psoriasis
PSORIASIS

Psoriasis is a systemic chronic skin disorder characterized by excessive keratinocytes proliferation that results into thickened scaly plaques, itching and inflammatory changes in the epidermis and dermis. It is transmitted genetically but can be provoked by environmental factors.
It is found in approximately 2% of the population that primarily affects the skin and joints.
It is associated with other inflammatory disorders and autoimmune diseases (eg psoriatic arthritis, inflammatory bowel disease, coronary artery disease).
Generally, it begins as red scaling papules that coalesce to form round-to-oval plaques. The rashes are often pruritic and may be painful.

Principles of Therapy

  • Choice of therapy should be individualized
  • Most patients will undergo multiple simultaneous therapies
  • Clinician should become familiar with all treatment options so that the right therapy can be chosen for each individual patient
  • Mild disease can usually be treated by topical therapy
  • Moderate to severe disease cannot achieve adequate control using topical agents alone

The following considerations will influence the choice and frequency of therapy:

  • Severity, BSA involved, body region involved
  • Effect of psoriasis on quality of life
  • Degree of psychological impairment caused by the disease
  • Risk versus benefit ratio must be considered for each treatment regimen
  • Presence of comorbidities (eg hepatic disease, hypertension)
  • Patient preference
  • Cost of therapy
  • Other factors to consider include the goals of therapy, presence of psoriatic arthritis and outcomes of prior psoriatic treatments

Baseline Studies

  • Eg CBC with platelet, creatinine, electrolytes, LFT, hepatitis panel screening, latent TB screening, HIV screenig
  • Advised prior to starting, resuming or increasing therapy with systemic and immunosuppressive agents

Vaccinations

  • May consider administration of influenza, hepatitis A and B, tetanus-diphtheria and pneumococcal vaccines prior to therapy
  • Once treatment is initiated, live vaccines and live-attenuated vaccines should be avoided
  • Avoid live vaccinations in infants until 6 months of age if mothers have received biologic therapy beyond 16 weeks’ gestation

Pharmacotherapy

 Topical Therapy

  • First-line treatment for all types of psoriasis
  • Appropriate for patients with mild psoriasis and with areas not involving the face, hand, feet or genitals

Emollients

  • Considered as the standard adjunctive therapeutic approach to the treatment of psoriasis, particularly in non-acute phase
  • Used in combination with other topical treatments
    • One study established that the combination increase the efficacy of corticosteroids and provide better control of psoriasis with lower doses of corticosteroids
  • Soften and smoothen the stratum corneum, achieved by a trapping mechanism that decreases the rate of transepidermal water loss
    • Some like petrolatum or mineral oil may enhance efficacy of phototherapy
    • Some like those containing acids may irritate broken/inflamed skin
  • Patient preference and treatment area will determine formula used
    • Eg Petrolatum, Liquid paraffin, Mineral oils, Glycerine, Ichthammol
  • Various emollient products for psoriasis are available. Please see the latest MIMS for prescribing information of specific formulations

Calcineurin Inhibitors

  • Indicated for psoriasis located in facial and intertriginous areas only
  • Not generally effective in plaque psoriasis
  • Blocks the synthesis of inflammatory cytokines that have an important role in the pathogenesis of psoriasis

Corticosteroids

  • First-line treatment for patients with mild or limited psoriasis and for plaque psoriasis
  • Have anti-inflammatory, antiproliferative, immunosuppressive and vasoconstrictive effects
  • Tachyphylaxis (development of tolerance) leading to decreased efficacy and side effects from long-term treatment may limit use
    • Use judiciously to obtain max benefit with minimum side effects 
  • Available in different potencies from mild to very high
    • Low to Mid Potency
      • Not to be used at any site for >8 weeks
      • Combination with Vitamin D recommended as initial treatment for adults with trunk and/or limb psoriasis
      • Mid potency recommended as initial treatment for scalp, face, flexures and genital psoriasis
    • High Potency
      • Highest potency agents were found to be the most effective followed by vitamin D analogues
      • Potent to very potent topical corticosteroids are not advisable for use on the face, flexures and genitals, over 4 weeks, and in children <1 year old
  • Choice of product will depend on site of lesion to be treated, age of patient, patient preference, severity of lesions, steroid potency and formulation
    • Scalp: Lotions, sprays, solutions and gels are preferred since they can be rubbed on the scalp
    • Face: Low potency is recommended; avoid potent steroids
    • Body folds: Cream or gel of low potency is recommended
    • Palms and soles: Very potent steroids are typically necessary; only mildly effective
  • Flare-up of psoriasis may occur upon discontinuation; corticosteroid therapy should be reduced slowly
  • Use as adjunct with agents that are better tolerated; increase potency of corticosteroid during flare-ups and taper down when in remission
  • Commonly used in combination with vitamin D analogue, topical retinoid, UV light, or systemic agents
  • Advise regular skin examination for all patients having long-term treatment to assess atrophy

Dithranol (Anthralin)

  • Effective treatment for large plaque psoriasis
  • Commonly used as short-contact therapy (20-30 minutes) in an outpatient setting
  • Slows down the proliferation of stem cells and prevents T-lymphocyte activation so that normal keratinization may occur
  • Has lower efficacy than more potent topical corticosteroids or vitamin D analogues
  • Not suitable for large areas of small lesions, flexure areas or face; may be used on the trunk, limbs only when treatment with other topicals have failed
  • Staining and irritating properties may limit use

Keratolytics

  • Salicylic acid is the most commonly used keratolytic
  • Remove hyperkeratosis, break down, peel off excess scales and soften the psoriatic plaques
  • May be used alone or in combination with other forms of therapy (eg corticosteroids and topical immunomodulators)
    • Combination is more effective because of increased skin penetration
  • Should not be used together with other oral salicylates or before UVB phototherapy

Retinoid

  • Tazarotene is a topical retinoid effective in psoriasis
  • May be used for the treatment of mild-moderate psoriasis involving ≤20% of BSA
  • Mediates cell differentiation and proliferation
  • Similar efficacy as topical corticosteroids
  • Can achieve remission of psoriatic plaques
  • Has slow onset of action and when used as monotherapy, skin irritation (retinoid dermatitis) may limit use
  • May be combined with topical corticosteroids to enhance therapeutic effects and reduce the local irritation produced by retinoids
  • Teratogenic: Should not be used in pregnant women or those planning to become pregnant

Tars

  • Effective for use in chronic plaques in mild-moderate psoriasis
  • May be used if vitamin D analogue and corticosteroid is ineffective or not tolerated
  • May be used alone as a tar bath or applied directly to psoriatic plaques; avoid face and flexures
  • Most popularly used as scalp treatment with corticosteroid or combined with UVB (Goeckerman treatment)
  • Suppress DNA synthesis in the epidermis; may cause sterile folliculitis
  • Low patient tolerance as most products are messy and odorous
  • Many tar preparations in combination with other psoriasis medications are available. Please see the latest MIMS for prescribing information of specific formulations

Vitamin D Analogues

  • Indicated in chronic plaque psoriasis especially for long therapy and for patients with mild to moderate scalp psoriasis
  • Inhibit keratinocyte proliferation and enhance keratinocyte differentiation, after binding to vitamin D receptors
  • Studies showed more improvement in psoriasis when used in combination with topical corticosteroids than when either agent is used alone

Systemic Non-Biological Therapy

Indications for Systemic Non-Biological Therapy:

  • Symptoms cannot be controlled by topical medications or
  • Total wellbeing (psychological, physical, social) greatly affected or
  • ≥1 of the following:
    • Diagnosed severe psoriasis or
    • Localized, affected part significantly impaired or distressed or
    • Failure of phototherapy (treatment failure or relapse > 50% of baseline within 3 months)

Ciclosporin (Cyclosporine)

  • Reserved for intermittent control and should not be given for >12 weeks unless clinically indicated
  • Inhibits T-cell activation
  • Effective for moderate-severe plaque type psoriasis
  • First line in treatment of patients with indications for systemic non-biologic therapy and who:
    • Need fast control of disease
    • with palmoplantar pustulosis
    • Need systemic therapy but have plans to have children in the future
    • Had treatment failure after Methotrexate therapy
  • Should only be used by experienced practitioners and in patients who have failed topical treatment, phototherapy and other systemic treatments
  • If possible, rotate its use with other treatments or use during severe inflammatory flare-ups
  • Has been used with topical vitamin D analogue or Methotrexate which lowers effective dose of both agents
  • Should only be used for <2 years; long-term use (>2 years) can lead to nephrotoxicity and possible malignancies (eg squamous cell carcinoma and non-melanoma skin cancers)

Corticosteroids

  • Systemic corticosteroids are generally not recommended as they can lead to generalized pustular psoriasis and rebound exacerbations; should only be used if absolutely needed
  • Intralesional steroids may be used in patients with few small plaques, on isolated recalcitrant plaques, but are rarely used

Hydroxyurea

  • Inhibits DNA replication
  • Antimetabolite which can be effective as monotherapy, though less effective than other systemic agents
  • Indicated for patients who fail topical therapies, UVB, or who cannot tolerate PUVA, Methotrexate or other systemic therapies
  • Nearly half of patients who show improvement with Hydroxyurea develop bone marrow toxicity with leukopenia or thrombocytopenia
  • Avoid in pregnant and breastfeeding women

Methotrexate

  • Inhibitor of folate biosynthesis thereby impairs DNA replication
    • Has cytostatic and anti-inflammatory properties
  • Antimetabolite that may be used in patients who have failed topical therapies and photochemotherapy
  • Most frequently used agent in moderate-severe, recalcitrant and disabling psoriasis (psoriasis covering >10% BSA)
  • Highly effective especially for long-term treatment of severe forms of psoriasis including psoriatic erythroderma and pustular psoriasis
  • May be combined with UVB, PUVA, retinoids or Ciclosporin; may be taken with Folate supplements to reduce toxicity
  • Side effects like bone marrow depression, hepatotoxicity or pneumonitis may limit use; monitoring of LFTs, CBC and renal profile is recommended
  • Avoid in pregnant and breastfeeding women

Mycophenolic acid

  • Interferes with T-cell proliferation
  • Antimetabolite initially developed for organ transplantation
  • Some reports show beneficial effect of Mycophenolic acid in psoriasis patients
  • Many patients achieve long remissions but may take up to 12 weeks to see maximal effects
  • As it is an immunosuppressant, there is a small risk of developing lymphoproliferative disease and non-cutaneous malignancies
  • In patients receiving this drug with other immunosuppressants, pure red cell aplasia has been reported
  • Avoid in pregnant and breastfeeding women

Retinoid

  • Acitretin
    • Oral retinoid of choice; effective systemic agent that is not immunosuppressive
    • May be used as monotherapy for pustular, erythrodermic and moderate-severe plaque psoriasis
    • Beneficial effect occurs much more slowly when used for plaque and guttate psoriasis but improves dramatically when combined with PUVA and UVB (lower doses of agents are required)
    • May be combined with UVB, PUVA, biologic agents
      • Although combination with Methotrexate is contraindicated in official labeling, this can be used when needed with appropriate hepatic monitoring
      • May be used with Ciclosporin for a short period of time with close monitoring of lipid profiles
  • Highly teratogenic and tend to persist in body tissues
    • Female patients should not become pregnant for 3 years after treatment has been discontinued
  • Avoid in patients taking excessive amounts of vitamin A and in breastfeeding women
  • Mucocutaneous side effects and dyslipidemia may occur

Sulfasalazine

  • Useful in moderate-severe plaque type psoriasis; effects are less than other systemic agents
  • Side effects are common but are not severe and are typically reversible
Immunosuppressive/Biological Therapy
  • May be considered for patients who have severe disease
    • Severe disease is defined as having a Psoriasis Area Severity Index (PASI) score of ≥10 and a Dermatology Life Quality Index (DLQI) of >10
    • Very severe disease quantified as total PASI of ≥20 and DLQI of >18
  • In addition to severity of the disease, the patient should also have one of the following clinical conditions:
    • At high risk or has developed clinically significant drug-related toxicity and alternative standard therapy cannot be utilized
    • Has contraindications to, intolerance/inaccessibility to, and/or failure to respond to phototherapy and standard systemic therapy, eg Methotrexate and Ciclosporin
    • Severe, unstable, life-threatening disease or severe localized psoriasis with significant impairment of function and/or high levels of distress
    • Psoriatic arthritis making the patient eligible for anti-tumor necrosis factor (anti-TNF) agent therapy
  • Monitor adverse effects during and after biological therapy

Adalimumab

  • Indicated in patients with moderate-severe plaque-type psoriasis and psoriatic arthritis
  • May also be considered in patients with erythrodermic psoriasis and chronic plaque psoriasis
  • Human anti-TNF-alpha monoclonal antibody
  • Studies showed 80% of patients achieve 75% improvement in the PASI score at week 12
  • Appropriate for long-term continuous use
  • Rebound does not usually occur when discontinued; may lose efficacy after reinitiation

Alefacept

  • Indicated in adult patients with moderate-severe chronic plaque psoriasis who are candidates for systemic agents or phototherapy
  • Inhibits T-cell activation
  • Studies showed 21% of patients achieved 75% improvement in the PASI score at week 14
  • In some cases caused long remissions
  • Used for intermittent rather than long-term continuous use since long-term safety is still unknown
  • Do not use concurrently with other immunosuppressive agents or phototherapy

Efalizumab

  • Indicated in patients with moderate-severe chronic plaque psoriasis
  • A humanized monoclonal antibody that inhibits T-cell activation
  • Studies showed 27% of patients achieve 75% improvement in the PASI score at 3 monthsx
  • May cause rebound or flare in some patients

Etanercept

  • Indicated in patients with moderate-severe plaque psoriasis
    • Response is maintained up to 24 weeks in patients with severe chronic plaque psoriasis
    • Disease clearance may be improved when combined with Methotrexate or narrow band UVB phototherapy
  • A human recombinant TNF receptor p75 fusion protein that inhibits TNF
  • Appropriate for long-term continuous use
  • Rebound does not usually occur when discontinued
  • May lose its efficacy over time due to antibody development

Infliximab

  • Indicated in patients with moderate-severe plaque psoriasis
  • May be given in erythrodermic psoriasis
  • A human murine chimeric monoclonal antibody that inhibits TNF; with high binding affinity and specificity for TNF-alpha
  • Has rapid clinical response, highly effective on initial exposure and in severe acute flares
  • Variable efficacy after restarting or beyond the first year of continuous use

Ixekizumab

  • Indicated in patients with moderate-severe plaque psoriasis who are candidates for phototherapy/systemic therapy
  • A humanized IgG4 monoclonal antibody with neutralizing activity against interleukin-17A (IL-17A)

Secukinumab

  • Indicated in patients with moderate-severe plaque psoriasis who are candidates for phototherapy/systemic therapy
  • A recombinant human monoclonal antibody that binds IL-17A

Ustekinumab

  • Indicated in patients with moderate-severe plaque-type psoriasis
  • Human monoclonal antibody that targets interleukin (IL)-12 and IL-23 on the p40 subunit
  • Studies showed 67% of patients achieved 75% improvement in the PASI score at week 12
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