Diagnosis and management

of Drug Allergy

Fajar Waskito
What’s the problems with drug allergy

Morbidity
Mortality
Cost
Public health problem

Doctor Clinical practice Patients

 Classification of drug reactions

Type A Type B
• Dose dependent • Non Dose dependent
• Predictable • Non Predictable
• More common • Less common

• Overdose • Intolerance
• Side effects • Idiosyncracy
• Drug interactions • Drug Allergy
 Drug allergy

Pseudoallergic reaction
Immunologic reactions

Type 1 Type 2 Type 3 Type 4

Ig E mediated/ *Antibody Immune T cell mediated
Anaphylactic dependent Complex
Urticaria Cytotoxicity
Angioedem *IgG/IgM binds
Bronchospasm To antigen
Hypotension On cells

2-30 min 5-8 hours 2-8 hours 24-72 hours

 How’s the symptom?
It depends on the organ involvement
 Multi system
• Anaphylaxis
• Serum sicknes or serum sickness-like
• Drug fever
• Hypersensitivity syndrome
• Vasculitis
• Lupus erythematosus-like syndrome
• Generalized lymphadenopathy
Lung: Bronchospasm, pneumonitis, pulmonary oedem
Liver: Hepatitis, cholestasis
Heart: Myocarditis
Kidney: Interstitial nephritis, nephrotic syndrome
Skin: Vasculitis, SJS, TEN, Eryth multiforme, uricaria,
FDE, Rashes etc
Bone marrow: Hemolytic-aplastic anemia, eosinophylia,
netropenia, thrombocytopenia
 The 10th commoner agents as a cause
No Drugs Common manifestations
1 Amoxycillin Exanthematous
2 TMP + SMZ Exanthematous, bullous, Fixed drug
3 Ampicillin Exanthematous
4 Blood Exanthematous
5 Semisynthetic Exanthematous
penicillin
6 Penicillin G Exanthematous
7 Allopurinol Exanthematous
8 Dipyron Exanthematous, bullous, Fixed drug
9 Fenitoin Exanthematous, bullous
10 Karbamazepin Exanthematous, bullous
 Exanthematous = Morbiliform = Maculopapular
• Commonest morphology
• Centrifugal rash, symetric fashion
• Pruritus
• Appear 1 week of initiation Tx, resolve 1-2 weeks
• Penicillin, sulfonamide, Nevirapine, Anticonvuslant
• DD: Viral exanthema, bact/Ricketsial Infect., collagen vascular
diseases

Achtung
• Exanthematous + Fever + internal organ involvement =
Hypersensitivity Syndrome reactions (HSR)
• Nitrofurantoin, allopurinol, Minocycline, Nevirapine
• Appear 1-6 weeks of initiation
 Urticarial

• Appear at last 24 hours

• Commonly Ig E Mediated
• Penicillin
• Urticaria, flushing, abdominal and upper/lowerrespiratory
tract complaint, hypotension

Serum sickness-like:
• Urticarial + Fever + arthralgia + Lymphadenopathy
• Cefeclor, Cefprozil, Minocycline, Infliximab, Rituximab
• Pathogenesis: Reactive metabolites
 Pustular = Acneiform
• Iodides, bromides, ACTH, Glucocorticoid, INH,
Androgen, Lithium, Actinomycin D, Phenytoin
• Distribution atypical, monomorphous
Acute Generelized Exanthematous
Pustulosis (AGEP)
• Non follicular pustules on edematous and
exanthematous base + Fever
• Ca channel blocker, β-blockers, macrolide
antibiotic, β-lactam
• Appear 1-3 weeks after initiations
• Distribution start on face (creases), 2 weeks
desquamation
• DD: Subcorneal pustular dermatosis, Pustulation
HSR, Psoriasis pustulosa, Pustular vasculitis, TEN
 Bullous
Clinical Pattern & distr of Mucous Implicated drug Treatment
feature lessions membr
SJS Atypical targets, + Anticonvulsant, IV IG,
widespread sulfonamide, piroxicam, Cyclosporine
Allopurinol Supportive
TEN Epid. Necrosis with + Anticonvulsant, IV IG,
epid detachment sulfonamide, piroxicam, Cyclosporine
Allopurinol Supportive
Pseu-porph Fragility, blister in - Tetracyclin, Furosemide, Supportive
photodistribution Naproxen
Linear IgA Bullous dermatoses +/- Vancomycin, Li, Supportive
Diclofenac, Piroxicam
Pemphigus Flaccid bullae, +/- Penicillamine, Penicillin, Supportive
chest rifampin, Captopril,
Piroxicam, Propanolol
Bullous Tense bullae, +/- Furosemide, Penicillamine, Supportive
pemphigoid widespread Penicillin, Captopril,
Sulfazalasin
 Fixed Drug Eruption

• Solitair,
• Erythematous macules-edematous plaque-Bullous
• Genital, perianal, perioral
• Burning, stinging, Fever, malaise
• Develop 30 minutes-16 hours after ingestion
• Lasting days-week
• Sulfonamide, Tetracycline, Ibuprofen, Naproxen
• Dx: Rechallenge
 Pemeriksaan penunjang

Skin Test Provocative Test In-vitro test

Specific Ig E test:
• RAST, ELISA, FEIA
Basophyle test:
Patch Test • Basophyle activation test
Prick Test • Basophyle Mediator Release
Intradermal test Other test:
• Coomb Test
• Complement
• LTT
Diagnosis & Management
• Investigate many symptoms & Signs as internal organ
involvement
• Skin biopsy for uncertain diagnosis
• Analysis of constellation of feature such as:
• Timing between exposure and manifestations
• Course of reaction after drug withdrawal and
continuation
• Nature of reccurent eruption cause of rechallenge
• History of similar respons on cross reaction
• Previous report of similar reactions to the same drug
• Lymphocyte toxicity & LTT
• Penicillin skin testing
• Patch testing
Therapy:
• Alleviate suggestive causative agents
• Prednison 1-2 mg/BW/day except:
SJS &TEN
• Antihistamines
• Topical corticosteroid