Hostname: page-component-7b9c58cd5d-g9frx Total loading time: 0 Render date: 2025-03-14T02:05:32.564Z Has data issue: false hasContentIssue false
  • English
  • Français

Review of allergic reactions from use of chlorhexidine on medical products in clinical settings over 40 years: Risks and mitigations

Published online by Cambridge University Press:  03 June 2021

Bahgat Z. Gerges ,
Joel Rosenblatt ,
Y-Lan Truong ,
Ruth A. Reitzel  and
Isaam Raad
Bahgat Z. Gerges
Affiliation:
Department of Infectious Diseases, Infection Control and Employee Health, University of Texas, MD Anderson Cancer Center, Houston, Texas
Joel Rosenblatt*
Affiliation:
Department of Infectious Diseases, Infection Control and Employee Health, University of Texas, MD Anderson Cancer Center, Houston, Texas
Y-Lan Truong
Affiliation:
Department of Infectious Diseases, Infection Control and Employee Health, University of Texas, MD Anderson Cancer Center, Houston, Texas
Ruth A. Reitzel
Affiliation:
Department of Infectious Diseases, Infection Control and Employee Health, University of Texas, MD Anderson Cancer Center, Houston, Texas
Isaam Raad
Affiliation:
Department of Infectious Diseases, Infection Control and Employee Health, University of Texas, MD Anderson Cancer Center, Houston, Texas
*
Author for correspondence: Joel Rosenblatt, E-mail: JSRosenblatt@mdanderson.org
Rights & Permissions [Opens in a new window]

Abstract

Chlorhexidine is an antimicrobial agent widely used for infection prevention in medical settings. Nevertheless, allergic reactions ranging from mild to severe have been reported following its use. In this review, we analyzed all case reports published between the introduction of chlorhexidine and the end of 2019 for allergic responses associated with the use of medical devices and or other medical products containing chlorhexidine (CHX) to ascertain the prevalence of severe CHX allergic reactions and what practices might best mitigate those risks.

In total, 77 publications containing 124 reported cases of allergic reactions were grouped into 3 product categories, catheters, semisolids, and fluid products. The country, type of reaction, route of sensitization, allergy confirmation, and intervention or mitigation was extracted for each case. Overall, 30 cases were associated with catheters, 46 cases were associated with semisolid products, and 48 cases were associated with the use of other medical products. Severe cases were managed with intravenous fluids, steroids, and epinephrine (adrenaline). None of the reported cases were fatal. The allergy risks can be mitigated by better warning and training clinicians and by recording and screening patient histories for CHX presensitization from prior exposure. For patients undergoing pre-use blood tests, IgE antibody screens can also be performed. Finally, as a precaution in the event a rare severe allergic reaction occurs, procedure carts and rooms can be prestocked with injectable epinephrine and other rapidly acting anti-inflammatory medications.

Type
Review
Information
Infection Control & Hospital Epidemiology , Volume 43 , Issue 6 , June 2022 , pp. 775 - 789
Check for updates
Copyright
© The Author(s), 2021. Published by Cambridge University Press on behalf of The Society for Healthcare Epidemiology of America

Chlorhexidine (CHX) is a cationic polybiguanide that has bacteriostatic, bactericidal, and some antiviral and fungicidal activity. Since its discovery in 1954, CHX has become a mainstay of infection prevention for numerous medical and dental uses and its use is recommended by many guideline committees for infection prophylaxis. It is commonly found in, and its use is recommended for, topical skin disinfectants, preoperative surgical scrubs, and plaque-reducing mouthwashes. Reference Liippo, Kousa and Lammintausta1 Antimicrobial medical lubricants, contraceptive gels, eye-care products, facial cleansers, moisturizers, and wound-care products utilize CHX. Reference Liippo, Kousa and Lammintausta1,Reference Goon, White, Rycroft and McFadden2 It has also been used to impregnate the surfaces of medical devices (eg vascular catheters, sponges, and orthopedic pins). Reference Goon, White, Rycroft and McFadden2 Chlorhexidine has good activity against gram-positive bacteria, somewhat less activity against gram-negative bacteria and fungi, and minimal activity against mycobacteria. Reference Krautheim, Jermann and Bircher3 Its broad-spectrum antimicrobial activity results from its binding to proteins that contain phosphate in the bacterial cell wall, causing the bacterial cytoplasmic membrane to break and the cytoplasmic components to leak. Reference Calogiuri, Di Leo and Trautmann4

Despite its significant benefits for preventing infections, CHX is a potential allergen that can trigger IgE-mediated hypersensitivity reactions in sensitized individuals. Reference Nagendran, Wicking, Ekbote, Onyekwe and Garvey5 Allergic reactions to CHX have been reported, ranging from allergic contact dermatitis, erythema, urticaria, to anaphylaxis reactions. Reference Rose, Garcez, Savic and Garvey6 Diagnosis of reactions to CHX have been based on skin tests and specific IgE determinations. Reference Opstrup, Malling and Krøigaard7 Reports of allergic contact dermatitis to CHX are rare despite its frequent use Reference Goon, White, Rycroft and McFadden2,Reference Le Corre, Barbarot, Frot and Milpied8 ; however, reports of serious allergic reactions to these products have continued over the last decade. 9 Given the importance and significance of CHX medical products in preventing infections in hospital and clinical settings, we present the results of our comprehensive survey and our summaries of case reports published worldwide over several decades associated with use of CHX medical products to assess the extent of the risk of allergic reactions associated with its use as well as to identify measures that can make its use safer.

Methods

We searched 4 electronic databases (Medline, EMBASE, CINAHL, and Scopus) for studies published between 1946 and 2019 regarding allergy due to use of medical devices and or other medical or cosmetic products containing CHX. The following search string was applied: (chlorhexidine OR chlorhexidine gluconate OR chlorhexidine diacetate) AND (IgE OR IgE mediated OR itching OR pruritus OR hives OR urticaria OR angioedema OR anaphylaxis OR allergic contact dermatitis OR irritants OR occupational dermatitis OR irritant dermatitis OR irritant contact dermatitis OR contact dermatitis OR non-IgE mediated OR radioallergosorbent test OR RAST). The search string yielded 468 publications for title and abstract screening. Search results were first screened by title and abstract by 2 independent reviewers. Any disagreements were discussed by authors and consensus was reached. Resulting articles were read for full-text review and data abstraction. Reports were excluded if they could not be obtained in the English language, if they did not assess a medical device or a topically or orally applied fluid, or if they did not report an allergic reaction. Literature reviews were also excluded from the primary assessment; however, they were used to identify additional case reports and to identify inconsistencies with our findings.

For each case report or case report series, we abstracted the product type, route of exposure, type and severity of reaction (ie, how the reaction presented), time from initial exposure to reaction, the resolution of the reaction and any interventions that were required to resolve the reaction. In addition, information on presensitization was recorded, including the exposure route and how presensitization reactions presented. Finally, we collected information on whether testing was conducted to confirm CHX allergy was present and whether the allergic reaction due to exposure to CHX was confirmed or suspected. Cases were classified as confirmed cases of anaphylaxis or allergic reaction to CHX if a skin test with a second positive challenge was performed or if CHX-specific IgE antibodies were detected. Cases with single skin tests with or without positive tryptase tests (but lacking second challenges or IgE antibody detection) were classified as suspected cases of allergic reaction to CHX.

Results

In this study, we reviewed case report literature pertaining to allergic reactions with the use of CHX in medical devices as well as due to the use of CHX in gel, disinfectant solutions for skin wash, and other medical uses. Cases were stratified both by route of exposure (type of device or medical product) as well as by country.

Central venous catheter (CVC) associated allergic reaction cases

Globally from 1997 to 2019, 30 were reported in the literature with allergy reaction due to CVCs coated with CHX, for an average of 1.36 case reports per year. All cases were managed with intravenous fluids, steroids, and adrenaline (epinephrine). None of the cases were fatal. Most of these cases were reported in England (11 cases), and 1 case was reported in the United States. Of these 30 allergic cases, 17 (56.7%) were presensitized with CHX containing substances prior CVCs insertion. The period elapsed between presensitization and insertion of CVCs ranged from 6 minutes to 3 years. Most of these cases (20 cases, 66.7%) were confirmed using CHX-specific IgE detection or using a positive second skin-prick test. The itemized citation, case exposure route, time from initial sensitization, presentation, treatment, and diagnosis are summarized in Table 1.

Table 1. Chlorhexidine (CHX) Allergy Cases Associated With Central-Venous Catheter (CVC) Devices

Note. BAT, basophil activation test; CHX-SS, CHC-silver sulfadiazine treated; NA, not available; POS, positive.

a Skin-prick tests conducted after presensitization, no additional studies conducted after second episode anaphylaxis. Reference Oda, Hamasaki, Kanda and Mikami10

b CVC not labeled to contain CHX – processed by sterile services unit, subsequently added warning label. Reference Jee, Nel, Gnanakumaran, Williams and Eren14

c CHX mouthwash was used while intubated after anaphylaxis. Reference Jee, Nel, Gnanakumaran, Williams and Eren14

d CVC left in place postoperatively, additional hypotensive episodes. Reference Baird and Cokis23

e CVC removed postoperatively continued airway/tongue swelling. Removed CVC line dressings, patient resolved. Reference Baird and Cokis23

f Anaphylaxis occurred prior to CHX-SS insertion and was resolved, further hypotension after CHX-SS insertion. Reference Zheng, Fang and Cai27

Semisolid gels, pastes, pads, creams, or dressings

In total, 46 cases were reported with allergy reaction due to use of CHX in gel, creams, toothpastes, or cannulas during the period of the first report in 1992 through 2019 all over the world (with average 1.7 cases reported per year). All cases were managed with intravenous fluids, steroids, and adrenaline (epinephrine) or local treatment with hydrocortisone or wound care. None of the cases were fatal. Most of these cases were reported in England (17 cases), and 7 cases were reported in the United States. Of 46 allergic cases; 26 (56.5%) were presensitized with CHX containing substances. The elapsed time between presensitization and symptoms presentation ranged from 3 days to 22 years. Also, 15 cases (32.6%) were confirmed using Specific IgE-CHX detection or positive second-prick test. Case exposure route, time from initial sensitization, presentation, treatment, and diagnosis are summarized in Table 2.

Table 2. Chlorhexidine (CHX) Allergy Due to Gels, Creams, and Oral Products

Note. NA, not available; POS, positive; ART, arterial catheter; UR, urinary catheter.

Topical washes, wipes, rinses, sprays or other fluid medical products

Globally, 48 cases were reported with allergy reaction from the appearance of first case in 1984 through 2019, with an average of 1.37 cases reported each year. All cases were managed with local treatment with hydrocortisone or wound care, while severe cases were managed with intravenous fluids, steroids, and adrenaline. None of the cases were fatal. Most cases were reported in England (14 cases), whereas 2 cases were reported in the United States. Of 48 allergic cases; 27 (56.3%) were presensitized with CHX-containing substances. The elapsed time between presensitization and symptoms presentation ranged from 15 minutes to 10 years. Moreover, 18 cases (37.5%) were confirmed using CHX-specific IgE detection or using a positive second skin-prick test. Case exposure route, time from initial sensitization, presentation, treatment, and diagnosis are summarized in Table 3.

Table 3. Chlorhexidine (CHX) Allergy Cases Associated With Topical Washes, Wipes, Rinses, Sprays or Other Fluid Medical Products

Note. NA, not available; POS, positive.

Discussion

Chlorhexidine is used extensively in healthcare products, including preoperative shower solutions and antiseptic skin preparations, and it is bonded to devices such as surgical mesh, dressings, and the outer surfaces of urinary and CVCs. CHX also is a component of several commercial products such as mouthwashes, dental gels, contact lens solutions, toothpastes, moisturizers, and lubricants. Given the extensive use of products containing CHX in both community and healthcare settings, there is potential for allergic sensitization of patients. CHX can cause a spectrum of allergic reactions ranging from contact dermatitis to generalized urticaria and life-threatening allergic hypersensitivity. Practice guidelines published by the American Academy of Allergy, Asthma and Immunology and the American College of Allergy, Asthma and Immunology suggest taking a careful medical history focusing on prior adverse reactions. Reference Lieberman, Nicklas and Oppenheimer76 Any prior medication reactions increase the likelihood of adverse reactions, and multiple previous medication reactions pose yet a greater risk. When no prior sensitivity reaction has occurred or no information is available for a patient, it is necessary to be prepared because reactions can potentially occur and progress rapidly.

In this review, we analyzed 124 case reports of allergy due to CHX published between 1981 and 2019, ranging from mild allergic contact dermatitis to severe anaphylaxis. All mild cases were managed by local treatment with hydrocortisone or wound care, and severe cases were managed with intravenous fluids, steroids, and adrenaline (epinephrine). None of the cases was fatal. Recent reviews of CHX allergy have focused on the most prevalent types of topically or mucosally derived allergic reactions, Reference Sharp, Green and Rose77-Reference Dyer, Taktak, Parkes, Garcez and Gall80 so we have focused the discussion on analyzing vascular-catheter–associated CHX allergic reactions. Of 124 case reports of CHX allergic reactions, 30 cases of allergic reaction due to CVCs coated with CHX were reported from 1997 to 2019 all over the world, for an average of 1.36 cases reported each year. All cases were managed with intravenous fluids, steroids, and epinepherine. Of the reported allergic cases due to CHX CVCs, 17 patients (56.7%) were presensitized with CHX-containing substances prior to CVC insertion such as skin wash or wound disinfectants. The interval between presensitization and insertion of CVCs ranged from 6 minutes to 3 years.

The cases surveyed in this review reported only those that had published case reports. Potentially, more cases occurred that were not published as case reports. For example, a recent study Reference Rose, Garcez, Savic and Garvey6 consisted of surveys on CHX allergy cases reported by comprehensive surveys of 13 international institutions (members of the International Suspected Perioperative Allergic Reaction Group) spanning periods as long as 20 years. They report 252 cases from all routes of exposure, 16 of which were attributed to CVCs. It was unclear how many of the reactions were confirmed due to CHX allergy; however, similar to our study, most cases were associated with CHX products other than vascular catheters. Thus, many adverse reactions to CHX products are underreported and are not thoroughly investigated for causation, particularly those that resolve quickly or have mild symptoms.

The merits of using CHX CVCs warrant weighing the risk of allergic reaction against the risk of infection. Our study found an incidence of 30 documented cases over >30 years, or roughly 1 CHX CVC allergic reaction per year (most of these were outside the United States). The number of central-line–associated bloodstream infections (CLABSIs) in the United States has been estimated to be 400,000 per year. Reference Raad and Chaftari81 Compounding the relative benefit for infection prevention is that a significant percentage of CLABSIs cause mortality while no mortalities have been reported from CHX CVC allergic reactions.

Although the risk of infection and mortality from CLABSI far outweighs the risk of severe allergic reaction to CHX on CVCs, several steps can be taken to further mitigate the risk of allergic reaction to CHX, particularly since anaphylactic reactions can be severe. These include carefully reviewing patient history of prior allergic reactions as well as the history of prior patient exposure to CHX products. For patients at elevated risk for allergic reaction or with unknown histories of CHX exposure and for those undergoing blood chemistry testing prior to being catheterized, CHX IgE antibodies can be readily screened for using automated machines with commercially available IgE antibody detection kits such as ImmunoCap. Reference Johansson82 In addition, notification of the allergy risk should be prominently presented and an allergy risk question list Reference Rose, Garcez, Savic and Garvey6 can be included with CVC insertion kits. Since the use of perioperative CHX is increasing, continued vigilant surveillance of the incidence of allergic reaction to CVCs is warranted. Finally, as a precaution for rare but severe anaphylactic shock reactions, epinephrine should be routinely present on procedure carts or available in rooms where catheter insertion procedures are performed for rapid intervention to restore patient vitality.

Acknowledgments

The authors thank Ms Salli Saxton for her assistance in preparing the manuscript.

Financial support

Partial financial support for this work was received from Cook Advanced Technologies.

Conflicts of interest

Drs I. Raad and J. Rosenblatt are inventors of a minocycline, rifampin, CHX antimicrobial coating technology which is owned by the University of Texas MD Anderson Cancer Center and has been licensed by Cook Medical. All other authors report no conflicts of interest relevant to this article.

References

Liippo, J, Kousa, P, Lammintausta, K. The relevance of chlorhexidine contact allergy. Contact Dermatitis 2011;64:229–234.CrossRefGoogle ScholarPubMed
Goon, AT, White, IR, Rycroft, RJG, McFadden, JP. Allergic contact dermatitis from chlorhexidine. Dermatitis 2004;15:45–47.CrossRefGoogle ScholarPubMed
Krautheim, AB, Jermann, TH, Bircher, AJ. Chlorhexidine anaphylaxis: case report and review of the literature. Contact Dermatitis 2004;50:113–116.CrossRefGoogle ScholarPubMed
Calogiuri, G, Di Leo, E, Trautmann, A, et al. Chlorhexidine hypersensitivity: a critical and updated review. J Allergy Ther 2013;4(141). doi: 10.4172/2155-6121.1000141.Google Scholar
Nagendran, V, Wicking, J, Ekbote, A, Onyekwe, T, Garvey, LH. IgE-mediated chlorhexidine allergy: a new occupational hazard? Occup Med (Lond) 2009;59:270–272.CrossRefGoogle ScholarPubMed
Rose, MA, Garcez, T, Savic, S, Garvey, LH. Chlorhexidine allergy in the perioperative setting: a narrative review. Br J Anaesth 2019;123:e95–e103.CrossRefGoogle ScholarPubMed
Opstrup, MS, Malling, H-J, Krøigaard, M,et al. Standardized testing with chlorhexidine in perioperative allergy—a large single-centre evaluation. Allergy 2014;69:1390–1396.CrossRefGoogle ScholarPubMed
Le Corre, Y, Barbarot, S, Frot, AS, Milpied, B. Allergic contact dermatitis to chlorhexidine in a very young child. Pediatr Dermatol 2010;27:485–487.CrossRefGoogle Scholar
FDA warns about rare but serious allergic reactions with the skin antiseptic chlorhexidine gluconate. Food and Drug Administration website. https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-warns-about-rare-serious-allergic-reactions-skin-antiseptic. Published February 2, 2017. Accessed September 14, 2020.Google Scholar
Oda, T, Hamasaki, J, Kanda, N, Mikami, K. Anaphylactic shock induced by an antiseptic-coated central venous [correction of nervous] catheter. Anesthesiology 1997;87:1242–1244.CrossRefGoogle ScholarPubMed
Weng, M, Zhu, M, Chen, W, Miao, C. Life-threatening anaphylactic shock due to chlorhexidine on the central venous catheter: a case series. Int J Clin Exp Med 2014;7:5930–5936.Google ScholarPubMed
Faber, M, Leysen, J, Bridts, C, Sabato, V, De Clerck, LS, Ebo, DG. Allergy to chlorhexidine: beware of the central venous catheter. Acta Anaesthesiol Belg 2012;63:191–194.Google ScholarPubMed
Guleri, A, Kumar, A, Morgan, RJM, Hartley, M, Roberts, DH. Anaphylaxis to chlorhexidine-coated central venous catheters: a case series and review of the literature. Surg Infect (Larchmt) 2012;13:171–174.CrossRefGoogle ScholarPubMed
Jee, R, Nel, L, Gnanakumaran, G, Williams, A, Eren, E. Four cases of anaphylaxis to chlorhexidine impregnated central venous catheters: a case cluster or the tip of the iceberg? Br J Anaesth 2009;103:614–615.CrossRefGoogle ScholarPubMed
Khoo, A, Oziemski, P. Chlorhexidine impregnated central venous catheter inducing an anaphylatic shock in the intensive care unit. Heart Lung Circ 2011;20:669–670.CrossRefGoogle Scholar
Kluger, M. Anaphylaxis to chlorhexidine-impregnated central venous catheter. Anaesth Intensive Care 2003;31:697–698.Google ScholarPubMed
Nakonechna, A. Chlorhexidine/Lidocaine. Reactions Wkly 2015;1548:66.Google Scholar
Pittaway, A, Ford, S. Allergy to chlorhexidine-coated central venous catheters revisited. Br J Anaesth 2002;88:304–305.Google Scholar
Qin, Z, Zeng, Z. Anaphylaxis to chlorhexidine in a chlorhexidine-coated central venous catheter during general anaesthesia. Anaesth Intensive Care 2016;44:297–298.Google Scholar
Stephens, R, Mythen, M, Kallis, P, Davies, DW, Egner, W, Rickards, A. Two episodes of life-threatening anaphylaxis in the same patient to a chlorhexidine-sulphadiazine–coated central venous catheter. Br J Anaesth 2001;87:306–308.CrossRefGoogle ScholarPubMed
Terazawa, E, Shimonaka, H, Nagase, K, Masue, T, Dohi, S. Severe anaphylactic reaction due to a chlorhexidine-impregnated central venous catheter. Anesthesiology 1998;89:1296–1298.CrossRefGoogle Scholar
Zhou, E, Parikh, PS, Kanchuger, MS, Balsam, LB. Intraoperative anaphylaxis to chlorhexidine during LVAD and transplant surgery. J Cardiothorac Vasc Anesth 2019;33:169–172.CrossRefGoogle Scholar
Baird, PA, Cokis, CJ. A case series of anaphylaxis to chlorhexidine-impregnated central venous catheters in cardiac surgical patients. Anaesth Intensive Care 2019;47:85–89.CrossRefGoogle ScholarPubMed
Wang, ML Chang, CT, Huang, HH, Yeh, YC, Lee, TS, Hung, KY. Chlorhexidine-related refractory anaphylactic shock: a case successfully resuscitated with extracorporeal membrane oxygenation. J Clin Anesth 2016;34:654–657.CrossRefGoogle ScholarPubMed
Chen, P, Huda, W, Levy, N. Chorhexidine anaphylaxis: Implications for post-resuscitation management. Anaesthesia 2016; 71:242–243.CrossRefGoogle Scholar
Ho, A, Zaltzman, J, Hare, GMT, et al. Severe and near-fatal anaphylactic reactions triggered by chlorhexidine-coated catheters in patients undergoing renal allograft surgery: a case series. Can J Anaesth 2019;66:1483–1488.CrossRefGoogle Scholar
Zheng, X, Fang, X, Cai, X. Two episodes of anaphylaxis caused by a chlorhexidine sulfadiazine-coated central venous catheter. Chin Med J (Engl) 2014;127:2395–2397.Google ScholarPubMed
Beatty, P, Kumar, N, Ronald, A. A complicated case of chlorhexidine-associated anaphylaxis. Anaesthesia 2011;66:60–61.CrossRefGoogle ScholarPubMed
Rutkowski, K, Wagner, A. Chlorhexidine: a new latex? Eur Urol 2015;68:345–347.CrossRefGoogle ScholarPubMed
Jayathillake, A, Mason, DF, Broome, K. Allergy to chlorhexidine gluconate in urethral gel: report of four cases and review of the literature. Urology 2003;61:837.CrossRefGoogle ScholarPubMed
Lasa, EM, González, C, García-Lirio, E, Martínez, S, Arroabarren, E, Gamboa, PM. Anaphylaxis caused by immediate hypersensitivity to topical chlorhexidine in children. Ann Allergy Asthma Immunol 2017;118:118–119.CrossRefGoogle Scholar
Nakonechna, A, Dore, P, Dixon, T. Immediate hypersensitivity to chlorhexidine is increasingly recognised in the United Kingdom. Allergol Immunopathol (Madr) 2014;42:44–49.CrossRefGoogle ScholarPubMed
Parkes, AW, Harper, N, Herwadkar, A, Pumphrey, R. Anaphylaxis to the chlorhexidine component of Instillagel: a case series. Br J Anaesth 2009;102:65–68.CrossRefGoogle Scholar
Pham, NH, Weiner, JM, Reisner, GS, Baldo, BA. Anaphylaxis to chlorhexidine. Case report. Implication of immunoglobulin E antibodies and identification of an allergenic determinant. Clin Exp Allergy 2000;30:1001–1007.CrossRefGoogle ScholarPubMed
Sijbesma, T, Röckmann, H, van der Weegen, W. Severe anaphylactic reaction to chlorhexidine during total hip arthroplasty surgery. A case report. Hip Int 2011;21:630–632.CrossRefGoogle ScholarPubMed
Stables, GI, Turner, WH, Prescott, S, Wilkinson, SM. Generalized urticaria after skin cleansing and urethral instillation with chlorhexidine-containing products. Br J Urol 1998;82:756–757.CrossRefGoogle ScholarPubMed
Bergqvist-Karlsson, A. Delayed and immediate-type hypersensitivity to chlorhexidine. Contact Dermatitis 1988;18:84–88.CrossRefGoogle ScholarPubMed
Dyer, JE, Nafie, S, Mellon, JK, Khan, MA. Anaphylactic reaction to intraurethral chlorhexidine: sensitisation following previous repeated uneventful administration. Ann Roy Coll Surg Engl 2013;95(6):e105–e118.Google ScholarPubMed
Garvey, LH, Roed-Petersen, J, Husum, B. Anaphylactic reactions in anaesthetised patients—four cases of chlorhexidine allergy. Acta Anaesthesiol Scand 2001;45:1290–1294.CrossRefGoogle ScholarPubMed
Knight, BA, Puy, R, Douglass, J, O’Hehir, RE, Thien, F. Chlorhexidine anaphylaxis: a case report and review of the literature. Intern Med J 2001;31:436–437.CrossRefGoogle Scholar
Koch, A, Wollina, U. Chlorhexidine allergy. Allergo J Int 2014;23:84–86.CrossRefGoogle Scholar
Noel, J, Temple, A, Laycock, GJ. A case report of anaphylaxis to chlorhexidine during urinary catheterisation. Ann R Coll Surg Engl 2012;94:e159–e160.CrossRefGoogle ScholarPubMed
Ramselaar, CG, Craenen, A, Bijleveld, RT. Severe allergic reaction to an intraurethral preparation containing chlorhexidine. Br J Urol 1992;70:451–452.CrossRefGoogle Scholar
Weitz, NA, Lauren, CT, Weiser, JA, et al. Chlorhexidine gluconate–impregnated central access catheter dressings as a cause of erosive contact dermatitis: a report of 7 cases. JAMA Dermatol 2013;149:195–199.CrossRefGoogle ScholarPubMed
Wicki, J, Deluze, C, Cirafici, L, Desmeules, J. Anaphylactic shock induced by intraurethral use of chlorhexidine. Allergy 1999;54:768–769.CrossRefGoogle ScholarPubMed
Stewart, M, Lenaghan, D. The danger of chlorhexidine in lignocaine gel: a case report of anaphylaxis during urinary catheterisation. Australas Med J 2015;8:304–306.CrossRefGoogle ScholarPubMed
Thong, CL, Lambros, M, Stewart, MG, Kam, PCA. An unexpected cause of an acute hypersensitivity reaction during recovery from anaesthesia. Anaesth Intensive Care 2005;33:521–524.CrossRefGoogle Scholar
Totty, J, Forsyth, J, Mekako, A, Chetter, I. Life-threatening intraoperative anaphylaxis as a result of chlorhexidine present in Instillagel. BMJ Case Rep 2017. doi: 10.1136/bcr-2017-221443.CrossRefGoogle Scholar
Wittczak, T, Dudek, W, Walusiak-Skorupa, J, Świerczyńska-Machura, D, Pałczyński, C. Chlorhexidine—still an underestimated allergic hazard for healthcare professionals. Occup Med (Lond) 2013;63:301–305.CrossRefGoogle Scholar
Evans, RJ. Acute anaphylaxis due to topical chlorhexidine acetate. BMJ 1992;304:686.CrossRefGoogle ScholarPubMed
Porter, BJ, Acharya, U, Ormerod, AD, Herriot, R. Latex/chlorhexidine-induced anaphylaxis in pregnancy. Allergy 1998;53:455–457.CrossRefGoogle Scholar
Mushtaq, U, Tan, A, Tan, JA, Smith, WB. Acute allergic reaction after intravenous saline injection: an unusual presentation of chlorhexidine allergy. Med J Aust 2014;200:599–600.CrossRefGoogle ScholarPubMed
Ebo, DG, Stevens, WJ, Bridts, CH, Matthieu, L. Contact allergic dermatitis and life-threatening anaphylaxis to chlorhexidine. J Allergy Clin Immunol 1998;101:128–129.CrossRefGoogle Scholar
Russ, BR, Maddern, PJ. Anaphylactic reaction to chlorhexidine in urinary catheter lubricant. Anaesth Intensive Care 1994;22:611–612.CrossRefGoogle Scholar
Fisher, AA. Contact urticaria from chlorhexidine. Cutis 1989;43:17–18.Google ScholarPubMed
Bahal, S, Sharma, S, Garvey, LH, Nagendran, V. Anaphylaxis after disinfection with 2% chlorhexidine wand applicator. BMJ Case Rep 2017. doi: 10.1136/bcr-2017-219794.CrossRefGoogle ScholarPubMed
Conraads, VM, Jorens, PG, Ebo, DG, Claeys, MJ, Bosmans, JM, Vrints, CJ. Coronary artery spasm complicating anaphylaxis secondary to skin disinfectant. Chest 1998;113:1417–1419.CrossRefGoogle Scholar
Doolan, BT, Crilly, HM. Chlorhexidine wipes: time to stop and think about allergy. Anaesth Intensive Care 2019;47:90–95.CrossRefGoogle Scholar
Khan, RA, Kazi, T, O’Donohoe, B. Near fatal intraoperative anaphylaxis to chlorhexidine—is it time to change practice? BMJ Case Rep 2011. doi: 10.1136/bcr.09.2009.2300.CrossRefGoogle ScholarPubMed
McEnery-Stonelake, M, Silvestri, DL. Allergic contact dermatitis to chlorhexidine after oral sensitization. Dermatitis 2013;24:92–93.CrossRefGoogle ScholarPubMed
Ohtoshi, T, Yamauchi, N, Tadokoro, K, et al. IgE antibody-mediated shock reaction caused by topical application of chlorhexidine. Clin Allergy 1986;16:155–161.CrossRefGoogle ScholarPubMed
Snellman, E, Rantanen, T. Severe anaphylaxis after a chlorhexidine bath. J Am Acad Dermatol 1999;40:771–772.CrossRefGoogle ScholarPubMed
Teixeira de Abreu, AP, Ribeiro de Oliveira, LR, Teixeira de Abreu, AF, et al. Perioperative anaphylaxis to chlorhexidine during surgery and septoplasty. Case Rep Otolaryngol 2017. doi: 10.1155/2017/9605804.CrossRefGoogle Scholar
Toletone, A, Dini, G, Massa, E, et al. Chlorhexidine-induced anaphylaxis occurring in the workplace in a healthcare worker: case report and review of the literature. Med Lav 2018;109:68–76.Google Scholar
Bae, YJ, Park, CS, Lee, JK, et al. A case of anaphylaxis to chlorhexidine during digital rectal examination. J Korean Med Sci 2008;23:526–528.CrossRefGoogle ScholarPubMed
Gu, JQ, Liu, S, Zhi, YX. Provocation test-confirmed chlorhexidine-induced anaphylaxis in dental procedure. Chin Med J (Engl) 2018;131:2893–2894.Google Scholar
Magdaleno-Tapial, J, Martínez-Doménech, A, Valenzuela-Oñate, C, Ferrer-Guillén, B, Esteve-Martínez, A, Zaragoza-Ninet, V. Allergic contact dermatitis to chlorhexidine in pediatric patients. Pediatr Dermatol 2019;36:540–541.CrossRefGoogle Scholar
Mitchell, DJ, Parker, FC. Anaphylaxis following urethral catheterisation. Br J Urol 1993;71:613.CrossRefGoogle ScholarPubMed
Okano, M, Nomura, M, Hata, S, et al. Anaphylactic symptoms due to chlorhexidine gluconate. Arch Dermatol 1989;125:50–52.CrossRefGoogle ScholarPubMed
Peutrell, JM. Anaphylactoid reaction to topical chlorhexidine during anaesthesia. Anaesthesia 1992;47:1013.CrossRefGoogle ScholarPubMed
Reynolds, NJ, Harman, RR. Allergic contact dermatitis from chlorhexidine diacetate in a skin swab. Contact Dermatitis 1990;22:103–104.CrossRefGoogle Scholar
Roberts, DL, Summerly, R, Byrne, JP. Contact dermatitis due to the constituents of Hibiscrub. Contact Dermatitis 1981;7:326–328.CrossRefGoogle Scholar
Shoji, A. Contact dermatitis to Aloe arborescens . Contact Dermatitis 1982;8:164–167.CrossRefGoogle Scholar
Vu, M, et al. Immediate hypersensitivity to chlorhexidine. Australas J Dermatol 2018;59:55–56.CrossRefGoogle Scholar
Hong, CC, Wang, SM, Nather, A, Tan, JH, Tay, SH, Poon, KH. Chlorhexidine anaphylaxis masquerading as septic shock. Int Arch Allergy Immunol 2015;167:16–20.CrossRefGoogle ScholarPubMed
Lieberman, P, Nicklas, RA, Oppenheimer, J, et al. The diagnosis and management of anaphylaxis practice parameter: 2010 update. J Allergy Clin Immunol 2010;126:477–480.CrossRefGoogle ScholarPubMed
Sharp, G, Green, S, Rose, M. Chlorhexidine-induced anaphylaxis in surgical patients: a review of the literature. ANZ J Surg 2016;86:237–243.CrossRefGoogle ScholarPubMed
Chiewchalermsri, C, Sompornrattanaphan, M, Wongsa, C, Thongngarm, T. Chlorhexidine allergy: current challenges and future prospects. J Asthma Allergy 2020;13:127–133.CrossRefGoogle Scholar
Harper, NJN, Cook, TM, Garcez, T, et al. Anaesthesia, surgery, and life-threatening allergic reactions: epidemiology and clinical features of perioperative anaphylaxis in the 6th National Audit Project (NAP6). Br J Anaesth 2018;121:159–171.CrossRefGoogle Scholar
Dyer, JE, Taktak, SY, Parkes, AW, Garcez, T, Gall, Z. Chlorhexidine-related anaphylaxis in urological practice. J Clin Urol 2019;12:32–38.CrossRefGoogle Scholar
Raad, I, Chaftari, AM. Advances in prevention and management of central line-associated bloodstream infections in patients with cancer. Clin Infect Dis 2014;59 suppl 5:S340–S343.CrossRefGoogle ScholarPubMed
Johansson, SG. ImmunoCAP Specific IgE test: an objective tool for research and routine allergy diagnosis. Expert Rev Mol Diagn 2004;4:273–279.CrossRefGoogle Scholar
Figure 0

Table 1. Chlorhexidine (CHX) Allergy Cases Associated With Central-Venous Catheter (CVC) Devices

Figure 1

Table 2. Chlorhexidine (CHX) Allergy Due to Gels, Creams, and Oral Products

Figure 2

Table 3. Chlorhexidine (CHX) Allergy Cases Associated With Topical Washes, Wipes, Rinses, Sprays or Other Fluid Medical Products