302 Drug allergy Flashcards
What is DHR?
Drug hypersensitivity reaction
What is the Type A WHO classification for adverse drug reaction?
Related to Pharmacology of drug
Predictable
Usually dose-dependent
High morbidity, Low mortality
Eg.
-Drowsiness with first-generation anti-histamines
-Liver failure in paracetamol overdose
-Nausea and constipation with opiates
-Dry mouth with tricyclic anti-depressants
What is the Type B WHO classification for adverse drug reaction?
Not (directly) related to the pharmacology
Unpredictable
(Often) dose-independent
High mortality
What happens in the clinical classification of DHR?
Immediate reaction within 1 hour of administration
Skin: urticaria, angioedema
Respiratory: rhinitis, bronchospasm, laryngeal oedema
Cardiovascular collapse
Generally result of mast cell mediator release
What happens after mast cell IgE ligation?
-IgE binds its specific allergen
-Cross-linking of IgE antibodies by allergen leads to clustering of FcεR1 receptors
-The intracellular portion of the receptor becomes phosphorylated
-The resulting intracellular cascade leads to cellular activation
-Mast cell ‘degranulates’ releasing histamine, tryptase and other pre-formed mediators
Name some medications which non-specifically increase mast cell activation
Opiates, myorelaxants, radiocontrast media, vaccines, NSAIDS
Example of Immediate DHR: non-IgE mediated
Name some co-factors which non-specifically increase mast cell activation
Fever, infection, exercise, spontaneous urticaria
Example of Immediate DHR: non-IgE mediated
What are some non-immediate DHR key features?
Not directly related to a drug dose, although may appear to be so by chance
Typically during treatment course:
3-5 days if treated with drug before
5-8 days if first sensitisation
-Taken together, clinical features not in keeping with mast cell degranulation
-Typically continue for some time after drug is stopped
Antimicrobials = biggest group
What is SJS/ TENS?
AKA: Stevens-Johnson syndrome/toxic epidermal necrolysis
A severe skin reaction most often triggered by particular medication
Symptoms: Fever, cough, conjunctivitis, mucosits
Men>greater women, mostly 30 years or under
Typically 3-8 days after dose
Antibiotics, anticonvulsants most common culprit drugs
Can also be infection-induced
Very high mortality and gets worse with each exposure
What is standard type IV hypersensitivity?
Onset 3-8 days into course
Maculo-papular
Skin may be dry/ inflamed
Gradually fades over days and weeks
No systemic upset
How common is B lactam allergy?
Reported by 10% of UK population, and a much higher proportion of hospital inpatients, true prevalence closer to 1-2%
Over-reported because sensitisation lost at a rate of 10% per year
Rash was caused by something else eg infection, primary dermatological disorder such as spontaneous urticaria
Side-effects mis-reported as allergy
How do you test for B lactam allergy?
First-line test is skin prick testing with B Lactams and B Lactam reagents
Why would you refer someone to immunology following a drug reaction?
Drug will be needed again
Choice restricted
Cross-reactivity questions
Diagnostic doubt
Why would you not refer someone to immunology following a drug reaction?
Drug unlikely to be needed again
Minor reaction (eg maculo-papular rash)
Alternatives readily available
Nothing more to add (eg TENS)
