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Molecular weight plays a significant role in the percutaneous penetration of chemicals. Atopic dermatitis is a chronic inflammatory skin disease associated with cutaneous hyperactivity to environmental triggers and is characterized by dry skin and increased transepidermal water loss. Percutaneous penetration of chemicals and drugs might be higher not only in involved but also in non-involved skin of atopic dermatitis patients. The objective of this study was to investigate the differences in percutaneous penetration of polyethylene glycol (PEGs) in subjects with normal skin barrier and subjects with the history of atopic dermatitis in relation to the molecular weight. Twenty healthy and twenty subjects with history of atopic dermatitis were exposed to water solution of PEGs in range of 150– 590 Da for 6 hours on the volar forearm. After the end of exposure the stratum corneum was totally removed by means of tape stripping and the concentration of PEGs and proteins were determined in each strip. Using Fick’ s second law of diffusion the permeation parameters were determined. The penetration of all PEGs into the stratum corneum was enhanced in non-involved skin of atopic dermatitis patients. This suggests that even the non-involved skin in atopic dermatitis patients has a compromised barrier function.

Psoriasis is a chronic, immune-mediated disorder that usually requires long-term treatment for control. Approximately 25% of patients have moderate to severe disease and require phototherapy, systemic therapy or both. Despite the availability of numerous therapeutic options, the long-term management of psoriasis can be complicated by treatment-related limitations. With advances in molecular research and technology, several biological therapies are in various stages of development and approval for psoriasis. Biological therapies are designed to modulate key steps in the pathogenesis of psoriasis. Collectively, biologicals have been evaluated in thousands of patients with psoriasis and have demonstrated significant benefit with favourable safety and tolerability profiles. The limitations of current psoriasis therapies, the value of biological therapies for psoriasis, and guidance regarding the incorporation of biological therapies into clinical practice are discussed.

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.

In view of evidence suggesting vitiligo is an autoimmune disease, we investigated whether vitiligo is associated with inherited deficiencies of the fourth (C4) and second (C2) component of complement and with certain human leukocyte antigens (HLA). Analysis of functional activities of C4 and C2 in sera of patients with vitiligo (n = 42) showed that 17% of them had a heterozygous C4 deficiency and 5% had a heterozygous C2 deficiency. In the normal control group (n = 30), 3% had a heterozygous C4 deficiency and none had a C2 deficiency. C4 typing by Western blot analysis showed the frequency of the C4A*QO allele in the vitiligo patient group to be close to normal. However, the frequency of one C4B*Q0 allele was three times higher, and that of two C4B*Q0 alleles five times higher in the vitiligo patient group than the reported frequencies in normal control groups. Southern blot analysis of Taq1 digests of DNA using C4 and 21-hydroxylase probes showed that two patients with two C4B*Q0 alleles had a deletion of a 21-OHA-C4B segment. In the other patients, having one or two C4B*Q0 alleles, these null alleles probably occurred due to a loss of C4 gene expression. HLA analysis did not show any allelic association of C4A*Q0 or C4B*Q0 with any HLA antigen in vitiligo, but confirmed the previous findings of a negative association with HLA-DR3 and a positive association with HLA-DR4. These results suggest that abnormalities of the C4B gene and the above-mentioned associations with HLA antigens may be some of the risk factors in vitiligo.

An indirect immunofluorescence test (IIF) using guinea pig lip as a substrate was performed with sera from 10 patients with Behçet's disease and the results were compared to IIF with sera of 16 patients with uveitis of Turkish origin, 62 patients with non- Behçet's uveitis, 9 patients with stomatitis aphtosa and 34 healthy controls. Antibodies to guinea pig lip cytoplasmic antigens were present in 70% of the Behçet patients, in 19% of uveitis patients of Turkish origin (P less than 0.05), in 12% of the non Behçet uveitis patients (P less than 0.001), in 11% of the stomatitis aphtosa patients (P less than 0.05) and in 9% of the healthy controls (P less than 0.001). A positive Behçet serum preincubated with the supernatant of guinea pig lip sections incubated in PBS gave an inhibition on the IIF test, indicating that the antigen involved in a soluble cytoplasmic substance. No significant increase in the presence of antibodies against iris, cornea or retina (mouse eye) were detected in the Behçet sera. Of interest was the finding of a positive reaction in 6 out of 10 patients in the episcleral region of the mouse eye. This positive reaction resembles immune complex like material. Our findings suggest that using the external surface of the guinea pig lip as a substrate is useful in selecting out those patients with Behçet's disease from uveitis patients with an unknown etiology and from patients with aphtous stomatitis.