Psoriasis

Question 1

Epidemiology of psoriasis

Answer 1

• Affects 2% of the population (150,000 new cases/yr)
• Average age of onset is 29 years in males and 27 years in females (equal prevalence in men vs women)
• There is some genetic predisposition (higher rates of concordance among monozygotic twins), 30-50% cases have family Hx
• Is a heritable disease with a multi-locus model of inheritance and environmental factors
• Disequilibrium of certain HLA genes

Question 2

Clinical features

Answer 2

• Psoriasis vulgaris (most common) consists of circular plaques of erythema and scaling, predominantly on the knees and elbows, scalp and nails
• Other areas affected: natal cleft, umbilicus, axilla, groin, genetalia
• There may be separation of the nail plate from the nail bed (onycholysis) and nail pitting (very characteristic)
• Guttate psoriasis (drops) is erythematous and scaly, often confined to the trunk and proximal extremities (possibly related to strep throat)
• Psoriatic erythroderma involves the entire body and involves generalized erythema and varying degree of scaling

Question 3

Pustular psoriasis

Answer 3

• Sterile pustules on a background of erythema and scaling

- Usually generalized form but can also be confined to the palms and soles

Question 4

Psoriatic arthropathy

Answer 4

• 5 patterns are typically seen, only recognized non-cutaneous manifestation
• asymmetric oligo-arthritis
• symmetric poly-arthritis
• distal interphalangeal joint disease
• a form of ankylosing spondylitis
• arthritis mutilans

Question 5

Other complications of psoriasis

Answer 5

• Severe psoriasis sufferers have a 54% higher chance to have a stroke
• 21% higher chance of a heart attack
• and 53% more likely to die over a 10 yr period

Question 6

Etiology of psoriasis

Answer 6

• Due to increased proliferation of keratinocytes in conjunction with sustained and characteristic inflammatory response (TH1T cell mediated)
• Keratinocyte life cycle is greatly shortened
• There are high numbers of activated T cells within psoriatic lesions
• Endothelial cells and keratinocytes express immune-dependent adhesion molecules (ICAM and E-selectin), due to IL1 and TNF-a
• increase in langerhans and macrophages abundance
• Decrease in TH2 T cells abundance

Question 7

Pathogenesis

Answer 7

• Psoriatic lesions contain activated T cells (TH1 and CD8), macrophages, and PMNs
• Many T cells become memory cells (both CD4 and CD8), expressing CD45RO (memory surface marker)
• Migrating T cells also express skin homing markers (CD45RO, lack of CCR7 marker), leading to increased T cells in the skin
• CD4s mostly present in deeper dermis, CD8s mostly present in epidermo-dermal junction
• Activated CD4s releases IL12 and TNF-a

Question 8

Rx of psoriasis: Alefacept

Answer 8

• Fusion protein of LFA-3 (lymphocyte function antigen-3) linked to Fc fragment of human IgG
• LFA-3 is expressed on the surface of APCs (langerhans cells) and binds to CD2 on the T cell surface
• This drug competitively binds to the CD2 receptor of the T cell to prevent co-stimulation and activation of the T cells
• When the protein is bound to CD2, the Fc region binds to NK cells Fc receptor, causing the NK cell to kill the T cell

Question 9

Rx of psoriasis: Inflixamab, adalimumab, etanercerpt

Answer 9

• All are chimeric protein (fusion protein) of an Ab who’s binding region is engineered to bind to TNF-a
• These Abs bind both soluble and receptor-bound TNF-a, thus inhibit its ability to induce an up-regulation of ICAM and E-selectin in endothelial and keratinocytes
• Also prevents T cell reactivation

Question 10

Rx of psoriasis: Ustekinumab

Answer 10

• Ab that binds to IL-12 and IL-23 and inhibits their activity
• These IL’s normally stimulate T-cells growth and function
• Thus the drug blocks this stimulation and reduces inflammation