Immunity 3- drug allergy

Question 1

Drug hypersensitivity statistics

Answer 1

Direct cause for at least 50000 UK hospital admissions a year

10% UK population penicillin allergy

Anaphylaxis during 0.5-1/10000 anaesthetics

Question 2

Type A drug reaction
(side effects/ toxicity)
NOT ALLERGY

Answer 2

Related to pharmacology of drug

Predictable

Usually dose dependent

High morbidity, low mortality

Question 3

Examples of type A

Answer 3

Drowsiness with first generation anti-histamines

Liver failure in paracetamol overdose

Nausea and constipation with opiates

Dry mouth with tricyclic anti-depressants

Question 4

Type B drug reaction

includes allergy

Answer 4

Not (directly) related to pharmacology

Unpredictable

(often) dose- independent

High mortality

Question 5

Type B examples

Answer 5

Anything that clinically resembles and ‘allergic’ or immunological reaction belongs to this group known as drug hypersensitivity reaction

Question 6

Immediate clinical classification of DHR

Answer 6

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

Question 7

Immediate DHR: non-IgE mediated

Answer 7

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

Question 8

Events that follow mast cell IgE ligation

Answer 8

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

Question 9

Immediate DHR: key features

Answer 9

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

Question 10

Biggest drug groups of DHR

Answer 10

Myorelaxants

Taxene based chemo

Question 11

Mast cell tryptase

Answer 11

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

Question 12

Allergic approach to immediate DHR

Answer 12

Often do diagnostic tests other than drug provocation (challenge test)- which is resource intensive and dangerous

All about the history

Question 13

B lactam allergy

Answer 13

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

Question 14

Pathophysiology of B lactam allergy

Answer 14

Includes multiple different antibiotic groups

• penicillin
• penicillinase resistant (fluclox)
• aminopenicillins (amoxycillin)
• extended spectrum (tazocin)
• cephalosporin
• carbopenems
• monobactams

All have B lactam ring

Question 15

Choosing alternative to penicillin

Answer 15

Must consider potential cross reactivity

No risk with non-B lactam

Cross reactivity with 2/3rd gen cephalalosporin very low

Question 16

Non immediate

Answer 16

Delayed: delayed urticaria, maculo-papular eruptions, fixed drug eruptions

Systemic: TEN, SJS, DRESS, vasculitis

Question 17

Non-immediate DHR: key features

Answer 17

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

Question 18

Biggest drug group for non-immediate DHR

Answer 18

Antimicrobials

Question 19

SJS

TENS

Answer 19

Steven johnson syndrome

Toxic epidermal necrolysis syndrome

Question 20

SJS/TENS: the dangerous non-immediate DHR

Answer 20

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

Question 21

SJS/ TENS biggest drug groups

Answer 21

Antibiotics

Anticonvulsants

Question 22

Standard type IV hypersensitivity

Answer 22

Onset 3-8 days into course

Maculo-papular

Skin may be dry/ inflamed

Gradually fades over days/ weeks

No systemic upset

Question 23

Testing for B lactam allergy

Answer 23

Negative results have high negative predictive value- usually confirm tolerance with brief challenge test

When positive, perform challenge with alternative to demonstrate tolerance

Question 24

Local anaesthesia

Answer 24

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

Question 25

NSAIDs

Answer 25

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