Psoriasis

• Definition and facts• Epidemiology• Classification• Signs and symptoms• Etiology • Diagnosis • Management • Prognosis

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• A a common chronic inflammatory skin disorder characterized by recurrent exacerbations and remissions of thickened, erythematous, and scaling plaques.

• Occurs when the immune system sends out faulty signals that speed up the growth cycle of skin cells.

• Is NOT contagious.

• Occurs on the skin of the elbows and knees, scalp, palms of hands and soles of feet, and genitals.

• Fingernails and toenails are frequently affected.

• Can also cause inflammation of the joints (psoriatic arthritis; 10-40%).

• The cause not fully understood, however, genetics plus local psoriatic changes are the favorable perpetrators.

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Epidemiology• Psoriasis affects both sexes equally.

• Can occur at any age (most commonly appears for the first time between the ages of 15 and 25 years).

• The prevalence of psoriasis in Western populations is estimated to be around 2-3%.

• Around one-third of people with psoriasis report a family history of the disease.

• Onset before age 40 usually indicates a greater genetic susceptibility and a more severe or recurrent course of psoriasis.

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Classification• Non-pustular: - Psoriasis vulgaris: the most common (80-90)% - Psoriatic erythroderma: often results from exacerbation of

vulgaris particularly following the abrupt withdrawal of systemic treatment.

• Pustular: - Appears as raised bumps that are filled with pus. - The skin under and surrounding the pustules is red and

tender. - Can be localized to the hands and feet or generalized with

widespread patches occurring randomly on any part of the body.

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Signs• The typical lesion is a well-demarcated, pink to salmon-colored

plaque covered by loosely adherent scale that is characteristically silver-white in color.

• Nail changes occur in 30% of cases of psoriasis and consist of yellow-brown discoloration, with pitting, dimpling, separation of the nail plate from the underlying bed, thickening, and crumbling.

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Symptoms

• Relatively asymptomatic.

• Pruritus is a complaint in about 25% of patients.

• Severe, widespread psoriasis can involve fever and chills.

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• Severity: - Mild - Moderate - Severe

• The Psoriasis Area Severity Index (PASI): - The most widely used measurement tool for psoriasis. - Combines the assessment of the severity of lesions and

the area affected into a single score in the range 0 (no disease) to 72 (maximal disease).

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Etiology • There are two main hypotheses: 1. Considers it as a disorder of excessive growth and

reproduction of skin cells (the problem is simply seen as a fault of the epidermis and its keratinocytes).

2. Considers it as being an immune-mediated disorder in which the excessive reproduction of skin cells is secondary to factors produced by the immune system.

- T cells become active, migrate to the dermis and trigger the release of cytokines (TNFα) which cause inflammation and the rapid production of skin cells.

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• Triggering/Aggravating factors: - Stress (physical and mental) - Skin injury (Koebner phenomenon) - Streptococcal infection - Changes in season and climate - Certain medicines (lithium salt, β-blockers & chloroquine) - Excessive alcohol consumption, smoking and obesity - Hairspray, some face creams and hand lotions27/03/2011 University of Jordan/Faculty of Pharmacy 11

Genetics• Psoriasis has a large hereditary component.• The MHC and T cells play pivotal role.• PSORS1 through PSORS9.• The major determinant is PSORS1 (accounts for 35-50%). It

controls genes that affect the immune system or encode proteins that are found in the skin in greater amounts in psoriasis:

- HLA (MHC-1) - IL12B - IL23R (interleukin-23 receptor)

upregulating TNFα and NFκB

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CMI Cell Type Outcome

GM-CSF T cells mononuclear cells,  neutrophils

INF- γ T cells E selectin, ICAM, IL-4,  keratinocytes,  MHC I and II,

VCAM, TH2

 

IL-2 T cells macrophages, TH1 cells

 

IL-3 T cells dendritic cells, macrophages

IL-8 Keratinocytes, neutrophils vascular response

IL-12 APC TH1 cells

 

IP-10 Keratinocytes leukocyte adhesion

MIG Keratinocytes leukocyte adhesion

RANTES Keratinocytes IL-12

TNF- α Keratinocytes, macrophages, E selectin, ICAM

T cells TH1 cells, VCAM

 

VEGF Keratinocytes, T cells angiogenesis

APC, antigen-presenting cell; GM-CSF, granulocyte-macrophage colony-stimulating factor; ICAM, intercellular adhesion molecule; INF, interferon; IL, interleukin; IP, inflammatory protein; MHC, major histocompatibility complex; MIG, monokine induced by interferon-; RANTES, regulated on activation, normal T-cell expressed and secreted; TNF, tumor necrosis factor; TH1, T-helper cell type 1; TH2, T-helped cell type 2; VCAM, vascular cell adhesion molecule; VEGF, vascular endothelial growth factor.

Data from Mehlis S, Gordon KB. From laboratory to clinic: Rationale for biologic therapy. Dermatol Clin 2004;22(4):371–377, vii–viii.

Chemical Mediators of Inflammation in Psoriasis (CMI)

• Diagnosis: - Based on the appearance of the skin. - There are no special blood tests or diagnostic procedures. - A skin biopsy (or scraping) may be needed to rule out other

disorders and to confirm the diagnosis.

- When the plaques are scraped, one can see pinpoint bleeding from the skin below (Auspitz's sign)

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Management/Treatment • Topical agents: 1. Moisturizers, mineral oil, and petroleum jelly may help

soothe affected skin and reduce the dryness which accompanies the build-up of skin on psoriatic plaques.

2. Ointment and creams containing: - coal tar - dithranol (anthralin) - corticosteroids (desoximetasone & fluocinonide) - vitamin D3 analogues

- retinoids

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• Phototherapy: - Wavelengths of 311–313 nm are most effective. - The amount of light used is determined by a persons skin

type. - Increased rates of cancer from treatment appear to be small. - Psoralen and ultraviolet A phototherapy (PUVA).

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• Systemic agents: - Patients are required to have regular blood and liver function

tests because of the toxicity of the medication. - Pregnancy must be avoided for the majority of these

treatments. - Most people experience a recurrence of psoriasis after

systemic treatment is discontinued. - Three main traditional systemic treatments are

methotrexate, cyclosporine and retinoids. - Two drugs that target T cells are efalizumab and alefacept. - MAbs (infliximab, adalimumab, golimumab and certolizumab

pegol). - Recombinant TNF-α decoy receptor (etanercept). - Antibodies have been developed against pro-inflammatory

cytokines IL-12/IL-23 and IL-17.27/03/2011 University of Jordan/Faculty of Pharmacy 17

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• Alternative therapy: - Fasting periods, low energy diets and vegetarian diets have

improved psoriasis symptoms in some studies, and diets supplemented with fish oil.

- Ichthyotherapy, which is practised at some spas in Turkey, Iran, Iraq, Croatia, Ireland, Hungary and Serbia.

- Hypnotherapy.

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