N. J. Levell

Maintenance treatment with cyclosporin in atopic eczema

Summary We have studied two reducing‐dose regimens intended to minimize toxicity of cyclosporin A (CyA) while maintaining its capacity to control atopic eczema following induction of remission. Twenty‐four patients with severe chronic atopic eczema were first treated in a double‐blind randomized placebo‐controlled cross‐over study of CyA (5 mg/kg/day). All 19 who completed the study showed the expected highly significant improvements, compared with placebo, in area involved, erythema, excoriation, lichenification, itch and requirement for topical steroid. In 17 of the 19 patients, control was re‐established with CyA 5 mg/kg/day, and they were then re‐randomized to stepwise reduction at 2‐week intervals in either (i) the dose of CyA given daily, or (ii) the frequency with which the 5 mg/kg dose was given. Fifteen patients (seven continuous reducing dose, eight intermittent fixed dose) completed the planned reduction to either 1 mg/kg/day or 5 mg/kg every fifth day. In both groups the response was sustained despite dose reduction, although control was less good at a continuous dose of 1 mg/kg. Intermittent treatment was as good as or better than continuous reducing dosage in this study, and in both groups there was further deterioration after the drug was stopped. The findings suggest that the dose of CyA required to control atopic eczema is less than that required to achieve remission, and that the therapeutic index can be further improved by alternative dosing strategies. This offers a new approach to maintenance treatment of eczema and other chronic refractory dermatoses.

Melanoma epidemic: a midsummer night's dream?

Background  The reported incidence of melanoma has greatly increased and this has been attributed to ultraviolet exposure.

Elevated matrix metalloproteinase-2 and -3 production from human diabetic dermal fibroblasts.

Summary Background Diabetic foot ulcers are characterized by elevated levels of matrix metalloproteinases (MMP), which could lead to excessive matrix breakdown and disruption to healing. It is unknown if this elevation is a function of wound healing, or if it is present within normal skin and a primary contributor to the increased risk of impaired healing.

Severe lower limb cellulitis is best diagnosed by dermatologists and managed with shared care between primary and secondary care

Background  Cellulitis is responsible for over 400 000 bed days per year in the English National Health Service (NHS) at the cost of £96 million.

Systemic corticosteroids in the phenytoin hypersensitivity syndrome

A patient is described with the characteristic‐ features of phenytoin hypersensitivity syndrome (PHS) including fever, erythroderma, tibial and facial oedema. pinhead‐sized facial pustules und abnormal liver function tests. The use of systemic corticosteroids in this condition is not established. We report the resolution of all the features of PHS with systemic corticosteroids and recurrence on withdrawal, and further remission on reinstitution of systemic corticosteroids.

Doxycycline versus prednisolone as an initial treatment strategy for bullous pemphigoid: a pragmatic, non-inferiority, randomised controlled trial

Summary Background Bullous pemphigoid is a blistering skin disorder with increased mortality. We tested whether a strategy of starting treatment with doxycycline gives acceptable short-term blister control while conferring long-term safety advantages over starting treatment with oral corticosteroids. Methods We did a pragmatic, multicentre, parallel-group randomised controlled trial of adults with bullous pemphigoid (three or more blisters at two or more sites and linear basement membrane IgG or C3). Participants were randomly assigned to doxycycline (200 mg per day) or prednisolone (0·5 mg/kg per day) using random permuted blocks of randomly varying size, and stratified by baseline severity (3–9, 10–30, and >30 blisters for mild, moderate, and severe disease, respectively). Localised adjuvant potent topical corticosteroids (<30 g per week) were permitted during weeks 1–3. The non-inferiority primary effectiveness outcome was the proportion of participants with three or fewer blisters at 6 weeks. We assumed that doxycycline would be 25% less effective than corticosteroids with a 37% acceptable margin of non-inferiority. The primary safety outcome was the proportion with severe, life-threatening, or fatal (grade 3–5) treatment-related adverse events by 52 weeks. Analysis (modified intention to treat [mITT] for the superiority safety analysis and mITT and per protocol for non-inferiority effectiveness analysis) used a regression model adjusting for baseline disease severity, age, and Karnofsky score, with missing data imputed. The trial is registered at ISRCTN, number ISRCTN13704604. Findings Between March 1, 2009, and Oct 31, 2013, 132 patients were randomly assigned to doxycycline and 121 to prednisolone from 54 UK and seven German dermatology centres. Mean age was 77·7 years (SD 9·7) and 173 (68%) of 253 patients had moderate-to-severe baseline disease. For those starting doxycycline, 83 (74%) of 112 patients had three or fewer blisters at 6 weeks compared with 92 (91%) of 101 patients on prednisolone, an adjusted difference of 18·6% (90% CI 11·1–26·1) favouring prednisolone (upper limit of 90% CI, 26·1%, within the predefined 37% margin). Related severe, life-threatening, and fatal events at 52 weeks were 18% (22 of 121) for those starting doxycycline and 36% (41 of 113) for prednisolone (mITT), an adjusted difference of 19·0% (95% CI 7·9–30·1), p=0·001. Interpretation Starting patients on doxycycline is non-inferior to standard treatment with oral prednisolone for short-term blister control in bullous pemphigoid and significantly safer in the long-term. Funding NIHR Health Technology Assessment Programme.

Severe lichen planus clears with very low-dose cyclosporin

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Acupuncture in dermatology: an historical perspective

Classical acupuncture focuses primarily on treating the person, and secondarily treating the illness. The “symptoms” are regarded as “branch” expressions of a “root” (constitutional) imbalance. Different root imbalances can produce the same symptoms. Five patients with eczema, for example, may reveal five distinct root imbalances and would all be treated very differently. Because acupuncture treats the whole person, it has something to offer almost every condition. In many cases, acupuncture aims to bring about a complete cure; in others, it aims to manage the problem. Acupuncture remains a substantial part of the traditional Chinese medicine, which is used to treat many conditions including acne, alopecia, dermatitis, pruritus, psoriasis, rosacea, systemic lupus erythematosus, urticaria, herpes zoster, chicken pox, impetigo, leprosy, vitiligo, and tinea. This review introduces the historical context of acupuncture within Chinese medicine and how it relates to skin disease. Specifically, a key question is, what can we learn from the ancients with regard to their use of acupuncture as part of a holistic system of medicine, and how does this relate to the practice of modern dermatology?

Vitiligo: the historical curse of depigmentation

Vitiligo has been mentioned in the tomes of every major religion, with its first description dating back more than 3000 years, to the earliest Vedic and Egyptian texts. Despite this ancient recognition, confusion with disorders such as leprosy has been a problem throughout the ages. This has lead to the stigmatization of vitiligo sufferers. This is a social problem that is still widespread in some, but not all, parts of the world. The ancients also practiced phototherapy for vitiligo. This practice only became common in the Western world with development of psoralen plus ultraviolet A and later ultraviolet B phototherapy in the latter half of the 20th century. In this article, the history of vitiligo up until the end of the 20th century is outlined, covering medical, scientific, and social aspects.

Basal cell carcinoma epidemiology in the UK: the elephant in the room

UK Cancer registries have difficulties in recording the incidence of basal cell carcinoma (BCC).