Systemic agents should be given under the supervision of a dermatologist. They include:
- methotrexate - given as a single dose each week (max. 0.5 mg/kg); complications include myelosuppression; hepatic fibrosis; and teratogenesis
- indicated for recalcitrant disease unresponsive to topical or phototherapy and is particularly useful if the patient has an associated arthropathy
- long-term use of methotrexate is associated with liver toxicity so regular liver function tests are required
- incidence of cirrhosis is related to cumulative dose, and if this is below 1.5g the risk is low (1) - if this level has been reached then liver biopsy is required to check for signs of toxicity
- if serial propeptide of type III procollagen levels remain normal repeat liver biopsies can be avoided (1)
- retinoids
- useful agent for pustular and erythrodermic psoriasis but are less effective in chronic plaque psoriasis (1)
- if used as combination therapy with PUVA or UVB then this allows dose reduction and decreases the incidence of adverse effects
- ciclosporin - 2.5 mg/kg/day; complications include hypertension; renal impairment; hypertrichosis; and increased risk of skin malignancy and lymphoma
Indications for systemic therapy (2) include:
- failure of adequate trial of topical therapy
- repeated hospital admissions for topical therapy
- rxtensive chronic plaque psoriasis in the elderly or infirm
- reneralised pustular or erythrodermic psoriasis
- revere psoriatic arthropathy
Note that etretinate, methotrexate are specifically contraindicated for use in pregnancy.
NICE suggest (3):
- Choice of drugs
- methotrexate should be offered as the first choice of systemic agent for people with psoriasis who require systemic therapy
- in people with both active psoriatic arthritis and any type of psoriasis that fulfils the criteria for systemic therapy consider the choice of systemic agent in consultation with a rheumatologist
- ciclosporin should be offered as the first choice of systemic agent for people who fulfil the criteria for systemic therapy and who:
- need rapid or short-term disease control (for example a psoriasis flare) or
- have palmoplantar pustulosis or
- are considering conception (both men and women) and systemic therapy cannot be avoided
- consider changing from methotrexate to ciclosporin (or vice-versa) when response to the first-choice systemic treatment is inadequate
- acitretin should be considered for adults, and in exceptional cases only for children and young people, in the following circumstances:
- if methotrexate and ciclosporin are not appropriate or have failed or
- for people with pustular forms of psoriasis
- Biological Therapy (third line therapy)
- indicated when the following criteria are both met:
- disease is severe as defined by a total Psoriasis Area Severity Index (PASI) of 10 or more and a Dermatology Life Quality Index (DLQI) of more than 10
- the psoriasis has not responded to standard systemic therapies including ciclosporin, methotrexate and PUVA (psoralen and long-wave ultraviolet radiation); or the person is intolerant of, or has a contraindication to, these treatments
- third-line therapy refers to systemic biological therapies such as the tumour necrosis factor antagonists adalimumab, etanercept and infliximab, and the monoclonal antibody ustekinumab that targets interleukin-12 (IL-12) and IL-23
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