A randomized controlled trial protocol assessing the effectiveness, safety and cost-effectiveness of methotrexate vs. ciclosporin in the treatment of severe atopic eczema in children: the TREatment of severe Atopic eczema Trial (TREAT).

BACKGROUND: Oral systemic immunomodulatory medication is regularly used off-licence in children with severe atopic eczema. However, there is no firm evidence regarding the effectiveness, safety, cost-effectiveness and impact on quality of life from an adequately powered randomized controlled trial (RCT) using systemic medication in children. OBJECTIVES: To assess whether there is a difference in the speed of onset, effectiveness, side-effect profile and reduction in flares post-treatment between ciclosporin (CyA) and methotrexate (MTX), and also the cost-effectiveness of the drugs. Treatment impact on quality of life will also be examined in addition to whether FLG genotype influences treatment response. In addition, the trial studies the immune-metabolic effects of CyA and MTX. METHODS: Multicentre, parallel group, assessor-blind, pragmatic RCT of 36 weeks' duration with a 24-week follow-up period. In total, 102 children aged 2-16 years with moderate-to-severe atopic eczema, unresponsive to topical treatment will be randomized (1 : 1) to receive MTX (0·4 mg kg-1 per week) or CyA (4 mg kg-1 per day). RESULTS: The trial has two primary outcomes: change from baseline to 12 weeks in Objective Severity Scoring of Atopic Dermatitis (o-SCORAD) and time to first significant flare following treatment cessation. CONCLUSIONS: This trial addresses important therapeutic questions, highlighted in systematic reviews and treatment guidelines for atopic eczema. The trial design is pragmatic to reflect current clinical practice.

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.

Tackling tuberculosis in sub-Saharan Africa: EDCTP achievements and the road ahead.

The European and Developing Countries Clinical Trials Partnership (EDCTP) was established in 2003 to accelerate the development of medical interventions for tuberculosis (TB), human immunodeficiency virus (HIV) and malaria, with a particular focus on Phase II and III clinical trials. Between 2003 and 2015, the first EDCTP programme committed €65.6 million to research on TB and TB-HIV co-infection. The programme made a significant contribution to the first three elements of the DOTS TB control strategy, which mobilised European and African funding for TB-related research and generated important evidence on TB diagnostics and treatment regimens. As well as informing the development of international policy on TB diagnosis and treatment, the programme also significantly enhanced the capacity of countries in sub-Saharan Africa to undertake clinical trials and associated clinical research. The lessons learned from the first EDCTP programme have informed the development of a second, expanded EDCTP programme, EDCTP2, which was launched in 2014, and is due to run until 2024. One key lesson is the need for continued partnerships to fight the global threat of TB.

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.

Ultraviolet A1 phototherapy: a British Photodermatology Group workshop report.

Whole-body ultraviolet (UV)A1 (340-400 nm) phototherapy was first introduced 30 years ago, but is currently available in the UK in only three dermatology departments. A workshop to discuss UVA1 was held by the British Photodermatology Group in May 2009, the aim of which was to provide an overview of UVA1 phototherapy and its role in practice, and to identify areas in which further studies are required. The conclusions were that UVA1 phototherapy is an effective treatment in several inflammatory skin diseases, including localized scleroderma and atopic eczema (AE); however, deficiencies and limitations exist in the published evidence base. For most diseases, such as AE, other treatments also exist, which are generally more effective than UVA1. However, for some diseases, particularly morphoea, the evidence of efficacy is stronger for UVA1 than for other treatments. Acute adverse effects of UVA1 are minimal. The risk of long-term adverse effects, particularly skin cancer, is unknown. Medium to high doses of UVA1 are needed for efficacy in most situations, but the equipment to deliver such doses is large, expensive and difficult to install. UVA1 is currently underprovided, and the recommendation of the workshop is that more tertiary centres should have access to UVA1 phototherapy in the UK.

Which children should we patch test?

BACKGROUND: Allergic contact dermatitis (ACD) in childhood was considered rare until recently. However, reports are increasing, which may reflect an increased incidence and/or more frequent patch testing of children. It is also likely that allergen exposure in children has changed with time. AIMS: To determine the most common contact allergens and the rate of positive patch-test reactions among children with suspected contact allergy. METHODS: We carried out a retrospective case study of 114 children (66 girls and 48 boys) aged from 3 to 15 years (median 11.5) patch tested over a 3-year period. Indications for patch testing included uncontrolled or deteriorating atopic dermatitis, localized dermatitis or a history of reacting to a specific allergen. RESULTS: Of 110 children for whom we had notes, 83 (75%) had a history of atopy. Positive reactions that were of current, past or possible relevance were seen in 61 children (54%); in 58 (52%) of 111 tested with the standard series (SS) and in 6 (10%) of 60 tested with the medicament series. None of the children patch tested to the corticosteroid (n = 47), shoe (n = 15), fragrance (n = 12), cosmetic (n = 10) or rubber (n = 5) series had a positive reaction. However, 11 (10%) reacted to rubber allergens within the SS and one of five to their own shoes. The lowest rate of relevant positive reactions was among those with deteriorating atopic dermatitis (22%) and facial (33%) or perioral dermatitis (40%), and the highest rate amongst those with eyelid (86%) or hand (71%) dermatitis. Nickel was the most common allergen (20%) in line with previous reports (82% female), followed by rubber chemicals (10%), fragrance (7.2%), cobalt (5.4%) and lanolin (wool alcohol) (4.5%). CONCLUSIONS: The reported incidence of ACD among children, in particular nickel and rubber allergy, appears to be increasing, which may relate to changing fashions and hobbies. Contact allergy should be considered in all children with dermatitis, particularly with eyelid or hand dermatitis, and patch testing carried out more frequently.

An audit of the impact of a consultation with a paediatric dermatology team on quality of life in infants with atopic eczema and their families: further validation of the Infants' Dermatitis Quality of Life Index and Dermatitis Family Impact score.

BACKGROUND: Atopic dermatitis (AD) accounts for 10-20% of referrals to secondary care dermatology, often requiring multiple visits and occupying much valuable time and resources. OBJECTIVES: We audited the usefulness (ease of use, reliability and sensitivity to change) of two simple and easy to use quality of life (QoL) measures, the Infants' Dermatitis Quality of Life Index (IDQOL) and Dermatitis Family Impact (DFI), for assessing the impact on QoL of AD in infants and their families in a routine clinical setting. We also examined the impact of an initial consultation with a dermatology team on AD severity and QoL impairment from the parent's perspective. METHODS: The parents of 203 infants (mean age 19.8 months) with AD attending paediatric dermatology clinics completed the DFI and IDQOL. The parents of 50 of these infants completed both questionnaires before first and second consultations. RESULTS: In the 203 children the mean of both the IDQOL and DFI scores was 8.47 (median 8 and 7 and SD 5.8 and 6.5, respectively). The IDQOL and DFI correlated well (r(s) = 0.776, P < 0.0001). The parent's assessment of the global severity of AD correlated well with the IDQOL score (r(s) = 0.636, P < 0.0001) but less well with the DFI (r(s) = 0.394, P < 0.001). The highest-scoring IDQOL items were itching and scratching, problems at bathtime and time taken to fall asleep. The highest-scoring DFI items were tiredness/exhaustion, sleep loss and emotional distress. In both measures these domains also correlated most strongly with eczema severity. After dermatology consultation the median global severity score, rated by 50 parents, fell from 2 (SD 0.83) to 1 (SD 0.8; 95% confidence interval, CI 0.5-1), the median IDQOL score fell from 8 (SD 5.92) to 5.5 (SD 5.92; 95% CI 2-5.5) and the median DFI score fell from 9 (SD 6.45) to 3 (SD 6.56; 95% CI 2-5.5). In 50 infants the median IDQOL scores for those infants with global AD severity scores of 1, 2 and 3 were 5 (SD 5.65), 8 (SD 4.27) and 14 (SD 5.67), respectively and improved by 10%, 38% and 64%, respectively while the median DFI scores improved by 54%, 56% and 79%, respectively. The most improved IDQOL items were the time taken to get to sleep and difficulty at mealtimes and the most improved DFI domains were tiredness/exhaustion and emotional distress in the parents. CONCLUSIONS: We have provided further important information on the effects of AD on infants and their families using the IDQOL and DFI QoL measures. We demonstrate the usefulness of these measures in routine clinical management of AD and show the beneficial effect for both infants and parents of the initial consultation by a dermatology team in a secondary care setting.

A comparative study of impairment of quality of life in children with skin disease and children with other chronic childhood diseases.

BACKGROUND: Chronic disease can have physical and psychological effects which affect social functioning. These effects can be better understood from the perspective of parent and child by the use of health-related quality of life (HRQL) measures. Various HRQL measures are now available, of which generic health measures have been the most widely used. These permit comparison between different diseases and also the normal population. OBJECTIVES: To cross-validate a new generic HRQL proxy measure for children, the Children's Life Quality Index (CLQI), with an established speciality-specific dermatological questionnaire, the Children's Dermatology Life Quality Index (CDLQI), in a group of children with chronic skin diseases. The impairment of HRQL in the same group of children with skin disease was then compared with that associated with other common chronic childhood diseases using the CLQI. METHODS: The CDLQI was completed by 379 children aged 5-16 years with skin disease of more than 6 months' duration. Their parents (n=379) and parents of 161 children aged 5-16 years with other chronic diseases were also asked to complete a proxy measure, the CLQI. RESULTS: Using linear regression analysis, the CLQI and the CDLQI scores showed a strong linear association (rs=0.72, P<0.001) and on a Bland-Altman plot, reasonably good agreement (expressing scores out of 100, the 95% limits of agreement were from -25.5/100 to 26.7/100). In the child's opinion psoriasis and atopic dermatitis (AD) caused the greatest impairment (CDLQI scores of 30.6% and 30.5%), followed by urticaria (20%) and acne (18%). Using the generic CLQI (scored 0-36), from the parental perspective the highest score was for AD (33%), followed by urticaria (28%), psoriasis (27%) and alopecia (19%). Comparing this with children with other chronic diseases, those with cerebral palsy had the highest score (38%), followed in descending order by those with generalized AD (33%), renal disease (33%), cystic fibrosis (32%), urticaria (28%), asthma (28%) and psoriasis (27%). Diseases such as epilepsy (24%) and enuresis (24%) scored higher than diabetes (19%), localized eczema (19%), alopecia (19%) and acne (16%). CONCLUSIONS: Using the CLQI we have shown that HRQL impairment in children with chronic skin disease is at least equal to that experienced by children with many other chronic diseases of childhood, with AD and psoriasis having the greatest impact on HRQL among chronic skin disorders and only cerebral palsy scoring higher than AD. Cross-validation of the CLQI with the CDLQI in the group of children with skin disease demonstrates a strong linear association and good agreement between the two.

UVA1 phototherapy for genital lichen sclerosus.

BACKGROUND: Lichen sclerosus (LS) is characterized histologically by an inflammatory T-cell infiltrate, sclerosis and thickening of the dermis, and epidermal atrophy. Ultraviolet (UV) A1 therapy has been shown to be effective in the management of morphea and scleroderma, diseases that have some histological and clinical similarities with LS, and more recently in extragenital LS. AIM: To determine the effectiveness of UVA1 therapy for genital LS. METHODS: Seven women with severe genital LS uncontrolled by ultrapotent topical corticosteroids, with a median age of 62 years (range 48-78) and disease duration of 6-47 years, were treated with UVA1 therapy from a high output source. After completion of UVA1 therapy, a clinician and the patient graded the overall response of symptoms and physical signs. RESULTS: Five patients improved with therapy. Three obtained moderate improvement in overall disease severity and two had minimal improvement. Of these five, one relapsed within 3 months and another after a year. Both had a further course of UVA1 therapy, resulting in minimal improvement in one and moderate improvement in the other. In the remaining three, disease severity had improved to a point where intermittent use of topical corticosteroids resulted in acceptable control. DISCUSSION: UVA1 therapy may be of benefit in the management of vulval LS, a disease that is often poorly responsive to standard therapies. The therapy is well tolerated and could provide an acceptable therapeutic option for patients with severe disease.

UVA1 phototherapy for treatment of necrobiosis lipoidica.

The primary cause of collagen degeneration in necrobiosis lipoidica (NL) is proposed to be immunologically mediated vascular disease. Ultraviolet (UV)A1 has been used successfully to treat scleroderma in which both vascular damage and collagen dysregulation also occur. We treated six patients with NL [(five women; mean age of 32 years (range 22-70) and mean disease duration of 2.9 years (range 6 months to 5 years)] with a high-output ultraviolet (UV)A1 2-kW filtered metal halide source (Dr Hönle; Dermalight ultrA 1) having an emission spectrum of 340-440 nm. All patients had NL on the shins, which had been unresponsive to potent topical corticosteroid therapy (n = 6) and had responded minimally or not at all to TL-01 UVB (n = 2), topical psoralen plus UVA (PUVA) soaking (n = 2) or oral PUVA (n = 1) therapy. Patients received a variable number of total exposures (15-51), given 3-5 times weekly. NL resolved completely in one patient; this patient had minimal improvement after the first course of 16 exposures, but after a further 13 exposures, resolution occurred 6 months later. Two subjects obtained moderate improvement in their overall disease severity after 15 and 24 exposures, while two had only minimal improvement after 15 and 51 exposures. The remaining patient had no improvement after 16 treatments. Patients with the shortest disease duration had the greatest response. UVA1 therapy may be of benefit for the treatment of NL as an adjuvant therapy to topical corticosteroids or as a second-line alternative to other phototherapies, and may have a superior outcome in a proportion of patients.

Can St John's wort (hypericin) ingestion enhance the erythemal response during high-dose ultraviolet A1 therapy?

BACKGROUND: St John's wort (SJW) is widely used as a treatment for depression. A phototoxic reaction, due to its content of hypericin, can occur in animals and in cell culture, and has been reported in humans. Hypericin displays absorption within the ultraviolet (UV) A1 spectrum and there may therefore be a potential for phototoxicity if taken during high-dose UVA1 therapy. OBJECTIVES: To assess the phototoxicity risk of SJW ingestion. METHODS: Eleven adult volunteers of skin types I and II were exposed to a geometric dose series of UVA1 irradiation from a high-output source (Dermalight Ultra 1; Dr Hönle, Martinsreid, Germany; irradiance 70-77 mW cm(-2)) on the photoprotected lower back skin at eight 1.5-cm(2) test areas. Irradiation was carried out at baseline and after 10 days of SJW extract 1020 mg (equivalent to 3000 microg of hypericin) daily. Four, 8, 24 and 48 h after each exposure, the minimal erythema dose (MED) and the presence or absence of pigmentation were recorded visually and erythema was assessed objectively with an erythema meter. RESULTS: The median MED and D(0.025), an objective measure of MED, were lower at all time-points after SJW ingestion. The visual erythemal peak (lowest median MED), which was seen at 8 h postirradiation, was lower after SJW (median 14 J cm(-2), range 10-56) than at baseline (median 20 J cm(-2), range 14-56) (P = 0.047). Similarly, the median D(0.025) at 8 h postirradiation was lower after SJW (median 22.0 J cm(-2), range 15.2-53.9) than at baseline (median 33.7 J cm(-2), range 22.9-136.0) (P = 0.014). The MED and D(0.025) were also significantly different at the 48-h and 4-h time-points, respectively. Significance was not reached at the 24-h time-point. Median intensity of postirradiation erythema increased at all time-points after ingestion of SJW. Despite these differences, the maximum slope of the dose-response curve was not increased after SJW ingestion. CONCLUSIONS: These data suggest that SJW extract has the potential to lower the erythemal threshold to UVA1 irradiation in a significant proportion of individuals and highlight the importance of ascertaining a full drug history, including herbal remedies, before initiating UVA1 phototherapy.

Differential effects of 5-aminolaevulinic acid photodynamic therapy and psoralen + ultraviolet A therapy on p53 phosphorylation in normal human skin in vivo.

BACKGROUND: Phosphorylation of the tumour suppressor p53 by the CK2/FACT pathway plays a central role in suppressing ultraviolet (UV)-induced skin cancer in animal models. Although p53 protein stabilization is induced after solar-simulated irradiation of human skin in vivo, p53 phosphorylation has not been defined. OBJECTIVES: To investigate the effects of clinically effective treatments for skin diseases including psoralen + UVA (PUVA) and photodynamic therapy (PDT) on p53 phosphorylation to determine whether the tumour-suppressing p53 kinase pathways are activated upon use of these therapies. METHODS: We used antibodies to the ATM/ATR and CK2/FACT phosphorylation sites on p53. RESULTS: We found that p53 activation was induced selectively by PUVA treatment, while 8-oxo-7,8-dihydroguanine DNA damage was induced selectively by 5-aminolaevulinic acid (ALA)-PDT treatment. Importantly, PUVA treatment resulted in p53 kinase activation, as defined by p53 modification at AT (serine-15) and CK2/FACT (serine-392) sites within the proliferative compartment. CONCLUSIONS: These data demonstrate that PUVA provokes accumulation and phosphorylation of p53 by AT and CK2/FACT within critical proliferative focal points (as determined by p63 colocalization studies) where DNA damage may lead to tumorigenesis. PDT is mechanistically distinct in that there is a lower level of induction of p53 expression with no evidence of AT- or CK2/FACT-mediated phosphorylation. This suggests that the type of DNA damage created by the reactive oxygen species generated by ALA-PDT does not induce the p53 pathway classically required for the repair of DNA photoadducts induced by UV.

The effect of ultraviolet (UV) A1, UVB and solar-simulated radiation on p53 activation and p21.

BACKGROUND: High-dose ultraviolet (UV) A1 therapy (doses in the order of 130 J cm(-2)) is effective for atopic dermatitis and scleroderma. UVA1 has been shown to induce a dose-dependent increase in p53 expression in keratinocytes. OBJECTIVES: To examine the effect of UVA1 on the activation of p53 by phosphorylation, which has not yet been studied. METHODS: Five adult volunteers were exposed to dose series of UVA1 (10-100 J cm(-2)) and, for comparison, narrowband UVB (TL-01) (25-550 mJ cm(-2)) and solar-simulated radiation (SSR) (5.6-30 J cm(-2)) on photoprotected buttock skin and the minimal erythema dose (MED) for each was determined at 24 h. Separate sites on the buttock were subsequently irradiated with a 3-MED dose of UVA1, TL-01 and SSR. At 24 h, punch biopsies (4 mm) were taken from each irradiated site and from an adjacent unirradiated control site, and immunohistochemical staining for p53 (Do-1), activation of p53 (assessed by phosphorylation at serine 15 and serine 392) and p21 was performed. Cell staining was expressed as the mean number of cells stained per three high-power fields (HPFs) and as a percentage of 1000 cells. Sunburn cells (SBCs) were also counted per HPF. RESULTS: UVA1 produced negligible numbers of SBCs, relatively little p53 (Do-1) staining (mean +/- SD cell count per HPF 16 +/- 10), no p53 activation and very little evidence of p21 expression (mean +/- SD cell count per HPF 5.3 +/- 7), in contrast to TL-01 (mean +/- SD cell count per HPF of 11.83 +/- 2.1 SBCs, 146.3 +/- 38 for Do-1, 26.6 +/- 15 for serine 15, 14.9 +/- 12 for serine 392 and 77.9 +/- 30 for p21) or SSR irradiation (mean +/- SD cell count per HPF of 3.5 +/- 1.2 SBCs, 147.5 +/- 62 for Do-1, 54 +/- 50 for serine 15, 38.9 +/- 18 for serine 392 and 56.7 +/- 30 for p21). CONCLUSIONS: These data indicate that there are fundamental differences in the effects of UVA1 on p53 and its activation pathways compared with TL-01 and SSR, and may in part explain the differential effects of these phototherapies.

Photogenotoxicity of hypericin in HaCaT keratinocytes: implications for St. John's Wort supplements and high dose UVA-1 therapy.

Extract of St. John's Wort (Hypericum perforatum) is commonly used as natural remedy for treatment of mild to moderate depression. However, it contains a powerful photoactive component, hypericin, which can cause a severe photodermatitis when eaten by grazing animals (hypericism). In humans, there is evidence that supplementation with St. John's Wort can reduce the minimal erythemal dose (MED) in patients undergoing high dose UVA-1 phototherapy. This is a recent development in phototherapy where the most erythemogenic parts of the UVA spectrum are filtered out, allowing delivery of higher doses of the longer wavelengths of UVA. Although current published evidence suggests that the plasma levels of hypericin are unlikely to cause clinical phototoxicity, it has been established that photoactive compounds can cause DNA damage at sub-toxic and sub-erythemal doses, the effects of which might not be apparent for many years after the event. The present study used HaCaT keratinocytes to investigate the photoclastogenic ability of hypericin on irradiation with UVA. The results show that although the combination of hypericin and UVA light increased the genotoxic burden, when all factors are taken into account, the risk of significant photogenotoxic damage incurred by the combination of Hypericum extracts and UVA phototherapy may be low in the majority of individuals.

Can a positive photopatch test be elicited by subclinical irritancy or allergy plus suberythemal UV exposure?

Photopatch test (PhPT) interpretation is difficult and clinical relevance is not always apparent. A positive PhPT may reflect photocontact allergy or phototoxicity. We hypothesized that it may also reflect the additive or synergistic effects of a suberythemal reaction to a contact irritant [e.g. sodium lauryl sulfate (SLS)] or allergen (e.g. nickel) and suberythemal UV exposure. 10 nickel allergic volunteers had duplicate SLS and nickel series applied on either side of the back for 24 h and 48 h, respectively. After removal, one side was irradiated with 5 J/cm(2) UVA or the dose below the minimal erythema dose for solar-simulated radiation (SSR). The minimal irritancy dose (MID) for SLS and the minimal allergenic dose (MAD) for nickel were determined visually and objectively by erythema meter. While photoaugmentation of subclinical contact allergy or irritancy occurred in some subjects, photosuppression occurred in roughly an equal number. UVA changed the nickel MAD at 48 h in 2 of 5 volunteers but not the SLS MID. SSR changed the nickel MAD in 4 of 5 and the SLS MID in 3 of 5. 2 subjects (none after UVA) showed erythema only in the irradiated set of patches, which could have been interpreted as a positive PhPT. We have demonstrated photoaugmentation and photosuppression of contact allergy and irritancy, which could result in false-positive or false-negative interpretation of PhPTs.

A pilot study on the use of wet wraps in infants with moderate atopic eczema.

Wet wrap therapy (WWT) is a well-established treatment for severe atopic dermatitis (AD). However little evidence exists to justify widespread use in the community for less severe eczema. We compared the efficacy of WWT with a standard regime of hydrocortisone, to control moderate AD in children. We carried out a single-observer, randomized, controlled pilot study in 19 children under 5 years of age, with AD of 30% or more body surface area, using only 1% hydrocortisone (HC) prior to the study. Group one applied HC once in the morning for 2 weeks, with wet wraps twice daily for week 1, but only at night for week 2. Group two applied HC twice daily without wet wraps. Both applied emollient twice daily and as necessary. The primary outcome measure was the Six Area, Six Sign Atopic Dermatitis (SASSAD) severity score, and the secondary outcome measures were the Infants Dermatology Quality of Life Index (IDQOL), the Dermatitis Family Impact (DFI) score and the weight of topical steroids and emollients used. Over the 2-week active therapy period the mean fall in SASSAD was 8 [95% confidence interval (CI), -18 to +2; P = 0.11] more in the non-WWT group, the median change in the IDQOL was 2 for Group one and 7 for Group two (95% CI for difference, -10 to +3; P = 0.24) and the median change in DFI score was 2 for Group one and 5 for Group two (95% CI for difference, -14 to +2; P = 0.42). This small study has shown that conventional therapy with HC and emollients alone is as effective as WWT for infants with moderately severe, widespread AD, and provides weak evidence to suggest that it may be more effective. We would not advocate routine use of WWT for moderate eczema without further evaluation.

Parental knowledge of topical therapies in the treatment of childhood atopic dermatitis.

Poor adherence with therapy is a major cause of treatment failure in atopic dermatitis. Reasons given are multifactorial, and include fear of real or imaginary side-effects, under-prescribing, failure to renew prescriptions on time, lack of time, and child refusal of therapy. Most important, however, is lack of knowledge about treatment, in particular the use of topical corticosteroid (TCS) therapy. We conducted a questionnaire-based study to determine the level of use and knowledge of commonly prescribed TCS preparations amongst parents or carers of 100 children attending paediatric outpatient clinics. Weakly potent TCSs were the most commonly used (86%), but poorly understood. Only 35 (41%) who had used hydrocortisone were aware that it was weakly potent, and 44% graded it as moderately potent. Of 65 who had used the moderately potent TCS clobetasone butyrate 0.05% (Eumovate); Glaxo Wellcome, Uxbridge, UK), 19 (29%) graded it as potent and eight (12%) as weak. Of 50 who had used betamethasone valerate 0.1% (Betnovate); Glaxo Wellcome, Uxbridge, UK), 42% did not grade it as potent. Understanding of TCS/antimicrobial combinations was generally worse. The hydrocortisone 1%/fusidic acid 2% combination (Fucidin H(R); Leo, Risborough, Bucks, UK) was graded as moderate or strong by 88% of the 74 who had used it. Over half (53%) of the 34 using the combination of clobetasone butyrate 0.05%/nystatin 100000 i.u./g tetracycline 3% (Trimovate); Glaxo Wellcome, Uxbridge, UK) assumed that it was a potent TCS. Forty-nine had used Fucibet (betamethasone valerate 0.1%, fusidic acid 2%; Leo, Risborough, Bucks, UK) but 34.5% did not grade it as potent. There was poor knowledge of the strengths of some of the most commonly used TCSs, and all steroid/antimicrobial combinations were perceived as being of greater potency than the constituent steroid alone. Fusidic acid was thought to be a steroid by almost half (46.9%) of the respondents. The packaging of the different products by some pharmaceutical companies is remarkably similar and labelling contains information on the compound and percentage rather than potency of the TCS. This may be a source of confusion. We recommend that manufacturers clearly label TCS products by potency as mild, moderate, potent or very potent and that packaging is sufficiently different for each strength of TCS or emollient to avoid confusion. In order to achieve optimal topical treatment for atopic dermatitis, patients and their carers must receive adequate information and training in how and when to use topical therapies in conjunction with written care plans.