Psoriasis

Question 1

Describe the epidemiology of psoriasis.

Answer 1

a. 2% of the population affected
b. 150,000 new cases per year
c. age of onset: any
i. typically 27 y in women and 29 in men
d. prevalence of men=females
e. multi locus inheritance
f. family history positive in 30-50% of cases
g. increased concordance for psoriasis in monozygotic twins
h. increased frequency of HLA B13, HLA B17, disequilibrium of certain HLA genes

Question 2

Describe classical plaque psoriasis

Answer 2

a. Aka psoriasis vulgaris-most common type
b. Circular plaques of erythema and scaling on elbows and knees
c. commonly affected sites: scalp and nails
i. Onycholysis-separation of nail plate from nail bed
ii. Nail pitting
d. Other common sites: natal cleft, umbilicus, axillae, groins, genitalia

Question 3

Describe Guttate psoriasis

Answer 3

i. Possibly related to strep throat
ii. Eruptive erythematous and scaly guttate “drops”
iii. Trunk and proximal extremities

Question 4

Describe erythrodermic psoriasis

Answer 4

Total body

i. Generalized erythema and varying degrees of scale

Question 5

Describe pustular psoriasis

Answer 5

total body

sterile pustules on background of erythema and scaling

Question 6

What are other site specific subtypes of psoriasis.

Answer 6

i. Scalp only
ii. Nail only
iii. Flexoral psoriasis
iv. Palmo-plantar pustular psoriasis

Question 7

What are associated diseases of psoriasis

Answer 7

a. Psoriatic arthritis

b. Stroke, coronary heart disease, angioplasty procedures, death

Question 8

What are the predominant underlying changes of psoriasis

Answer 8

1. hyper proliferation of keratinocytes

2. sustained inflammatory response

Question 9

Explain the hyper proliferation of keratinocytes in psoriasis

Answer 9

i. Clinically: scaling
ii. Histopathologically: hyperkeratosis and parakeratosis
iii. Shortened cell cycle, 30x as many cells produced per day

Question 10

Explain the sustained inflammatory response in psoriasis?

Answer 10

i. Characteristic feature: cellular inflammation
ii. Clinically: erythema
iii. Histopathologically:
1. inflammatory cell infiltrate of t cells.
a. Most t cells show CD45RO+ cell surface marker (skin homing memory effector T cells)
2. expression of adhesion molecules on keratinocytes in plaques
a. increased t cell activation with expression of t cell receptor, CD-2, LFA-1, stimulated by Il-12
b. increased endothelial cell expression of ICAM-1, stimulated by Il-1 and TNF-a
3. alternations in number and distribution of langerhans cells and macrophages
4. absence of Th2 skin disorders

Question 11

How does Alefacept work?

Answer 11

i. Fusion protein made of cytosolic portion of human lymphocyte function associated antigen 3 (LFA-3)linked to Fc fragment of human IgG1
ii. Mechanism:
1. Attaches to CD2 on t cells
a. Prevents LFA-3 and CD2 interaction→inhibit T cell activation and reactivation
2. Natural Killer Effects
a. Depletion of CD2+ T cells
b. Fc portion binds to NK cells, activating them to kill T cell

Question 12

How does inflixamab work?

Answer 12

i. Chimeric fusion protein consisting of Fc fragment of human IgG linked with mouse Fab fragment specific for TNF-a

Question 13

How does Adalimumab work?

Answer 13

i. Human monoclonal IgG1 antibody with specificity to human TNF-a

Question 14

How does Etanercept work?

Answer 14

i. Fusion protein: Fc fragment of human IgG1 linked with human TNF-a receptor

Question 15

What is the general principle behind psoriasis drugs?

Answer 15

They all bind TNF-a, prevents T cell reactivation & immune stimulated expression of ICAM-1 on endothelial cells and keratinocytes

Question 16

How does Ustekinumab or stelera work?

Answer 16

i. Human monoclonal antibody that’s specific for human p40 subunit common to Il-12 and Il-23
ii. Prevents: T cell activation