Hypersensitivity Reaction to Chlorhexidine Gluconate Following Cardiac Implantable Electronic Device Procedure

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EP LAB DIGEST. 2024;24(2):20-21.

Chlorhexidine is commonly used as a disinfectant and preoperative surgical site prep.¹ It is an effective antiseptic against bacteria, fungi, and viruses.² We present a case report of a hypersensitivity reaction to chlorhexidine gluconate following an implantable loop recorder (ILR) removal and replacement procedure, and present this case as something all electrophysiologists should be aware of.

Case Presentation

In May 2019, a 70-year-old woman presented with a history of recurrent palpitations and 3 episodes of syncope following exercise at the gym. Her past medical history was remarkable for breast cancer treated with mastectomy 13 years prior without complications, except for a self-limiting rash around the surgical site following the procedure. The patient was referred by neurology following a normal brain magnetic resonance imaging without contrast, brain magnetic resonance angiography, and electroencephalogram. Following the referral, the patient underwent an electrophysiology study (EPS) and subsequent ILR implantation due to the frequency of her palpitations and syncopal episodes. EPS results were unremarkable; there was no evidence of a jump or extra pathway, and no supraventricular or ventricular arrhythmias were induced. During the 4 years of remote ILR monitoring, the patient exhibited recurrent episodes of nonsustained supraventricular tachycardia (SVT) (Figure 1). These episodes were mildly symptomatic and associated with her palpitations. To address these episodes, the patient began taking 25 mg of metoprolol succinate extended-release once daily. In April 2023, the patient underwent the removal and replacement of her ILR. Prior to the procedure, she informed her EP team that she had a previous “Steri-Strip allergy.”

The patient’s ILR replacement procedure was performed in May 2023. The surgical prep agent prior to incision was ChloraPrep (BD) (active ingredient chlorhexidine gluconate 2%). The skin was anesthetized with lidocaine 1% and epinephrine 1:100,000, and the procedure used a standard disposable scalpel and the LINQ II (Medtronic) delivery kit. A small incision was made, the ILR was removed with blunt dissection, and the new ILR (LINQ II) was injected in the fourth intercostal space along the left sternal border. The surgical incision was closed with a 4-0 Monocryl suture and 0.8 mL of Covidien topical skin adhesive (2-octyl-cyanoacrylate). No Steri-Strips were used based on the patient’s history and request not to receive them. Approximately 24 hours post procedure, the patient noted a localized maculopapular rash across her chest that was associated with erythema and pruritus (Figure 2). The rash surrounded the entire insertion site, crossed the sternum, and spread toward her left shoulder. Post procedure, the patient recalled a similar reaction after the implantation of her first ILR, which was managed by her primary care physician and not her EP team. She saw her dermatologist the same day, who diagnosed her with contact dermatitis and prescribed topical clobetasol propionate (.05%). This cream was applied once daily for the next 7 days. The patient’s symptoms improved within 48 hours with complete resolution after 1 week (Figure 3). The patient underwent patch testing, which confirmed the chlorhexidine gluconate allergy.

Discussion

Chlorhexidine gluconate is widely used as a periprocedural skin prep, but it is also used in topical antiseptics, lubricant gels, and ophthalmic agents.³ It is considered safe and effective when used topically in concentrations between .5% and 4.0%, but in rare cases, hypersensitivity reactions have occurred. A recent study by the North American Contact Dermatitis Group found that of 14,731 patients patch tested for chlorhexidine allergy, only 107 patients (.7%) had a reaction.⁴

Two types of topical skin hypersensitivity reactions have been reported following the use of chlorhexidine gluconate during intravenous cannulation,⁵ coated central venous catheter insertion,⁶ and various surgical procedures.^7-9 Type I hypersensitivity reactions are immediate (within 1 hour after exposure) with pruritus, erythema, and urticaria. In severe cases, life-threatening anaphylaxis can occur.⁶ Type IV hypersensitivity reactions are delayed (12 or more hours after exposure), less common, and present with contact dermatitis³ with severe erythema, swelling, and blistering.¹⁰ The dermatologist classified this case as a mild type IV chlorhexidine gluconate hypersensitivity reaction.

As seen in this case, after being diagnosed with chlorhexidine hypersensitivity, many patients will recall similar reactions following previous exposures in the health care setting. Due to the mild severity of these past reactions, the hypersensitivity goes unreported and undiagnosed. In some cases, these mild reactions are not reported until the occurrence of a more severe reaction upon re-exposure to the causative agent.¹¹

Summary

This case report emphasizes the importance of recognizing hypersensitivity reactions to chlorhexidine gluconate and other contact irritants prior to routine cardiac procedures. A detailed medical history and diagnostic allergic testing can identify a hypersensitivity to this antiseptic. When identified, alternative antiseptics such as povidone-iodine, benzalkonium chloride, or isopropyl alcohol should be considered. A proper investigation into the causative agent of a perioperative hypersensitivity reaction, regardless of the severity, will help prevent additional exposures and potentially more severe reactions. Ultimately, all EPs should be aware of the potential for an allergic reaction from chlorhexidine, a common skin prep prior to cardiac implantable electronic device procedures. 

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest, and report no conflicts of interest regarding the content herein.

References

1. Koch A, Wollina U. Chlorhexidine allergy. Allergo J Int. 2014;23(3):84-86. doi:10.1007/s40629-014-0012-6

2. Opstrup MS, Jemec GBE, Garvey LH. Chlorhexidine allergy: on the rise and often overlooked. Curr Allergy Asthma Rep. 2019;19(5):23. doi:10.1007/s11882-019-0858-2

3. Chiewchalermsri C, Sompornrattanaphan M, Wongsa C, Thongngarm T. Chlorhexidine allergy: current challenges and future prospects. J Asthma Allergy. 2020;13:127-133. doi:10.2147/JAA.S207980

4. Warshaw EM, Han J, Kullberg SA, et al. Patch testing to chlorhexidine digluconate, 1% aqueous: North American Contact Dermatitis Group Experience, 2015-2020. Dermatitis. Published online June 6, 2023. doi:10.1089/derm.2023.0077

5. Xiao H, Zhang H, Jia Q, Xu F, Meng J. Immediate hypersensitivity to chlorhexidine: experience from an allergy center in China. Anesthesiology. 2023;138(4):364-371. doi:10.1097/ALN.0000000000004495

6. Amano Y, Matsuura A, Tamura T, et al. Life-threatening chlorhexidine anaphylaxis caused by skin preparation before chlorhexidine-free central venous catheter insertion: a case report and literature review. J Anesth. 2023;37(3):474-481. doi:10.1007/s00540-023-03189-1

7. Garvey LH, Krøigaard M, Poulsen LK, et al. IgE-mediated allergy to chlorhexidine. J Allergy Clin Immunol. 2007;120(2):409-415. doi:10.1016/j.jaci.2007.04.029

8. Toomey M. Preoperative chlorhexidine anaphylaxis in a patient scheduled for coronary artery bypass graft: a case report. AANA J. 2013;81(3):209-214.

9. Bhardwaj P, Bekeny JC, Zolper EG, Nigam M, Sher SR. Chlorhexidine hypersensitivity: a case report of delayed reactions associated with epidermal preparations. Plast Reconstr Surg Glob Open. 2020;8(8):e2945. doi:10.1097/GOX.0000000000002945

10. Burkemper NM. Contact dermatitis, patch testing, and allergen avoidance. Mo Med. 2015;112(4):296-300.

11. Opstrup MS, Garvey LH. Chlorhexidine allergy: mild allergic reactions can precede anaphylaxis in the healthcare setting. Turk J Anaesthesiol Reanim. 2019;47(4):342-344. doi:10.5152/TJAR.2019.22058