Beta-lactam allergy in pediatric population

Question 1

What is a drug allergy?

Answer 1

immunologically mediated drug hypersensitivity reaction

Question 2

What is the classification of drug allergies?

Answer 2

immediate: occurring within 1 hour
- only IgE-mediated drug allergy falls into this category

non-immediate: occurring after 1 hour, but often days or weeks later

Question 3

What are the 4 types of immune reaction?

Answer 3

Type 1: IgE-mediated (=<1-2 hours)
- urticaria/angioedema, respiratory distress, GI sx, hypotension, anaphylaxis

Type 2: cytotoxic (10 hr-wks)
- anemia, thrombocytopenia

Type 3: immune-complex (1-3 wk)
- serum sickness-like reaction: fever, urticaria, vasculitis, arthritis/arthralgia

Type 4: T cell-mediated (2-14 days)
- maculopapular rash, SJS, DRESS, acute generalized exanthematous pustulosis (AGEP)

Question 4

What is the percentage of pen anaphylaxis?

Answer 4

< 1%

beta-lactam allergy: 5-8% (N America and Europe)

Question 5

What increases the risk of beta-lactam allergy?

Answer 5

• parenteral
• long-term
• high-dose

(as compared to oral, intermittent therapy )

Question 6

Does FamHx of beta lactam allergy increase risk?

Answer 6

• famhx beta-lactam allergy doesn’t increase risk

Question 7

What is the percentage of Type 4 pen reaction (maculopapular exanthem)?

Answer 7

• 5% of adults (true allergy)
• 2% children
• Most due to infection & don’t contraindicate further use of antibiotics

Question 8

What is the rate of beta lactam allergy?

Answer 8

5-8% (N America and Europe)

Question 9

Why does misdiagnosis of drug allergy occur?

Answer 9

• due to misclassification of symptoms of illness or common SE of abx
• interaction b/w abx and pathogen can mimic reaction
• circulating beta-lactam-specific IgE antibodies decrease naturally over time (many kids not reassessed to delabel)

Question 10

What is the rate of cross-reactivity between pen and cephalosporins?

Answer 10

• True rate 2%

* 1% in self-reported but unconfirmed allergy

Question 11

What is the NPV and PPV of intradermal testing for penicillin?

Answer 11

• NPV 100% adults; 94% children —> less useful in children than adults
• PPV as low as 40% —> not helpful for screening

Question 12

what are contraindications to Provocative drug challenges?

Answer 12

• hx consistent with previous recent anaphylaxis
• systemic, non-immediate immunologic reaction (serum sickness-like reaction, SJS, DRESS, drug-induced hemolytic anemia)
• recent data: going directly to oral challenge, without skin testing, more reliable

Question 13

What are clinical implications of erroneous beta-lactam allergy labelling ?

Answer 13

• second-line non-beta-lactam antimicrobials inferior for infection management
  
  • prolong hospital stays
  • higher admission rate for ICU
  • readmissions
  • mortality
• Broad-spectrum antibiotics:
  
  • resistance (VRE, MRSA)
  • C diff infection
• Rising health care costs
  
  • higher antibiotics costs per hospitalization
  • prolonged hospital stays

Question 14

How many pts non-allergic to pen could be identified by hx alone?

Answer 14

• 60% non-allergic could be identified by low-risk hx alone

Question 15

How frequent should kids with pen allergies be seen by allergist?

Answer 15

after 5 yrs (can be outgrown)

Question 16

What is management of kids with severe systemic or cutaneous delayed adverse reactions following pen?

Answer 16

• shouldn’t have abx in future
  
  • future decisions for penicillin based on benefit vs risk
• avoid cephalosporins with similar side chains (some recommend)
  
  • no robust evidence of cross-reactivity b/w penicillins and cephalosporins with similar side chains
• refer to allergist

Question 17

What is management of kids with Suspected IgE penicillin allergy?

Answer 17

• don’t prescribe pen or cephalosporins with similar side chains
• refer to allergist
• dissimilar cephalosporin side chains can be prescribed
  
  • provocative challenge to specific cephalosporin can be used (when necessary or certain cephalosporin desirable)

Question 18

What is management of kids with mild, delayed exanthems following pen?

Answer 18

• don’t contraindicate future use abx
• single dose amoxil (15 mg/kg) with 1 hr observation provides reassurance & confirms no allergy
• can have cephalosporins (all), carbapenems, monobactams (without monitoring dose)

Question 19

What is management of kids with suspected pen reaction who have since tolerated?

Answer 19

• not allergic –> no restrictions!

Question 20

What do you ask on history when assessing drug allergies?

Answer 20

o Which medication and indication?
o How many courses of this med or related?
o How many doses before reaction?
o Concurrent medication?

o How soon after most recent dose did reaction occur?
o Nature of reaction? (photographs optimal)
o any symptoms of severe cutaneous drug reaction? (SJS, DRESS, AGEP)
o Symptoms of unexplained fever, arthritis/arthralgia, lymphadenopathy, skin exfolation or mucous membrane involvement?

o Was medication stopped?
o Medication attention sought? How was reaction managed?
o how long did symptoms last?
o Subsequent administration? reaction?

Question 21

After doing a history, what are the next steps for a drug allergy? (to delabel the allergy)

Answer 21

• recent data: going directly to oral challenge, without skin testing, more reliable
• provocative drug challenge (unless previous recent anaphylaxis or serious drug reaction like SS, SJS, DRESS, hemolytic anemia)