psoriasis
Introduction
a chronic skin condition characterized by scaly hyperplastic areas of skin especially over extensor surfaces of joints such as elbows and knees but may be more widespread over the body as plaques or is some cases as pustular lesions
pitting of the nails is common
some will develop psoriatic arthritis
mild increased neoplasia risk
2.3x risk of keratinocyte cancer risk (esp. SCC) - partly due to Rx with PUVA, etc
1)
lymphoma - almost 2x risk of Hodgkin's lymphoma and 50% increased risk of other lymphomas which may be due to the higher risk of cutaneous T-cell lymphoma, which is markedly more common in people with severe psoriasis
2)
26% increased risk of lung cancer
3)
13% increased risk of melanoma
4)
treatments for severe psoriasis (2009)
these systemic psoriasis therapies are C/I in pregnancy and lactation and planned pregnancies should be postponed for several years after stopping acitretin Rx. Cyclosporin has been used in pregnancy when severe psoriasis has not responded to other therapies.
standard treatment options
acitretin
oral retinoid agent with usual doses 10-50mg daily
low initial dose then increase dose during induction Rx stage
maintenance Rx may be daily, alternate days or less frequent, and is used long term, often years
the only non-immunosuppressive standard agent but only a third with chronic plaque psoriasis achieve control when acitretin is used as monotherapy.
more effective for pustular and erythrodermic psoriasis than for plaque psoriasis
watch for hepatotoxicity
avoid pregnancy for several years after stopping Rx.
cyclosporin
oral immunosuppressive agent which works quickly to clear psoriasis within 6-12 weeks and is generally very effective in maintaining disease remission
usually bd dosing with 3.5-5mg/kg daily during induction phase then 2-4mg/kg daily maintenance for 6-24 months
longer duration Rx is limited due to concerns of hypertension, nephrotoxicity, malignancy and metabolic effects.
a rise in BP after 1st 1-2 months of Rx suggests nephrotoxicity, especially if serum creatinine rises > 30% above baseline levels.
good dental hygiene essential on patients with immunosuppressives to prevent periodontal disease.
methotrexate
oral or im immunosuppressive agent
slower at clearing psoriasis lesions than cyclosporin, partly because of cautious initial dosing
often takes more than 3 months to induce remission, but if tolerated and no haematologic or hepatic toxicity, it can be continued for many years to maintain good disease control.
5-25mg weekly with close clinical and blood monitoring
taking 5mg folate daily may help prevent GIT and bone marrow adverse effects
narrow band phototherapy
usually 6-12 week course of 3 sessions per week
moderate psoriasis can be cleared with about 6 weeks of Rx and will normally result in 3-6 months of improved disease control
can be combined with topical Rx
concurrent acitretin Rx can speed up response to phototherapy
may cause erythema, pruritus, nausea and high cumulative doses risk of skin cancer.
biological therapies
these generally target T cells or block pro-inflammatory cytokines and are generally given parenterally
usually start to improve psoriasis by 4 weeks and achieve good reductions in severity by 12 weeks
long term safety unclear
potential for more severe rebound state after cessation of Rx and may require combination Rx during transition between therapies to prevent such rebound states.
any required vaccinations should be given before commencing biological therapies
efalizumab
recombinant monoclonal Ab against cells with CD11a marker and thus interferes with T cell activation in lymph nodes and T cell trafficking to skin.
weekly s/c doses can be given long term
cessation appears to have a significant risk of a rebound episode with unstable and rapidly more severe psoriasis that can result in prolonged hospitalisation.
alefacept
binds to CD2 receptor on lymphocytes, and reduces the number of T cells and interferes with their activation
given iv or im weekly for 12 week courses separated by at least 12 weeks between courses
TNF inhibitors
etanercept
infliximab
adalimumab
ustekinumab
psoriatic arthritis
approximately 10% of patients with psoriasis also have psoriatic arthropathy
drugs which improve the skin may have less effect on the arthritis.
-
the TNF inhibitors and ustekinumab can be used to Rx severe active psoriatic arthritis
references and resources