22 - Drugs & Allergy Flashcards
What is considered a serious allergic reaction to penicillin? Was is not a serious reaction?
- Serious = swollen lips, tongue, shortness of breath
- Not serious = N/V, GI upset
Define macule
Flat area of altered colour less than 1 cm
Define patch
Large macule over 1 cm
Define papule
Elevated skin lesion less than 1 cm
Define nodule
Elevated skin lesion greater than 1 cm
Define plaque
Elevated flat topped, irregular border less than 1 cm
Define vesicles
Clear fluid filled blisters less than 0.5 cm
Define bulla
Large fluid filled blisters greater than 0.5 cm
Define pustule
Vesicle filled w/ purulent exudate
Define wheal
Accumulation of dermal fluid
What are the different classifications of allergic reactions?
- Immediate (0-1 h); type 1 = severe or possibly non-immunologic
- Accelerated (2-72 h); may be any type
- Late (over 72 h); may be any type, but rarely type 1
What is a non-immunologic reaction?
- Looks like an allergic reaction, but actually due to toxicity
- Ex: red man’s syndrome from vancomycin; tx is to slow down vancomycin infusion
What are the types of allergic reactions?
- Type 1 or anaphylaxis (IgE mediated)
- Type 2 or cytotoxic (IgG or IgM mediated)
- Type 3 immune complex or serum sickness
- Type 4 or cutaneous eruptions (T-cell mediated)
What are the sx of a type 1 allergic reaction?
Urticaria, laryngeal edema, bronchospasm, anaphylaxis
What are the sx of a type 2 allergic reaction?
- Hemolytic anemia
- Thrombocytopenia
- Granulocytopenia
What is the onset time of type 2 allergic reactions?
Variable
What is the onset time of type 3 allergic reactions?
5-21 days after exposure
What is the difference between type 2 and type 3 allergic reactions?
Same, except type 3 is non-hematologic
What are the sx of a type 3 allergic reaction?
- Fever
- Arthralgias
- Skin rash
- Lymphadenopathy
What is unique about type 4 allergic reactions?
Not mediated by antibodies like the other 3
What are the subtypes of type 4 allergic reactions? What is an example of each?
- Type 4a - contact dermatitis
- Type 4b - DRESS syndrome
- Type 4c - contact dermatitis, maculopapular reactions, bullous drug eruptions, Stevens-Johnson syndrome
- Type 4d - acute generalized exanthematous pustulosis (AGEP)
What are the 2 main types of contact dermatitis?
- Antigen type (20%) takes several days of exposure **true allergic reaction
- Irritant type (80%) w/in hours of exposure
What are the sx of AGEP? What is the onset and duration?
- Pustules and fever, but non-infectious
- Onset w/in 3 days
- Resolves in 10 days of stopping drug
What is erythema multiforme often associated w/?
- Herpes infection or histoplasmosis
- Not associated w/ a drug
What are the sx of erythema multiforme?
- Eruption of erythematous, raised patches of skin
- Center of lesion eventually clears and forms “target” appearance in 24-48 h
- Lesions appear on 1 mucosal surface and on hands and feet
- Pruritic and sudden onset
- Rash usually distributed symmetrically over body
Is Stevens-Johnson syndrome a form of serum sickness?
No!! SJS involves mucosa surfaces, while serum sickness never does
What are the sx of Stevens-Johnson syndrome?
- Similar to erythema multiforme but lesions break out at multiple sites (2 or more mucosal membranes); less than 10% BSA involved
- Lining of mouth, throat, genital region, and eyes
- May not see target lesions
Which drugs are associated w/ SJS and TENS?
- Sulfonamides*
- Beta-lactams
- NSAIDs
- Anticonvulsants
Can desensitization be used for an SJS or TENS reaction?
No
Can SJS or TENS be fatal?
Yes
What is the difference between SJS and TENS? When is a reaction considered SJS/TENS overlap?
- SJS involves less than 10% BSA; TENS involves more than 30% BSA
- SJS/TENS overlap is when 10-30% BSA involved
What is the typical onset for SJS or TENS?
- 4 days to 3 weeks after first dose of the offending drug
- We generally consider up to 8 weeks for it still being related to that drug
What are the sx of TENS?
- Top layer of skin peeling off in sheets
- Greater than 30% BSA involved
- Begins w/ painful red area that spreads quickly (days)
- Affected area has scaled appearance, blisters may develop
- Spreads to mucous membranes of eyes, mouth, and genitals
When is SJS/TENS more common?
- HIV-infected patients
- Possibly those w/ SLE (lupus)
What happens when a px has an SJS or TENS reaction a drug?
Can never use that drug again or associated classes of drugs
What does DRESS stand for? What is another name for DRESS?
- Drug rash, eosinophilia, and systemic symptoms
- Aka drug-induced hypersensitivity syndrome or anticonvulsant hypersensitivity syndrome
What is the onset of DRESS syndrome?
4 days to 3 weeks
What are the sx of DRESS syndrome?
- May initially appear as simple morbilliform rash, but febrile
- Facial edema and erythema are hallmarks of DRESS
- Rash may become purpuric (purplish discolouration), especially on lower legs
- Mucous membranes not involved
What drugs are often associated w/ DRESS syndrome?
- Anticonvulsants (phenobarbital, phenytoin)
- Allopurinol
- NSAIDs
- Sulfonamides
- Dapsone
- Thiazides
Can desensitization be used for DRESS syndrome?
No
If a drug causes histamine release, is it a true anaphylactic reaction?
No, not IgE mediated
What can be detected to determine if a reaction is anaphylactic?
- Mast cell tryptase
- Serum tryptase levels should be drawn 1-4 hours after reaction in order to get a definitive diagnosis (if don’t test in this window, levels will be too low)
What reactions can occur from penicillin allergies?
- Type 1, 2, 3, or 4
- Rash can be hive-like or urticarial
- Classically an erythematous, maculopapular rash
Which penicillins most commonly cause rashes?
Ampicillin, amoxicillin
What type of allergic reaction is a maculopapular or morbilliform rash to penicillin? If a px experiences this reaction, can they receive penicillins in the future?
- Not IgE mediated, so not type 1
- Either type 4b or 4c
- Not immediate type
- Can receive penicillins or cephalosporins again
What type of allergic reaction is urticaria to penicillin? If a px experiences this reaction, can they receive penicillins in the future?
- IgE mediated, immediate type reaction
- Never give offending agent again
When doing penicillin skin testing, what is tested?
- IgE antibodies for accelerated reactions (2-72 h)
- Parent compound or secondary metabolite (penicillin or penicillate) for immediate reactions
If a px is negative on a penicillin skin test, can they receive penicillin?
Yes, anaphylaxis has never occurred in a skin test negative px
Do corticosteroids or antihistamines alter the results of a penicillin skin test?
- Corticosteroids no
- Antihistamines yes (must stop all drugs w/ antihistamine properties 24 h before test)
If a px is positive on a penicillin skin test, can they receive penicillin?
No
Can penicillin skin testing predict non-IgE mediated reactions (ex: DRESS, SJS, TENS, cytopenias)?
No, so can have a negative test & still experience a non-IgE mediated reaction
If a px is positive on a penicillin skin test, can they receive cephalosporins?
- Yes, but only if alternatives are less desirable
- Never should receive them if px has a history of anaphylaxis or urticaria
What type of reaction is a sulfonamide rash?
Delayed reaction (week 2 of tx)
What often accompanies a sulfonamide rash?
- Pruritus and fever
- Morbilliform eruption
What is desensitization? Which reactions can this be done for?
- Temporary induction of drug tolerance through exposing px to very minute quantities of the offending drug (ex: 1/10,000 dilution) and then rapidly increasing concentrations of exposure (ie: doubling dose every 15-20 mins) until full dose is tolerated
- Only lasts as long as the drug is in the body
- Only for type 1 reactions (IgE mediated)
What is graded challenge? When is it used?
- Administration of a graduated amount under close supervision
- Used to exclude drug allergy in those who you suspect to be unlikely allergic to the drug
What are contraindications to the graded challenge?
- Suspected type 1 reaction (graded challenge could induce anaphylaxis)
- History of blistering dermatitis (ex: SJS/TENS) or severe hypersensitivity reactions (ex: DRESS)
What should be done if you can’t determine which drug is the culprit of an allergic reaction?
Stop newest medication first, w/ subsequent withdrawal of older agents until rash resolves
What is the tx for mild drug allergic reactions?
Treat symptoms w/ topical corticosteroid and systemic antihistamines for pruritus
