Pathogenesis of psoriasis
Psoriasis is a polygenic disorder. Susceptibility is determined by a large number of genes, each with a low penetrance. Important genetic associations are with HLA-Cw6, HLA-B27, and the genes PSOR-S1 and PSOR-S2 on chromosome 6 and 17, respectively.
Several triggering factors are identified, of which streptococcal antigens and certain drugs seem important, but the specific antigens are still unknown. The end result is activation of T-cells, overexpression of cytokines, and an inflammatory response.
Review of the classic treatments for psoriasis
Topical therapy
Topical therapy is indicated when psoriasis is limited to less than 20% of the body surface. Potent class I and II topical corticosteroids are the most widely used treatment for mild disease. After plaque clearance they can be given intermittently for maintenance.
The vitamin D3 derivative calcipotriene (Dovonex) is another first-line agent. Tazarotene (Tazorac), a topical retinoid prodrug, is a second-line agent used as monotherapy or in combination. Many combined regimens use topical corticosteroids, calcipotriene, and tazarotene. Coal tar—different concentrations in liquid form—is useful in treating extensive areas of the body and scalp psoriasis.
Phototherapy
Failure of topical therapy or extensive disease are indications for phototherapy or systemic medications. The trend is to use phototherapy in the form of narrowband UVB, which has proven more effective than broadband UVB and to have fewer adverse effects than psoralen UVA therapy (PUVA).3 Other light sources for home use are being developed.
Systemic agents
Methotrexate, given as a single weekly dose or in divided doses, has been used for more than 30 years; it inhibits the enzyme dihydrofolate reductase. An alternative immunosuppressive agent is cyclosporine. These 2 agents have high efficacy, but due to potential adverse effects they require careful patient selection and close follow-up.
Acitretin (Soriatane), an oral retinoid, is the treatment of choice for generalized pustular and erythrodermic psoriasis. It is also used in chronic plaque psoriasis, often in combination with phototherapy, which has a synergistic effect.New treatments
Our understanding of the immunopathogenesis of psoriasis has led to the development of therapies designed specifically to interfere with T-cell activation and effector functions. Three new immunomodulatory biologics are FDA-approved for the treatment of moderate to severe psoriasis. Typical cost of this therapy is more than $1000/month.
Anti-TNF-α strategies
Etanercept (Enbrel) is an antibody against the cytokine tumor necrosis factor alpha (TNF-α). It is self-administered at 25 mg to 50 mg subcutaneously twice weekly. Studies with 50-mg injections have shown a 75% clinical improvement in 49% of patients at 12 weeks and 59% of patients at 24 weeks.4
The most common side effect is reaction at the injection site. It was reported to produce dramatic remission of psoriatic arthritis and prevent radiographic progression of the disease.4-5 Due to raised concern about the risk of opportunistic infections, a purified protein derivative (PPD) test is advised before initiation of therapy to detect potential latent tuberculosis. Other risks include sepsis, pancytopenia, and worsening of multiple sclerosis.