English summaries
The pathogenesis and new treatments of psoriasis
Julkaistu 30.04.2010 00.01
Psoriasis is a multifactorial and polygenic chronic inflammatory skin disease that affects 2-3% of the population. About one-fifth of patients also have concomitant psoriatic arthritis. Psoriasis has a marked negative impact on the quality of life and has recently been shown to confer an independent risk for myocardial infarction and other cardiovascular diseases.
Several psoriasis-related genes have been identified. The most important one seems to be the HLA-Cw6 allele in the HLA-C gene in chromosome 6, which is present in 90% of patients with type I psoriasis. This type is characterized by younger age of onset and more severe disease and is more often associated with psoriatic arthritis than type II psoriasis. T-cell-mediated chronic inflammation and keratinocyte proliferation are central features in the pathogenesis of psoriasis. Many Th1- and Th17-type cytokines, for example TNF-a, IFN-γ, and IL-22, are pivotal in triggering and maintaining psoriatic inflammation. Recent advances in the immunopathology of psoriasis and related inflammatory conditions such as rheumatoid arthritis and Crohn’s disease have led to the development of new biological therapies.
Moderate and severe psoriasis can be treated with three different traditional systemic medications (acitretin, methotrexate, and cyclosporine A). However, not infrequently, adverse events and lack of efficacy limit their use. Biological therapies are indicated in the treatment of (moderate to) severe psoriasis if other treatments have been ineffective, are contraindicated, or have caused considerable side-effects.
Three anti-TNF therapy options exist for psoriasis: two monoclonal antibodies (infliximab and adalimumab) and one receptor fusion protein (etanercept). The IL-12/23 antibody ustekinumab is the newest option in the treatment of severe psoriasis. Contrary to the TNF-inhibitors, this therapy is not been indicated for the treatment of rheumatoid diseases. All biological therapies have been shown to have remarkable efficacy in patients with severe psoriasis. Major concerns with anti-TNF therapies include serious infections, activation of latent tuberculosis and possible malignancies. The risk for serious infections is about twice that in patients without biological treatments and is greatest during the first six months. The risk of tuberculosis, on the other hand, depends very much on how systematic and accurate the pre-treatment screening is for latent tuberculosis. Evaluation of the cancer risk associated with biological therapies is especially challenging because cancers are rare, clinical trials are often too short for the development of malignancies, and the underlying diseases themselves as well as previous treatments can carry an increased risk. However, the majority of studies suggest that TNF-a inhibitors may cause a slightly increased risk of lymphomas and nonmelanoma skin cancers. The risk for solid cancers is not increased.
For many patients with severe psoriasis, the benefits of TNF-a inhibitors may greatly outweigh the risks, and biological therapies are a very welcome and efficient treatment option.
Tarja Mälkönen, M.D., Ph.D., Specialist in Dermatology, Skin and Allergy Hospital, Helsinki University Central Hospital, E-mail: tarja.malkonen@hus.fi
Finnish Medical Journal 2010;65:1511–20.
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