psoriasis

see also:

• dermatology

• 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⁾

• various mutations in CARD14 can promote different skin diseases, including atopic dermatitis and psoriasis
  • CARD14-NFκB signaling pathway is thought to promote psoriatic diseases when elevated and to promote atopic dermatitis when reduced
  • altered CARD14-MYC signaling could affect barrier function with hypermorph function causing psoriasis and hypomorph function causing atopic dermatitis and allergic diseases in other tissues, contributing to asthma by affecting airway tissue linings or contributing to eosinophilic esophagitis by affecting the digestive tract ⁵⁾
• blocking PDE4 activity with PDE4 inhibitors increases intracellular cAMP levels and effectively relieves the skin inflammatory phenotype of psoriasis.⁶⁾
• fatty acid-binding protein 5 (FABP5) drives ferroptosis and amplifies inflammatory processes in the skin. Blocking this protein significantly improved the skin changes typically associated with psoriasis. ⁷⁾

• 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.

• 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.

• 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

• 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.

• 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)

• 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.

• 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

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

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

• approximately 10% of patients with psoriasis also have psoriatic arthropathy
• tend to have morning stiffness of the joints
• 5 main types:
  • Asymmetric Psoriatic Arthritis
    • occurs in ~1/3rd of those with psoriatic arthritis but is usually mild
    • limited to just one side of your body, mostly often in the knee, hip, fingers, or toes
    • can look like rheumatoid arthritis but finger swelling usually results in more sausage shaped swelling
  • Symmetric Psoriatic Arthritis
    • most common pattern accounting for half of those with psoriatic arthritis
    • affects matching pairs of joints - most commonly knees, hands, feet, or hips
  • Distal Psoriatic Arthritis
    • mainly affects distal joints of fingers and toes which may be confused with osteoarthritis
    • usually also associated with nail pitting or nails lifting from the nail bed
  • Spondylitis
    • spine and sacro-iliac joints are affected which may result in a range of symptoms in addition to chronic back or neck pains and stiffness
    • 70% of those with psoriatic arthritis have some spondylitic component with about one half of those with psoriatic arthritis having symptomatic sacroiliitis and this is assymetric in ~ half of cases of sacroiliitis
    • may get stiff shoulders, weakness of arms and legs, headaches, bladder or bowel neurologic disturbances
    • symptoms of sacroiliitis in PsA may include lower back pain, especially when standing up from a seated position or after prolonged sitting or standing but it is asymptomatic in 70% of cases
    • Dx is best with MRI
    • CRP levels are often higher in patients with psoriatic arthritis if they also have symptomatic sacroiliitis
  • Arthritis Mutilans
    • most severe form but rarest form with 1 in 20 with psoriatic arthritis developing this
    • damages the small joints and tissues in the ends of hands and feet resulting in disfigured fingers and toes
• 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

• Aust. Prescriber Vol 32 Number 1, Feb 2009