R.A.C. Graham-Brown

Double-blind, controlled, crossover study of cyclosporin in adults with severe refractory atopic dermatitis

A few patients remain severely affected by atopic dermatitis into adult life despite treatment with systemic steroids, azathioprine, and photochemotherapy. 33 patients took part in a double-blind, placebo-controlled, crossover study to assess the efficacy and safety of cyclosporin (5 mg/kg per day) in adults with severe refractory atopic dermatitis. Treatments were given for eight weeks each with one group (n = 16) receiving placebo followed by cyclosporin and another (n = 17) receiving cyclosporin and then placebo. Disease activity, extent of disease, sleep and itch, topical steroid use, and adverse events were assessed every two weeks. Both extent and activity of dermatitis were significantly improved (p less than 0.001) as were subjective measures of disease. 20 patients receiving cyclosporin reported adverse events compared with 8 taking placebo, although no patient required withdrawal from the study. Cyclosporin therapy led to an increase in the mean serum urea, creatinine, and bilirubin concentrations, although only the rise in bilirubin was significant (p = 0.001). Our results confirm that cyclosporin is a safe and effective short-term treatment for severe, refractory atopic dermatitis.

Cyclosporin for severe childhood atopic dermatitis: short course versus continuous therapy.

Cyclosporin (CyA) has been shown to be highly effective and well tolerated in the short‐term treatment of severe childhood atopic dermatitis; however, there is limited experience in its longer‐term use. The aim of this study was to compare multiple short courses of CyA with continuous therapy for 1 year, with respect to efficacy, safety, tolerability and quality of life. Children aged 2–16 years, with a diagnosis of severe atopic dermatitis refractory to topical steroid therapy, were randomly assigned to receive short course therapy (multiple courses of 12 weeks) or continuous therapy. The starting dose and maximum dose for all patients was 5 mg/kg per day. Disease activity was monitored using the Six Area Six Sign Atopic Dermatitis score and the ‘Rule of Nines’ area score. Pruritus, sleep disturbance and irritability were measured using visual analogue scales, and topical therapy was monitored. Safety measurements included monitoring of serum creatinine, blood pressure and adverse events. Forty patients were included in the efficacy analysis, 21 of whom were randomized to the short course group (of whom six were withdrawn) and 19 to the continuous group (of whom five were withdrawn). Significant improvements were seen in all efficacy parameters at every time‐point. There were no significant differences between groups, although the improvement was more consistent in the continuous arm. In the short course arm, 7 out of 21 patients could be managed by at least two short courses. The remaining 14 patients includes 12 who could not be controlled by at least two short courses, one patient who failed to return after week 12 and another patient who was withdrawn at week 4 due to an adverse event. Quality of life improved for both the children and their families. Tolerability was considered good or very good in at least 80% of the patients at week 12 and at the end of the study. No clinically significant change was seen in mean serum creatinine and no change was seen in mean blood pressure in either group. CyA is effective in controlling severe atopic dermatitis in children over a 1‐year period and is well tolerated. More consistent control is achieved with continuous treatment; however, short course therapy was adequate for some patients, indicating that treatment should be tailored to the individual patient’s needs. Short course treatment may produce prolonged remission in some cases and reduce the cumulative exposure to the drug.

Cyclosporin greatly improves the quality of life of adults with severe atopic dermatitis. A randomized, double-blind, placebo-controlled trial.

A multicentre, randomized, double‐blind, controlled crossover clinical trial was conducted on 33 patients with severe refractory atopic dermatitis, to determine the effects of cyciosporin (5 mg/kg/day) on their health‐related quality of life. Treatments were administered for 8‐week periods. One group (n=16) received placebo followed by cyclosporin, and the other (n=17) received cyclosporin and then placebo. Health‐related quality of life was assessed at o, 8 and 16 weeks using a general measure, the United Kingdom Sickness Impact Profile (UKSIP), an eczema‐specibic measure, the Eczema Disability Index (EDI), and a global 5‐point rating scale of overall health (very good to very poor). In addition, clinical assessments (i.e. extent and activity of disease) were made by the investigators.

Azathioprine in severe adult atopic dermatitis: a double-blind, placebo-controlled, crossover trial

Summary Background There is a limited range of treatments for severe atopic dermatitis (AD). Azathioprine has often been used but there has been no randomized controlled trial of this drug to confirm its efficacy in AD.

Cyclosporine in severe childhood atopic dermatitis: A multicenter study

BACKGROUND Severe atopic dermatitis (AD) remains difficult to treat. Cyclosporine is effective in adults but has not previously been investigated in children with AD. OBJECTIVE The aims were to investigate the efficacy, safety, and tolerability of cyclosporine in severe refractory childhood AD. METHODS Subjects 2 to 16 years of age were treated for 6 weeks with cyclosporine, 5 mg/kg per day, in an open study. Disease activity was monitored every 2 weeks by means of sign scores, visual analogue scales for symptoms, and quality-of-life questionnaires. Adverse events were monitored. Efficacy and tolerability were assessed with five-point scales. RESULTS Twenty-seven children were treated. Significant improvements were seen in all measures of disease activity. Twenty-two showed marked improvement or total clearing. Quality of life improved for both the children and their families. Tolerability was considered good or very good in 25 subjects. CONCLUSION Cyclosporine may offer an effective, safe, and well-tolerated short-term treatment option for children with severe AD.

Long-term efficacy and safety of cyclosporin in severe adult atopic dermatitis.

A prospective, open, multicentre study was performed to investigate the efficacy and safety of longterm treatment with cyclosporin in adults with severe atopic dermatitis. Subjects were treated for a maximum of 48 weeks. For the first 8 weeks, cyclosporin was administered at 2.5 mg/kg per day. The dose was then adjusted according to response. Disease activity was monitored using the six‐area. six‐sign score and the proportion of skin involved. Pruritus and sleep disturbance were assessed using four‐point scales. Response was further evaluated on a five‐point scale. Adverse events. blood pressure and serum biochemistry were monitored. Tolerability was assessed on a five‐point scale.

Placebo-controlled trial of essential fatty acid supplementation in atopic dermatitis

Treatment of atopic dermatitis with essential fatty acids remains controversial. A double-blind, placebo-controlled, parallel-group study was done to investigate the response of patients with atopic dermatitis to essential fatty acid supplements. Patients with atopic dermatitis were randomised to receive evening primrose oil, evening primrose oil and fish oil, or placebo for 16 weeks. Disease activity was monitored by clinical severity scores recorded by the investigator, topical steroid requirement, and symptom scores recorded by subjects. Of 123 subjects recruited, 102 completed the treatment period. No improvement with active treatment was demonstrated. Our study, which avoided the methodological and analytical problems of previous studies, found no effect of essential fatty acid supplementation in atopic dermatitis.

Anti-e-selectin is ineffective in the treatment of psoriasis: A randomized trial

Summary Background Skin‐homing, memory T lymphocytes play an important role in the pathogenesis of psoriasis by interacting with the vascular addressin, E‐selectin and trafficking into lesional skin. Thus an attractive option for targeted therapy of the disease would be blockade of skin‐homing T cells with an antibody directed at E‐selectin.

Sweet's syndrome and malignancy in the U.K.

Acute febrile neutrophilic dermatosis (Sweets syndrome) is reported to be a marker for underlying malignancy. Much of the evidence for this is based on case reports, small series of cases and reviews of the literature. In order to clarify the association with malignancy and determine the common clinical features of Sweets syndrome, we reviewed the case notes of patients presenting to six dermatology units in the U.K. Eighty‐seven cases of histologically proven Sweets syndrome were reviewed. Fourteen patients (16%) developed associated malignancy, predominantly haematological, two patients (2%) had a history of previous malignancy and four patients (5%) had premalignant conditions (monoclonal gammopathy, two: myelodysplasia, two). Malignancy developed up to a year after presentation with Sweets syndrome. Patients with associated malignancy were more likely to be anaemic (P<0·01) at presentation, had a lower mean platelet count (207 × 109/L vs. 332 × 109/L: P<0·003) and were, on average, older (59 years vs. 49 years: P = 0·002). Contrary to previous reports, a greater percentage of females developed malignancy than males.

An evaluation of the revised seven-point checklist for the early diagnosis of cutaneous malignant melanoma.

Summary The seven‐point checklist has been widely advocated as a sensitive screening test for malignant melanoma. A number of groups have questioned the sensitivity of this system, especially in the detection of early lesions. We have assessed the sensitivity and specificity of the revised seven‐point checklist when applied to lesions seen in our department over a 26‐month period and compared it with the American ABCDE evaluation system. All melanomas (n= 65) were detected using the revised seven‐point checklist and all were found to have at least one of the three major criteria defined by that system. Five (7·7%) melanomas were not picked up by the ABCDE checklist. Of 100 randomly selected patients who attended the clinic during the same period, with clinically diagnosed benign pigmented lesions, 63 had at least one major feature of the revised seven‐point checklist. Forty (62%) of the melanomas, compared with only (4%) of the benign lesions, had more than one major feature. This study confirms the sensitivity of the revised seven‐point checklist in the diagnosis of cutaneous malignant melanoma.