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.

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.

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.

Systemic mastocytosis with diffuse cutaneous involvement and haematological disease presenting in utero treated unsuccessfully with vincristine.

Mastocytosis is a disorder characterised by abnormal mast cell proliferation. The diverse spectrum of clinical presentations is dependent on the tissues and organs involved. We report a rare case of aggressive systemic mastocytosis presenting in utero with diffuse cutaneous involvement, and haematological abnormalities. There is little published evidence to guide treatment.

Efficacy of oral isotretinoin in the control of skin and nasal colonization by antibiotic-resistant propionibacteria in patients with acne.

BACKGROUND: Skin colonization by antibiotic-resistant propionibacteria is commonplace among acne patients globally. Increasing attention is now being paid to how resistance rates might be reduced to preserve the future efficacy of antibiotics, especially erythromycin and clindamycin in acne therapy. OBJECTIVE: To assess the efficacy of oral isotretinoin in the control of antibiotic-resistant propionibacteria. METHODS: Acne patients (72 in the U.K., 62 in the U.S.A.) colonized with high numbers of antibiotic-resistant propionibacteria were sampled before, during and 12 weeks after oral isotretinoin therapy. Propionibacterial samples were collected from five acne-prone skin surface sites using a detergent scrub method and from the anterior nares using moistened swabs. Total and antibiotic-resistant propionibacteria were enumerated by viable counting on media with and without selective antibiotics. RESULTS: After 16 weeks of oral isotretinoin therapy, mean population densities of viable propionibacteria and variants resistant to erythromycin, clindamycin or tetracycline had fallen by more than 90% at all skin sites and in the nares. The sole exception was a smaller reduction in tetracycline-resistant strains on the lower back. In general, greater reductions were observed on skin than in the nares. By the end of the treatment period only three patients (all in Philadelphia) yielded no antibiotic-resistant strains from any site. Post-treatment, propionibacterial counts remained well below pretreatment levels but had begun to recover on the face and in the nares. The recovering propionibacterial population included both susceptible and resistant strains. Changes during and post-treatment at the two centres were similar but not identical. CONCLUSIONS: Oral isotretinoin effectively reduced skin and nasal colonization by antibiotic-resistant propionibacteria. However, viable populations of resistant isolates persisted post-treatment at multiple sites. Novel methods are required to eradicate antibiotic-resistant propionibacteria completely, especially from the nasal reservoir.

Short-term effects of topical fusidic acid or mupirocin on the prevalence of fusidic acid resistant (FusR) Staphylococcus aureus in atopic eczema.

BACKGROUND: Staphylococcus aureus has a role in the pathophysiology of atopic eczema. Topical fusidic acid is widely used in its treatment. There is concern that topical use of fusidic acid may be driving the selection and dissemination of fusidic acid-resistant (FusR) S. aureus. OBJECTIVES: To test the hypothesis that treatment of atopic eczema for 2 weeks with topical fusidic acid/steroid combination can increase carriage of FusRS. aureus. METHODS: Forty-six patients with atopic eczema were allocated randomly to one of two treatment groups. Group 1 (28 patients) were treated with topical 2% fusidic acid plus 0.1% betamethasone cream, and group 2 (18 patients) with topical 2% mupirocin and 0.1% betamethasone cream. The clinical response and nasal and skin colonization with S. aureus were recorded before treatment and after 1 and 2 weeks of therapy. RESULTS: Baseline samples from the site of worst eczema showed S. aureus (sensitive and resistant) in 76% of patients, and FusRS. aureus in 26%, with no significant difference between treatment groups. After 1 and 2 weeks, both groups showed similar significant clinical improvement. The overall median clinical improvement was paralleled by a reduction in prevalence and population density of S. aureus (sensitive and resistant) at the worst eczema site (P < 0.0001). However, for FusRS. aureus there was no significant change in the prevalence of carriage, or population density in either group compared to baseline. Over 50% of patients carried S. aureus in the nerves and over 20% carried FusRS. aureus. Neither regimen affected either the prevalence or population density of S. aureus or FusRS. aureus in the nerves. CONCLUSIONS: In this small study there is no evidence to support the hypothesis that short-term treatment of atopic eczema with fusidic acid/steroid combination increases fusidic acid resistant S. aureus during a 2-week period.

Widespread insecticide resistance in head lice to the over-the-counter pediculocides in England, and the emergence of carbaryl resistance.

BACKGROUND: Increasing resistance to insecticides used for the control of head lice infestation has been documented over the last decade. Treatment failure and tolerance to insecticides have been validated in a number of studies undertaken in several U.K. centres. OBJECTIVES: To establish the extent of insecticide resistance in head lice and acetylcholinesterase activity in the presence of carbaryl in head lice. METHODS: Head lice were collected from school children in four centres across England (Exmouth, Loughborough, Leeds and South Shields), and tested in their response to the insecticides permethrin, phenothrin, malathion and carbaryl. Data were compared with information collected in Bristol and Bath in 1998 and with susceptible body lice. The activity of louse acetylcholinesterase was measured with and without carbaryl in head lice collected in Bristol, Leeds, Loughborough and in body lice. The efficacy of a 1% carbaryl lotion was compared in children in Bristol and Leeds. RESULTS: Compared with body lice, head lice from all six centres were significantly different in their response (P < 0.0001) to permethrin, phenothrin and malathion after 2-h exposure tests. There were significant differences in louse acetylcholinesterase activity in body lice, and head lice collected in Loughborough and Bristol in the presence or absence of carbaryl (P < 0.001), indicating enzyme inhibition. However, the difference for lice from Leeds was not significant (P = 0.363) suggesting that the enzyme was resistant to carbaryl. Eighty-nine per cent of children treated in Leeds with carbaryl were cured compared with 100% in Bristol. CONCLUSIONS: The data suggest head lice resistance is present in many parts of England to over-the-counter products containing synthetic insecticides (permethrin, phenothrin and malathion). They further suggest that resistance is starting to develop to carbaryl in head lice in Leeds and that extensive use of this product would lead to significant resistance.

Observations on high levels of fusidic acid resistant Staphylococcus aureus in Harrogate, North Yorkshire, UK.

A retrospective study was carried out to investigate possible reasons for a marked increase in fusidic acid-resistant Staphylococcus aureus (FusR S. aureus) identified by our routine hospital microbiology service. Information was obtained on a sample of 64 consecutive patients from whom resistant S. aureus had been cultured. The source of isolates was found to be diffuse within the hospital and community. The site of sample was most frequently chronic cutaneous infections (68%). All the S. aureus isolates were resistant to both fusidic acid and penicillin and many were resistant to multiple antibiotics. Topical fusidic acid had been used by 40% of patients in the preceding 6 months and none had received oral fusidic acid (sodium fusidate). Most (80%) had received an oral antibiotic in the preceding 2 years. Information from the Prescriptions Pricing Authority revealed that the total number of prescriptions for fusidic acid-containing preparations for the period September 1997 to August 1998 was markedly higher in Harrogate than in five other local areas where increases in (FusR) S. aureus have not been observed.