Identifying the best predictive diagnostic criteria for psoriasis in children (< 18 years): a UK multicentre case-control diagnostic accuracy study (DIPSOC study).

BACKGROUND: In children, psoriasis can be challenging to diagnose. Difficulties arise from differences in the clinical presentation compared with adults. OBJECTIVES: To test the diagnostic accuracy of previously agreed consensus criteria and to develop a shortlist of the best predictive diagnostic criteria for childhood psoriasis. METHODS: A case-control diagnostic accuracy study in 12 UK dermatology departments (2017-2019) assessed 18 clinical criteria using blinded trained investigators. Children (< 18 years) with dermatologist-diagnosed psoriasis (cases, N = 170) or a different scaly inflammatory rash (controls, N = 160) were recruited. The best predictive criteria were identified using backward logistic regression, and internal validation was conducted using bootstrapping. RESULTS: The sensitivity of the consensus-agreed criteria and consensus scoring algorithm was 84·6%, the specificity was 65·1% and the area under the curve (AUC) was 0·75. The seven diagnostic criteria that performed best were: (i) scale and erythema in the scalp involving the hairline, (ii) scaly erythema inside the external auditory meatus, (iii) persistent well-demarcated erythematous rash anywhere on the body, (iv) persistent erythema in the umbilicus, (v) scaly erythematous plaques on the extensor surfaces of the elbows and/or knees, (vi) well-demarcated erythematous rash in the napkin area involving the crural fold and (vii) family history of psoriasis. The sensitivity of the best predictive model was 76·8%, with specificity 72·7% and AUC 0·84. The c-statistic optimism-adjusted shrinkage factor was 0·012. CONCLUSIONS: This study provides examination- and history-based data on the clinical features of psoriasis in children and proposes seven diagnostic criteria with good discriminatory ability in secondary-care patients. External validation is now needed.

What is the demand for out-of-hours dermatology? A UK-based region-wide survey of dermatology demand and provision during the evenings and at weekends.

BACKGROUND: Little is known about the demand for out-of-hours (OOH) dermatology in the UK, and this can make commissioning of acute services difficult. The East Midlands region has a population of 4.5 million people, with variable access to OOH dermatology services. AIM: We sought to investigate the provision of, and demand for, OOH dermatology services across the region with a view to informing commissioning decisions for the future. METHODS: We contacted all dermatology departments in the East Midlands region to establish what level of service was commissioned at evenings and weekends. At the sites providing any form of OOH service, we recorded all requests for advice received after 17.00 h on weekdays, or at any time during weekends and bank holidays over a 3-month period from October to December 2019. RESULTS: The OOH services provided ranged from 24 h/day cover 7 days/week at one site, to no formal provision across much of the rest of the region. In total, 125 calls were received during the study period, averaging 1 call per day on weekday evenings, and 2 calls per day at weekends and on bank holidays. Of these 125 calls, 11 patients (9%) were prioritized and seen by the on-call dermatologist on the day of referral, and 9 of these had potentially life-threatening skin conditions. A further 39 (31%) were deemed to need review within 24 h and 22 (18%) within 48 h. The remaining 42% were given appointments within 7 days or dealt with by telephone advice. CONCLUSION: The demand for OOH dermatology across the East Midlands is low, but access to timely dermatology advice is essential in some situations. Commissioning of a regional dermatology OOH service incorporating digital technology may help to improve the equity of access for all patients across the region.

An economic evaluation of the randomized controlled trial of topical corticosteroid and home-based narrowband ultraviolet B for active and limited vitiligo (the HI-Light Vitiligo Trial).

BACKGROUND: Economic evidence for vitiligo treatments is absent. OBJECTIVES: To determine the cost-effectiveness of (i) handheld narrowband ultraviolet B (NB-UVB) and (ii) a combination of topical corticosteroid (TCS) and NB-UVB compared with TCS alone for localized vitiligo. METHODS: Cost-effectiveness analysis alongside a pragmatic, three-arm, placebo-controlled randomized controlled trial with 9 months' treatment. In total 517 adults and children (aged ≥ 5 years) with active vitiligo affecting < 10% of skin were recruited from secondary care and the community and were randomized 1: 1: 1 to receive TCS, NB-UVB or both. Cost per successful treatment (measured on the Vitiligo Noticeability Scale) was estimated. Secondary cost-utility analyses measured quality-adjusted life-years using the EuroQol 5 Dimensions 5 Levels for those aged ≥ 11 years and the Child Health Utility 9D for those aged 5 to < 18 years. The trial was registered with number ISRCTN17160087 on 8 January 2015. RESULTS: The mean ± SD cost per participant was £775 ± 83·7 for NB-UVB, £813 ± 111.4 for combination treatment and £600 ± 96·2 for TCS. In analyses adjusted for age and target patch location, the incremental difference in cost for combination treatment compared with TCS was £211 (95% confidence interval 188-235), corresponding to a risk difference of 10·9% (number needed to treat = 9). The incremental cost was £1932 per successful treatment. The incremental difference in cost for NB-UVB compared with TCS was £173 (95% confidence interval 151-196), with a risk difference of 5·2% (number needed to treat = 19). The incremental cost was £3336 per successful treatment. CONCLUSIONS: Combination treatment, compared with TCS alone, has a lower incremental cost per additional successful treatment than NB-UVB only. Combination treatment would be considered cost-effective if decision makers are willing to pay £1932 per additional treatment success.

Randomized controlled trial of topical corticosteroid and home-based narrowband ultraviolet B for active and limited vitiligo: results of the HI-Light Vitiligo Trial.

BACKGROUND: Evidence for the effectiveness of vitiligo treatments is limited. OBJECTIVES: To determine the effectiveness of (i) handheld narrowband UVB (NB-UVB) and (ii) a combination of potent topical corticosteroid (TCS) and NB-UVB, compared with TCS alone, for localized vitiligo. METHODS: A pragmatic, three-arm, placebo-controlled randomized controlled trial (9-month treatment, 12-month follow-up). Adults and children, recruited from secondary care and the community, aged ≥ 5 years and with active vitiligo affecting < 10% of skin, were randomized 1 : 1 : 1 to receive TCS (mometasone furoate 0·1% ointment + dummy NB-UVB), NB-UVB (NB-UVB + placebo TCS) or a combination (TCS + NB-UVB). TCS was applied once daily on alternating weeks; NB-UVB was administered on alternate days in escalating doses, adjusted for erythema. The primary outcome was treatment success at 9 months at a target patch assessed using the participant-reported Vitiligo Noticeability Scale, with multiple imputation for missing data. The trial was registered with number ISRCTN17160087 on 8 January 2015. RESULTS: In total 517 participants were randomized to TCS (n = 173), NB-UVB (n = 169) and combination (n = 175). Primary outcome data were available for 370 (72%) participants. The proportions with target patch treatment success were 17% (TCS), 22% (NB-UVB) and 27% (combination). Combination treatment was superior to TCS: adjusted between-group difference 10·9% (95% confidence interval 1·0%-20·9%; P = 0·032; number needed to treat = 10). NB-UVB alone was not superior to TCS: adjusted between-group difference 5·2% (95% CI - 4·4% to 14·9%; P = 0·29; number needed to treat = 19). Participants using interventions with ≥ 75% expected adherence were more likely to achieve treatment success, but the effects were lost once treatment stopped. Localized grade 3 or 4 erythema was reported in 62 (12%) participants (including three with dummy light). Skin thinning was reported in 13 (2·5%) participants (including one with placebo ointment). CONCLUSIONS: Combination treatment with home-based handheld NB-UVB plus TCS is likely to be superior to TCS alone for treatment of localized vitiligo. Combination treatment was relatively safe and well tolerated but was successful in only around one-quarter of participants.

Genotype-phenotype correlation in a large English cohort of patients with autosomal recessive ichthyosis.

BACKGROUND: Recessive forms of congenital ichthyosis encompass a group of rare inherited disorders of keratinization leading to dry, scaly skin. So far, 13 genes have been implicated, but there is a paucity of data on genotype-phenotype correlation in some populations. OBJECTIVES: We compiled an English cohort of 146 individuals with recessive ichthyosis and assessed genotype-phenotype correlation. METHODS: Deep phenotyping was undertaken by history-taking and clinical examination. DNA was screened for mutations using a next-generation sequencing ichthyosis gene panel and Sanger sequencing. RESULTS: Cases were recruited from 13 National Health Service sites in England, with 65% of patients aged < 16 years at enrolment. Pathogenic biallelic mutations were found in 83% of cases, with the candidate gene spread as follows: TGM1 29%, NIPAL4 12%, ABCA12 12%, ALOX12B 9%, ALOXE3 7%, SLC27A4 5%, CERS3 3%, CYP4F22 3%, PNPLA1 2%, SDR9C7 1%. Clinically, a new sign, an anteriorly overfolded ear at birth, was noted in 43% of patients with ALOX12B mutations. The need for intensive care stay (P = 0·004), and hand deformities (P < 0·001), were associated with ABCA12 mutations. Self-improving collodion ichthyosis occurred in 8% of the cases (mostly TGM1 and ALOX12B mutations) but could not be predicted precisely from neonatal phenotype or genotype. CONCLUSIONS: These data refine genotype-phenotype correlation for recessive forms of ichthyosis in England, demonstrating the spectrum of disease features and comorbidities, as well as the gene pathologies therein. Collectively, the data from these patients provide a valuable resource for further clinical assessment, improving clinical care and the possibility of future stratified management. What's already known about this topic? Recessive forms of ichthyosis are rare but often difficult to diagnose. Mutations in 13 genes are known to cause recessive forms of ichthyosis: ABCA12, ALOX12B, ALOXE3, CERS3, CYP4F22, LIPN, NIPAL4, PNPLA1, SDR9C7, SLC27A4, SULT2B1, ST14 and TGM1. Some phenotypic features may associate with certain gene mutations, but paradigms for genotype-phenotype correlation need refining. What does this study add? The genotypic spectrum of recessive ichthyosis in England (based on 146 cases) comprises TGM1 (29%), NIPAL4 (12%), ABCA12 (12%), ALOX12B (9%), ALOXE3 (7%), SLC27A4 (5%), CERS3 (3%), CYP4F22 (3%), PNPLA1 (2%) and SDR9C7 (1%). New or particular phenotypic clues were defined for mutations in ALOX12B, ABCA12, CYP4F22, NIPAL4, SDR9C7 and TGM1, either in neonates or in later life, which allow for greater diagnostic precision. In around 17% of cases, the molecular basis of recessive ichthyosis remains unknown.

Oral propranolol in the treatment of proliferating infantile haemangiomas: British Society for Paediatric Dermatology consensus guidelines.

BACKGROUND: Infantile haemangiomas (IH) are the most common vascular tumours of infancy. Despite their frequency and potential complications, there are currently no unified U.K. guidelines for the treatment of IH with propranolol. There are still uncertainties and diverse opinions regarding indications, pretreatment investigations, its use in PHACES (posterior fossa malformations-haemangiomas-arterial anomalies-cardiac defects-eye abnormalities-sternal cleft and supraumbilical raphe) syndrome and cessation of treatment. OBJECTIVES: To provide unified guidelines for the treatment of IH with propranolol. METHODS: This study used a modified Delphi technique, which involved an international treatment survey, a systematic evidence review of the literature, a face-to-face multidisciplinary panel meeting and anonymous voting. RESULTS: The expert panel achieved consensus on 47 statements in eight categories, including indications and contraindications for starting propranolol, pretreatment investigations, starting and target dose, monitoring of adverse effects, the use of propranolol in PHACES syndrome and how to stop treatment. CONCLUSIONS: These consensus guidelines will help to standardize and simplify the treatment of IH with oral propranolol across the U.K. and assist in clinical decision-making.

Propranolol in the treatment of infantile haemangiomas: lessons from the European Propranolol In the Treatment of Complicated Haemangiomas (PITCH) Taskforce survey.

BACKGROUND: Oral propranolol is widely prescribed as first-line treatment for infantile haemangiomas (IHs). Anecdotally, prescribing practice differs widely between centres. OBJECTIVES: The Propranolol In the Treatment of Complicated Haemangiomas (PITCH) Taskforce was founded to establish patterns of use of propranolol in IHs. METHODS: Participating centres entered data on all of their patients who had completed treatment with oral propranolol for IHs, using an online data capture tool. RESULTS: The study cohort comprised 1097 children from 39 centres in eight European countries. 76·1% were female and 92·8% had a focal IH, with the remainder showing a segmental, multifocal or indeterminate pattern. The main indications for treatment were periocular location (29·3%), risk of cosmetic disfigurement (21·1%) and ulceration and bleeding (20·6%). In total 69·2% of patients were titrated up to a maintenance regimen, which consisted of 2 mg kg(-1) per day (85·8%) in the majority of cases. 91·4% of patients had an excellent or good response to treatment. Rebound growth occurred in 14·1% upon stopping, of whom 53·9% were restarted and treatment response was recaptured in 91·6% of cases. While there was no significant difference in the treatment response, comparing a daily maintenance dose of < 2 mg kg(-1) vs. 2 mg kg(-1) vs. > 2 mg kg(-1) , the risk of adverse events was significantly higher: odds ratio (OR) 1 vs. adjusted OR 0·70, 95% confidence interval (CI) 0·33-1·50, P = 0·36 vs. OR 2·38, 95% CI 1·04-5·46, P = 0·04, Ptrend < 0·001. CONCLUSIONS: The PITCH survey summarizes the use of oral propranolol across 39 European centres, in a variety of IH phases, and could be used to inform treatment guidelines and the design of an interventional study.

Translating Patient-Oriented Eczema Measure (POEM) scores into clinical practice by suggesting severity strata derived using anchor-based methods.

BACKGROUND: The Patient-Oriented Eczema Measure (POEM) is a validated, patient-derived assessment measure for monitoring atopic eczema severity, although further information on how different POEM scores translate into disease severity categories is needed for clinical trials, epidemiological research and audit. OBJECTIVES: We sought to determine the relationship between Patient-Oriented Eczema Measure (POEM) scores (range 0-28) and two Global Questions (GQ1 and 2) concerning patients'/parents' views of the overall severity of their/their child's atopic eczema, in order to stratify POEM scores into five severity bands. METHODS: POEM scores and GQs were completed by 300 patients from general practice and 700 patients from dermatology outpatient clinics, including 300 adults aged ≥ 16 years and 700 children. RESULTS: The mean POEM score was 13·6 (range 0-28), and standard deviation (SD) was 7·2. Mean GQ1/GQ2 scores were 2·1/2·1, respectively (range 0-4 and SD 1·1 for both). The mean, mode and median of the GQ scores for each POEM score were used to devise possible POEM bandings. The proposed banding for POEM scores are: 0-2 (clear/almost clear); 3-7 (mild); 8-16 (moderate); 17-24 (severe); 25-28 (very severe), kappa coefficient 0·46. CONCLUSIONS: Severity banding of the POEM will allow more clinically meaningful use in everyday clinical practice and as a core outcome measure in future atopic eczema research.

The Eczema Priority Setting Partnership: a collaboration between patients, carers, clinicians and researchers to identify and prioritize important research questions for the treatment of eczema.

BACKGROUND: Eczema is a common condition, yet there are uncertainties regarding many frequently used treatments. Knowing which of these uncertainties matter to patients and clinicians is important, because they are likely to have different priorities from those of researchers and funders. OBJECTIVES: To identify the uncertainties in eczema treatment that are important to patients who have eczema, their carers and the healthcare professionals (HCPs) who treat them. METHODS: An eczema Priority Setting Partnership was established, including patients, HCPs and researchers. Eczema treatment uncertainties were gathered from patients and clinicians, and then prioritized in a transparent process, using a methodology advocated by the James Lind Alliance. RESULTS: In the consultation stage 493 participants (including 341 patients/carers) made 1070 submissions, of which 718 were uncertainties relating to the treatment of eczema. Treatment uncertainties with more than one submission were grouped into 52 'indicative uncertainties', which were then ranked by 514 participants (including 399 patients/carers). The top 14 treatment uncertainties were prioritized for research. The first four were common to patients/carers and HCPs (shared uncertainties): (i) the best and safest way of using topical steroids (including frequency of application, potency, length of time, alternation with other topical treatments and age limits); (ii) the long-term safety of topical steroids; (iii) the role of food allergy tests; and (iv) the most effective and safe emollients in treating eczema. The remaining 10 of the top 14 uncertainties comprised the next five highest ranked uncertainties for patients and the next five highest ranked uncertainties for HCPs. At a workshop involving 40 participants (patients, HCPs and researchers), shared uncertainties were formulated into possible research questions. CONCLUSIONS: The top 14 treatment uncertainties around the treatment of eczema provide guidance for researchers and funding bodies to ensure that future research answers questions that are important to both clinicians and patients.

Which outcomes should we measure in vitiligo? Results of a systematic review and a survey among patients and clinicians on outcomes in vitiligo trials.

BACKGROUND: Relevant and reliable outcomes play a crucial role in the correct interpretation and comparison of the results of clinical trials. There is a lack of consensus around methods of assessment and outcome measures for vitiligo, which makes it difficult to compare results of randomized controlled trials (RCTs) and perform meta-analysis. OBJECTIVES: To describe the heterogeneity in outcome measures used in published RCTs of vitiligo treatments, and to report the most desirable outcomes from patients' and clinicians' perspectives. METHODS: We conducted a systematic review of outcome measures used in RCTs as well as a survey of the most desirable outcomes identified by patients and clinicians as part of a Vitiligo Priority Setting Partnership. RESULTS: Outcomes from 54 eligible trials were analysed and compared with outcomes suggested by patients and clinicians. In the systematic review, 25 different outcomes were reported. Only 22% of trials had clearly stated primary outcome measures. Repigmentation was the most frequently reported outcome in 96% of trials and was measured using 48 different scales. Only 9% of trials assessed quality of life. Thirteen per cent measured cessation of spreading of the disease and 17% of studies reported patients' opinions and satisfaction with the treatment. In contrast, out of 438 suggestions made by patients and clinicians, cosmetically acceptable repigmentation (rather than percentage of repigmentation) was the most desirable outcome (68%), followed by cessation of spread of vitiligo (15%), quality of life (8%) and maintenance of repigmentation (4%). CONCLUSIONS: We propose that future vitiligo trials should include repigmentation, cosmetic acceptability of results, global assessment of the disease, quality of life, maintenance of repigmentation, stabilization of vitiligo and side-effects. International consensus among clinicians, researchers and patients is needed to establish an agreed core outcome set for future vitiligo trials.

Future research into the treatment of vitiligo: where should our priorities lie? Results of the vitiligo priority setting partnership.

BACKGROUND: Vitiligo is the most frequent depigmentation disorder of the skin and is cosmetically and psychologically devastating. A recently updated Cochrane systematic review 'Interventions for vitiligo' showed that the research evidence for treatment of vitiligo is poor, making it difficult to make firm recommendations for clinical practice. OBJECTIVES: To stimulate and steer future research in the field of vitiligo treatment, by identifying the 10 most important research areas for patients and clinicians. METHODS: A vitiligo priority setting partnership was established including patients, healthcare professionals and researchers with an interest in vitiligo. Vitiligo treatment uncertainties were gathered from patients and clinicians, and then prioritized in a transparent process, using a methodology advocated by the James Lind Alliance. RESULTS: In total, 660 treatment uncertainties were submitted by 461 participants. These were reduced to a list of the 23 most popular topics through an online/paper voting process. The 23 were then prioritized at a face-to-face workshop in London. The final list of the top 10 treatment uncertainties included interventions such as systemic immunosuppressants, topical treatments, light therapy, melanocyte-stimulating hormone analogues, gene therapy, and the impact of psychological interventions on the quality of life of patients with vitiligo. CONCLUSIONS: The top 10 research areas for the treatment of vitiligo provide guidance for researchers and funding bodies, to ensure that future research answers questions that are important both to clinicians and to patients.

Interventions to reduce Staphylococcus aureus in the management of atopic eczema: an updated Cochrane review.

BACKGROUND: An association between the bacterium Staphylococcus aureus and atopic eczema has been recognized for many years. Although few would dispute the benefit of systemic antibiotics in people with overtly clinically infected eczema, the clinical role of S. aureus in causing inflammatory flares in clinically uninfected eczema is less clear. OBJECTIVES/METHODS: To see if atopic eczema can be improved by antistaphylococcal agents, we performed a systematic review of randomized controlled trials (RCTs) using Cochrane Skin Group's Specialised Register, the Cochrane Central Register of Controlled Trials, MEDLINE (from 2000), EMBASE (from 1980), the metaRegister of Current Controlled Trials (to March 2009), plus manual searching of references and conference proceedings. RCTs that compared interventions to reduce S. aureus in people with atopic eczema with no treatment, vehicle, or another active compound were included. Publication status and language were not barriers to inclusion. RESULTS: Twenty-six studies involving 1229 participants were included. The studies were generally short term and of poor quality. There was no significant difference in global outcome for clinically infected eczema when oral antibiotics were compared with placebo [one study, relative risk (RR) 0.40, 95% confidence interval (CI) 0.13-1.24] or when topical steroid antibiotic combinations were compared with steroid alone (two studies, RR 0.52, 95% CI 0.23-1.16). One study of children with infected eczema that added bleach to bathwater showed a significant improvement in eczema severity when compared with bathwater alone, although the difference could have been explained by regression to the mean. Although antistaphylococcal interventions reduced S. aureus numbers in people with clinically uninfected eczema, none of the studies showed any clinical benefit. CONCLUSIONS: We failed to find any evidence that commonly used antistaphylococcal interventions are clinically helpful in people with eczema that is not clinically infected. Their continued use should be questioned in such situations, until better and longer-term studies show clear evidence of clinical benefit.