银屑病免疫学研究新进展

银屑病免疫学是近年研究活跃的领域,进展迅速,不仅加深了对银屑病发病机制的认识,还有力地推动了银屑病靶向治疗的快速发展。在固有免疫方面,角质形成细胞（KC）和树突细胞（DC）是主要的细胞成分,介导银屑病发病的起始环节;而T细胞则仍然代表着适应性免疫反应中的主要角色,在银屑病发病的多个方面发挥关键作用［１］。各种细胞成分通过一系列细胞因子等炎症介质,介导免疫通路,形成级联放大和恶性循环,最终导致银屑病病理改变的发生……     

T helper type 17 in psoriasis: From basic immunology to clinical practice

Psoriasis is a chronic inflammatory disease mediated by a complex interplay between immune system and keratinocytes. Initially considered as a keratinocyte proliferation/differentiation disorder, an immune dysregulation was confirmed after the successful treatment of psoriasis with cyclosporine. The ying–yang theory, or T helper type 1 (Th1)/Th2 concept, was then introduced to explain the rarity of atopic dermatitis in patients with psoriasis and the aggravation of psoriasis after interferon-γ treatment. However, recent advances have revised the Th1/Th2 paradigm after the discovery of a novel subset of T cells, called Th17 cells. Th17 cells produce interleukin (IL)-17 and IL-22, and have other important downstream proinflammatory effects on skin, leading to clinical and pathological features typical of psoriasis. Nowadays, emerging evidence suggests integrative and complicated inflammatory circuits among Th1 and Th17 cells and keratinocytes in the pathogenesis of psoriasis, with Th17 cells playing a central role. Herein, we review the biology of Th17 cells as well as the reciprocal interplay between Th17 and regulatory T cells in psoriasis. Integration of the IL-23/Th17 axis into a revised concept of psoriasis has already been translated into novel therapeutic strategies. Studies investigating the effect and molecular mechanism of conventional and biological therapy for psoriasis on the IL-23/Th17 pathway were also discussed.     

The immunology of Contact dermatitis

This review summarizes current knowledge of the pathophysiological events which lie behind the development of contact dermatitis. The clinical distinction between allergic and irritant eczema is discussed. New observations are evaluated on our understanding of how allergic and irritant eczema may in many respects be similar, evolving through common physiological pathways of immune inflammation.     

The genetics of psoriasis

There is considerable epidemiologic evidence that genetic component plays a key role in the pathogenesis of psoriasis. The disease is multifactorial in origin and shows polygeneic inheritance. In the last decade, there have been significant advances in our understanding of the genetic basis of this common disease. Susceptibility gene characterization and knowledge of the immune basis of psoriasis have better defined the disease pathways involved in the pathogenesis of psoriasis. A number of genetic loci have been identified by genome wide-linkage scans. In particular, the importance of PSORS 1 linkage characterization is emphasized, as this information will help develop more specific diagnostic and prognostic tools.     

The pathogenesis of psoriasis

Ildamen has a positive effect on the course of psoriasis in patients with cardiovascular diseases. Its effect in psoriasis appears to be explained by its stimulating action on skin beta-adrenoreceptors. The study carried out by the authors confirms the contribution of beta-adrenoreceptors to the pathogenesis of psoriasis.     

The age-of-onset of psoriasis and the relationship to parental psoriasis

In series of 419 consecutive patients with psoriasis the peak age-of-onset was between 5 and 9 years of age in girls and between 15 and 20 years in boys. Subsequently, there was a gradual decline in relation to age. The incidence of psoriasis in a parent of a proband was shown to be significantly higher in those patients where a detailed exmination of the family was undertaken, as compared with the information obtained only from case records.     

The immunology of CD4-negative skin hematosarcomas

A wide panel of monoclonal antibodies to hematopoietic cell differentiation antigens was applied to the study of CD4-negative skin hematosarcomas on cryostat secretions. The most frequent CD4-negative type was the B-cell one identified in 6 of 10 cases. In this type the use of monoclonal antibodies in addition to standard immunoglobulin markers seemed to be very important. T-cell type (CD3+ CD8+), histiocytic variant (CD11+Ia+), pseudolymphoma (polyclonal markers pattern), and Kaposi's sarcoma (hematopoietic cell negative antigen) were identified in 1 case each. The authors emphasize the importance of immunological studies of hematosarcomas because of the high frequency of the generalization of B-cell lymphomas; such studies may also help in the differential diagnosis between pseudolymphoma and hematosarcoma.     

The burden of childhood psoriasis

A pilot study of the effect on quality of life of childhood psoriasis is presented. Of the children interviewed, 65% experienced stigmatization to a certain extent, 71% reported itching, and 43% complained about fatigue. Clinicians should pay attention to these items to initiate patient-tailored treatment.     

The endothelium in psoriasis

Summary This article is a review of the role of the endothelium in psoriasis, with emphasis on angiogenesis and lymphocyte—endothelial interactions.     

The topical treatment of psoriasis

According to the patients, improvement of efficacy, long-term safety and improvement of compliance are needed. The topical treatment has been innovated during the last decade. Most important are the introduction of two new classes of treatments: topical vitamin D(3) analogues and the retinoid tazarotene. To what extent, however, have we achieved developments which are in line with the needs as expressed by the patients? Improved efficacy has been realized by successful combinations of topical treatments. In particular, the combinations of dithranol, vitamin D(3) and tazarotene with a topical corticosteroid proved to be very effective with a reduced profile of side-effects. The efficacy of vitamin D(3) analogues and tazarotene is such that the efficacy of a potent corticosteroid (betamethasone-17-valerate) is approached; calcipotriol even showed an efficacy which is at least as good as this corticosteroid. The long-term safety of new compounds has been evaluated for at least 12 months in large studies. Remarkably for corticosteroids such information is available for only 12 weeks. However, intermittent applications of a topical corticosteroid in combination with another topical treatment provide an effective and safe long-term control of psoriasis. Compliance is a conditio sine qua non for an effective topical treatment. Important progress has been made to increase compliance. Short-contact dithranol has been popularized as an ambulatory treatment which is a highly effective approach as a care instruction programme. Formulations which are better from a cosmetical point of view have been developed for various topical treatments. Reduction of the frequency of applications proved to be possible for most treatments. Once daily applications for corticosteroids, vitamin D(3) analogues and retinoids have been developed, and intermittent applications, a few times per week, are possible for corticosteroids, which proved to be very effective with a reduced profile of side-effects, and are also developed for dithranol.