Psoriasis

Definition

  • Chronic inflammatory skin disease

  • Characterised by erythematous, circumscribed scaly papules, and plaques on elbows, knees, extensor limbs, scalp, and, less commonly, nails, ears, and umbilical region

  • Typically lifelong, with a fluctuating course of exacerbations and remission.

  • Causes itching, irritation, burning, and stinging in half the cases

Risk Factors

    • Genetic

      • Linked to the class I and II major histocompatibility complex on human chromosome 6.

      • Genetic foci found to be associated with psoriasis include PSOR1 and PSOR2.[9] [10]

    • Immune response

      • Associated with increased activity of T cells in underlying skin.

      • Biological agents used to treat severe psoriasis directly modify the function of T cells

      • HIV-positive patients develop more severe psoriasis. [10][11] [12]

    • Infection

      • Guttate psoriasis is observed to follow an upper respiratory infection, such as streptococcal pharyngitis, and is believed to be an infection-induced disease.

      • Viral infection and immunisation have also been linked to the flare of psoriasis. [10] [13]

    • Stress

      • Stress aggravates the occurrence of psoriasis and makes psoriasis worse.

      • Stress reduction techniques may be useful in controlling psoriasis. [15] [16]

    • Trauma

      • Trauma, such as surgical scars and injection sites, may result in the appearance of new psoriatic lesions at the sites of injury. [17]

    • Smoking

      • Smokers have a higher risk of psoriasis.

      • This has been documented in several population studies.

      • In one study the risk of having psoriasis was 1.7 to 1.9 times more likely in former or current smokers.

      • The risk of having pustular psoriasis was even higher at 5.3 times. [16]

Differential diagnosis

Epidemiology

    • The incidence of psoriasis is around 60 per 100,000 people[2]

    • In general, about 1.5% to 3.5% of the white population has psoriasis. [3]

    • The mean age of onset is 28 years, with equal distribution between men and women. [4]

    • Asian populations appear to have a very low prevalence of psoriasis (0.3%). [5]

    • The incidence of psoriatic arthritis is 1.4 per 100,000 and a prevalence of 24 per 100,000

      • this is a conservative figure including only those with significant arthritis [6]

      • Another estimate suggests an incidence of 6.6 per 100,000 and a prevalence of 100 per 100,000. [7]

    • Around 7% to 11% of psoriatic patients have arthritis. [2] [7] [8]

Aetiology

    • The aetiology is unknown. Several factors have been suggested:

      • Immunology

        • Psoriasis appeared after cessation of systemic corticosteroids (rebound)

        • It is aggravated by the use of anti-malarials, lithium, and beta-blocker drugs

        • Lesions of psoriasis are associated with increased activity of T cells in underlying skin

        • Biological agents used to treat severe psoriasis directly modify the function of T cells

        • HIV patients have more severe and frequent psoriasis. [10] [11] [12]

      • Infection

        • Guttate psoriasis is observed to follow an upper respiratory infection, such as streptococcal pharyngitis

        • Viral infection and immunisation have also been linked to the flare of psoriasis. [10] [13]

Clinical features

    • Skin lesions

      • Typically erythematous, circumscribed scaly papules and plaques

        • On elbows, knees, extensor surfaces of limbs, scalp, and, less commonly, nails, ears, and umbilical region

        • Typically blanching

      • In plaque psoriasis, there are raised inflamed plaque lesions with a superficial silvery-white scaly eruption

        • The scale may be scraped away to reveal inflamed and sometimes friable skin beneath

      • In guttate psoriasis, there are widespread, erythematous, fine, scaly papules (water drop appearance) on trunk, arms, and legs.

        • The lesions often erupt after an upper respiratory infection. [1]

      • In pustular psoriasis, (von Zumbusch) there are sterile pustules on the hands and feet

        • Diffuse or circular erythematous lesions with pustules and scaling on the trunk. [1]

      • In erythroderma (erythrodermic psoriasis), there is generalised erythema with fine scaling.

        • It is often associated with pain, irritation, and sometimes severe itching. [1]

    • Auspitz's sign is the appearance of punctate bleeding spots when psoriasis scales are scraped off, named after Heinrich Auspitz

    • FHx

    • Light skin

      • Psoriasis is around twice as common in white populations as in black people

    • Skin discomfort

      • Skin is highly sensitive and itching can be severe.

      • Bleeding may occur if the lesions are scratched.

      • The skin can be painful, particularly if joints are involved

    • Smoking

      • Smokers are at higher risk of psoriasis.

Pathophysiology

    • Psoriasis is a hyperproliferative disorder, involving a complex cascade of inflammatory mediators

    • Mitotic activity of basal and suprabasal cells is significantly increased, with cells migrating from the basal layer to the stratum corneum in just a few days

      • The silver scale on the surface of psoriasiform lesions is simply a layer of dead cells. [10] [14]

    • Cytokines, particularly proinflammatory cytokines, T cells, macrophages, and vascular endothelial growth factor are heavily involved in pathogenesis

      • Tumour necrosis factor-alpha (TNF-alpha), in particular, has been a target of biological therapy.

      • TNF-alpha is high in serum, synovium and psoriatic plaques.

    • Human monoclonal antibodies that block TNF-alpha receptors, or inhibit binding or activation of TNF-alpha receptors, have been shown to significantly control psoriasis

Investigations

    • Skin biopsy

      • Intraepidermal spongiform pustules and Munro neutrophilic microabscess within the stratum corneum

    • In addition to these classical features, others include focal parakeratosis and epidermal acanthosis with dilated capillaries within dermal papillae.

  • Skin biopsy should be ordered only when diagnosis is in doubt, but biopsy does not always show classic pathological features.

Management

a) conservative

b) medical

    • Emolients

      • Ointments (such as Aquaphore) or thick creams (such as Cerave, Nivea, or Eucerin) that are used to reduce scale and irritation. [22]

      • They are available as over-the-counter preparations and should be applied at least once a day, preferably twice a day, but can be applied more often if required

      • Although both preparations are effective, most patients prefer creams to ointments, and compliance tends to be better with cream preparations.

    • Topical corticosteroids

      • Generally, the lowest potency of topical corticosteroid should be used.

      • This often means a mid-potency agent for adults and most body areas.

      • Low-potency treatments are appropriate for lesions on the face or intertriginous areas or for infants.

      • High-potency topical corticosteroids are usually reserved for adults requiring short-term treatment of thick plaques that are resistant to lower-potency agents. [19]

    • Topical vitamin D analogues

      • Agents such as calcipotriol bind with vitamin D-selective receptors

      • Have been shown to inhibit the hyperproliferation and abnormal differentiation of keratinocytes characteristic of psoriatic lesions. [19]

      • These agents do not smell or stain clothes and may be more acceptable than tar or dithranol products.

      • Calcipotriol has a relatively slow onset of action and its maximal effect is after 6 to 8 weeks

      • For patients with scalp psoriasis, combination preparations consisting of a topical vitamin D analogue and corticosteroid (calcipotriene plus betamethasone dipropionate) are a welcome addition to the available topical therapies. [35]

    • Oral retinoids

      • These drugs (e.g., acitretin) are moderately effective in many cases and are often combined with other treatments.[C Evidence]

      • Treatment is not recommended for >6 months.

      • Liver function and blood lipid concentration should be monitored.

      • Women of childbearing ages are not suitable for this regimen as retinoid agents are teratogenic.

    • Methotrexate

      • Folic acid antagonist and works as an antiproliferative and anti-inflammatory agent.[C Evidence]

      • Although effective in most patients, it has the potential for hepatotoxicity. [24]

      • Methotrexate is contraindicated in the following groups:

        • pregnant patients; people with renal impairment, hepatitis, or cirrhosis;

        • people who abuse alcohol;

        • unreliable patients;

        • patients with leukaemia or thrombocytopenia

      • Folic acid may be used in addition to methotrexate to minimise adverse effects (such as GI symptoms).

    • Dithranol cream

    • Ciclosporin

      • An effective treatment for psoriasis but has significant adverse effects.[C Evidence]

      • Long-term use (i.e., >12 months) is not recommended.

      • A break (i.e., drug vacation) is recommended after 1 year, switching to other drugs such as methotrexate.

        • Ciclosporin can then be restarted

    • Biological agents

      • Newer biological therapies are recommended as possible treatment

        • if the psoriasis is very severe and the disease has not improved with other treatments such as ciclosporin, methotrexate, or PUVA,

        • or the patients have had adverse effects with these in the past, or such therapy is contraindicated. [24]

      • Alefacept

        • Has a dual mechanism of action that involves induction of T-lymphocyte apoptosis and interruption of T-lymphocyte activation.[A Evidence]

      • Etanercept

        • Inhibits tumour necrosis facto-alpha (TNF-alpha), an important cytokine involved in the pathogenesis of psoriasis

        • Has been shown to significantly reduce the severity of plaque psoriasis.[A Evidence]

        • Furthermore, etanercept has been demonstrated effective in treating psoriasis in adults, children, and adolescents.[25]

      • Infliximab

        • Also inhibits the activity of TNF-alpha and has been shown to have efficacy in the treatment of chronic plaque psoriasis

        • It has also been demonstrated to improve health-related quality of life in patients with psoriasis. [28]

        • Meta-analysis has demonstrated that infliximab is more effective than adalimumab and etanercept. [29]

      • Adalimumab

        • Inhibits the activity of TNF-alpha and has been shown to have efficacy in in the treatment of chronic plaque psoriasis. [30] [31]

        • It is more effective than methotrexate and placebo. [32]

        • Studies have demonstrated improvement in health-related quality of life. [33]

      • Ustekinumab

        • Humanized monoclonal antibody

        • Inhibits Interleukins 12 and 23.

        • It has been shown to be effective in clinical trial for psoriasis. [34]

    • Retinoid-PUVA (re-PUVA)

      • The re-PUVA regimen consists of methoxsalen and ultraviolet A (PUVA) with an oral retinoid

      • May prevent antigen presentation process by Langerhans cells in the skin

      • Acitretin is given the day before PUVA therapy, which enhances the efficacy.

      • Adverse features include inconvenient scheduling (treatment is delivered 3 to 5 times per week), phototoxicity (during and after treatment), and burning if the dose is not adequately controlled

c) surgical

    • n/a

Prognosis