phrm 82400: exam 3: lecture 27: drug-induced hypersensitivity

what is the definition of drug-induced hypersensitivity?

low frequency serious adverse drug reaction with an immunological etiology to an otherwise safe and effective therapeutic agent

what are the key characteristics of DIHR?

- rare

- unpredictable

- complex

- potentially fatal

what are the categories in the complex interplay for determinants for DIHR?

- chemistry

- immunology

- patient factors

- pharmacology

what are the two types of DIHR?

- immediate hypersensitivity

- delayed hypersensitivity

what are the characteristics of immediate hypersensitivity?

- occur within 1 hour

- type I

- IgE-mediated

what are the characteristics of delayed hypersensitivity?

- occurs >1 hour

- type IV or III

- T cell-mediated

what do immune responses require?

haptenation and a second signal

- causes the expression of costimulatory molecules

- absent the second signal, immune tolerance will occur

what is a hapten?

a low molecular weight chemical with the propensity to bind irreversibly to protein

- might or might not stimulate an immune response

what is a costimulatory agent?

a substance that interacts with dendritic cells, stimulating maturation and possibly polarization of an immune response

what is an immunogen?

a substance that stimulates an immune response, having stimulatory capacity for the innate and adaptive immune systems

what is an antigen?

a substance that interacts with high affinity with immunologic receptors

what are examples of urticarial skin lesions resulting from drug hypersensitivity?

- localized raised erythematous papules with subtle or absent central pallor

- extensive wheal and flare reaction with central blanching sharply circumscribed by and erythematous raised border

what is anaphylaxis?

a life-threatening reaction that requires immediate medical intervention

- respiratory and cardiovascular manifestations are most prominent

- reactions may or may not be associated with swelling of the lips, tongue, and/or throat

most patients with penicillin allergy lose sensitivity within __________. why?

10 years; many people with a history of penicillin allergy can tolerate penicillin

while cross-reactivity between __________ and __________ is possible, it occurs at low frequency

penicillin; other beta-lactam antibiotics

what are three ways of test sensitivity?

- skin prick

- intradermal

- oral challenge

what are some causes of allergic contact dermatitis?

plants, fragrances, nickel, latex, hair dyes

T-cell proliferation requires __________

costimulation

what is the effect of no costimulation on T-cell proliferation?

- no response

- potential anergy

what is the effect of costimulation on T-cell proliferation?

T cell proliferation and differentiation

what is the most common organ that is the target of DIHR?

skin

what are the classification of drug eruptions?

- exanthemas (~90%)

- urticarial eruptions (~5%)

- fixed drug eruptions (FDE)

- acute generalized exanthematous pustulosis (AGEP)

- erythema multiforme, stevens-johnson syndrome, toxic epidermal necrolysis

what is an exanthema?

a rash that exhibits erythematous macules or papules, most commonly initially appearing on the trunk

what is a macule?

a rash that appears as flat, distinct colored area less than 1 cm in area

what is a papule?

a raised rash with distinct color that may have distinct or non-distinct edges, with overall size <1 cm

what are the characteristics of exanthemas?

- onset 4-14 days after start of therapy

- last ~1 week

- may exhibit pruritus

- self-limiting

- often caused by viruses and not drug

- associated with many drugs; sulfonamides and penicillins among most common

what are the characteristics of erythema multiforme, stevens-johnson syndrome, toxic epidermal necrolysis?

- distinct reactions

- onset 1-3 weeks after start of therapy

- mortality in SJS/TEN is 10-30%

- causative agents: allopurinol, carbamazepine, nevirapine, phenytoin, sulfonamides

what does DRESS stand for?

drug reaction with eosinophilia and systemic symptoms

how is DRESS characterized?

fever, skin rash, lymphadenophathy, hematological abnormalities, and internal organ involvement

what are the characteristics of DRESS?

- 10% mortality

- onset 2-8 weeks after start of therapy

- anticonvulsants, antibiotics, and allopurinol

how is DRESS differentiated from other DIHRs?

it involves internal organs in addition to the skin

which of the following is not a key characteristic of DIHRs?

a. rare

b. predictable

c. complex

d. potentially fatal

e. a and d

b. predictable

RB received a dose of cephalexin and within 30 minutes developed wheezing and a raised skin rash across her chest and face. this is most likely a reaction that is

a. IgE-mediated

b. T cell-mediated

a. IgE-mediated

most people who claim to be allergic to penicillin can safely take the drug

a. true

b. false

a. true

DRESS is primarily differentiated from other DIHRs by

a. significant mortality

b. the extent of skin involvement

c. internal organ involvement

d. the causative drugs

e. none of the above

c. internal organ involvement