Psoriasis: General principles section 4

In the past, conventional systemic psoriasis therapies-methotrexate, cyclosporine (CSA), and acitretin-were used when psoriasis was too extensive for topical therapy or refractory to topical therapy and phototherapy. Although a minimum body surface area, eg, 10%, has been traditionally used as a prerequisite to starting a systemic therapy for psoriasis, a subset of patients with limited disease have debilitating symptoms. For example, although severe psoriasis of the palms and soles or severe scalp psoriasis affects less than 5%of the body surface area, the significant negative affect on the quality of life of the patient makes a systemic approach to treatment appropriate.  

In recent years, biologics have changed the treatment of psoriasis, giving us additional therapeutic options that are potentially less toxic to the liver, kidneys, and bone marrow and are not teratogenic. Nevertheless, traditional systemic therapies continue to play an important role in the treatment of psoriasis with their oral route of administration and low cost (compared with biologics) making them an important treatment option in the appropriate patient.

Methotrexate is the most commonly prescribed traditional systemic therapy worldwide for psoriasis. Detailed guidelines concerning its dosing and monitoring in patients with psoriasis have recently been published by the National Psoriasis Foundation.4 It is noteworthy that the rheumatology guidelines for the use of methotrexate5 are less stringent than those in dermatology, especially in the monitoring of hepatotoxicity. The difference in this monitoring may be that patients with psoriasis with more severe disease are more likely to be obese than patients with rheumatoid arthritis, and thus be more prone to have underlying nonalcoholic steatohepatitis. Methotrexate can be dramatically effective with even the most severe cases of psoriasis. The potential role of pharmacogenetic testing to improve our ability to predict the efficacy and safety of methotrexate suggests the possibility of personalizing the use of methotrexate in the years ahead.6 Methotrexate has been used in combination with all of the approved biologic agents for psoriasis. The greatest experience is with tumor necrosis factor inhibitors. Methotrexate has been used to suppress antibodies against the two monoclonal tumor necrosis factor inhibitors, adalimumab and infliximab.7 It is not known whether the use of methotrexate and biologics causes additive immunosuppression as this combination has primarily been studied in patients without psoriasis, and the differing baseline risks associated with these diseases make this distinction uncertain.

CSA is one of the most effective treatments available for psoriasis.8 However, when used in the longer term (3-5 years), a significant proportion of patients will develop some degree of glomerulosclerosis.9 Published guidelines in the United States therefore limit its use to 1 year,8 whereas in the United Kingdom it is allowed for 2 years.10 In patients with severe flares of psoriasis, CSA frequently induces a rapid remission. Rebound flares of psoriasis after discontinuation of systemic steroids or efalizumab can be prevented or rapidly controlled with CSA11 or methotrexate.

Navigate section 4 of the psoriasis guideline: Systemic agents

Citation note

When referencing this guideline in a publication, please use the following citation: Menter A, Korman NJ, Elmets CA, Feldman SR, Gelfand JM, Gordon KB, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: section 4. Guidelines of care for the management and treatment of psoriasis with traditional systemic agents. J Am Acad Dermatol. 2009 Sep;61(3):451-85. 



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