R.J.G. Chalmers

The effect of addition of calcipotriol ointment (50 μg/g) to acitretin therapy in psoriasis

Our purpose was to find out whether the addition of calcipotriol ointment (50 μg/g) to systemic treatment with acitretin produces additional therapeutic effects and thereby an acitretin‐sparing effect, and further to investigate the safety and tolerability of this combination. A multicentre, randomized, double‐blind placebo‐controlled study was designed. Patients were randomized to receive calcipotriol or placebo. All patients were treated with a starting dose of 20 mg acitretin per day and doses were adjusted at 2‐weekly intervals with increments of 10 mg per day up to a maximum of 70 mg per day. The dose requirement for acitretin, clinical signs and adverse events were recorded. Seventy‐six patients were randomized to treatment with calcipotriol 50 μg/g ointment twice daily and 59 patients to treatment with the vehicle only twice daily. Clearance or marked improvement was achieved by 67% of the patients in the calcipotriol group and by 41% of the patients in the placebo group (P = 0.006). Calcipotriol treatment proved to have a statistically significant additional effect to acitretin on the Psoriasis Area and Severity Index, redness, thickness and scaliness as compared with placebo. Clearance or marked improvement was achieved with a statistically significantly lower cumulative dose of acitretin by the patients in the calcipotriol group as compared with the placebo group. The number of patients reporting adverse events was pronounced and largely related to acitretin. No significant differences were observed between the two treatment groups with respect to adverse events. Laboratory assessments were essentially normal. The addition of calcipotriol ointment to acitretin treatment contributes to the efficacy, reduces the cumulative dose of acitretin to reach marked improvement or clearance, and is well‐tolerated and safe.

Treatment of psoriasis with intermittent short course cyclosporin (Neoral®). A multicentre study

A 1 year, prospective multicentre study was performed to investigate the efficacy and safety of intermittent treatment with cyclosporin in psoriasis vulgaris. Subjects received cyclosporin (Neoral(r)) 5mg/kg per day until achieving 90% reduction in area affected, or for a maximum of 12 weeks. Those failing to demonstrate a satisfactory response were withdrawn. When further treatment was required, cyclosporin was recommenced. This cycle was repeated up to three times. Psoriasis activity was recorded using the area affected and sign scores for erythema, scaling and infiltration. Overall assessments of response and tolerability were recorded.

Reversible dilated cardiomyopathy following treatment of atopic eczema with Chinese herbal medicine

Chinese herbal medicines are increasingly being used as an alternative treatment for chronic skin disease. Most patients and many doctors remain insufficiently aware of their potential toxicity. We report a patient with eczema who developed a severe cardiomyopathy following a 2‐week course of Chinese herbal medicine. The connection between the two conditions was not made until 2 weeks after presentation when the patient was specifically asked if she had ingested any unusual substances. The belief that herbs, as natural products available without prescription, are harmless, is commonplace and patients may not consider them worthy of mention during a standard medical history.

Drug-induced Sweet's syndrome (acute febrile neutrophilic dermatosis) associated with hydralazine

We report a case of Sweets syndrome associated with hydralazine. The association of Sweets syndrome with hydralazine, and with the oral contraceptive, minocycline, and trimethoprim/ sulphamethoxazole, has been reported previously. We suggest that a drug aetiology should be sought in cases of Sweets syndrome.

A quantitative immunohistochemical study of the expression of integrins by nerves in psoriatic and normal skin

Summary Qualitative and quantitative assessment of integrin expression by dermal nerves was made by an avidin‐biotin immunoperoxidase method on snap‐frozen biopsies from affected psoriatic skin, and skin from normal control subjects with no history of skin disease. Nerves expressed α1, α2, α3, α6 β1 and β4 integrin subunits, and perineural sheaths in the mid‐dermis also expressed these subunits, with the exception of α2. There were more upper dermal nerve segments expressing αl integrin compared with other integrins both in controls and in psoriatic skin. The greater number of nerves expressing αl integrin compared with other integrins may be due to anatomical or functional differences between groups of nerves. There were significantly more nerves expressing αl, α2, α3, α6 and β4 integrins in psoriatic skin compared with control skin. This generalized increase may indicate a secondary trophic effect on all nerves rather than a specific increase in one type of nerve. However, the expression of α2 integrin may be significant in the pathogenesis of the psoriatic plaque, in that it was barely detectable in the normal site‐matched biopsies, but much greater in psoriatic plaques. The study of the expression of adhesion molecules by neurones in psoriasis offers a new avenue for investigation of the role of neuronal hypertrophy in the initiation and maintenance of psoriatic plaques.

Allopurinol-induced toxic pustuloderma

SIR, The rising tide of skin cancers is emphatically confirmed hy Ko et al.,^ hut in the Health of the Nation^ document the stated aim is to reduce the year on year rise in skin cancers hy the year 2005. How this is to he achieved is less clear. Jarrett et al^ showed how frequently children are still heing humed hecause of lack of hasic sun protection. Requests hy Evans* to estahlish information posts to educate the puhlic on the heaches ofthe west country were almost universally dismissed hy local councils. General practitioners are well placed to act on prevention and early detection, hut few initiatives are forthcoming.

Changes in numbers of epidermal cell adhesion molecules caused by oral cyclosporin in psoriasis.

AIM--To determine the effects of a three month course of low dose cyclosporin on the expression of epidermal cell adhesion molecules. METHODS--Eighteen patients with psoriasis were treated for 12 weeks with either 2.5 or 5 mg/kg/day of oral cyclosporin. Biopsy specimens taken from skin before, during, and after cyclosporin treatment were stained immunohistochemically for CD 54 (ICAM-1), CD 29 (beta-1 integrins), and CD18 (beta-2 integrins). RESULTS--There was a highly significant (p < 0.01) clinical response after 12 weeks of cyclosporin as assessed by the Psoriasis Area and Severity Index (PASI) score. The staining of CD 29 on keratinocytes of affected and unaffected psoriatic skin was not affected by cyclosporin. Epidermal CD54 was variably expressed in active psoriatic plaques and changed unpredictably after cyclosporin (p = NS). Staining for CD18 on large epidermal dendritic cells was reduced after cyclosporin (p < 0.02). The expression of CD18 by large epidermal dendritic cells during treatment correlated strongly with the PASI score at that time and one month after stopping cyclosporin (p < 0.02). CONCLUSIONS--Persistence of epidermal staining for CD 54 in psoriasis is compatible with a good clinical response to cyclosporin. Residual staining for CD 18 on large epidermal dendritic cells may be a useful marker for early clinical relapse.

Retinoid therapy—a real hazard for the developing embryo

a few babies who are recognized clinically by their unusually small size and high risk of perinatal complications and death. We need to know more about the effects of intrauterine growth retardation on different organs and systems in the human fetus. For example, the paper by Hinchcliffe et al. in this issue of the Journal (p 296) has shown for the first time that asymmetrical retardation is associated with a substantial reduction in the number of nephrons, and that there is no post-natal compensation for this (Hinchcliffe at al. 1992). Recent studies of 4-year old children in Salisbury, and 20year-old men in Southampton, have shown similar associations between fetal growth, blood pressure and insulin response as were found in older people. We therefore know that these associations depend on influences which still affect fetal growth today: but we know little about what these influences may be. There are, however, clues. For example, a survey of 8600 pregnant women in Oxford showed that the highest ratio of placental weight to birthweight occurred in women who had the lowest haemoglobins and largest fall in mean cell volume during pregnancy (Godfrey et al. 1991). Research into the nutritional and other influences that modulate the growth of the fetus and permanently programme its metabolism is now a priority. It may hold the key to preventing cardiovascular disease and other important disorders in adult life. David J. P. Barker Director MRC Environmental Epidemiology Unit University of Southampton Southampton General Hospital Southampton SO9 4XY References