Die Anwendung des Excimerlasers 308 nm zur Psoriasis‐Behandlung

Background and Objective: Standard phototherapy for psoriasis (311 nm UVB or photochemotherapy) exposes the non‐affected skin to potentially damaging irradiation. The use of 308 nm XeCl excimer laser allows the selective irradiation of psoriatic lesions. We evaluated its therapeutic effectiveness. Patients/Methods: 28 patients with plaque stage psoriasis were involved in the study, 26 of them could be evaluated. In each patient a single plaque was chosen and then exposed to the laser irradiation thrice weekly. The initial dose was twice the MED (minimal erythema dose); the dosage was increased by one MED every second treatment. The usual dosages were 2 – 5 MED, while the cumulative UVB dosage was 3.6 – 15.2 J/cm². 17 Patients were treated 6 times, while 11 were treated 10 times. The Psoriasis Severity Index (PSI) was calculated for the individual plaque in order to assess the effectiveness of the therapy. The patients were followed regularly for 3 months following treatment, and then checked again at 1 year. Results: Most patients showed clear improvement. In 90 % the PSI at the end of treatment was reduced by at least 50 %; in 72 % it was only 33 % of the pre‐treatment value. The results between the patients receiving 6 and 10 treatments were similar. In 6 patients, the psoriatic lesion was still absent after 1 year, while in an additional 7, there had been long term improvement. The most common side effects were erythema and pruritus (100 %), blisters (35 %) and post‐inflammatory hyperpigmentation (80 %). Conclusion: The use of the 308 nm excimer laser is effective for chronic localized psoriasis and may lead to long‐lasting remissions.     

UV‐induzierte regulatorische T‐Zellen

Regulatory T cells belong to a subset of T lymphocytes which suppress immune reactions in an antigen‐specific fashion. Regulatory T cells play an important role in the prevention of autoimmune diseases. Ultraviolet (UV) radiation suppresses the immune system in antigen‐specific fashion. This effect is mediated by UV‐induced regulatory T cells. UV‐induced regulatory T cells express CD4 and CD25 and upon activation release the immunosuppressive cytokine interleukin‐10. Upon intravenous injection UV‐induced regulatory T cells primarily migrate into the lymph nodes, explaining why they preferentially suppress sensitization. Recently, the development of regulatory T cells was demonstrated in an experimental model of photopheresis. The further characterisation of these cells will determine whether they can be applied in the future therapeutically with the ultimate aim to induce specific immunosuppression.     

Klinik und Pathogenese UV‐induzierter Pigmentveränderungen

Solar and ultraviolet (UV) radiation, respectively, are the strongest stimuli for the induction of pigmentation in human skin. UV radiation induces pigmentation by exerting direct and indirect effects on melanocytes. Melanogenesis is a very complex process whose molecular mechanisms are not yet completely understood. Acute UV exposure induces the non‐protective immediate pigment darkening as well as delayed tanning which exerts photoprotective effects. Chronic UV exposure causes permanent pigmentary changes by inducing solar lentigines and pigmented actinic keratoses as well hypopigmentated areas. Artificial UV irradiation (UVA, PUVA) can also induce pigmentary disorders, including lentigines. Since the therapeutic options for UV‐induced pigmentary changes are limited consequent protection as a prophylactic measure is recommended.     

TNF‐alpha‐Antagonisten in der Therapie der Psoriasis – Nutzen und Risiken

Summary: Anti‐TNF‐α agents including etanercept, a fusion protein of the p75 TNF receptor and IgG1 and infliximab, a chimeric human‐mowie monoclonal antibody. They have been approved for the treatment of rheumatoid arthritis and/or Crohn's disease. New understanding of the importance of the inlammatory cytokine TNF‐α in the pathophysiology of psoriasis led to the use in open‐label and randomized studies in patients with psoriasis and psoriatic arthritis. Although larger randomized trials are needed to confirm early results, both anti‐TNF‐α agents, have demonstrated activity in improving the signs and symptoms of psoriatic arthritis and psoriasis. Further investigations will fully elucidate the role of infliximab in these and other dermatological diseases.     

Interleukin (IL)‐22, IL‐17, IL‐23, IL‐8, vascular endothelial growth factor and tumour necrosis factor‐α levels in patients with psoriasis before,during and after psoralen–ultraviolet A and narrowband ultraviolet B therapy

Background Several cross‐sectional studies have shown that different cytokines and growth factors are enhanced in psoriasis. Objectives We aimed to understand the role/relation of interleukin (IL)‐22, IL‐17, IL‐23, IL‐8, vascular endothelial growth factor (VEGF) and tumour necrosis factor (TNF)‐α in psoriasis vulgaris, addressing their levels and changes before, during and after psoralen–ultraviolet A (PUVA) and narrowband ultraviolet B (NB‐UVB) treatment. Methods A cross‐sectional and a longitudinal study (n = 34) – before (T0) and at 3 (T3), 6 (T6) and 12 (T12) weeks of NB‐UVB and PUVA therapy – were performed; 17 patients started NB‐UVB and 17 PUVA, and IL‐22, IL‐17, IL‐23, IL‐8, TNF‐α and VEGF levels were evaluated. Results At T0, compared with controls (n = 20), all the parameters were significantly higher in patients, except for TNF‐α. Both NB‐UVB and PUVA treatment gave, at T3, a significant decrease in TNF‐α and IL‐23; IL‐22 and IL‐17 decreased significantly at T6; all parameters and Psoriasis Area and Severity Index decreased significantly at T12. However, in both groups, at T12, VEGF was still significantly higher than control. Conclusions Psoriasis seems to be a complex disease in which the cytokine network is disturbed, namely in levels of IL‐22, IL‐17, IL‐23, IL‐8, TNF‐α and VEGF. NB‐UVB and PUVA follow‐up studies suggested that the reduction in the IL‐23/Th17 axis might be important in the pathogenic mechanisms of psoriasis. Further follow‐up studies of patients with psoriasis treated with these and other therapies could be very helpful for the understanding of the disturbance in the cytokine network in psoriasis and indirectly in its pathogenesis.     

Therapeutischer Einsatz der Tumor‐Nekrose‐Faktor‐α‐Hemmer Infliximab und Etanercept bei entzündlichen Hauterkrankungen

Background: The treatment of inflammatory skin diseases is at present often empirical as causal therapeutic approaches are not available because of incomplete knowledge of the immune pathogenesis. The current therapeutic approaches can induce remission, but often produce undesirable side effects. On the basis of experience gained in cytokine modulation therapy of chronic inflammatory diseases such as rheumatoid arthritis and psoriasis, the use of TNF‐alpha inhibitors could represent a further, more specific and effective therapeutic option for other selected inflammatory skin diseases. Patients and Methods: The current status of the therapeutic effect of anti‐TNF‐alpha blockers is discussed based on our own observations and a review of the current literature. Potential undesirable side effects and possible contraindications for this therapy are also considered. Results and Conclusions: Based on the recent findings, the use of TNF‐alpha blockers seems to be promising in the treatment of therapy‐resistant inflammatory dermatoses. At present, guidelines for indications and contraindications for anti‐TNF‐alpha treatment of inflammatory skin disorders do not exist. Such guidelines are necessary to improve the efficacy of anticytokine treatment and to reduce side effects.     

Z‐ligustilide ameliorated ultraviolet B‐induced oxidative stress and inflammatory cytokine production in human keratinocytes through upregulation of Nrf2/HO‐1 and suppression of NF‐κB pathway

Ultraviolet B (UVB), a harmful environmental factor, is responsible for a variety of skin disorders including skin inflammation through reactive oxygen species (ROS) and inflammatory mediator production. Here, we investigated the effect of Z‐ligustilide (Z‐lig), an active ingredient isolated from the medicinal plants Cnidium officinale and Angelica acutiloba, on UVB‐induced ROS generation and inflammatory mediator production in normal human epidermal keratinocytes (NHEKs) as well as its underlying mechanisms. Z‐lig significantly rescued UVB‐induced NHEKs damage in a dosage‐dependent manner. Pretreatment of NHEKs with Z‐lig inhibited UVB‐induced ROS production in NHEKs. Both silencing the nuclear factor E2‐related factor 2 (Nrf2) and the supplement of tin protoporphyrin IX (SnPP), a haeme oxygenase‐1 (HO‐1) inhibitor, cancelled the inhibitory effect of Z‐lig on UVB‐induced ROS upregulation in NHEKs. Moreover, pretreatment of NHEKs with Z‐lig reduced UVB‐induced nuclear factor kappa B (NF‐κB)‐dependent inflammatory mediators (IL‐6, IL‐8 and MCP‐1) production at both mRNA and protein level. In the presence of Z‐lig, UVB‐induced NF‐κB subunit p65 nuclear translocation was abolished, and the IκBα degradation was suppressed. Taken together, these findings suggest that Z‐lig can suppress UVB‐induced ROS generation through Nrf2/HO‐1 upregulation and inflammation by suppressing the NF‐κB pathway, suggesting that Z‐lig may be beneficial in protecting skin from UVB exposure.     

Real‐time polymerase chain reaction analysis of a 3895‐bp mitochondrial DNA deletion in epithelial swabs and its use as a quantitative marker for sunlight exposure in human skin

Background The use of mitochondrial DNA (mtDNA) damage as a reliable and highly sensitive biomarker of ultraviolet (UV) radiation exposure in both the dermis and epidermis has now been well developed by our group and others. We have previously identified a 3895‐bp mtDNA deletion which occurred more frequently and to a higher level in usually sun‐exposed skin as opposed to occasionally sun‐exposed skin. This work focused on older‐aged individuals and, in particular, perilesional, histologically normal skin biopsies taken from patients with skin cancer. Objectives To develop novel, less‐invasive methods of obtaining skin samples (i.e. epidermis) from volunteers covering a much wider age range and larger number of individuals (n = 239). Methods The 3895‐bp deletion was quantified by a specific real‐time polymerase chain reaction assay in normal human epidermis samples taken from three body sites with differing sun exposure. Results The results show a statistical increase of the level of the 3895‐bp deletion with increasing sun exposure in the epidermal swabs of human skin (P < 0·001) and with increasing age of the donor in the needle biopsy samples. Conclusions These data suggest that the upper layers of the epidermis are an accessible and reliable site for assessing mtDNA damage caused by UV exposure.