Psoriasis Flashcards

1
Q

What are some features of cutaneous immunity?

A

both the physical means to keep pathogens out and responses centered in the skin when pathogens get in

can be broken down into innate and adaptive responses

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2
Q

What are the layers of innate immunity in the skin?

A

encompasses those elements that are not specific to the pathogen and require no memory

  • physical barrier
  • epidermal production of protective proteins
  • local cytokine production
  • blood derived cells
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3
Q

What is the most superficial barrier of the skin?

A

stratum corneum

filaggrin - blocks microbes from penetrating the skin

atopic dermatitis when filaggrin breaks down

normal skin flora are competitive for spots to bind to skin

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4
Q

What is the second layer of barrier in the skin?

A

the microbe encounters constitutively expressed anti-microbial proteins in the stratum corneum

defensins are the most common

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5
Q

What is the third layer of barrier of the skin?

A

after the stratum corneum, the microbe separates tight junctions and activates toll-like receptors inducing and immune reaction

new AMPs are produced and blood borne immune cells are activated

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6
Q

What are the important factors of immune activation in the skin?

A

activation of TLRs to induce the production of cytokines like tumor necrosis factor-alpha (TNF) and interleukin-1 (IL-1)

blood borne cells including dendritic cells, neutrophils, mast cells, T cells can all be activated

dendritic cells, in particular, produce IL-23

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7
Q

What is the hypothesized pathophysiology of a psoriatic plaque?

A

TNF -> IL-23 -> IL-17 -> keratinocyte proliferation -> psoriasis

vicious cycle of keratinocyte release of proinflammatory cytokines and epidermal remodeling

chemotaxins are also involved in exacerbating the disease

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8
Q

What is the effect of IL-23?

A

impacts many blood borne cells including T cells, neutrophils, and basophils

multiple cytokines are produced with the most interesting being the IL-20 family (IL-20,22, and 24) and, most importantly IL-17 of multiple types

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9
Q

What is the role of IL-17?

A

induces further changes in the epidermis, including thickening and induced AMP production

promotes increased recruitment of new cells

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10
Q

What is the epidemiology psoriasis?

A

most common inflammatory skin diseaes in adults - about 3% of the population

men = women

significant gentic predisposition, though about 50% of patients do not report a family history

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11
Q

Where are the most common areas for psoriasis?

A

elbos, knees, and scalp

these areas are most common place of trauma

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12
Q

What are the types of psoriasis?

A

limited plaque psoriasis

extensive plaque psoriasis

palmar-plantar psoriasis

scalp psoriasis

psoriatic nails

pustular psoriasis

erythrodermic psoriasis

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13
Q

What are histological findings of psoriatic skin?

A

thickened skin, scaly - live to dead keratinocyte is 7 days as opposied to 24 days

inflammation is present underneath

redness of the skin

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14
Q

What are some co-morbidities with psoriasis?

A

psoriatic arthritis

depression

diabetes mellitus

chron’s disease

psoriasis decreases work productivity

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15
Q

What are the risks of MI in patients with psoriasis?

A

increased risk in patients with severe psoriasis

risk is about 6.2% over 10 years, about quivalent to very high cholesterol

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16
Q

What are the common treatments for psoriasis?

A

topical therapies - corticosteroids, topical vitamin A and D derivatives

photoherapies - UV B, psoralen + UVA

synstemic therapies - methotrexxate, cyclosporine, retinoids

17
Q

What is the clinical presentation of psoriasis?

A

scale - abnormal keratinocyte maturation, abnormal keratin expression (keratin 16)

thickness - rapid keratinocyte proliferation, increase in cell cycle markers (Ki-67)

redness - cutaneous vascular proliferation and dilation

18
Q

What is the role of STAT-3 in psoriasis?

A

links activated keratinocytes and immunocytes required for development of psoriasis in a novel transgenic mouse model

19
Q

Ustekinumab

A

useful drug for psoriasis

human monoclonal antibody that blocks IL-12 and IL-23

20
Q

Brodalumab

A

monoclonal antibody that blocks IL17RA

inhibits IL17 A, C, and F

21
Q

Ixekizumab and Secukinumab

A

monoclonal antibodies that inactivate only IL17A

treatment for psoriasis

22
Q

What is IL-12, and what is its role in psoriasis?

A

heterodimer composed of p35 and p40 subunits

produced by activated dendritic cells and macrophages

promotes growth and differentiation of naivev T cells into Th1 cells and cytotoxic T cells

down regulates Th2 cytokines such as IL-10

23
Q

What is the role of the p40 subunit in psoriasis?

A

subunit of IL-12 and IL-23

upregualted in lesional skin of psoriatic patients

initially interpreted as increased IL-12

later analysis showed not increase of p35 subunit in psoriatic plaques

IL-23, rather than IL-12, mediates psoriasis

24
Q

What is the role of IL-23 in psoriasis?

A

can activate local inflammatory cells to produce:

  • IL-17 family cytokines
  • IL-20 family cytokines