Contact Dermatitis

Contact Allergy to Topical Medicaments, Part 1: A Double-edged Sword

Author and Disclosure Information

Topical drugs are used to treat a variety of cutaneous and noncutaneous conditions. Direct application to the skin can result in adverse cutaneous effects, including allergic contact dermatitis (ACD). In this article, we review medicament ACD with a focus on acne and rosacea medications, antimicrobials, antihistamines, and topical pain preparations.

Practice Points

  • Allergic contact dermatitis should be suspected in patients with persistent or worsening dermatitis after use of topical medications.
  • Prior sensitization is not always apparent, and cross-reactions may occur between structurally similar compounds.
  • Although most medicaments can be patch tested as is, patch testing to the individual components may be necessary to identify the causative allergen.



Topical medications frequently are prescribed in dermatology and provide the advantages of direct skin penetration and targeted application while typically sparing patients from systemic effects. Adverse cutaneous effects include allergic contact dermatitis (ACD), irritant contact dermatitis (ICD), photosensitivity, urticaria, hyperpigmentation or hypopigmentation, atrophy, periorificial dermatitis, and acneform eruptions. Allergic contact dermatitis can develop from the active drug or vehicle components.

Patients with medicament ACD often present with symptoms of pruritus and dermatitis at the site of topical application. They may express concern that the medication is no longer working or seems to be making things worse. Certain sites are more prone to developing medicament dermatitis, including the face, groin, and lower legs. Older adults may be more at risk. Other risk factors include pre-existing skin diseases such as stasis dermatitis, acne, psoriasis, atopic dermatitis, and genital dermatoses.1 A review of 14,911 patch-tested patients from a single referral clinic revealed that 17.4% had iatrogenic contact dermatitis, with the most common culprits being topical antibiotics, antiseptics, and steroids.2

In this 2-part series, we will focus on the active drug as a source of ACD. Part 1 explores ACD associated with acne and rosacea medications, antimicrobials, antihistamines, and topical pain preparations.

Acne and Rosacea Medications

Retinoids—Topical retinoids are first-line acne treatments that help normalize skin keratinization. Irritant contact dermatitis from retinoids is a well-known and common side effect. Although far less common than ICD, ACD from topical retinoid use has been reported.3,4 Reactions to tretinoin are most frequently reported in the literature compared to adapalene gel5 and tazarotene foam, which have lower potential for sensitization.6 Allergic contact dermatitis also has been reported from retinyl palmitate7,8 in cosmetic creams and from occupational exposure in settings of industrial vitamin A production.9 Both ICD and ACD from topical retinoids can present with pruritus, erythema, and scaling. Given this clinical overlap between ACD and ICD, patch testing is crucial in differentiating the underlying etiology of the dermatitis.

Benzoyl Peroxide—Benzoyl peroxide (BP) is another popular topical acne treatment that targets Cutibacterium acnes, a bacterium often implicated in the pathogenesis of acne vulgaris. Similar to retinoids, ICD is more common than ACD. Several cases of ACD to BP have been reported.10-14 Occasionally, honey-colored crusting associated with ACD to BP can mimic impetigo.10 Aside from use of BP as an acne treatment, other potential exposures to BP include bleached flour13 and orthopedic bone cement. Occupations at risk for potential BP exposure include dental technicians15 and those working in plastic manufacturing.

Brimonidine—Brimonidine tartrate is a selective α2-adrenergic agonist initially used to treat open-angle glaucoma and also is used as a topical treatment for rosacea. Allergic reactions to brimonidine eye drops may present with periorbital hyperpigmentation and pruritic bullous lesions.16 Case reports of topical brimonidine ACD have demonstrated mixed patch test results, with positive patch tests to Mirvaso (Galderma) as is but negative patch tests to pure brimonidine tartrate 0.33%.17,18 Ringuet and Houle19 reported the first known positive patch test reaction to pure topical brimonidine, testing with brimonidine tartrate 1% in petrolatum.20,21 Clinicians should be attuned to ACD to topical brimonidine in patients previously treated for glaucoma, as prior use of ophthalmic preparations may result in sensitization.18,20


Clindamycin—Clindamycin targets bacterial protein synthesis and is an effective adjunct in the treatment of acne. Despite its widespread and often long-term use, topical clindamycin is a weak sensitizer.22 To date, limited case reports on ACD to topical clindamycin exist.23-28 Rare clinical patterns of ACD to clindamycin include mimickers of irritant retinoid dermatitis, erythema multiforme, or pustular rosacea.25,26,29


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