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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
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