Cutaneous Drug Reactions
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- An adverse cutaneous reaction in response to administration of a drug. Rashes are the most common adverse drug reactions.
- Severity can range from mild eruptions that resolve within 48 hours after the removal of the inciting agent, to severe skin damage with multiorgan involvement.
- Morbilliform/simple exanthem (75–95%) and urticarial (5–6%) eruptions are most common, but multiple morphologic types may occur.
- System(s) affected: skin/mucosa/exocrine, hematologic/lymphatic/immunologic
- All ages are affected.
- Predominant sex: female > male
- There is no correlation between development of adverse reaction and patient’s age, diagnosis, or survival.
- Special consideration in the geriatric population who are on multiple medications: increased likelihood of severe cutaneous and systemic reactions; also consider in the pediatric group: difficult to distinguish from viral exanthems
In the United States, prevalence of 2–3% in hospitalized patients; estimated 1/1,000 hospitalized patients has had a severe cutaneous reaction.
Etiology and Pathophysiology
- Predictable adverse reactions are due to overdose, side effect, or drug interaction.
- Unpredictable reactions include intolerance, drug idiosyncrasy secondary to abnormality in metabolism, or immune reaction. >700 drugs are known to cause a dermatologic reaction:
- Immunologically mediated reaction: immunoglobulin (Ig) E–mediated reaction (type I hypersensitivity), cytotoxic/IgG/IgM induced (type II), immune complex reactions (type III), and delayed-type hypersensitivity (type IV) with T cells, eosinophils, neutrophils, and monocytes
- Acneiform: OCPs, corticosteroids, iodinated compounds, hydantoins, lithium
- Erythema multiforme/Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN): >100 drugs reported. Most common include sulfonamides, cephalosporins, NSAIDs, barbiturates, hydantoins, anticonvulsants tetracycline, terbinafine.
- Fixed drug eruptions: NSAIDS, sulfonamides, tetracycline, barbiturates, salicylates, OCPs
- Lichenoid: thiazides, NSAIDs, gold, ACE inhibitors, proton pump inhibitors, antimalarials, sildenafil
- Photosensitivity: doxycycline, thiazides, sulfonylureas, quinolones, sulfonamides, NSAIDs
- Hypersensitivity vasculitis: hydralazine, penicillins, cephalosporins, thiazides, gold, sulfonamides, NSAIDs, propylthiouracil
- Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome: anticonvulsants, sulfonamides, dapsone, minocycline, allopurinol
- Acute generalized exanthematous pustulosis (AGEP): penicillins, cephalosporins, macrolides, calcium channel blockers, antimalarials, carbamazepine, acetaminophen, terbinafine, nystatin, vancomycin
- Sweet syndrome (acute febrile neutrophilic dermatosis): sulfa drugs, granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), diazepam, minocycline, nitrofurantoin, captopril, penicillamine
- Serum sickness-like reaction: cephalosporins, penicillins, TMP/SMX, propranolol, bupropion, minocycline
- Morbilliform/urticarial/exfoliative erythroderma: numerous medications, including penicillins, cephalosporins, sulfonamides, tetracyclines, ibuprofen, naproxen, allopurinol, acetylsalicylic acid, radiocontrast media (1)[A]
Genetics may play a role, as certain HLA antigens have been associated with increased predisposition to specific drug eruptions:
- HLA-B*5801, HLA-B*5701, and HLA-B*1502 have been linked to allopurinol-induced and carbamazepine-induced SJS/TEN, respectively.
- HLA class I antigens, such as HLA-A2, HLA-B12, and HLA-B22, have been linked to TEN and fixed drug eruptions, respectively.
Previous drug reaction, multiple medications, concurrent infections, immunocompromised, disorders of metabolism, and certain genetic HLA haplotypes
Always ask patients about prior adverse drug events. Be aware of medications with higher incidence of reactions as well as drug cross-reactions.