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.

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.

Chronic urticaria in the real-life clinical practice setting in the UK: results from the noninterventional multicentre AWARE study.

BACKGROUND: Chronic urticaria (CU) is a skin condition characterized by repeated occurrence of itchy weals and/or angio-oedema for > 6 weeks. AIM: To provide data demonstrating the real-life burden of CU in the UK. METHODS: This UK subset of the worldwide, prospective, noninterventional AWARE study included patients aged 18-75 years diagnosed with H1-antihistamine (H1-AH)-refractory chronic spontaneous urticaria (CSU) for > 2 months. Baseline characteristics, disease activity, treatments, comorbidities and healthcare resource use were documented. Quality of life (QoL), work productivity and activity impairment were assessed. RESULTS: Baseline analysis included 252 UK patients. Mean age and body mass index were 45.0 years and 29.0 kg/m2 , respectively. Most patients were female (77.8%) and had moderate/severe disease activity (mean Urticaria Activity Score over 7 days was 18.4) and a 'spontaneous' component to their CU (73.4% CSU; 24.6% CSU and chronic inducible urticaria). Common comorbidities included depression/anxiety (24.6%), asthma (23.8%) and allergic rhinitis (12.7%). A previous treatment was recorded for 57.9% of patients. Mean Dermatology Life Quality Index score was 9.5, and patients reported impairments in work productivity and activity. Healthcare resource use was high. Severity of CSU was associated with female sex, obesity, anxiety and diagnosis. Only 28.5% of patients completed all nine study visits, limiting analysis of long-term treatment patterns and disease impact. CONCLUSIONS: Adult H1-AH-refractory patients with CU in the UK reported high rates of healthcare resource use and impairment in QoL, work productivity and activity at baseline. The differing structures of UK healthcare may explain the high study discontinuation rates versus other countries.

Steady-state pharmacokinetics of hydroxychloroquine in patients with cutaneous lupus erythematosus.

Background Hydroxychloroquine (HCQ), a 4-aminoquinolone antimalarial, is regarded as the oral therapy of choice for cutaneous and systemic lupus erythematosus (SLE). It is also licensed for rheumatoid arthritis (RA). Studies of HCQ-treated patients with SLE or RA have demonstrated a positive correlation between whole-blood HCQ levels and clinical response. Such studies have involved measuring whole-blood concentrations at any given time point after HCQ ingestion assuming that steady-state concentrations would undergo limited fluctuation over a daily interval because HCQ has a long half-life. This approach might not sufficiently take into account the potential intra-patient variation in HCQ blood levels that can occur over a 24-hour period. Such variation, if significant, could affect the credibility of any concentration-response relationship provided from these previous studies. Objectives The objectives of this report are to: (a) investigate the intra-patient variation in HCQ whole-blood levels and (b) suggest an optimum time for sampling patients for future studies. Methods Six patients were recruited with cutaneous lupus erythematosus who had each been on HCQ 200 mg twice daily for at least six months, so that they were at steady-state. Each patient was fasted overnight and had standardized meals and dosing schedule. Whole blood was sampled at seven time points over 24 hours. Whole-blood HCQ levels were measured with high-performance liquid chromatography using gradient elution, fluorimetric detection and chloroquine as an internal standard. The assay had a mean inter- and intra-day coefficient of variation of 10% and 5% respectively and a limit of detection of 5ng/ml. Results HCQ levels appeared to follow a biphasic pattern over the sampling period. Maximum levels were noted a median of four hours (range 2-6) after ingestion. Median intra-patient variation between trough and peak levels, 'Cmax' ((peak - trough)/trough × 100%), was 27% (range 8-150%). Conclusions This study demonstrated that whole-blood HCQ levels vary 27% (median, range 8-150%) within an individual over a 12-hour period. Drug levels might differ between individuals because of multiple factors, including variable adherence to medication. Measuring HCQ levels for assessment of drug adherence could be valuable in the 'real-world' clinical setting. This could be assessed by taking a blood sample at any time following HCQ ingestion. If patients were found to have very low or undetectable levels of HCQ, non-adherence to HCQ should be suspected.

Severity of polymorphic light eruption in pre- and post-menopausal women: a comparative study.

BACKGROUND: Polymorphic light eruption (PLE) is approximately four times more common in women than in men and often begins in young adult life. It is hypothesized that patients with PLE have an inherent resistance to UVL-induced immunosuppression, which is a physiological phenomenon in normal healthy individuals. Consequently, in PLE there is a delayed-type hypersensitivity reaction to a UVL-modified skin antigen, which results in an inflammatory reaction and a variable rash. The female hormone, 17ß-oestradiol, has been shown to inhibit UVL-induced physiological suppression of contact hypersensitivity responses. This has been postulated to account for the female preponderance of PLE. If 17ß-oestradiol plays a significant part in the disease, one might hypothesize that the severity of PLE might reduce in women after menopause. OBJECTIVES: To compare the severity of PLE in pre-menopausal women with that in post-menopausal women. METHODS: Eighteen pre-menopausal and 18 post-menopausal women with PLE had their Polymorphic Light Eruption Severity Index (PLESI) scored by a single investigator. RESULTS: Pre-menopausal women (mean age 40 years; range 25-50) had a mean PLESI of 54.8 (range 0-86, SD 20.2). Post-menopausal women (mean age 63 years; range 53-78) had a mean PLESI of 36.8 (range 0-74, SD 18.2). A significant difference in mean PLESI values between pre- and post-menopausal women was noted (18.0; 95% CI 4.9-31.0; P = 0.008). At the time of the study, three subjects in the pre-menopausal group and one subject in the post-menopausal group were on oestrogen preparations. Even after excluding the four patients on oral oestrogens, there remained a statistically significant difference in the mean PLESI scores between the pre-menopausal and post-menopausal groups (55.10 vs. 36.64; difference of 18.46, 95% CI: 4.0-32.91; P = 0.014). CONCLUSIONS: The severity of PLE was significantly less in post-menopausal women as compared with pre-menopausal women.

Long-term response to hydroxychloroquine in patients with discoid lupus erythematosus.

BACKGROUND: The recommended first-line oral therapy for discoid lupus erythematosus (DLE) is the antimalarial hydroxychloroquine. To the best of our knowledge, there is no published information regarding the long-term (i.e. > 6 months) response of DLE to hydroxychloroquine in clinical practice. OBJECTIVES: To describe the long-term clinical response of DLE to hydroxychloroquine after 6 months of use. METHODS: A multicentre retrospective cohort study was conducted in patients with DLE who had received treatment with hydroxychloroquine. All patients were recruited and interviewed by a single investigator and response to hydroxychloroquine assessed by the same individual through a retrospective review of case notes using a specified protocol. RESULTS: A total of 200 patients with DLE were recruited (F:M = 4 : 1) with a median age at diagnosis of 40 years (range 16-81) and median follow-up of 8 years (range 0·5-37). An adequate clinical response to hydroxychloroquine was recorded in 91 patients (45·5%) but nonresponse occurred in 85 patients (42·5%). The remainder of patients either had partial response or withdrew from therapy due to toxicity or were unclassifiable. Importantly, of those individuals that did respond to hydroxychloroquine within the first 6 months of use, almost one in five eventually lost their response, despite continued administration, after a median interval of 2 years. These patients often regained disease control if treated with a combination of hydroxychloroquine and mepacrine. Of those that did not respond to hydroxychloroquine within the first 6 months of use, almost one in 10 became eventual responders either after continued administration for up to 2 years or when rechallenged on hydroxychloroquine. The remaining nonresponders relied frequently on oral corticosteroid. CONCLUSIONS: In this cohort of patients with DLE, long-term clinical response to hydroxychloroquine occurred in less than 50% of patients. Nonresponders to hydroxychloroquine frequently required oral steroid to achieve disease control. These findings merit further investigation through a multicentre prospective study using a validated disease activity measure.

Cutaneous features of intravascular lymphoma.

Intravascular lymphoma (IVL) is a subset of extranodal non-Hodgkin lymphoma, with an estimated incidence of <1 case per million people. It is characterised by extensive proliferation of lymphoma cells within small to medium-sized blood vessels. Most IVLs are B-cell tumours. IVL can present primarily in any organ system, including the skin. The disease is often disseminated at diagnosis. The overall mortality rate is thought to be >80%, and >50% of patients are diagnosed at postmortem examination. There is wide variability in the clinical appearance of cutaneous lesions, which may simulate inflammatory skin disease. Therefore, awareness by dermatologists is important to enable early diagnosis when cutaneous signs are present. We report two patients with unexplained systemic disease and a skin eruption, leading to the diagnosis of IVL, and outline the range of cutaneous features reported.

Measuring disease activity and damage in discoid lupus erythematosus.

BACKGROUND: Discoid lupus erythematosus (DLE) is a disfiguring inflammatory skin disease. There is no specific tool for measuring disease severity. OBJECTIVES: To determine the features needed in a score measuring activity and damage in DLE and to investigate the score's reliability and its correlation with the physician's global assessment of disease severity and the patient-reported Dermatology Quality of Life Index (DLQI). METHODS: The content of the score was determined following a peer review, pilot work in patients and a preliminary inter-rater reliability study. The Score of Activity and Damage in DLE (SADDLE) measures severity of activity (erythema, scale, induration) and damage (scarring/atrophy and dyspigmentation) attributable to DLE. Summed scores range between 0 and 195. Inter- and intrarater reliability of the score was tested using six assessors and nine patients with DLE. Intraclass correlation coefficients (ICCs) > 0.7 were considered evidence of good inter- and intrarater agreement. RESULTS: The mean +/- SD SADDLE score of nine patients in the inter-rater reliability study was 47 +/- 22 (range 14-102). There was good inter-rater agreement for the total score [ICC 0.82; 95% confidence interval (CI) 0.61-0.95] and for the activity and damage scales, the individual physical signs and the total scores at individual body sites. The total score demonstrated excellent intrarater reliability (ICC 0.98; 95% CI 0.86-1.00). Although there was poor inter-rater agreement for global assessments (ICC 0.28; 95% CI 0.06-0.66), a good correlation was demonstrated between total scores and global assessments (r = 0.7). A weaker positive correlation was observed between disease activity scores and DLQI (r = 0.4). CONCLUSIONS: The SADDLE measures activity and damage in patients with DLE. It demonstrates good inter- and excellent intrarater agreement, over and above that for global assessment. It correlates well with global assessment scores. Further studies are required to investigate SADDLE's responsiveness to change with therapy.

Pityriasis lichenoides: the differences between children and adults.

BACKGROUND: Pityriasis lichenoides (PL) is a skin disease that affects both children and adults. Anecdotally, it is said to run a more benign course in children, with a frequent tendency to self-resolution. However, to our knowledge, there have been no published studies comparing PL in both age groups. OBJECTIVE: To evaluate the clinicopathological features, overall efficacy of treatments and disease outcomes in children and adults diagnosed with PL. METHODS: A retrospective review of records was undertaken on all patients diagnosed with PL at two regional centres during an 8-year period (from 1998 to 2006). For each individual, data were collected on age, sex, number of lesions, lesional morphology and distribution, symptoms, histopathological features, treatment modalities (and response), overall follow-up and length of remission. RESULTS: We recorded 25 children (median age 8 years, range 2-18) and 32 adults (median age 40 years, range 20-65) with PL. All the children and adults had more than 20 scaly, papular lesions. Children had greater lesional body involvement than adults. Lesions on the legs and trunk were present in 23 children (92%) compared with 19 adults (59%) (P < 0.01) and facial involvement was observed more commonly in children (n = 10, 40%) compared with adults (n = 8, 25%). Dyspigmentation was significantly more common in children (n = 18, 72%) compared with adults (n = 6, 19%) (P < 0.001). Topical corticosteroids were used by 16 children (64%) and 18 adults (56%) but only half in each group found these effective. Eight children (32%) were treated with erythromycin, with only two (25%) clearing, and one of these subsequently relapsing. In contrast, four adults (13%) received antibiotics, with three (75%) clearing and none relapsing thereafter. Ultraviolet B phototherapy was used in eight children (32%), with seven (88%) completely or almost clearing, but four (57%) subsequently relapsed. Fourteen adults (44%) received phototherapy; 10 (71%) completely cleared and only two of these (20%) subsequently relapsed. Strikingly, after a median disease duration of 30 months, only five children (20%) went into complete remission compared with 25 adults (78%) (P < 0.001). CONCLUSIONS: This is the first study to compare PL in children and adults. Our findings suggest that, compared with adults, PL in children is more likely to run an unremitting course, with greater lesional distribution, more dyspigmentation and a poorer response to conventional treatment modalities.

Sunscreen ingredients and labelling: a survey of products available in the UK.

BACKGROUND: In Europe, where sunscreens are classified as cosmetics, products may contain one or several of 27 permitted 'ultraviolet filters'. We were unable to find published data on the frequency of usage of individual ultraviolet (UV)-absorbing chemicals in currently available sunscreens. AIM: To record the active ingredients and labelling characteristics of sunscreens available in the UK. METHODS: In 2005, two dermatologists visited seven retail outlets, which stocked a large range of sunscreens. Manufacturers were also contacted. For each product, the names of UV-protective ingredients and the labelling information, including sun protection factor (SPF), UVA protection and age group for which the product was marketed were recorded. RESULTS: Data on 308 skin sunscreen products and 21 lip sunscreens were recorded. For skin products, the SPF ranged from 2 to 60. In total, 23 different UV-absorbing ingredients were found, 4 of which were found in > 25% of products. The child and baby skin sunscreens (n = 52) had a significantly higher median SPF of 40, compared with 15 for the remaining 256 adult products (P < 0.001). The number of UV-absorbing chemicals and the frequency of those commonly used did not differ substantially between child and adult products. Of skin sunscreens marketed for babies, 60% contained 2-6 UV-absorbing chemicals. Nearly half of the skin sunscreens contained at least one of nine UV-absorbing chemicals not available in patch testing formulations from commercial suppliers. CONCLUSIONS: The results of this survey indicate current sunscreen content and labelling, and are a benchmark from which new developments can be tracked. More standard sunscreen labelling, particularly separate listing of active ingredients, would be helpful. It was surprising to find UV-absorbing chemicals in products sold for use on babies.

An open-label, dose-ranging study of methotrexate for moderate-to-severe adult atopic eczema.

BACKGROUND: Treatment options for moderate-to-severe atopic eczema are limited. Although methotrexate (MTX) is a widely used and effective treatment for psoriasis, there have been no previous prospective trials of its use in refractory atopic eczema, despite a few small, retrospective reports suggesting that it is a well-tolerated and effective treatment. OBJECTIVES: We have assessed the safety and efficacy of oral MTX in 12 adults with moderate-to-severe atopic eczema in an open-label, dose-ranging, prospective trial using objective outcome measures. METHODS: All patients had previously received other second-line therapies and had disease only partially responsive to potent topical steroids and emollients. During the 24-week MTX treatment period, unrestricted use of standard topical therapy was permitted. We used an incremental MTX dose regime, starting at 10 mg per week (following a 5-mg test dose) and increasing by 2.5 mg weekly until response was achieved or treatment was limited by toxicity. Disease activity [six area six sign atopic dermatitis (SASSAD) score] was assessed every 4 weeks during treatment and 12 weeks after stopping MTX. The primary endpoint was 24-week change in disease activity. RESULTS: On average, disease activity improved by 52% from baseline (95% confidence interval 45-60%). There were significant improvements in quality of life, body surface area affected and loss of sleep and itch scores. Global response was rated as 'marked improvement' in five of 12 and six of 12 patients, by investigators and patients, respectively. In all patients, the majority of improvement in disease activity was seen by week 12, and, interestingly, patients who had not responded well over this period despite reaching a dose of 15 mg weekly failed to improve with further dose escalation. Only one patient withdrew due to minor adverse effects. MTX was well tolerated by the remaining 11 patients, all of whom completed treatment, achieving a median dose of 15 mg weekly. Importantly, eight of nine patients had a persistent improvement 12 weeks after stopping MTX, with mean disease activity remaining 34% below baseline. CONCLUSIONS: We have shown that MTX is an effective, well-tolerated treatment for moderate-to-severe atopic eczema, and response appears to compare favourably with other second-line therapies. A randomized, controlled trial is now warranted.

Cutaneous signs as a presenting manifestation of alcohol excess.

We describe three patients who presented with a total of four episodes of an inflammatory dermatosis associated with alcohol abuse. In each case, the rash had similar characteristic features. The patients responded promptly to emollients and topical steroids but not to zinc replacement therapy. Other nutrient deficiencies were not identified. In addition, long-term remission seemed to be dependent on a reduction in alcohol consumption. We postulate that this is a separate cutaneous manifestation of chronic alcohol misuse and that this syndrome may be more common than previously thought.