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.

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 relationship between T lymphocyte subsets and Ia-like antigen positive nonlymphoid cells in early stages of cutaneous T cell lymphoma.

Immunofluorescence studies were carried out in cutaneous T cell lymphoma (mycosis fungoides) in order to analyse the microanatomical relationship of the different T lymphocyte subsets (inducer and suppressor/cytotoxic cell populations) to large nonlymphoid Langerhans-type and so-called "indeterminate" or interdigitating cells. The conventional and mouse (monoclonal) antibodies were used in various combinations using fluorescein and rhodamine labeled second layers. In 5 of the 7 cases studied the dermal infiltrate consisted of numerous T (HuTLA+) lymphocytes, 80-90% of which expressed the inducer phenotype (HuTLA+,OKT4+). Most of these cells formed close contact with large cells exhibiting large amounts of Ia-like antigens. These cells corresponded to the interdigitating and indeterminate cells in the sections. By contrast, only small numbers (10-20%) of T cells of suppressor/cytotoxic type (HuTLA+,OKT8+) were seen. These did not show a close affinity to the Ia-like antigen positive nonlymphoid component but appeared to have a predilection for the epidermis. Epidermal Langerhans cells, also strongly Ia-like antigen positive, were further defined by 2 monoclonal antibodies reacting with a cortical thymocyte antigen HTA-1. Although Langerhans cells are probably related to the Ia-like antigen positive dermal cells only a few of the abundant latter population were HTA-1+. In the remaining 2 cases, larger populations of OKT8+ (suppressor/cytotoxic) cells were seen and could be heralding a particularly benign course. These observations indicate a close functional relationship between the lymphoid and Ia-like antigen positive dermal cells during the pre-malignant phase of cutaneous T cell lymphoma.

Managing adults with atopic dermatitis.

The majority of the patients with atopic dermatitis (AD) that dermatologists see present to us in childhood. For most patients there is a relatively limited period during which AD is a major influence on their lives. For some patients, however, AD behaves differently and also may cause significant trouble during adolescence and adult life. In this article, adult hood means from approximately puberty onward, but in addition to the issues relating to what amounts to a lifelong chronic disability, there are some points that need to be made about adolescents in particular.

Median nasal dermoid fistulae.

Two cases of median nasal dermoid fistulae are presented. This is an uncommon developmental abnormality which may present either to ENT Surgeons, Plastic Surgeons, or Dermatologists. Although the extent of the tract in our cases was small, careful pre-operative assessment is required as the tract may be extensive.

How many GP referrals to dermatology outpatients are really necessary?

In a survey of patients referred to the dermatology outpatients department of a British teaching hospital, 26% of referrals were considered unnecessary by a senior house officer with three months practical dermatological experience. We conclude that better undergraduate and postgraduate education in dermatology is essential. A period spent in dermatology should be included in all vocational training schemes for general practice.

Treatment of basal cell carcinoma with intralesional interferon alpha-2b.

We report a series of 11 basal cell carcinomas of various types treated with nine intra-lesional injections of 1.5 million units of interferon alpha-2b. The diagnosis was confirmed histologically in each case. After 3 months' follow-up six tumours had resolved both clinically and histologically. In three cases the tumour size was reduced. One tumour grew larger. Side effects were well tolerated except by one subject who was withdrawn. Those cases which responded have now been followed-up for between 12 and 26 months with no clinical or histological evidence of tumour recurrence. This is the longest period of follow-up so far reported for this novel treatment. The results are encouraging and, if maintained in future series, may indicate a useful role for interferon alpha in the management of this common cutaneous malignancy.

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.