U.K. consensus statement on safe clinical prescribing of bexarotene for patients with cutaneous T-cell lymphoma.

BACKGROUND: Bexarotene is a synthetic retinoid from the subclass of retinoids called rexinoids which selectively activate retinoid X receptors. It has activity in cutaneous T-cell lymphoma (CTCL) and has been approved by the European Medicines Agency since 1999 for treatment of the skin manifestations of advanced-stage (IIB-IVB) CTCL in adult patients refractory to at least one systemic treatment. In vivo bexarotene produces primary hypothyroidism which may be managed with thyroxine replacement. It also affects lipid metabolism, typically resulting in raised triglycerides, which requires prophylactic lipid-modification therapy. Effects on neutrophils, glucose and liver function may also occur. These side-effects are dose dependent and may be controlled with corrective therapy or dose adjustments. OBJECTIVES: To produce a U.K. statement outlining a bexarotene dosing schedule and monitoring protocol to enable bexarotene prescribers to deliver bexarotene safely for optimal effect. METHODS: Leaders from U.K. supraregional centres produced this consensus statement after a series of meetings and a review of the literature. RESULTS: The statement outlines a bexarotene dosing schedule and monitoring protocol. This gives instructions on monitoring and treating thyroid, lipid, liver, blood count, creatine kinase, glucose and amylase abnormalities. The statement also includes algorithms for a bexarotene protocol and lipid management, which may be used in the clinical setting. CONCLUSION: Clinical prescribing of bexarotene for patients with CTCL requires careful monitoring to allow safe administration of bexarotene at the optimal dose.

A multicentre randomised controlled trial and economic evaluation of ion-exchange water softeners for the treatment of eczema in children: the Softened Water Eczema Trial (SWET).

OBJECTIVES: To determine whether installation of an ion-exchange water softener in the home could improve atopic eczema in children and, if so, to establish its likely cost and cost-effectiveness. DESIGN: An observer-blind, parallel-group randomised controlled trial of 12 weeks duration followed by a 4-week observational period. Eczema was assessed by research nurses blinded to intervention at baseline, 4 weeks, 12 weeks and 16 weeks. The primary outcome was analysed as intent-to-treat, using the randomised allocation rather than actual treatment received. A secondary per-protocol analysis excluded participants who failed to receive their allocated treatment and who were deemed to be protocol violators. SETTING: Secondary and primary care referral centres in England (UK) serving a variety of ethnic and social groups and including children living in both urban and periurban homes. PARTICIPANTS: Three hundred and thirty-six children (aged 6 months to 16 years) with moderate/severe atopic eczema, living in homes in England supplied by hard water (≥ 200 mg/l calcium carbonate). INTERVENTIONS: Participants were randomised to either installation of an ion-exchange water softener plus usual eczema care (group A) for 12 weeks or usual eczema care alone (group B) for 12 weeks. This was followed by a 4-week observational period, during which water softeners were switched off/removed from group A homes and installed in group B homes. Standard procedure was to soften all water in the home, but to provide mains (hard) water at a faucet-style tap in the kitchen for drinking and cooking. Participants were therefore exposed to softened water for bathing and washing of clothes, but continued to drink mains (hard) water. Usual care was defined as any treatment that the child was currently using in order to control his or her eczema. New treatment regimens used during the trial period were documented. MAIN OUTCOME MEASURES: Primary outcome was the difference between group A and group B in mean change in disease severity at 12 weeks compared with baseline, as measured using the Six Area, Six Sign Atopic Dermatitis (SASSAD) score. This is an objective severity scale completed by blinded observers (research nurses) unaware of the allocated intervention. Secondary outcomes included use of topical medications, night-time movement, patient-reported eczema severity and a number of quality of life measures. A planned subgroup analysis was conducted, based on participants with at least one mutation in the gene encoding filaggrin (a protein in the skin thought to be important for normal skin barrier function). RESULTS: Target recruitment was achieved (n = 336). The analysed population included 323 children who had complete data. The mean change in primary outcome (SASSAD) at 12 weeks was -5.0 [standard deviation (SD) 8.8] for the water softener group (group A) and -5.7 (SD 9.8) for the usual care group (group B) [mean difference 0.66, 95% confidence interval (CI) -1.37 to 2.69, p = 0.53]. The per-protocol analysis supported the main analysis, and there was no evidence that the treatment effect varied between children with and without mutations in the filaggrin gene. No between-group differences were found in the three secondary outcomes that were assessed blindly (use of topical medications; night-time movement; proportion showing reasonable, good or excellent improvement). Small, but statistically significant, differences in favour of the water softener were found in three of the secondary outcomes that were assessed by participants [Patient-Oriented Eczema Measure (POEM); well-controlled weeks (WCWs); Dermatitis Family Index (DFI)]. The results of the economic evaluation, and the uncertainty surrounding them, suggest that ion-exchange water softeners are unlikely to be a cost-effective intervention for children with atopic eczema from an NHS perspective. CONCLUSIONS: Water softeners provided no additional benefit to usual care in this study population. Small, but statistically significant, differences were found in some secondary outcomes as reported by parents, but it is likely that such improvements were the result of response bias. Whether or not the wider benefits of installing a water softener in the home are sufficient to justify the purchase of a softener is something for individual householders to consider on a case-by-case basis. This trial demonstrated overwhelming demand for non-pharmacological interventions for the treatment of eczema, and this is something that should be considered when prioritising future research in the field. TRIAL REGISTRATION: Current Controlled Trials ISRCTN71423189. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 15, No. 8. See the HTA programme website for further project information. Results of this trial are also published at www.plosmedicine.org.

Everyday clinical experience of alitretinoin in the treatment of severe chronic hand eczema: seven case studies.

Chronic hand eczema (CHE) is a debilitating and distressing disease for patients, the physical symptoms of which are compounded by psychosocial problems. Alitretinoin is an endogenously occurring physiological vitamin A derivative (retinoid) that possesses strong anti-inflammatory and immunomodulatory activity. It is currently the only licensed product for severe CHE unresponsive to treatment with potent topical corticosteroids, and has been proven to be highly effective in clinical trials with two-thirds of patients who responded to treatment remaining in remission at 6 months. For those that did relapse, a second study showed they could be successfully retreated with a further 3-6 month course of alitretinoin. Seven case studies of alitretinoin have been provided by consultant dermatologists showing its use in normal UK clinical practice. The cases chosen demonstrate the efficacy of alitretinoin across several different subtypes of CHE, and the positive effects the treatment brought to patients' quality of life.

Report from the 67th annual meeting of the American Academy of Dermatology.

The 67th Annual Meeting of the American Academy of Dermatology took place in San Francisco on 6-10 March 2009. The flavour of this busy but well-organized convention was a mixture of practical, hands-on teaching sessions, led and delivered by experts, with breakthrough cutting-edge scientific sessions. Aesthetic dermatology comprised a significant part of the meeting. It is impossible to encompass all the important presentations made at the meeting and satellite symposiums, but we highlight here a few medical pearls on dermoscopy, melanoma and oncology, inflammatory dermatoses and community-acquired methicillin-resistant Staphylococcus aureus. Our report is not intended as a substitute for reading the conference proceedings, educational session handouts, online updates and related references quoted in this article.

The use of dietary manipulation by parents of children with atopic dermatitis.

BACKGROUND: In 1989 we demonstrated that 71% of children referred to our paediatric dermatology clinic with atopic dermatitis (AD) had been subject to dietary manipulation by their parents in order to manage their disease. We have re-examined our clinic population to determine whether the documented rise in the use of complementary therapy in children with skin disease has been accompanied by a rise in dietary manipulation. OBJECTIVES: To qualify and quantify the usage of dietary manipulation in children with AD in secondary care. METHODS: A face-to-face structured questionnaire study of 100 children with AD. RESULTS: The mean age of the children interviewed was 7.3 years (median 5.9, range 0.6-17.1) and ethnic origin was 59% white, 35% Indo-Asian, 3% Afro-Caribbean and 3% mixed race. Seventy-five per cent of patients (75 of 100) had tried some form of dietary exclusion; the most common foods omitted were dairy products in 48% (36 of 75), eggs in 27% (20 of 75) and cow's milk in 25% (19 of 75). Forty-one per cent of patients (41 of 100) had tried some form of dietary supplementation. The most common dietary supplement was evening primrose oil in 59% (24 of 41), of whom 13% (three of 24) felt this had helped their skin. Only 51% (38 of 75) had consulted a doctor or dietician before commencing any dietary change, but 39% (29 of 75) felt that their skin had improved as a result of this dietary manipulation. CONCLUSIONS: In comparison with our previous study, the proportion of patients excluding foods from their diet had increased from 71% to 75%. The proportion of these dietary changes that are unsupervised has remained the same, as have the food types avoided. The proportion of patients who report that unsupervised dietary manipulation is beneficial has increased from 10% to 39%.

Nail dystrophy, an unusual presentation of incontinentia pigmenti.

We describe a 57-year-old woman with a history of nail dystrophy since the age of 11 years. Multiple nail clippings were negative and multiple empirical treatments for presumed onychomycosis were unsuccessful. The patient has a daughter with classical incontinentia pigmenti. Molecular genetic analysis was positive for the NEMO gene deletion on the X chromosome, confirming the diagnosis of incontinentia pigmenti. Nail dystrophy was the sole feature of the disease in our patient.

The use of complementary medicine in children with atopic dermatitis in secondary care in Leicester.

BACKGROUND: The use of 'complementary' or 'alternative' medicine continues to rise in patients with skin disease, especially in those with chronic, inflammatory dermatoses. OBJECTIVES: To qualify and quantify the usage of complementary medicine (CM) in children with atopic dermatitis (AD) in secondary care. METHODS: A face-to-face structured questionnaire study of 100 consecutive children with AD and their parent or guardian. RESULTS: The mean age of the children interviewed was 7.3 years (median age 6.0 years, range 0.6-17.1) and ethnic origin was 59% white, 35% Indian, 3% Afro-Caribbean and 3% mixed race. Forty-six of 100 patients (46%) had used, or were currently using, CM. Of the 54 patients who had not yet used CM, 17 of 54 (31%) said they intended to try this in the future. The most commonly used CM was Chinese herbal medicine by 20 of 46 patients (43% of those who had used CM), followed by herbal medicine (41%) and homeopathy (35%). Of 74 patients using CM, 26 (35%) felt their AD had improved while 39 of 74 (53%) reported that it had remained unchanged. Twenty-six of 46 (56%) CM users in this study would not recommend CM to other patients with AD. There was a strong association between the use of CM and ethnicity (P = 0.01). Half of the patients who had used CM (23 of 46) had used it on the recommendation of family or friends with skin disease, 17 of 46 (37%) from family or friends without skin disease and three of 46 (6%) each from health professionals or from the media or internet. Twenty-five of 46 (54%) of CM users did so because conventional treatment was not working, and eight of 46 (17%) because they were worried about the side-effects of conventional treatment. While 39 of 100 (39%) of all patients felt that CM was safer than conventional medicine, only 14 of 100 felt it was more efficacious. Fifty-one of 100 were happy to combine both types of treatment and 66 of 100 felt that CM should be available from the National Health Service. CONCLUSIONS: In a population of children with AD attending a teaching hospital clinic in Leicester, U.K., 63% use or intend to use CM. This use is associated with ethnicity.

Pimecrolimus: a review of pre-clinical and clinical data.

Pimecrolimus (Elidel) is a novel cell-selective inhibitor of inflammatory cytokines that has specifically been developed for the treatment of inflammatory skin diseases due to its favourable skin selective pharmacological profile. Therapeutic efficacy and safety of pimecrolimus cream 1% has been established in the short-term treatment and the long-term management of atopic eczema in clinical studies in adults, children and infants. It rapidly relieves pruritus, and redness and swelling disappear or are only mild in up to 70% of pimecrolimus treated patients during the first three weeks. When applied at the first signs and symptoms of atopic eczema, pimecrolimus has proven to prevent flare progression and to provide superior long-term disease control compared with a conventional treatment, based on reactive use of corticosteroids. Pimecrolimus cream 1% is well tolerated, even on sensitive areas such as the face and neck. Blood concentrations remain low, even when extensive body areas are treated and no clinically significant systemic effects have been observed during short- or long-term clinical studies with pimecrolimus.

Neonatal erythema multiforme major.

A 25-day-old neonate developed an unusual eruption with bullae and marked systemic symptoms. Investigation for bacterial, viral, autoimmune and immunobullous causes did not reveal any identifiable trigger and histological examination was highly suggestive of bullous erythema multiforme. Pulmonary infiltrates were noted late in the course of the disease. Differential diagnoses included bullous impetigo, primary herpes simplex infection, immunobullous disease, neonatal lupus and erythema multiforme. This case illustrates the difficulties in diagnosing and managing an unwell child with bullae and emphasizes the need to exclude treatable underlying causes.

Atopic dermatitis management: comparing the treatment patterns of dermatologists in Japan, U.S.A. and U.K.

BACKGROUND: The incidence of atopic dermatitis (AD) is increasing worldwide. No large-scale study has previously compared the therapeutic management of this condition in different countries. OBJECTIVES: The purpose of this study was to determine the treatment preferences of dermatologists in Japan, the U.S.A. and the U.K., and investigate their relationship with certain factors pertaining to the physician and his practice. METHODS: A questionnaire was sent to all registered members of dermatological societies in Japan, the U.S.A. and the U.K. Responses were collated and statistical analysis performed using chi2, Mantel-Haenszel and Breslow heterogeneity tests. RESULTS: Three thousand six hundred and eighty-eight completed surveys were returned. U.S.A. and U.K. physicians were significantly more aggressive in prescribing systemic medications, such as steroids, antibiotics and immunosuppressants, compared with those in Japan. Japanese dermatologists also utilized topical steroids significantly less. The use of alternative remedies was highest in Japan. All three countries had a relatively high degree of optimism for topical immunosuppressants, but less so for other emerging therapies. CONCLUSIONS: Both similarities and differences in the therapy of AD exist in the three countries studied. Factors related to the physician, patient population and culture may influence these observations.