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psoriasis

psoriasis

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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, etc1)
    • 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 psoriasis2)
    • 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
    • all patients with severe psoriasis should be offered hepatitis A and B vaccination and those about to undergo immunosuppression or biologic therapies should be offered vaccination as for transplant patients which also includes pneumococcal, influenza and tetanus-diphtheria vaccines.
    • all patients being considered for TNF inhibitor therapies should be screen for tuberculosis (TB)

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
    • has the best response rate of the biological therapies with 80% achieving a 75% improvement in psoriasis lesions
  • adalimumab

ustekinumab

  • Ab against interleukin-12 and interleukin-23 which helps to rebalance T cell response away from psoriasis

psoriatic arthritis

  • approximately 10% of patients with psoriasis also have psoriatic arthropathy
  • drugs which improve the skin may have less effect on the arthritis.
  • Rx of the arthritis is similar to Rx of rheumatoid arthritis
  • the TNF inhibitors and ustekinumab can be used to Rx severe active psoriatic arthritis

references and resources

psoriasis.txt · Last modified: 2020/02/22 11:27 (external edit)