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- Immunologic hypersensitivity reaction to beta-lactam antibiotics. Allergy to one penicillin indicates potential allergy to all penicillins, but cross-reactivity between classes of beta-lactams is variable.
- 10% of adults in U.S. self-report penicillin allergy. But as many as 90% of these can tolerate penicillin.
- This high percentage may be due to:
- Waning of penicillin-specific IgE antibodies over time
- Mislabeling of a reaction (e.g., diarrhea) as allergic
- Illness or combination of illness and antibiotic causing symptoms attributed to allergy
- Identification of patients with IgE-mediated allergy or history of severe reaction is paramount.
- Severe reactions include:
- Mucocutaneous eruption with epidermal detachment: Stevens-Johnson syndrome (< 10% body surface area) and toxic epidermal necrolysis (>30% body surface area).
- Presents as painful new skin eruption, sore throat, and fever or malaise
- Associated with specific human leukocyte antigen allotypes
- Drug-induced hypersensitivity syndrome (DiHS) with multiorgan involvement; Drug Reaction/Rash with Eosinophilia and Systemic Symptoms (DRESS)
- Gell and Coombs classification based on immunopathology
- Type I, anaphylactic
- IgE ab bound to basophils and mast cells is cross-linked by drug with subsequent release of mediators: histamine, prostaglandins, proteases, and leukotrienes
- Produces urticaria, angioedema, laryngeal edema, bronchospasm, hypotension, abdominal distress (per oral)
- Type II, cytotoxic
- IgG ab binds to drug-haptenated host cells such as renal cells or red blood cells
- Causes interstitial nephritis, thrombocytopenia, or hemolytic anemia
- Type III, immune complex formation
- IgG- and IgM-mediated, soluble antigen-antibody complexes
- Leads to serum sickness syndromes
- Type IV, cell-mediated hypersensitivity
- Sensitized T lymphocytes
- Produces contact dermatitis, maculopapular eruptions, eosinophilia, Stevens-Johnson syndrome, exfoliative dermatitis
- Levine classification based on timing of symptom appearance
- Immediate (< 1hr) and accelerated (1-72hrs) reaction, IgE-mediated, includes:
- Skin: pruritus, flushing, urticaria, angioedema
- Respiratory: wheezing, laryngeal edema, dyspnea, bronchospasm
- Gastrointestinal: abdominal distress with emesis or diarrhea
- Cardiovascular: hypotension
- Late (>72hrs) reaction, non-IgE-mediated, multiple underlying immunologic mechanisms.
- Penicillin allergens derived from core ring structure, bicyclic structure consists of 4-member beta-lactam ring and 5-member thiazolidine ring.
- Penicillin covalently binds proteins spontaneously under physiologic conditions, enzymatic metabolism is not required.
- BenzylPenicilloyl poly-L-lysine (PrePen, ALK-Abello, Round Rock, TX), synthetic analog of major antigenic determinant: comprises 95% of tissue-bound penicillin.
- Benzylpenicillin + its alkaline product (penicilloate) and acid product (penilloate) (optimal reagents for skin testing) are minor determinants: formed less often than penicilloyl, but clinically important.
- R-group side chain, less commonly the epitope for allergic reactions
- Some immediate-type reactions to amoxicillin and ampicillin are due to IgE-ab directed at R-group side chains.
- Selective allergy to aminopenicillins is less common in the US than allergy to beta-lactam core ring structure.
- CF patients treated repeatedly with anti-pseudomonal antibiotics may develop side-chain specific allergy.
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