and patients often require systemic immunosuppression. Recurrent lesions of PG are common, but the relative rarity of this condition means that there is a lack of published evidence regarding its treatment. A systematic review published in 2005 found no randomised controlled trials (RCTs) relating to the treatment of PG. Since this time, one small RCT has been published comparing infliximab to placebo, but none of the commonly used systemic treatments for PG have been formally assessed. The UK Dermatology Clinical Trials Network's STOP GAP Trial has been designed to address this lack of trial evidence. METHODS: The objective is to assess whether oral ciclosporin is more effective than oral prednisolone for the treatment of PG. The trial design is a two-arm, observer-blind, parallel-group, randomised controlled trial comparing ciclosporin (4 mg/kg/day) to prednisolone (0.75 mg/kg/day). A total of 140 participants are to be recruited over a period of 4 years, from up to 50 hospitals in the UK and Eire. Primary outcome of velocity of healing at 6 weeks is assessed blinded to treatment allocation (using digital images of the ulcers). Secondary outcomes include: (i) time to healing; (ii) global assessment of improvement; (iii) PG inflammation assessment scale score; (iv) self-reported pain; (v) health-related quality of life; (vi) time to recurrence; (vii) treatment failures; (viii) adverse reactions to study medications; and (ix) cost effectiveness/utility. Patients with a clinical diagnosis of PG (excluding granulomatous PG); measurable ulceration (that is, not pustular PG); and patients aged over 18 years old who are able to give informed consent are included in the trial. Randomisation is by computer generated code using permuted blocks of randomly varying size, stratified by lesion size, and presence or absence of underlying systemic disease (for example, rheumatoid arthritis).Patients who require topical therapy are asked to enter a parallel observational study (case series). If topical therapy fails and systemic therapy is required, participants are then considered for inclusion in the randomised trial. TRIAL REGISTRATION: Current controlled trials: ISRCTN35898459. Eudract No.2008-008291-14.

Current patch test results with the European baseline series and extensions to it from the 'European Surveillance System on Contact Allergy' network, 2007-2008.

BACKGROUND: The pattern of contact sensitization to the supposedly most important allergens assembled in the baseline series differs between countries, presumably at least partly because of exposure differences. Objectives. To describe the prevalence of contact sensitization to allergens tested in consecutive patients in the years 2007 and 2008, and to discuss possible differences. METHODS: Data from the 39 departments in 11 European countries comprising the European Surveillance System on Contact Allergy network (www.essca-dc.org) in this period have been pooled and analysed according to common standards. RESULTS: Patch test results with the European baseline series, and country-specific or department-specific additions to it, obtained in 25 181 patients, showed marked international variation. Metals and fragrances are still the most frequent allergens across Europe. Some allergens tested nationally may be useful future additions to the European baseline series, for example methylisothiazolinone, whereas a few long-term components of the European baseline series, namely primin and clioquinol, no longer warrant routine testing. CONCLUSIONS: The present analysis points to 'excess' prevalences of specific contact sensitization in some countries, although interpretation must be cautious if only few, and possibly specialized, centres are representing one country. A comparison as presented may help to target in-depth research into possible causes of 'excess' exposure, and/or consideration of methodological issues, including modifications to the baseline series.

Effects of ultraviolet light on human serum 25-hydroxyvitamin D and systemic immune function.

BACKGROUND: Many immune-mediated diseases are associated with low levels of vitamin D and sunlight. UV light or supplementation with vitamin D can increase regulatory T-cell activity and prevent animal models of autoimmune disease. Increasing population vitamin D levels may therefore alleviate the burden of human immune-mediated disease. OBJECTIVE: To determine the responses of circulating 25-hydroxyvitamin D [25(OH)D] levels, regulatory T-cell numbers, and immune function to UV light exposure in patients being treated for skin disease. METHODS: Twenty-four subjects with skin disease from the North of Scotland were recruited between December and March. At baseline, and after 2 and 4 weeks of narrowband UV light exposure, we measured peripheral blood 25(OH)D level, numbers of regulatory T cells (CD4(+)CD25(hi)FoxP3(+)), and T-cell proliferative and cytokine responses to anti-CD3/CD28 stimulation. RESULTS: Median (interquartile range) narrowband UV-B received during the study was 39.1 (30.9) as standard erythema dose, comparable to a quarter of the median summer sunlight exposure received locally. This increased the 25(OH)D level from a mean ± SD of 34 ± 17 nmol/L to 58 ± 16 nmol/L after 2 weeks and 78 ± 19 nmol/L after 4 weeks. The mean proportion of circulating regulatory T cells increased from 0.5% to 1.6% CD3(+) cells, which significantly correlated with the increased 25(OH)D level. UV treatment was also followed by reduced proliferative and IL-10 responses to anti-CD3/CD28 independent of the 25(OH)D level. CONCLUSION: Narrowband UV light reduces systemic immune responsiveness via the induction of regulatory T cells. Light and 25(OH)D levels may affect particular immune functions independently. The levels of serum 25(OH)D over which these effects are apparent should guide future interventions.

Patient preferences for psoriasis treatment: process characteristics considered more important than outcome attributes.

In a recent paper by Schaarschmidt et al., patients with moderate-to-severe psoriasis completed a conjoint analysis survey (discrete choice experiment) to determine which factors had influenced their choice of treatment, and the relative importance of each factor. They also assessed how socioeconomic and demographic factors affected patient choice. Using relative importance scores, treatment location was found to be the more important attribute to patients, followed by probability of benefit and method of delivery.

Influence of isotretinoin on hippocampal-based learning in human subjects.

RATIONALE: The acne drug isotretinoin has 13-cis retinoic acid as its active agent. Adverse effects that have been described include severe depression. Animal studies indicate that the hippocampus is particularly sensitive to retinoic acid. Changes induced by isotretinoin to hippocampal function could contribute to depression but may be more evident in altered visuospatial learning and memory, the primary function of the hippocampus. OBJECTIVES: We aimed to test the hypothesis that a course of oral isotretinoin therapy would result in declining visuospatial learning and memory. METHODS: CANTAB tasks designed to assess visuospatial memory were performed repeatedly on 14 males and 3 females in an open prospective observational study of patients with severe acne undergoing isotretinoin therapy. Beck's Depression Inventory and Global Acne Grade were also administered. RESULTS: Performance stayed unchanged for DMS, SRM and PRM tasks, while surprisingly participants improved their speed on the PRM task. Performance improved across sessions on the PAL task, and moreover the dose of isotretinoin correlated with improvement in the total trial score, reduction in total error rate and stage completed at the first trial. CONCLUSION: Isotretinoin does not reduce learning and memory and our study suggests that it may instead lead to a dose-related improvement in specific aspects of hippocampal learning and memory. Retinoic acid functions in the hippocampus as the active metabolite of vitamin A, suggesting that this may be a limiting factor in the human hippocampus and addition of exogenous retinoic acid brings levels closer to an optimal state.