Skin as an immune organ Flashcards
What are the inherent non immune skin defenses via chemicals?
free fatty acids; free radical trapping; antimicrobial peptides
What is an inherent skin defense for photoprotection?
melanin as a UV chromophore
T/F skin is capable of both innate and adaptive immune responses
true
How does keratinocytes act as immune cells?
produce and respond to cytokines; upregulate ICAM-1; present antigen
What are the ‘team’ players for the immune system for the skin?
keratinocytes (sense pathogens); dendritic cells (uptake pathogens and initiate wide range of response); T cells (respond and perform effector fxn)
What are the 2 major adhesion molecules of the skin with clinical significance?
desmosomes; hemidesmosomes
What is a disorder of adhesion of 1 keratinocyte to another?
pemphigus vulgaris
How does pemphigus vulgaris start?
mucosal erosions
What is the pathogenesis of phemphigus vulgaris?
autoantibodies to molecule in desmosome that targets desmoglein 3
What is the prognosis of pemphigus vulgaris?
w/ Tx then disease remits after several years but untreated then mortality up to 30-70%
What is a disorder of adhesion of the epidermis to the underlying dermis?
Bullous pemphigoid
What is the etiology of bullous pemphigoid?
onset usually after 60 affecting men more than women
What is the classic clinical presentation of BP?
fairly sudden onset of very itchy wheals and tense blisters on trunk and extremities with the mouth and oral mucosa affected some
What may cause bullous pemphigoid?
idiopathic;
drugs (furosemide, NSAIDS, captopril, antibiotics;
pregnant women
What is the pathogenesis of BP?
production of Abs to molecules making up hemidesmosome preventing epidermis from binding to dermis (BPAg1,2)
What cell type is associated with BP that is not understood but causes some Sx?
eosinophils
What is the treatment for VP and BP?
require Tx with immunosuppressant agents
What is the pathogenesis of drug eruptions?
idiopathic; immunologic (allergic) such as langerhans cells presenting to T cells associated with perforin and granzyme produced to cause cell damage
T/F immunodeficiencies predispose to drug rxns
true (immunodeficiency (HIV, EBV) or acquired glutathione deficiency)
What are the mechanisms of ADEs that are immunologic?
IgE (type I); cytotoxic, drug induced (petechiae/TCP) (Type II); Immune complex (type 3); cell mediated (type 4)
What are morbilliform (maculopapular) eruptions?
common drug rxn=> pruritic, red, small papules starting w/in 2 wks of Tx and possible up to 10 days after
What are commonly associated with hypersensitivity rxns?
Antibiotics (semisynthetic penicillins and Bactrim); anticonvulsant; sulfa antibiotic; drugs with ‘p’
Drug hypersensitivity syndromes have internal involvement. Name them and what is the Tx
fever, rash, eosinophilia, LAD, hepatitis, nephritis => stop drug immediately
What happens in anticonvulsant HSR?
due to deficiency of epoxide hydroxylase and inability to detoxify arene oxide metabolites that then bind to proteins and elicit an immune response
What typically causes urticaria?
most commonly associated with penicillin and related to B-lactam antibiotics associaed with IgE Abs to PCN or metabolites
How will angioedema present?
edema in eyelids, lips, ears, external genitalia, mucous membranes that is occasionally caused by ACE-inhibitors (lisinopril/enalapril > captopril)
Who is at greater risk for angioedema?
Blacks and patients who have already suffered one episode
Why does angioedema occur?
blocking of kinase II increasing tissue kinin that may be dose dependent if caused by drug
What is red man syndrome caused by and how will it present? Tx?
infusion of vancomycin leads to macular eruption causing pruritis, heat and hypotension leading to elevated histamine => slow infusion and pretreat w/ antihistamines
What are photsensitivity rxns caused by?
UVA as drugs absorb UVA range wavelengths and it is able to penetrate into the dermis; drugs may cause photsensitivity too
What are the photallergic rxns presesntations? What is common cause?
eczematous pruritic rxns involving immune system that happen later; NSAIDs, Bactrim, thiazide diuretics
What leads to phototoxicity?
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
What is the pathogenesis of toxic epidermal necrolysis?
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)
What is the most serious drug reaction and what is the mortality?
toxic epidermal necrolysis with up to 30% mortality
What are drugs that may cause toxic epidermal necrolysis?
anticonvulsants; antibiotics; NSAIDs
What syndrome is associated with toxic epidermal necrolysis? Tx?
Stevens-Johnson syndrome => supportive care and manage burn
