Coming clean on chlorhexidine-induced dermatoses

By Warren R. Heymann, MD, FAAD
March 13, 2024
Vol. 6, No. 11

Dermatologic surgeons use a variety of products that may cause an irritant or allergic contact dermatitis, including antiseptics, anesthetics, gloves, suture materials, tissue adhesives, topical antibiotics, and bandages. Antiseptic agents are the most frequent cause of contact dermatitis in surgical patients. (1)

My interest in this topic was piqued after seeing the following patient in consultation:

A 40-year-old man with a history of esophageal strictures since childhood had an esophageal perforation that required a surgical repair; the esophageal biopsy demonstrated eosinophilic esophagitis. His right posterolateral thoracotomy, esophogectomy and tube thorocotomy was prepped with chlorhexidine. Four days later, he underwent the second stage of the esophogectomy, with a retrogastric pull through and J tube placement. He was prepped with chlorhexidine at that time as well. One day following the second surgery, he was found to have a pruritic rash in the right axilla extending to the upper back (see image). Physical examination demonstrated geometric erythematous patches and bullae along right axilla, right upper back, and on the abdomen adjacent to his incision site. This improved with topical steroids.

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Although the diagnosis and treatment of a presumed allergic (rather than irritant) contact dermatitis was straightforward, what intrigued me was the realization that I could not recall having encountered this before.

Beaumont et al state, “Antiseptics belong to different chemical classes, mainly halogens (povidone iodine), biguanides (chlorhexidine), diamidines (hexamidine), and quaternary ammonium compounds (benzalkonium chloride, cetrimide). Allergic contact dermatitis (ACD) to povidone iodine, chlorhexidine, and hexamidine has been reported mainly in adultsand more rarely in children. The role of benzalkonium chloride has been discussed in inducing irritant and/or ACD in adults. ACD to benzalkonium chloride has also been reported in children.” (2) This commentary will focus on chlorhexidine.

A chlorhexidine contact allergy rate between 0.5% and 2% has been reported and does not appear to be increasing. (3) Assuming this is an accurate rate, I suspect that I should have seen this problem far more frequently — that I have not could be for several reasons: missing the diagnosis, not being consulted for a “routine” disorder, or the incidence being less frequent than stated in the literature.

Aside from its preoperative use, chlorhexidine is also used as an excipient of drugs and cosmetics due to its antimicrobial activity. (4)

Aside from ACD, chlorhexidine may induce immediate IgE-mediated contact urticaria. Contact urticaria (CU) develops within 20 to 30 minutes of exposure and resolves within 24 hours. CU can evolve to generalized urticaria and anaphylaxis. Chorhexidine may also cause photosensitivity and a fixed drug eruption. (1,4,5)

It is essential to keep ACD to chlorhexidine in mind — the diagnosis may be delayed for months or years, as skin lesions may be misdiagnosed as cellulitis, local reactions to vaccines, or ACD from plasters, among others. (4,6) Importantly, presumed ACD to chlorhexidine may be due to the dye in the preparation, not chlorhexidine itself. (7)

Patch testing can confirm the diagnosis of ACD to chlorhexidine. Often combination products are used. In France, an aqueous antiseptic containing “chlorhexidine digluconate/benzalkonium chloride/benzyl alcohol” (CBB) is widely used. Beaumont et al studied a total of 102 patients (71 adults and 31 children). CBB patch tests were positive in 93.8% of cases. The allergen was identified in 97% of patients, mainly benzyl alcohol in adults (81.7%) and chlorhexidine digluconate in children (54.8%). About 32.4% of the patients were sensitized to several components. The authors concluded that CBB is a cause of ACD at all ages. The components of the antiseptic should be tested. The sensitization profile seems to be different between adults and children. (2) Kefala and Ponvert reported the cases of 6 children with ACD to ingredients commonly contained in commercial antiseptic and cosmetic products. Patch test responses to chlorhexidine, benzyl alcohol, and benzalkonium chloride varied from one child to another one, but most children were sensitized to at least two components. In several of the cases, exposure had initially occurred in the neonatal period, but diagnosis occurred only after multiple reactions of increasing severity. (8) If immediate hypersensitivity is a concern, prick testing is advised. (6)

In conclusion, chlorhexidine may present with a variety of morphologies in adults and children; ACD is most frequent, and patch testing is useful in confirming (or refuting) the diagnosis.

Point to Remember: Chlorhexidine may induce allergic contact dermatitis or other dermatoses. This should be kept in mind to avoid delay in diagnosis.

Our experts’ viewpoints

Naomi Lawrence, MD, FAAD
Head, Section of Procedural Dermatology, Division of Dermatology
Cooper University Health Care

From a surgeon’s viewpoint, there is no better surgical prep than chlorhexidine when considering duration of action and bactericidal activity. There are issues with ocular and ototoxicity but these are sporadic, poorly documented cases and more often in patients undergoing general anesthesia where there is prolonged contact under occlusion. It is quite rare to see ACD from skin surgery probably because the contact time is brief and the area that was prepped is unlikely to be occluded. Betadine, the best alternative is theoretically inactivated by blood, stains the skin, and has the risk of iodine allergy. To date, there is no “perfect” scrub — an opportunity for innovation.

Christen Mowad, MD, FAAD
Chair of Dermatology
Geisinger Medical Center
Danville, Pennsylvania

Chlorhexidine is an antibacterial that is used commonly in cleansers and disinfectants, especially in the hospital setting where it is used as a wash, as a cleanser prior to procedures, and even impregnated in some medical products. Chlorhexidine is also used as a preservative in personal care products and cosmetics. The most recent North American Contact Dermatitis Group data cites a positivity rate of 0.6% of patients tested but 0.7% over the testing period 2015-2020. (9, 10) Patch testing with the FDA approved standard series will miss this allergen. Given the variations in adverse reactions and the difficulty in easily identifying an allergen by history alone, patch testing is necessary to determine the allergen and help advise the patient on how to avoid this chemical. Although an uncommon finding on patch testing, it is often clinically relevant. In the 10.3% of patients where the cause was occupational, 81.8% of the time this was in health care workers. (10) Since both Type I and Type IV reactions have been reported and can be seen in the same patient, immediate hypersensitivity testing to chlorhexidine should be considered in addition to patch testing in the appropriate setting. (11)

1. Lauriola MM, Corazza M. Allergic contact dermatitis due to a preoperative antiseptic solution. Contact Dermatitis. 2021 Oct;85(4):460-462. Doi: 10.1111/cod.13879. Epub 2021 May 18. PMID: 33942918.

2. Beaumont C, Darrigade AS, Barbaud A, Collet E, Raison-Peyron N, Bourrain JL, Assier H, Giordano-Labadie F, Bara-Passot C, Milpied B, Tétart F, Armingaud P, Castelain F, Benkalfate L, Boulard C, Delaunay J, Mathelier-Fusade P, Pecquet C, Pralong P, Vital-Durand D, Genillier Foin N, Lefèvre MA, Hacard F, Nosbaum A, Pasteur J, Valois A, Vigan M, Ferrier le Bouëdec MC; REVIDAL-GERDA Network. Multiple cases of sensitization to an antiseptic containing chlorhexidine digluconate/benzalkonium chloride/benzyl alcohol with different profiles of sensitization in adults and children. Contact Dermatitis. 2022 Jul;87(1):62-70. Doi: 10.1111/cod.14085. Epub 2022 Mar 29. PMID: 35213760.

3. Calado R, Calvão da Silva J, Gomes T, Gonçalo M. Is there a place for chlorhexidine in the European baseline series? Contact Dermatitis. 2021 Sep;85(3):372-373. Doi: 10.1111/cod.13861. Epub 2021 Apr 21. PMID: 33843062.

4. Evangelista V, Vincenzi C, Bruni F, Piraccini BM, Neri I. Contact dermatitis apparently triggered by meningococcal and polyvalent vaccines: A case of allergic contact dermatitis due to chlorhexidine. Contact Dermatitis. 2021 Sep;85(3):354-355. Doi: 10.1111/cod.13846. Epub 2021 Mar 30. PMID: 33763887.

5. Lahouel I, Ben Salah N, Ben Fadhel N, Belhadjali H, Aouam K, Youssef M, Zili J. Contact urticaria caused by chlorhexidine in hydroalcoholic gel. Contact Dermatitis. 2021 May;84(5):338-339. Doi: 10.1111/cod.13735. Epub 2020 Nov 15. PMID: 33131054.

6. Villa-Gonzalez JM, Gonzalez-Hermosa MR, Gardeazabal García J, Aramburu González A, Orbea Sopeña A, Pascual Ares M, Ugedo Alzaga J, Pérez Blasco R, Ratón Nieto JA. When the cure becomes worse than the disease: A case series of children with allergic contact dermatitis from chlorhexidine. J Eur Acad Dermatol Venereol. 2023 Mar 13. Doi: 10.1111/jdv.19034. Epub ahead of print. PMID: 36913262.

7. Carle AL, Martyr JW, Boddu K, Archer SG. Allergic contact dermatitis to a dye or alcohol in a chlorhexidine-based skin preparation: A case report. Anaesth Intensive Care. 2021 Jan;49(1):70-73. Doi: 10.1177/0310057X20973046. Epub 2021 Jan 27. PMID: 33504168.

8. Kefala K, Ponvert C. Allergic contact dermatitis to chlorhexidine-containing antiseptics and their excipients in children: A series of six cases. Pediatr Dermatol. 2023 Jan;40(1):151-153. Doi: 10.1111/pde.15127. Epub 2022 Dec 13. PMID: 36511886.

9. DeKoven JG, Warshaw EM, Reeder MJ, et al. North American Contact Dermatitis Group Patch Test Results: 2019-2020. Dermatitis. 2023;34(2):90-104. Doi:10.1089/derm.2022.29017.jdk

10. Warshaw EM, Han J, Kullberg SA, et al. Patch Testing to Chlorhexidine Digluconate, 1% Aqueous: North American Contact Dermatitis Group Experience, 2015-2020 [published online ahead of print, 2023 Jun 6]. Dermatitis. 2023;10.1089/derm.2023.0077. doi:10.1089/derm.2023.0077

11. Silvestri DL, McEnery-Stonelake M. Chlorhexidine: uses and adverse reactions. Dermatitis : Contact, Atopic, Occupational, Drug. 2013 May-Jun;24(3):112-118. DOI: 10.1097/der.0b013e3182905561. PMID: 23665831.

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