Skin as an immune organ

Question 1

What are the inherent non immune skin defenses via chemicals?

Answer 1

free fatty acids; free radical trapping; antimicrobial peptides

Question 2

What is an inherent skin defense for photoprotection?

Answer 2

melanin as a UV chromophore

Question 3

T/F skin is capable of both innate and adaptive immune responses

Answer 3

true

Question 4

How does keratinocytes act as immune cells?

Answer 4

produce and respond to cytokines; upregulate ICAM-1; present antigen

Question 5

What are the ‘team’ players for the immune system for the skin?

Answer 5

keratinocytes (sense pathogens);
dendritic cells (uptake pathogens and initiate wide range of response);
T cells (respond and perform effector fxn)

Question 6

What are the 2 major adhesion molecules of the skin with clinical significance?

Answer 6

desmosomes; hemidesmosomes

Question 7

What is a disorder of adhesion of 1 keratinocyte to another?

Answer 7

pemphigus vulgaris

Question 8

How does pemphigus vulgaris start?

Answer 8

mucosal erosions

Question 9

What is the pathogenesis of phemphigus vulgaris?

Answer 9

autoantibodies to molecule in desmosome that targets desmoglein 3

Question 10

What is the prognosis of pemphigus vulgaris?

Answer 10

w/ Tx then disease remits after several years but untreated then mortality up to 30-70%

Question 11

What is a disorder of adhesion of the epidermis to the underlying dermis?

Answer 11

Bullous pemphigoid

Question 12

What is the etiology of bullous pemphigoid?

Answer 12

onset usually after 60 affecting men more than women

Question 13

What is the classic clinical presentation of BP?

Answer 13

fairly sudden onset of very itchy wheals and tense blisters on trunk and extremities with the mouth and oral mucosa affected some

Question 14

What may cause bullous pemphigoid?

Answer 14

idiopathic;
drugs (furosemide, NSAIDS, captopril, antibiotics;
pregnant women

Question 15

What is the pathogenesis of BP?

Answer 15

production of Abs to molecules making up hemidesmosome preventing epidermis from binding to dermis (BPAg1,2)

Question 16

What cell type is associated with BP that is not understood but causes some Sx?

Answer 16

eosinophils

Question 17

What is the treatment for VP and BP?

Answer 17

require Tx with immunosuppressant agents

Question 18

What is the pathogenesis of drug eruptions?

Answer 18

idiopathic; immunologic (allergic) such as langerhans cells presenting to T cells associated with perforin and granzyme produced to cause cell damage

Question 19

T/F immunodeficiencies predispose to drug rxns

Answer 19

true (immunodeficiency (HIV, EBV) or acquired glutathione deficiency)

Question 20

What are the mechanisms of ADEs that are immunologic?

Answer 20

IgE (type I);
cytotoxic, drug induced (petechiae/TCP) (Type II);
Immune complex (type 3);
cell mediated (type 4)

Question 21

What are morbilliform (maculopapular) eruptions?

Answer 21

common drug rxn=> pruritic, red, small papules starting w/in 2 wks of Tx and possible up to 10 days after

Question 22

What are commonly associated with hypersensitivity rxns?

Answer 22

Antibiotics (semisynthetic penicillins and Bactrim); anticonvulsant; sulfa antibiotic; drugs with ‘p’

Question 23

Drug hypersensitivity syndromes have internal involvement. Name them and what is the Tx

Answer 23

fever, rash, eosinophilia, LAD, hepatitis, nephritis => stop drug immediately

Question 24

What happens in anticonvulsant HSR?

Answer 24

due to deficiency of epoxide hydroxylase and inability to detoxify arene oxide metabolites that then bind to proteins and elicit an immune response

Question 25

What typically causes urticaria?

Answer 25

most commonly associated with penicillin and related to B-lactam antibiotics associaed with IgE Abs to PCN or metabolites

Question 26

How will angioedema present?

Answer 26

edema in eyelids, lips, ears, external genitalia, mucous membranes that is occasionally caused by ACE-inhibitors (lisinopril/enalapril > captopril)

Question 27

Who is at greater risk for angioedema?

Answer 27

Blacks and patients who have already suffered one episode

Question 28

Why does angioedema occur?

Answer 28

blocking of kinase II increasing tissue kinin that may be dose dependent if caused by drug

Question 29

What is red man syndrome caused by and how will it present? Tx?

Answer 29

infusion of vancomycin leads to macular eruption causing pruritis, heat and hypotension leading to elevated histamine => slow infusion and pretreat w/ antihistamines

Question 30

What are photsensitivity rxns caused by?

Answer 30

UVA as drugs absorb UVA range wavelengths and it is able to penetrate into the dermis; drugs may cause photsensitivity too

Question 31

What are the photallergic rxns presesntations? What is common cause?

Answer 31

eczematous pruritic rxns involving immune system that happen later; NSAIDs, Bactrim, thiazide diuretics

Question 32

What leads to phototoxicity?

Answer 32

dose of medications and UVR exposure (tetraceyclines, amiodarone, NSAIDs) leading to pruritic, red painful burn after minimal sun exposure leading to dusky, blue-red erythema of face, hands

Question 33

What is the pathogenesis of toxic epidermal necrolysis?

Answer 33

immune related cytotoxic rxn aimed at destroying keratinocytes that express a foreign antigen where keratinocytes undergo apoptosis and die leading to epidermis sloughing (minimal inflammation)

Question 34

What is the most serious drug reaction and what is the mortality?

Answer 34

toxic epidermal necrolysis with up to 30% mortality

Question 35

What are drugs that may cause toxic epidermal necrolysis?

Answer 35

anticonvulsants; antibiotics; NSAIDs

Question 36

What syndrome is associated with toxic epidermal necrolysis? Tx?

Answer 36

Stevens-Johnson syndrome => supportive care and manage burn