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Notes: Background SDZ ASM 981 is a selective inhibitor of the production of pro-inflammatory cytokines from T cells and mast cells in vitro. It is the first ascomycin macrolactam derivative under development for the treatment of inflammatory skin diseases. Objectives This study was designed to determine the safety and efficacy of SDZ ASM 981 cream at concentrations of 0·05%, 0·2%, 0·6% and 1·0% in the treatment of patients with atopic dermatitis and to select the concentration to be used in phase III studies. Methods This was a double-blind, randomized, parallel-group, multicentre dose-finding study. A total of 260 patients were randomly assigned to treatment with SDZ ASM 981 cream at concentrations of 0·05%, 0·2%, 0·6%, or 1·0%, matching vehicle cream, or the internal control 0·1% betamethasone-17-valerate cream (BMV). Treatment was given twice daily for up to 3 weeks. Results A clear dose–response relationship for SDZ ASM 981 was evident, with 0·2%, 0·6% and 1·0% SDZ ASM 981 creams all being significantly more effective than vehicle (P = 0·041, 0·001 and 0·008, respectively) in terms of baseline to end-point changes in the Eczema Area Severity Index (EASI) and pruritus score. The 1·0% cream was the most effective SDZ ASM 981 concentration. BMV was more effective than the SDZ ASM 981 creams tested in this study. It appears that the efficacy plateau was not reached with the SDZ ASM 981 creams within 3 weeks treatment. SDZ ASM 981 was well tolerated. Burning or a feeling of warmth were the only adverse events reported more frequently in the 0·6% and 1·0% SDZ ASM 981 treatment groups than in the vehicle treatment group (42·9%, 48·9% and 34·9%, respectively). Few systemic adverse events were reported during the study (headache was the most frequent systemic event reported by 15 of 252 patients) and none was considered to be related to treatment. The local tolerability profile of the 1·0% cream was similar to that of the lower concentrations. Conclusions 1·0% SDZ ASM 981 cream, which was shown to be safe, well tolerated and the most effective concentration in this study, was selected as the concentration to be further developed in phase III studies.

Notes: Eleven patients with mycosis fungoides (MF) were treated with recombinant alpha-intcrfcron (rIFN-α2a2) in combination with etretinate (seven patients) or alone. One patient, who also received etretinate, went into complete remission and remained without signs of MF after 18 months. Six patients experienced partial remission; one of these was treated with rIFN-α2a alone and was clinically in complete remission, but had still a pteomorphic skin infiltrate. Two patients were non-evaluable, and two stopped therapy due to progressive disease. Five patients discontinued therapy due to side-effects although three had partial remission of their disease. Only four patients received 12 months therapy. The study shows that rIFN-α2a in combination with etretinate or alone can induce remission of MF.

Notes: Polymorphonuclear leukocyte (PMN) and monocyte (MN) chemotaxis in nine patients with pustulosis palmo-plantaris (PPP) and ten patients with pustular psoriasis (PP) was determined by an objective in vitro assay employing a 51Cr-labelling technique.PMN chemotaxis was significantly enhanced in both groups of patients compared with controls. MN chemotaxis was normal.There was no difference in the chemotactic responsiveness of leukocytes from patients with PPP and PP. The random migration of PMN and MN from the patients was normal. Homogenized tissue specimens from lesional skin with and without pustules, and from perilesional, normal-looking skin of PPP and PP were analysed for the presence of chemoattractants(s) for PMN. Lesional skin had considerable chemoattractant properties, but perilesional skin did not induce directed migration of PMNs.

Notes: Dry skin and eczema only seldomly occur in workers in the Danish fish-processing industry (FPI) during work, when their fingers and palms have a low skin surface temperature, low transepidermal water loss (TEWL), and a high capacitance. However, shortly after work, when the skin temperature has become normal, TEWL levels increase to above normal, and capacitance decreases to below normal, followed by the development of dry skin or chapping, which subsequently revert to normal over a period of hours. These observations suggest that workers in the FPI may have a delect in skin barrier function, which is, however, masked by a low skin temperature, resulting in misleadingly low TEWL levels during work. To test this hypothesis, we disrupted the permeability barrier in hairless mice with topical acetone, and exposed the treated skin to ice for 3–5h. Although TEWL rates immediately after cold exposure were low, suggesting normal barrier recovery, TEWL increased to levels slightly above pre-cold exposure levels (i.e. levels just after the barrier was disrupted with acetone) when the skin temperature reverted to normal (≥ 15min). The changes in TEWL were paralleled by equivalent changes in percutaneous penetration of the electron-dense tracer lanthanum nitrate. This indicates that cold masks a defective barrier, and inhibits barrierrepair. After a few hours at ambient temperatures, normal barrier recovery was observed. Electron microscopy revealed empty or partially empty lamellar bodies during the first 30 min post-cold exposure. After 1 h the majority of nascent LBs displayed normal morphology. Moreover, histochemical studies showed a delayed reappearance of stratum corneum intercellular lipids following cold exposure. These results demonstrate that cold exposure prevents barrier recovery after acetone disruption, and provide an explanation for the occupatonal dermatosis observed in the fish-processing industry and related occupations.

Notes: Background  Three years ago, the nonablative wrinkle reduction laser (a 585-nm laser, Chromogenex V3; Chromogenex Light Technologies, Llanelli, U.K.) was developed, and there have already been several reports about its clinical effectiveness. The Chromogenex V3 laser has also been reported to be effective in treating acne and atopic dermatitis. These results suggest that the Chromogenex V3 laser has some immunological role. In this study, we investigated immunological changes elicited by laser irradiation at the ultrastructural level and by analysis of interleukin (IL)-2 and IL-4 mRNA in skin homing T lymphocytes.Materials and methods  Eight healthy adult volunteers (mean age 56·3 years, range 25–66 years) were recruited for this study. Ultrastructural analysis was done 3 h after the laser irradiation, as well as 1 day, 3 days, 1 week, 2 weeks, 4 weeks and 5 weeks later. IL-2 and IL-4 mRNAs in skin homing T cells cultured for 6 weeks were semiquantitatively measured using reverse transcriptase-polymerase chain reaction.Results  Ultrastructural observations revealed that at 3 h after laser therapy, neutrophils, monocytes and mast cells could already be seen in the extravascular dermis. These dermal acute inflammatory changes were observed also at 1 week after laser treatment. Two weeks after laser treatment, the capillaries showed an almost normal structure. Four weeks after laser treatment, many lymphocytes and fibroblasts were observed. The numbers of these lymphocytes increased further at 5 weeks after the laser treatment. One week after the laser irradiation, all subjects were positive for IL-2 mRNA and for IL-4 mRNA. The level of IL-4 mRNA was larger compared with that of IL-2 mRNA in all subjects.Conclusion  The Chromogenex V3 is a 585-nm visible light laser, and it may affect the skin not only by selective photothermolysis but also by direct cutaneous immunological activation.

Notes: For more than five decades, topical corticosteroids and emollients have been the mainstay of therapy for atopic dermatitis. However, the potential for side-effects limits the clinical utility of corticosteroids in providing long-term disease control. With a unique mode of action that differs from that of corticosteroids, the steroid-free topical calcineurin inhibitors (TCIs), tacrolimus ointment and pimecrolimus cream, provide skin-selective treatment that targets key factors involved in the pathogenesis of this chronic disease. An extensive series of clinical trials involving more than 16 000 patients with predominately moderate to severe atopic dermatitis in tacrolimus studies and over 2000 patients with primarily mild to moderate disease in pimecrolimus studies has shown that both TCIs provide effective and well-tolerated treatment for atopic dermatitis. Randomized controlled trials have demonstrated that tacrolimus is superior to conventional hydrocortisone-based regimens and does not cause skin atrophy or other steroidal side-effects. Both tacrolimus and pimecrolimus prevent disease flares and provide progressive and sustained disease improvement with long-term therapy. These and other clinical benefits of TCIs are discussed, together with the safety profiles of tacrolimus and pimecrolimus and their use in clinical practice. In addition, this review summarizes findings from the many trials carried out with these agents and outlines how TCIs can provide long-term treatment and control of a chronic skin disease that may persist for years.

Notes: Background  A standardized instrument is needed to rate the overall severity of chronic hand dermatitis (CHD), in particular during clinical trials.Objectives  To design and validate a photographic guide.Methods  Initially, five experts were asked to grade 50 photographs of CHD, first individually, then as a consensus-building group, in order to select the photographs included in the guide. Then, a validation session with 11 different dermatologists evaluating 28 patients was conducted to assess the interrater reliability and test–retest reproducibility of the assessment of disease severity, relying on the photographic guide, on two consecutive days. Patient order was randomized, and only diseased hands were visible to prevent any bias in evaluation.Results  The experts reached a consensus for development of a photographic guide composed of five severity levels and four photographs per severity level. Results of the validation session showed a high level of interrater reliability and test–retest reproducibility.Conclusions  The photographic guide is a reliable tool for assessing the morphological severity of hand dermatitis, and can be used as part of a comprehensive evaluation of disease in international multicentre clinical trials.