Selective immunotherapy for psoriasis

Symposium

s22

S12. Management

as well as knock-out mice showed characteristic features of this diesease. Examples include mice transgenic for cytokines or adhesion molecules as well as CD18 deficient mice. iii) “Psoriasis onto animals”: Attempts to study lesional and non-lesional skin from psoriatic patients in xenogeneic translantation models were only successful when mice with severe combined immunodeficiency (SCID) served as recipients. These models were helpful in finding some answers to questions central for the understanding of the pathogenesis of psoriasis. However, the simple fact that so many different strategies yielded models mimicking aspects of psoriasis documents that this disease is polygeneic and multicausal. Sl l-4

Selective

C.E.M. Griffiths. Medicine, Manchester

University UK

immunotherapy

for psoriasis

Section of Demzatology. Department of of Manchester School of Medicine,

As our basic understanding of tire immunopathogenesis of psoriasis becomes more detailed so do opportunities for targeted immunotherapy of this disease. The cytokine profile of a psoriatic plaque fits best with a Tht subset ie IL-2 and interferon-y prevalent; T cells are predominant within the cutaneous infiltrate and following initial T cell/endothelial cell adhesion integral to cutaneous T-cell trafficking it appears that T cells play an important role in the initiation (CD4’) and maintenance (CD89 of psoriatic plaques. Recent research has identified the role of superantigens in the genesis of guttate psoriasis particularly as there is evidence for preferential expansion of Vb-expressing T cells. Antigen-presenting celm cell interactions within psoriatic plaques depend on activation signals derived from binding of accessory molecules such as B7 and CD28. AU of the above cellular and cytokine pathways provide logical targets for immunotherapeutic intervention. Immunotherapy for psoriasis consists of: (i) selective immunopharmacologicai agents such as cyclosporin and FK506 which inhibit T-cell activation; (ii) highly specific approaches including anti-CD3, anti-CD4, IL-2 fusion toxin, anti-ESelectin antibodies, and inhibition of accessory signalling incorporating the use of CTLA4-Ig. Future therapies for psoriasis may include: anti-cytokines, immune deviation with IL-IO; or other Ths cytokines; peptide vaccination; and, if the autoantigen is known, even oral tolerance. Sll-5

Novel retinoids psoriasis

(topical

J.-H. Saurat. Dept of Dermatology Geneva-Lausanne,

and oral) for

Geneva;

of non-melanoma

skin cancer

liferative activity; no molecule is available so far for psoriasis. subtype-specific retinoids, that preferentially bind to nuclear retinoic acid receptors RAR or RKR subtypes, although the theoretical basis for their putative usefulness in psoriasis is not well established. Tazarotenic acid pertains to this class; its position in the strategy of psoriasis treatment will be discussed. 31 receptor antagonists, which have to be more carefully reconsidered as a topical treatment of psoriasis because untreated psoriatic plaque appears to show retinoid excess rather than retinoid deficiency. Such compounds may well prove to be active topically, whereas retinoic acid as well as older synthetic retinoids were not. 41 the application to therapy of the “nuclear cross-talk’ concept between vit. A and vit. D suggest that both compounds may act synergistically in the treatment of psoriasis. 21 receptor

Sll-6

Optimizing psoriasis

the clinical

management

Peter C.M. van de Kerkhof. Dept. of Demlatology, Hospital

Nijmegen,

of University

The Netherlands

A spectrum of antipsoriatic treatments is available for the patient of today. In view of the variability between psoriatic patients, various treatments with different modes of actions are needed in order to individualise the treatment. Combination treatments have been developed resulting in an optimized efficacy and a decrease of side effects. The topical treatment of psoriasis consists of Vitamin D3 derivatives, dithranol, tar and topical corticosteroids. Of these treatments the vitamin D3 analoque calcipotriol proved to be a topical drug of first choice, combining efficacy and safety. Phototherapy (UVB) and photochemo therapy (PUVA) are well established approaches for the treatments of psoriasis. A new development is the treatment with UVB narrow band (310 nm). Systemic treatment with methotrexate, cyclosporin and acitretin are well established approaches for patients with severe psoriasis. Guidelines for these treatments have been developed further. Combination treatment of different pharmacological apmaches proved to enhanced efficacy considerably. Most important combinations are retinoids/photo(chemo)therapy, cyclosporin/calcipotriol and calcipotrioUretinoids.

s12.

Management of non-melanoma skin cancer

DHURDV

Switzerland

The discovery that retinoids may be. used for treating psoriasis was a major advance. Etretinate, and then its acidic metabolite acitretin, were used either in monotherapy or in association. The mechanism of their action in psoriasis is still not establihed. The use of topical retinoic acid RA is limited by its irritating pmperties. With the major advances in the biology of retinoids, one may anticipate new opportunities for the treatment of psoriasis. There are four directions for pmgresses: l] the recent identification of dissociating retinoids, that have only antipm-

S12-1

Non-melanoma skin cancer-An challenge for dermatologists

R. Kaufmann. Department Goethe-University,

Frankfurt

emerging

of Dermatology, J. W am Main, Gemtany

A rising incidence of non melanoma skin cancer among the white population stresses the need for prevention strategies aiming at an early recognition and removal of potential precursors or initial tumour lesions. They include destructive procedures, as well as primary surgical resection. Non melanoma skin cancer comprise a variety of different epithelial tumour enti-