Immunity 3- drug allergy Flashcards
Drug hypersensitivity statistics
Direct cause for at least 50000 UK hospital admissions a year
10% UK population penicillin allergy
Anaphylaxis during 0.5-1/10000 anaesthetics
Type A drug reaction
(side effects/ toxicity)
NOT ALLERGY
Related to pharmacology of drug
Predictable
Usually dose dependent
High morbidity, low mortality
Examples of type A
Drowsiness with first generation anti-histamines
Liver failure in paracetamol overdose
Nausea and constipation with opiates
Dry mouth with tricyclic anti-depressants
Type B drug reaction
includes allergy
Not (directly) related to pharmacology
Unpredictable
(often) dose- independent
High mortality
Type B examples
Anything that clinically resembles and ‘allergic’ or immunological reaction belongs to this group known as drug hypersensitivity reaction
Immediate clinical classification of DHR
Within 1 hour
- skin: urticaria, angiodema
- resp: rhinitis, bronchospams, laryngeal oedema
- gut: vomiting, diarrhoea
- cardiovascular collapse
Generally result of mast cell activation
May be IgE mediated or form of non-allergic immediate DHR
Immediate DHR: non-IgE mediated
Non-specific mast cell activation
- opiates, myorelaxants, radiocontrast media
ACEi
- also inhibit de-activator of bradykinin
- angioedema
- timing not related to symptoms
NSAIDs
- urticaria/ angioedema
- aspirin sensitive asthma/ rhinitis
- true anaphylaxis
Events that follow mast cell IgE ligation
IgE binds to specific allergen
Cross linking of IgE antibodies by allergen leads to clustering of FcεR1 receptors
Intracellular portion of receptor becomes phosphorylated
Resulting intracellular cascade leads to cellular activation
Mast cell ‘degranulates’ releasing histamine, tryptase and other preformed mediators
Immediate DHR: key features
Within 1 hour of last dose
- often much quicker, particularly iv treatment
- NSAIDs may be little delayed
Soon after initiation, usually 1st dose
- sensitisation typically during an earlier course
- usually takes 14 days to class switch to IgE
Appropriate clinical features of mast cell degranulation
Recede rapidly after drug is stopped
Biggest drug groups of DHR
Myorelaxants
Taxene based chemo
Mast cell tryptase
Released from mast cells during anaphylaxis; easier to measure than histamine
Serum tryptase recommended to confirm acute anaphylaxis
Take blood 1-2 hours after onset of symptoms, again after 24 hours
Increase followed by normalisation in correct context confirms anaphylaxis
Allergic approach to immediate DHR
Often do diagnostic tests other than drug provocation (challenge test)- which is resource intensive and dangerous
All about the history
B lactam allergy
Reported by 10% of UK population
True prevalence 1-2%
Over reported because
- sensitisation lost at a rate of 10% per year, label persists
- rash may have been infection rather than drug related
- different drug caused the rash
Pathophysiology of B lactam allergy
Includes multiple different antibiotic groups
- penicillin
- penicillinase resistant (fluclox)
- aminopenicillins (amoxycillin)
- extended spectrum (tazocin)
- cephalosporin
- carbopenems
- monobactams
All have B lactam ring
Choosing alternative to penicillin
Must consider potential cross reactivity
No risk with non-B lactam
Cross reactivity with 2/3rd gen cephalalosporin very low
Non immediate
Delayed: delayed urticaria, maculo-papular eruptions, fixed drug eruptions
Systemic: TEN, SJS, DRESS, vasculitis
Non-immediate DHR: key features
Not directly related to 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
Biggest drug group for non-immediate DHR
Antimicrobials
SJS
TENS
Steven johnson syndrome
Toxic epidermal necrolysis syndrome
SJS/TENS: the dangerous non-immediate DHR
Fever, cough, conjunctivitis, mucositis
Men> women, mostly 30 years or under
Typically 3-8 days after dose
Very high mortality and gets worse with each exposure
SJS/ TENS biggest drug groups
Antibiotics
Anticonvulsants
Standard type IV hypersensitivity
Onset 3-8 days into course
Maculo-papular
Skin may be dry/ inflamed
Gradually fades over days/ weeks
No systemic upset
Testing for B lactam allergy
Negative results have high negative predictive value- usually confirm tolerance with brief challenge test
When positive, perform challenge with alternative to demonstrate tolerance
Local anaesthesia
Most reactions involve local swelling/ syncope/ sensitivity to adrenaline
Virtually never reproducible- presumably related to dental procedures/ anxiety
Drugs will generally not be given again without confirmation of tolerance
NSAIDs
Wide spectrum of reactions
- cutaneous only (usually urticaria/ angioedema often on background of spontaneous urticaria)
- true anaphylaxis
- aspirin sensitive asthma/ rhinitis
10% react to paracetamol as well
