Type of immunologic drug reaction | Incidence | Signs and symptoms | Timing | Common culprit drugs | Diagnostic testing available? |
IgE, mast cell and basophil mediated Type I Gell and Coombs | Common | Urticaria/angioedema, bronchospasm, laryngeal edema, nausea, vomiting, hypotension, shock | Immediate - Seconds to one hour after last dose May be slightly more delayed if drug slowly absorbed Faster and more severe upon reexposure | Beta-lactam antibiotics (penicillins and cephalosporins), muscle relaxants, foreign proteins (eg, cetuximab, rituximab), platinum-based chemotherapy (eg, carboplatin, cisplatin) | YES At time of reaction - Serum tryptase Later - Skin prick and intradermal testing, basophil activation test (BAT) |
Antibody-mediated (IgG and IgM) cell destruction Type II Gell and Coombs | Uncommon | Hemolytic anemia Thrombocytopenia Neutropenia or agranulocytosis | Delayed - Days to weeks after beginning therapy May occur months into long-term treatments Faster upon reexposure | Beta-lactam antibiotics, NSAIDs, quinidine, methyldopa, ticlopidine | YES Direct Coombs Tests for antiplatelet antibodies Tests for antineutrophil antibodies |
Immune complex-mediated tissue damage Type III Gell and Coombs | Uncommon | Serum sickness, serum-sickness like reactions Vasculitis (eg, cutaneous) Drug fever Acute glomerulonephritis | Delayed - Weeks to months after beginning therapy Faster on reexposure | Beta-lactam antibiotics, sulfonamide antibiotics, sirolimus/tacrolimus | No direct diagnostic testing available. Diagnosis is based on patterns of clinical and laboratory findings. Biopsy of affected tissue is sometimes helpful. |
Mediated by T cells +/– other cell types (esp eosinophils, neutrophils) Type IV Gell and Coombs | Common | Prominent skin findings +/– other organ involvement - Exanthematous (morbilliform) eruption DRESS/DiHS AGEP Exfoliative dermatoses (SJS/TEN) | Delayed at least 24 to 48 hours after beginning therapy and may begin weeks to months after treatment began | Beta-lactam antibiotics, sulfonamide antibiotics and sulfasalazine, minocycline, phenytoin, carbamazepine, lamotrigine, allopurinol, abacavir, nevirapine | VARIABLE* ANY form of reexposure to the culprit drug is CONTRAINDICATED in patients with past severe or exfoliative reactions, including DRESS/DiHS and SJS/TEN. |
Unclassified | Drug-induced lupus | Procainamide, phenytoin, isoniazid, sulfasalazine, amiodarone, minocycline, and penicillamine | NO | ||
Fixed drug eruption | Sulfonamides, anticoagulants, others | Patch testing performed on the affected skin may be useful |
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