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Cutaneous Drug Reactions

Cutaneous Drug Reactions is a topic covered in the 5-Minute Clinical Consult.

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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.

Risk Factors

Previous drug reaction, multiple medications, concurrent infections, immunocompromised, disorders of metabolism, and certain genetic HLA haplotypes

General Prevention

Always ask patients about prior adverse drug events. Be aware of medications with higher incidence of reactions as well as drug cross-reactions.

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Stephens, Mark B., et al., editors. "Cutaneous Drug Reactions." 5-Minute Clinical Consult, 27th ed., Wolters Kluwer, 2019. Medicine Central, im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116159/all/Cutaneous_Drug_Reactions.
Cutaneous Drug Reactions. In: Stephens MB, Golding J, Baldor RA, et al, eds. 5-Minute Clinical Consult. 27th ed. Wolters Kluwer; 2019. https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116159/all/Cutaneous_Drug_Reactions. Accessed April 26, 2019.
Cutaneous Drug Reactions. (2019). In Stephens, M. B., Golding, J., Baldor, R. A., & Domino, F. J. (Eds.), 5-Minute Clinical Consult. Available from https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116159/all/Cutaneous_Drug_Reactions
Cutaneous Drug Reactions [Internet]. In: Stephens MB, Golding J, Baldor RA, Domino FJ, editors. 5-Minute Clinical Consult. Wolters Kluwer; 2019. [cited 2019 April 26]. Available from: https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116159/all/Cutaneous_Drug_Reactions.
* Article titles in AMA citation format should be in sentence-case
TY - ELEC T1 - Cutaneous Drug Reactions ID - 116159 ED - Stephens,Mark B, ED - Golding,Jeremy, ED - Baldor,Robert A, ED - Domino,Frank J, BT - 5-Minute Clinical Consult, Updating UR - https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116159/all/Cutaneous_Drug_Reactions PB - Wolters Kluwer ET - 27 DB - Medicine Central DP - Unbound Medicine ER -