Lidocaine Contact Allergy Is Becoming More Prevalent Derek To, BSc,* Irèn Kossintseva, MD, FRCPC, FAAD,† and Gillian de Gannes, MD, FRCPC, FAAD*†‡
BACKGROUND Allergic contact dermatitis (ACD) to lidocaine is rising in prevalence. This is due to a growing number of over-the-counter (OTC) products containing topical amide and ester anesthetics. The phenomenon poses a real threat to the authors’ surgical anesthetic options. OBJECTIVE To investigate the epidemiology of topical anesthetic ACD in British Columbia, Canada and provide an approach for clinicians to deal with this problem. MATERIALS AND METHODS A retrospective chart review of 1,819 patients who underwent patch testing at the University of British Columbia Contact Dermatitis Clinic between January 2009 and June 2013 was completed. The authors also performed a detailed review of Canadian OTC preparations containing lidocaine in 2013. RESULTS The prevalence of ACD to local anesthetics is significant at 2.4%. The most common allergen is benzocaine (45%) followed by lidocaine (32%) and dibucaine (23%). CONCLUSION The proportion of ACD caused by lidocaine is higher than expected. This is likely secondary to an increase in OTC medicaments containing lidocaine. Patients who are patch test–positive to a local anesthetic should be challenged intradermally to confirm clinical relevance. Because ACD is a delayed Type IV hypersensitivity reaction (localized dermatitis), the risk of anaphylaxis is not a concern. The authors have indicated no significant interest with commercial supporters.
A
llergic contact dermatitis (ACD) is a Type IV or delayed type hypersensitivity reaction that develops at the site of contact with an allergen.1 This presents as pruritic erythematous papules and vesicles that coalesce into edematous plaques and bullae.2 The lesions begin at the primary site of contact but may manifest at multiple distant sites (autoeczematization) with chronic exposure to an allergen.3 Anesthetics are divided into 2 classes: ester and amide compounds. Esters such as benzocaine tend to be used in topical over-the-counter (OTC) or in-office preparations. Amides such as lidocaine are the anesthetics of choice in local intradermal or nerve block pain management. Traditionally, the ACD prevalence of ester anesthetics significantly outnumbered that of the amides.4,5 This owed to the easy
sensitization from frequent, often unknowing topical ester exposure. Previous literature quotes the occurrence of a Type I (or anaphylactoid) hypersensitivity to amides as rare and much less frequent than Type IV hypersensitivity.6–10 Newer literature shows that ACD to many commonly used local anesthetics is not infrequent among patients presenting for patch testing.11 Data from multiple countries highlight the variability in anesthetic ACD as being a reflection of different types of sensitizers present in OTC products in different geographic locations (Table 1).12 The addition of amide to many topical OTC preparations may be a key factor in the increasing prevalence of lidocaine ACD.13–15 These can be found in a vast array of medicaments like hemorrhoidal preparations, oral ulcer care, athlete’s foot remedies,
*Faculty of Medicine, University of British Columbia, Vancouver, Canada; †Department of Dermatology and Skin Science, University of British Columbia, Vancouver, Canada; ‡Division of Dermatology, Department of Medicine, St. Paul’s Hospital, Vancouver, Canada
·
© 2014 by the American Society for Dermatologic Surgery, Inc. Published by Lippincott Williams & Wilkins ISSN: 1076-0512 Dermatol Surg 2014;40:1367–1372 DOI: 10.1097/DSS.0000000000000190
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LOCAL ANESTHETIC CONTACT ALLERGY
corn and callus treatments, and antibiotic ointments.9,11,14,16,17 The phenomenon is concerning not only in the isolated surgical population but also in the aging population at large. The elderly tend to be more frequent users of these highly sensitizing topical anesthetic preparations18–20 and require local anesthesia on a more frequent basis, such as for skin cancer surgeries21 or for other minimally invasive in-office procedures.22 These OTC products result in unnecessary exposure and create potential sensitization to a very clinically important class of medications. Therefore, the authors aimed to assess the epidemiology of ACD to local anesthetics.
Dermatitis Group 70 allergen series, to additional anesthetic allergens when supplied by the patient (presurgical or dental assessment), and to the patient’s own products when ACD to anesthetics was clinically suspected. Patch testing and data collection were performed as per Fransway and colleagues.23 Data collected from all patients with a positive patch test reaction to a topical anesthetic were used for analysis of the ACD prevalence, for characterization of the proportion of local anesthetic types associated with ACD, for clinical presentation of ACD to topical anesthetics, and for assessment of patient demographics.
Methods
A detailed review of OTC preparations containing lidocaine was performed by examining the ingredients found in all suspect products stocked in major chain pharmacies and those listed on the Health Canada Drugs and Products website (Table 1).
A retrospective chart review was performed on 1,819 patients who had undergone patch testing for suspected ACD at the University of British Columbia (UBC) Contact Dermatitis Clinic between January 2009 and June 2013. Patients are referred to the UBC Contact Dermatitis Clinic by dermatologists, allergists, and family physicians from British Columbia for comprehensive patch testing when there is a suspicion of ACD to either a personal product or an occupational allergen. This tertiary care clinic maintains an inventory of over 500 allergens and is the only dermatology center providing access to patch testing in the province of British Columbia. Patients were patch tested to the North American Contact
Results The overall prevalence of ACD to topical anesthetics was 2.4% after reviewing the charts of 1,819 patients who were referred to the UBC Contact Dermatitis Clinic for any type of ACD. Among the patients who developed ACD to local anesthetic, the female to male ratio was 1.6:1 (3.2% male vs. 1.9% female prevalence). Benzocaine had the highest prevalence at 1.1% followed by lidocaine (0.77%) and dibucaine
TABLE 1. Multi-Country Epidemiology of ACD to Local Anesthetics Overall Incidence of ACD to Anesthetics
Country
ACD to Benzocaine
ACD to Lidocaine Proportion (%)
Denmark
N/A
0.5% (1985–2010) 1% (1986, 2004, 2010)
0.3% (1994–2001) 0.14% (2007–2009)
N/A
Finland16
4%
N/A
N/A
Dibucaine (80)
Australia25
N/A
N/A
0.3%–0.7%
Hong Kong26
N/A
1.4%
N/A
N/A
3.4% (2001–2004)
1.7%–3.5% (1984–2001)
0.7% (2001–2002)
Benzocaine (44)
24
Lidocaine (8)
The United States27–29
2% (1996–1998) Canada
2.4% (2009–2013)
N/A
N/A
Dibucaine (32) N/A
Lidocaine (23) Benzocaine (45) Lidocaine (32) Dibucaine (23)
N/A, not applicable.
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TO ET AL
(0.55%). With the prevalence known, the majority of ACD was found to be caused by benzocaine at 45.5%. Lidocaine and dibucaine each contributed to 31.8% and 22.7% of the cases of ACD, respectively. Of the patients with ACD to local anesthetics, 13.6% had a concomitant ACD to Polysporin Complete ointment (Johnson & Johnson, Guelph, Canada) that contains lidocaine (Table 2). Most frequently affected sites of ACD were the head, which accounted for 44% of the events, followed by the hands (30%), whereas the body and other extremities accounted for 26% and 12%, respectively (Table 2). Lidocaine was found to be an active ingredient in several OTC pain- or itch-relief lotions, creams, sprays, drops, and antibiotic preparations available in major Canadian pharmaceutical chain stores (Table 3).
Discussion The authors’ comprehensive data at their facility for patients who presented between 2009 and 2013 showed an overall prevalence of ACD to local and topical anesthetics at 2.4%. Although this figure is lower compared with some previous reports,4,31,32 it presents a significant problem. As expected, the face, trunk, and hands are the major sites of predilection for anesthetic ACD, consistent with previous studies.27,33,34 This is reflective of common locations of OTC sensitizer application, but also poses a concern because these same locations tend to be the sites
TABLE 2. Characteristics of ACD to Local Anesthetics in British Columbia, Canada ACD Prevalence Proportion of Local Site of (Overall 2.4%) Anesthetics Predilection (%) Causing ACD (%) (%) Benzocaine (1.1)
Benzocaine (45.5)
Head (44)*
Lidocaine (0.77)
Lidocaine (31.8)
Hands (30)
Dibucaine (0.55)
Dibucaine (22.7)
Body (26)
Carbocaine (3)
Extremities (12)
Carbocaine (0.07)
*Twenty-one percent occurred on the eyelids.
TABLE 3. Canadian OTC Products Containing Lidocaine30 Product
Company
Aloe vera gel with lidocaine Bactine liquid first aid spray
Safeway
Solarcaine first aid lotion
Generic
Band-Aid Hurt-Free antiseptic wash
Johnson & Johnson
Polysporin antibiotic and pain-relief ear drops
Johnson & Johnson
Polysporin Complete ointment
Johnson & Johnson
Antibiotic plus pain-relief cream for kids After sunburn-relief lidocaine continuous spray
Life
After sun soothing spray
KINeSYS Pharmaceutical Inc.
After burn
Tender Corp.
Bayer
Prime Enterprises, Inc.
APR15
Aleviar Pharma Corp.
Betacaine gel
Prollenium Medical Technologies, Inc.
Bikini zone
CCA Industries, Inc.
Caribbean breeze burn relief
Caribbean Breeze International, Inc.
Dr. Numb
Shinsachi Media Inc.
EMLA cream
AstraZeneca Canada Inc.
Hawaiian Tropic after sunburn relief
Energizer Canada Inc.
Soothing gel with lidocaine
Energizer Canada Inc.
Safetec Sting Relief
Safetec of America Inc.
Skin envy soothing cream
Farleyco Marketing Inc.
SmartShield Aftersun Stallion
SmartShield Sunscreens Lockerroom Marketing Ltd.
STUD 100
Pound International Ltd.
Topicaine 5
ESBA Laboratories, Inc.
TPR20
Trans Research Labs Inc.
Water-Jel Burn-Jel 2%
ZEE Medical Inc.
X3 On-the-go first aid burn-relief spray PMS-Lidocaine Viscous 2%
X3 Labs Inc. Pharmascience Inc.
Oraqix
Dentsply Canada Ltd.
Maxilene 4/5
RGR Pharma Ltd.
Lidomyxin
Sandoz Canada Inc.
Lidomax 5
Vivier Canada Inc.
Lidodan Viscous 2%/Jelly 2%
Odan Laboratories Ltd.
Lidocaine hydrochloride solution
Prime Enterprises, Inc.
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LOCAL ANESTHETIC CONTACT ALLERGY
most commonly requiring surgery under local anesthesia. Benzocaine proved to be the most common anesthetic allergen, comprising of 45.5% of the positive patch tests, as expected because of its ubiquitous presence in many OTC topical analgesic medicaments, and in keeping with previous reports of its highly antigenic metabolite, para-aminobenzoic acid (PABA).4,28,35 Warshaw and colleagues31 and Beck and Holden36 demonstrate similar results of benzocaine being the most common contact allergen, outnumbering the prevalence of dibucaine. In contrast, Sidhu and colleagues12 and Wilkinson and colleagues37 report British data that show the opposite prevalence with dibucaine being a more frequent ACD offender than benzocaine. The difference likely lies in the geographic variation of what anesthetic additive is more commonly found in OTC products of a given location. Hence, it is not surprising that a larger number of OTCs contain dibucaine in the United Kingdom, where these 2 studies were conducted.12 The most significant finding is the 0.77% prevalence of lidocaine ACD that this study reveals. Lidocaine comprised of a greater proportion of the reactions than anticipated, and this was greater than that of dibucaine (31.8% vs. 22.7%). This may be related to an increase in the OTC products containing lidocaine. Because there is no literature that can accurately quantify this increase, the authors have put together a list of common Canadian OTC products containing lidocaine (Table 3) that can be compared with the US data from more than 10 years ago.11 Lidocaine allergy is reflected in patients presenting to the UBC Contact Dermatitis Clinic for patch testing as a result of strong ACD reactions after minor procedures under local anesthesia or skin injury (Figures 1 and 2). These patients subsequently demonstrate positive patch test results to lidocaine (Figure 3). Furthermore, the problem is often exacerbated by the lidocaine-containing analgesic portion of postoperative antibiotic ointments. The authors observed a clinically significant 13.6% portion of patients who are allergic to Polysporin Complete ointment. Of those with an ACD to Polysporin Complete, none had
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Figure 1. Delayed hypersensitivity reaction to lidocaine 4 days after a dental procedure.
a concomitant ACD to bacitracin or benzocaine. This finding provides strong support for avoidance of postoperative topical antibiotic ointments to minimize the risk of ACD to the various components in these ointments, some of which may include lidocaine. Patients who are patch test–positive to lidocaine will require further testing, because the possibility of cross-reactivity may also be an issue. Both mepivacaine and prilocaine have been shown to cosensitize to lidocaine.38–42 In this study, 2 patients developed ACD to both benzocaine and lidocaine. However, clear data to support or refute such cross-reactivity are lacking in the literature.11,43,44 Patients who are patch test–positive to local anesthetics should be challenged with an intradermal injection of 0.1-mL preservative-free 1% lidocaine with the rubber stopper removed. Not aspirating through the rubber stopper avoids false positive results in patients with sensitivities to rubber compounds.33,45 Solutions must be preservative-free because methylparaben is
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TO ET AL
Preoperatively, all patients should be questioned to discern any known allergies including local anesthetics. If the history is suggestive of an ACD to local anesthetics, ideally the patient should be referred for patch testing and intradermal challenge. However, if the patient immediately undergoes presurgery and their history is suggestive of ACD to lidocaine, the surgeon can safely proceed with the procedure using a different local anesthetic. If the choice is to use lidocaine, the patient can be pretreated with systemic corticosteroids or instructed to use topical corticosteroids if dermatitis develops. Anaphylaxis is not a concern in patients with delayed Type IV hypersensitivity reactions to lidocaine. Conclusion
Figure 2. Vesicles and bullae developed 3 days after the application of Polysporin Complete ointment following a minor abrasion on the palm of the hand.
metabolized to PABA, another common potential sensitizer.46 This intradermal test will facilitate accurate assessment of true ACD to lidocaine.47 Other local anesthetics should also be tested to provide the patient with a list of safe alternatives.
Allergic contact dermatitis to topical lidocaine is on the rise. The increase can be attributed to a growing number of OTC products containing lidocaine and the aging population who frequently use these preparations. If ACD is suspected in the preoperative setting, then probing further into a patient’s previous or current use of high-risk OTC preparations is justified. Patients who are both patch test– and intradermal challenge–positive to lidocaine should be provided with a list of alternative local anesthetics that can be used. This list can be presented to their primary and specialist care providers for future reference. Thus, education of the patient regarding sensitization in these OTC products is key. References 1. Cashman MW, Reutemann PA, Ehrlich A. Contact dermatitis in the United States: epidemiology, economic impact, and workplace prevention. Dermatol Clin 2012;30:87–98, viii. 2. Gehrig KA, Warshaw EM. Allergic contact dermatitis to topical antibiotics: epidemiology, responsible allergens, and management. J Am Acad Dermatol 2008;58:1–21. 3. Davis MD. Unusual patterns in contact dermatitis: medicaments. Dermatol Clin 2009;27:289–97, vi. 4. Warshaw EM, Belsito DV, Taylor JS, Sasseville D, et al. North American contact dermatitis group patch test results: 2009 to 2010. Dermatitis 2013;24:50–9. 5. Sobanko JF, Miller CJ, Alster TS. Topical anesthetics for dermatologic procedures: a review. Dermatol Surg 2012;38:709–21. 6. Fuzier R, Lapeyre—Mestre M, Mertes PM, Nicolas JF, et al. Immediateand delayed-type allergic reactions to amide local anesthetics: clinical features and skin testing. Pharmacoepidemiol Drug Saf 2009;18:595– 601.
Figure 3. Day 3 (48-hour) positive patch test reaction (+++, bulla) to lidocaine hydrochloride 15% in petrolatum.
7. Ismail K, Simpson PJ. Anaphylactic shock following intravenous administration of lignocaine. Acta Anaesthesiol Scand 1997;41:1071–2.
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LOCAL ANESTHETIC CONTACT ALLERGY
8. Ruzicka T, Gerstmeier M, Przybilla B, Ring J. Allergy to local anesthetics: comparison of patch test with prick and intradermal test results. J Am Acad Dermatol 1987;16:1202–8. 9. Gall H, Kaufmann R, Kalveram CM. Adverse reactions to local anesthetics: analysis of 197 cases. J Allergy Clin Immunol 1996;97: 933–7. 10. Skidmore RA, Patterson JD, Tomsick RS. Local anesthetics. Dermatol Surg 1996;22:511–22; quiz 523–4. 11. Mackley CL, Marks JG Jr, Anderson BE. Delayed-type hypersensitivity to lidocaine. Arch Dermatol 2003;139:343–6. 12. Sidhu SK, Shaw S, Wilkinson JD. A 10-year retrospective study on benzocaine allergy in the United Kingdom. Am J Contact Dermat 1999; 10:57–61. 13. Jussi L, Lammintausta K. Sources of sensitization, cross-reactions, and occupational sensitization to topical anaesthetics among general dermatology patients. Contact Dermatitis 2009;60:150–4. 14. Redfern DC. Contact sensitivity to multiple local anesthetics. J Allergy Clin Immunol 1999;104(4 Pt 1):890–1. 15. Vij A, Markus R. Immediate vesicular eruption caused by topical 23% lidocaine 7% tetracaine ointment in a patient scheduled for laser therapy: a new adverse drug reaction. J Cosmet Dermatol 2011;10:307–10. 16. Yuen WY, Schuttelaar ML, Barkema LW, Coenraads PJ. Bullous allergic contact dermatitis to lidocaine. Contact Dermatitis 2009;61: 300–1. 17. Redfern S. Older people and therapeutic care. J Clin Nurs 1999;8:327–8. 18. Hanlon JT, Fillenbaum GG, Ruby CM, Gray S, et al. Epidemiology of over-the-counter drug use in community dwelling elderly: United States perspective. Drugs Aging 2001;18:123–31. 19. Roumie CL, Griffin MR. Over-the-counter analgesics in older adults: a call for improved labelling and consumer education. Drugs Aging 2004;21:485–98. 20. Green CM, Holden CR, Gawkrodger DJ. Contact allergy to topical medicaments becomes more common with advancing age: an agestratified study. Contact Dermatitis 2007;56:229–31. 21. Firoz B, Davis N, Goldberg LH. Local anesthesia using buffered 0.5% lidocaine with 1:200,000 epinephrine for tumors of the digits treated with Mohs micrographic surgery. J Am Acad Dermatol 2009;61:639–43. 22. Kravitz ND. The use of compound topical anesthetics: a review. J Am Dent Assoc 2007;138:1333–9; quiz 1382. 23. Fransway AF, Zug KA, Belsito DV, Deleo VA, et al. North American contact dermatitis group patch test results for 2007–2008. Dermatitis 2013;24:10–21. 24. Thyssen JP, Engkilde K, Menne T, Johansen JD. Prevalence of benzocaine and lidocaine patch test sensitivity in Denmark: temporal trends and relevance. Contact Dermatitis 2011;65:76–80. 25. Weightman W, Turner T. Allergic contact dermatitis from lignocaine: report of 29 cases and review of the literature. Contact Dermatitis 1998; 39:265–6. 26. Lam WS, Chan LY, Ho SC, Chong LY, et al. A retrospective study of 2585 patients patch tested with the European standard series in Hong Kong (1995–99). Int J Dermatol 2008;47:128–33. 27. Marks JG Jr, Belsito DV, DeLeo VA, Fowler JF Jr, et al. North American contact dermatitis group patch-test results, 1996–1998. Arch Dermatol 2000;136:272–3. 28. Carazo JL, Morera BS, Colom LP, Galvez Lozano JM. Allergic contact dermatitis from ethyl chloride and benzocaine. Dermatitis 2009;20: E13–5.
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29. Wentworth AB, Yiannias JA, Keeling JH, Hall MR, et al. Trends in patch-test results and allergen changes in the standard series: a Mayo Clinic 5-year retrospective review (January 1, 2006, to December 31, 2010). J Am Acad Dermatol 2014;70:269.e4–75.e4. 30. Drug Product Database, 2013. Health Canada Web site. Available from: http://www.hc-sc.gc.ca/. Accessed April 1, 2014. 31. Warshaw EM, Schram SE, Belsito DV, DeLeo VA, et al. Patch-test reactions to topical anesthetics: retrospective analysis of cross-sectional data, 2001 to 2004. Dermatitis 2008;19:81–5. 32. Spring S, Pratt M, Chaplin A. Contact dermatitis to topical medicaments: a retrospective chart review from the Ottawa Hospital Patch Test Clinic. Dermatitis 2012;23:210–3. 33. Zug KA, Warshaw EM, Fowler JF Jr, Maibach HI, et al. Patch-test results of the North American contact dermatitis group 2005–2006. Dermatitis 2009;20:149–60. 34. Marks JG Jr, Belsito DV, DeLeo VA, Fowler JG Jr, et al. North American contact dermatitis group patch-test results, 1998 to 2000. Am J Contact Dermat 2003;14:59–62. 35. Koay J, Orengo I. Application of local anesthetics in dermatologic surgery. Dermatol Surg 2002;28:143–8. 36. Beck MH, Holden A. Benzocaine—an unsatisfactory indicator of topical local anaesthetic sensitization for the UK. Br J Dermatol 1988; 118:91–4. 37. Wilkinson JD, Andersen KE, Lahti A, Rycroft RJ, et al. Preliminary patch testing with 25% and 15% “caine”-mixes. The EECDRG. Contact Dermatitis 1990;22:244–5. 38. Suhonen R, Kanerva L. Contact allergy and cross-reactions caused by prilocaine. Am J Contact Dermat 1997;8:231–5. 39. Hardwick N, King CM. Contact allergy to lignocaine with crossreaction to bupivacaine. Contact Dermatitis 1994;30:245–6. 40. Garcia F, Iparraguirre A, Blanco J, Alloza P, et al. Contact dermatitis from prilocaine with cross-sensitivity to pramocaine and bupivacaine. Contact Dermatitis 2007;56:120–1. 41. Sanchez-Morillas L, Martinez JJ, Martos MR, Gomez-Tembleque P, et al. Delayed-type hypersensitivity to mepivacaine with cross-reaction to lidocaine. Contact Dermatitis 2005;53:352–3. 42. Curley RK, Macfarlane AW, King CM. Contact sensitivity to the amide anesthetics lidocaine, prilocaine, and mepivacaine. Case report and review of the literature. Arch Dermatol 1986;122:924–6. 43. Ramirez P, Sendagorta E, Floristan U, Feltes RA, et al. Allergic contact dermatitis from antihemorrhoidal ointments: concomitant sensitization to both amide and ester local anesthetics. Dermatitis 2010;21:176–7. 44. Gunson TH, Greig DE. Allergic contact dermatitis to all three classes of local anaesthetic. Contact Dermatitis 2008;59:126–7. 45. Bernardini R, Catania P, Caffarelli C, Cardinale F, et al. Perioperative latex allergy. Int J Immunopathol Pharmacol 2011;24(Suppl 3):S55–60. 46. Thyssen JP, Linneberg A, Menne T, Johansen JD. The epidemiology of contact allergy in the general population – prevalence and main findings. Contact Dermatitis 2007;57:287–99. 47. Amado A, Sood A, Taylor JS. Contact allergy to lidocaine: a report of sixteen cases. Dermatitis 2007;18:215–20.
Address correspondence and reprint requests to: Derek To, c/o Gillian de Gannes, Department of Dermatology and Skin Science, The Skin Care Center, 835 West 10th Avenue, Vancouver, BC V5Z 4E8, Canada, or e-mail: [email protected]
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Copyright © American Society for Dermatologic Surgery. Unauthorized reproduction of this article is prohibited.
BACKGROUND Allergic contact dermatitis (ACD) to lidocaine is rising in prevalence. This is due to a growing number of over-the-counter (OTC) products containing topical amide and ester anesthetics. The phenomenon poses a real threat to the authors’ surgical anesthetic options. OBJECTIVE To investigate the epidemiology of topical anesthetic ACD in British Columbia, Canada and provide an approach for clinicians to deal with this problem. MATERIALS AND METHODS A retrospective chart review of 1,819 patients who underwent patch testing at the University of British Columbia Contact Dermatitis Clinic between January 2009 and June 2013 was completed. The authors also performed a detailed review of Canadian OTC preparations containing lidocaine in 2013. RESULTS The prevalence of ACD to local anesthetics is significant at 2.4%. The most common allergen is benzocaine (45%) followed by lidocaine (32%) and dibucaine (23%). CONCLUSION The proportion of ACD caused by lidocaine is higher than expected. This is likely secondary to an increase in OTC medicaments containing lidocaine. Patients who are patch test–positive to a local anesthetic should be challenged intradermally to confirm clinical relevance. Because ACD is a delayed Type IV hypersensitivity reaction (localized dermatitis), the risk of anaphylaxis is not a concern. The authors have indicated no significant interest with commercial supporters.
A
llergic contact dermatitis (ACD) is a Type IV or delayed type hypersensitivity reaction that develops at the site of contact with an allergen.1 This presents as pruritic erythematous papules and vesicles that coalesce into edematous plaques and bullae.2 The lesions begin at the primary site of contact but may manifest at multiple distant sites (autoeczematization) with chronic exposure to an allergen.3 Anesthetics are divided into 2 classes: ester and amide compounds. Esters such as benzocaine tend to be used in topical over-the-counter (OTC) or in-office preparations. Amides such as lidocaine are the anesthetics of choice in local intradermal or nerve block pain management. Traditionally, the ACD prevalence of ester anesthetics significantly outnumbered that of the amides.4,5 This owed to the easy
sensitization from frequent, often unknowing topical ester exposure. Previous literature quotes the occurrence of a Type I (or anaphylactoid) hypersensitivity to amides as rare and much less frequent than Type IV hypersensitivity.6–10 Newer literature shows that ACD to many commonly used local anesthetics is not infrequent among patients presenting for patch testing.11 Data from multiple countries highlight the variability in anesthetic ACD as being a reflection of different types of sensitizers present in OTC products in different geographic locations (Table 1).12 The addition of amide to many topical OTC preparations may be a key factor in the increasing prevalence of lidocaine ACD.13–15 These can be found in a vast array of medicaments like hemorrhoidal preparations, oral ulcer care, athlete’s foot remedies,
*Faculty of Medicine, University of British Columbia, Vancouver, Canada; †Department of Dermatology and Skin Science, University of British Columbia, Vancouver, Canada; ‡Division of Dermatology, Department of Medicine, St. Paul’s Hospital, Vancouver, Canada
·
© 2014 by the American Society for Dermatologic Surgery, Inc. Published by Lippincott Williams & Wilkins ISSN: 1076-0512 Dermatol Surg 2014;40:1367–1372 DOI: 10.1097/DSS.0000000000000190
·
·
· 1367
Copyright © American Society for Dermatologic Surgery. Unauthorized reproduction of this article is prohibited.
LOCAL ANESTHETIC CONTACT ALLERGY
corn and callus treatments, and antibiotic ointments.9,11,14,16,17 The phenomenon is concerning not only in the isolated surgical population but also in the aging population at large. The elderly tend to be more frequent users of these highly sensitizing topical anesthetic preparations18–20 and require local anesthesia on a more frequent basis, such as for skin cancer surgeries21 or for other minimally invasive in-office procedures.22 These OTC products result in unnecessary exposure and create potential sensitization to a very clinically important class of medications. Therefore, the authors aimed to assess the epidemiology of ACD to local anesthetics.
Dermatitis Group 70 allergen series, to additional anesthetic allergens when supplied by the patient (presurgical or dental assessment), and to the patient’s own products when ACD to anesthetics was clinically suspected. Patch testing and data collection were performed as per Fransway and colleagues.23 Data collected from all patients with a positive patch test reaction to a topical anesthetic were used for analysis of the ACD prevalence, for characterization of the proportion of local anesthetic types associated with ACD, for clinical presentation of ACD to topical anesthetics, and for assessment of patient demographics.
Methods
A detailed review of OTC preparations containing lidocaine was performed by examining the ingredients found in all suspect products stocked in major chain pharmacies and those listed on the Health Canada Drugs and Products website (Table 1).
A retrospective chart review was performed on 1,819 patients who had undergone patch testing for suspected ACD at the University of British Columbia (UBC) Contact Dermatitis Clinic between January 2009 and June 2013. Patients are referred to the UBC Contact Dermatitis Clinic by dermatologists, allergists, and family physicians from British Columbia for comprehensive patch testing when there is a suspicion of ACD to either a personal product or an occupational allergen. This tertiary care clinic maintains an inventory of over 500 allergens and is the only dermatology center providing access to patch testing in the province of British Columbia. Patients were patch tested to the North American Contact
Results The overall prevalence of ACD to topical anesthetics was 2.4% after reviewing the charts of 1,819 patients who were referred to the UBC Contact Dermatitis Clinic for any type of ACD. Among the patients who developed ACD to local anesthetic, the female to male ratio was 1.6:1 (3.2% male vs. 1.9% female prevalence). Benzocaine had the highest prevalence at 1.1% followed by lidocaine (0.77%) and dibucaine
TABLE 1. Multi-Country Epidemiology of ACD to Local Anesthetics Overall Incidence of ACD to Anesthetics
Country
ACD to Benzocaine
ACD to Lidocaine Proportion (%)
Denmark
N/A
0.5% (1985–2010) 1% (1986, 2004, 2010)
0.3% (1994–2001) 0.14% (2007–2009)
N/A
Finland16
4%
N/A
N/A
Dibucaine (80)
Australia25
N/A
N/A
0.3%–0.7%
Hong Kong26
N/A
1.4%
N/A
N/A
3.4% (2001–2004)
1.7%–3.5% (1984–2001)
0.7% (2001–2002)
Benzocaine (44)
24
Lidocaine (8)
The United States27–29
2% (1996–1998) Canada
2.4% (2009–2013)
N/A
N/A
Dibucaine (32) N/A
Lidocaine (23) Benzocaine (45) Lidocaine (32) Dibucaine (23)
N/A, not applicable.
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TO ET AL
(0.55%). With the prevalence known, the majority of ACD was found to be caused by benzocaine at 45.5%. Lidocaine and dibucaine each contributed to 31.8% and 22.7% of the cases of ACD, respectively. Of the patients with ACD to local anesthetics, 13.6% had a concomitant ACD to Polysporin Complete ointment (Johnson & Johnson, Guelph, Canada) that contains lidocaine (Table 2). Most frequently affected sites of ACD were the head, which accounted for 44% of the events, followed by the hands (30%), whereas the body and other extremities accounted for 26% and 12%, respectively (Table 2). Lidocaine was found to be an active ingredient in several OTC pain- or itch-relief lotions, creams, sprays, drops, and antibiotic preparations available in major Canadian pharmaceutical chain stores (Table 3).
Discussion The authors’ comprehensive data at their facility for patients who presented between 2009 and 2013 showed an overall prevalence of ACD to local and topical anesthetics at 2.4%. Although this figure is lower compared with some previous reports,4,31,32 it presents a significant problem. As expected, the face, trunk, and hands are the major sites of predilection for anesthetic ACD, consistent with previous studies.27,33,34 This is reflective of common locations of OTC sensitizer application, but also poses a concern because these same locations tend to be the sites
TABLE 2. Characteristics of ACD to Local Anesthetics in British Columbia, Canada ACD Prevalence Proportion of Local Site of (Overall 2.4%) Anesthetics Predilection (%) Causing ACD (%) (%) Benzocaine (1.1)
Benzocaine (45.5)
Head (44)*
Lidocaine (0.77)
Lidocaine (31.8)
Hands (30)
Dibucaine (0.55)
Dibucaine (22.7)
Body (26)
Carbocaine (3)
Extremities (12)
Carbocaine (0.07)
*Twenty-one percent occurred on the eyelids.
TABLE 3. Canadian OTC Products Containing Lidocaine30 Product
Company
Aloe vera gel with lidocaine Bactine liquid first aid spray
Safeway
Solarcaine first aid lotion
Generic
Band-Aid Hurt-Free antiseptic wash
Johnson & Johnson
Polysporin antibiotic and pain-relief ear drops
Johnson & Johnson
Polysporin Complete ointment
Johnson & Johnson
Antibiotic plus pain-relief cream for kids After sunburn-relief lidocaine continuous spray
Life
After sun soothing spray
KINeSYS Pharmaceutical Inc.
After burn
Tender Corp.
Bayer
Prime Enterprises, Inc.
APR15
Aleviar Pharma Corp.
Betacaine gel
Prollenium Medical Technologies, Inc.
Bikini zone
CCA Industries, Inc.
Caribbean breeze burn relief
Caribbean Breeze International, Inc.
Dr. Numb
Shinsachi Media Inc.
EMLA cream
AstraZeneca Canada Inc.
Hawaiian Tropic after sunburn relief
Energizer Canada Inc.
Soothing gel with lidocaine
Energizer Canada Inc.
Safetec Sting Relief
Safetec of America Inc.
Skin envy soothing cream
Farleyco Marketing Inc.
SmartShield Aftersun Stallion
SmartShield Sunscreens Lockerroom Marketing Ltd.
STUD 100
Pound International Ltd.
Topicaine 5
ESBA Laboratories, Inc.
TPR20
Trans Research Labs Inc.
Water-Jel Burn-Jel 2%
ZEE Medical Inc.
X3 On-the-go first aid burn-relief spray PMS-Lidocaine Viscous 2%
X3 Labs Inc. Pharmascience Inc.
Oraqix
Dentsply Canada Ltd.
Maxilene 4/5
RGR Pharma Ltd.
Lidomyxin
Sandoz Canada Inc.
Lidomax 5
Vivier Canada Inc.
Lidodan Viscous 2%/Jelly 2%
Odan Laboratories Ltd.
Lidocaine hydrochloride solution
Prime Enterprises, Inc.
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LOCAL ANESTHETIC CONTACT ALLERGY
most commonly requiring surgery under local anesthesia. Benzocaine proved to be the most common anesthetic allergen, comprising of 45.5% of the positive patch tests, as expected because of its ubiquitous presence in many OTC topical analgesic medicaments, and in keeping with previous reports of its highly antigenic metabolite, para-aminobenzoic acid (PABA).4,28,35 Warshaw and colleagues31 and Beck and Holden36 demonstrate similar results of benzocaine being the most common contact allergen, outnumbering the prevalence of dibucaine. In contrast, Sidhu and colleagues12 and Wilkinson and colleagues37 report British data that show the opposite prevalence with dibucaine being a more frequent ACD offender than benzocaine. The difference likely lies in the geographic variation of what anesthetic additive is more commonly found in OTC products of a given location. Hence, it is not surprising that a larger number of OTCs contain dibucaine in the United Kingdom, where these 2 studies were conducted.12 The most significant finding is the 0.77% prevalence of lidocaine ACD that this study reveals. Lidocaine comprised of a greater proportion of the reactions than anticipated, and this was greater than that of dibucaine (31.8% vs. 22.7%). This may be related to an increase in the OTC products containing lidocaine. Because there is no literature that can accurately quantify this increase, the authors have put together a list of common Canadian OTC products containing lidocaine (Table 3) that can be compared with the US data from more than 10 years ago.11 Lidocaine allergy is reflected in patients presenting to the UBC Contact Dermatitis Clinic for patch testing as a result of strong ACD reactions after minor procedures under local anesthesia or skin injury (Figures 1 and 2). These patients subsequently demonstrate positive patch test results to lidocaine (Figure 3). Furthermore, the problem is often exacerbated by the lidocaine-containing analgesic portion of postoperative antibiotic ointments. The authors observed a clinically significant 13.6% portion of patients who are allergic to Polysporin Complete ointment. Of those with an ACD to Polysporin Complete, none had
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Figure 1. Delayed hypersensitivity reaction to lidocaine 4 days after a dental procedure.
a concomitant ACD to bacitracin or benzocaine. This finding provides strong support for avoidance of postoperative topical antibiotic ointments to minimize the risk of ACD to the various components in these ointments, some of which may include lidocaine. Patients who are patch test–positive to lidocaine will require further testing, because the possibility of cross-reactivity may also be an issue. Both mepivacaine and prilocaine have been shown to cosensitize to lidocaine.38–42 In this study, 2 patients developed ACD to both benzocaine and lidocaine. However, clear data to support or refute such cross-reactivity are lacking in the literature.11,43,44 Patients who are patch test–positive to local anesthetics should be challenged with an intradermal injection of 0.1-mL preservative-free 1% lidocaine with the rubber stopper removed. Not aspirating through the rubber stopper avoids false positive results in patients with sensitivities to rubber compounds.33,45 Solutions must be preservative-free because methylparaben is
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TO ET AL
Preoperatively, all patients should be questioned to discern any known allergies including local anesthetics. If the history is suggestive of an ACD to local anesthetics, ideally the patient should be referred for patch testing and intradermal challenge. However, if the patient immediately undergoes presurgery and their history is suggestive of ACD to lidocaine, the surgeon can safely proceed with the procedure using a different local anesthetic. If the choice is to use lidocaine, the patient can be pretreated with systemic corticosteroids or instructed to use topical corticosteroids if dermatitis develops. Anaphylaxis is not a concern in patients with delayed Type IV hypersensitivity reactions to lidocaine. Conclusion
Figure 2. Vesicles and bullae developed 3 days after the application of Polysporin Complete ointment following a minor abrasion on the palm of the hand.
metabolized to PABA, another common potential sensitizer.46 This intradermal test will facilitate accurate assessment of true ACD to lidocaine.47 Other local anesthetics should also be tested to provide the patient with a list of safe alternatives.
Allergic contact dermatitis to topical lidocaine is on the rise. The increase can be attributed to a growing number of OTC products containing lidocaine and the aging population who frequently use these preparations. If ACD is suspected in the preoperative setting, then probing further into a patient’s previous or current use of high-risk OTC preparations is justified. Patients who are both patch test– and intradermal challenge–positive to lidocaine should be provided with a list of alternative local anesthetics that can be used. This list can be presented to their primary and specialist care providers for future reference. Thus, education of the patient regarding sensitization in these OTC products is key. References 1. Cashman MW, Reutemann PA, Ehrlich A. Contact dermatitis in the United States: epidemiology, economic impact, and workplace prevention. Dermatol Clin 2012;30:87–98, viii. 2. Gehrig KA, Warshaw EM. Allergic contact dermatitis to topical antibiotics: epidemiology, responsible allergens, and management. J Am Acad Dermatol 2008;58:1–21. 3. Davis MD. Unusual patterns in contact dermatitis: medicaments. Dermatol Clin 2009;27:289–97, vi. 4. Warshaw EM, Belsito DV, Taylor JS, Sasseville D, et al. North American contact dermatitis group patch test results: 2009 to 2010. Dermatitis 2013;24:50–9. 5. Sobanko JF, Miller CJ, Alster TS. Topical anesthetics for dermatologic procedures: a review. Dermatol Surg 2012;38:709–21. 6. Fuzier R, Lapeyre—Mestre M, Mertes PM, Nicolas JF, et al. Immediateand delayed-type allergic reactions to amide local anesthetics: clinical features and skin testing. Pharmacoepidemiol Drug Saf 2009;18:595– 601.
Figure 3. Day 3 (48-hour) positive patch test reaction (+++, bulla) to lidocaine hydrochloride 15% in petrolatum.
7. Ismail K, Simpson PJ. Anaphylactic shock following intravenous administration of lignocaine. Acta Anaesthesiol Scand 1997;41:1071–2.
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8. Ruzicka T, Gerstmeier M, Przybilla B, Ring J. Allergy to local anesthetics: comparison of patch test with prick and intradermal test results. J Am Acad Dermatol 1987;16:1202–8. 9. Gall H, Kaufmann R, Kalveram CM. Adverse reactions to local anesthetics: analysis of 197 cases. J Allergy Clin Immunol 1996;97: 933–7. 10. Skidmore RA, Patterson JD, Tomsick RS. Local anesthetics. Dermatol Surg 1996;22:511–22; quiz 523–4. 11. Mackley CL, Marks JG Jr, Anderson BE. Delayed-type hypersensitivity to lidocaine. Arch Dermatol 2003;139:343–6. 12. Sidhu SK, Shaw S, Wilkinson JD. A 10-year retrospective study on benzocaine allergy in the United Kingdom. Am J Contact Dermat 1999; 10:57–61. 13. Jussi L, Lammintausta K. Sources of sensitization, cross-reactions, and occupational sensitization to topical anaesthetics among general dermatology patients. Contact Dermatitis 2009;60:150–4. 14. Redfern DC. Contact sensitivity to multiple local anesthetics. J Allergy Clin Immunol 1999;104(4 Pt 1):890–1. 15. Vij A, Markus R. Immediate vesicular eruption caused by topical 23% lidocaine 7% tetracaine ointment in a patient scheduled for laser therapy: a new adverse drug reaction. J Cosmet Dermatol 2011;10:307–10. 16. Yuen WY, Schuttelaar ML, Barkema LW, Coenraads PJ. Bullous allergic contact dermatitis to lidocaine. Contact Dermatitis 2009;61: 300–1. 17. Redfern S. Older people and therapeutic care. J Clin Nurs 1999;8:327–8. 18. Hanlon JT, Fillenbaum GG, Ruby CM, Gray S, et al. Epidemiology of over-the-counter drug use in community dwelling elderly: United States perspective. Drugs Aging 2001;18:123–31. 19. Roumie CL, Griffin MR. Over-the-counter analgesics in older adults: a call for improved labelling and consumer education. Drugs Aging 2004;21:485–98. 20. Green CM, Holden CR, Gawkrodger DJ. Contact allergy to topical medicaments becomes more common with advancing age: an agestratified study. Contact Dermatitis 2007;56:229–31. 21. Firoz B, Davis N, Goldberg LH. Local anesthesia using buffered 0.5% lidocaine with 1:200,000 epinephrine for tumors of the digits treated with Mohs micrographic surgery. J Am Acad Dermatol 2009;61:639–43. 22. Kravitz ND. The use of compound topical anesthetics: a review. J Am Dent Assoc 2007;138:1333–9; quiz 1382. 23. Fransway AF, Zug KA, Belsito DV, Deleo VA, et al. North American contact dermatitis group patch test results for 2007–2008. Dermatitis 2013;24:10–21. 24. Thyssen JP, Engkilde K, Menne T, Johansen JD. Prevalence of benzocaine and lidocaine patch test sensitivity in Denmark: temporal trends and relevance. Contact Dermatitis 2011;65:76–80. 25. Weightman W, Turner T. Allergic contact dermatitis from lignocaine: report of 29 cases and review of the literature. Contact Dermatitis 1998; 39:265–6. 26. Lam WS, Chan LY, Ho SC, Chong LY, et al. A retrospective study of 2585 patients patch tested with the European standard series in Hong Kong (1995–99). Int J Dermatol 2008;47:128–33. 27. Marks JG Jr, Belsito DV, DeLeo VA, Fowler JF Jr, et al. North American contact dermatitis group patch-test results, 1996–1998. Arch Dermatol 2000;136:272–3. 28. Carazo JL, Morera BS, Colom LP, Galvez Lozano JM. Allergic contact dermatitis from ethyl chloride and benzocaine. Dermatitis 2009;20: E13–5.
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29. Wentworth AB, Yiannias JA, Keeling JH, Hall MR, et al. Trends in patch-test results and allergen changes in the standard series: a Mayo Clinic 5-year retrospective review (January 1, 2006, to December 31, 2010). J Am Acad Dermatol 2014;70:269.e4–75.e4. 30. Drug Product Database, 2013. Health Canada Web site. Available from: http://www.hc-sc.gc.ca/. Accessed April 1, 2014. 31. Warshaw EM, Schram SE, Belsito DV, DeLeo VA, et al. Patch-test reactions to topical anesthetics: retrospective analysis of cross-sectional data, 2001 to 2004. Dermatitis 2008;19:81–5. 32. Spring S, Pratt M, Chaplin A. Contact dermatitis to topical medicaments: a retrospective chart review from the Ottawa Hospital Patch Test Clinic. Dermatitis 2012;23:210–3. 33. Zug KA, Warshaw EM, Fowler JF Jr, Maibach HI, et al. Patch-test results of the North American contact dermatitis group 2005–2006. Dermatitis 2009;20:149–60. 34. Marks JG Jr, Belsito DV, DeLeo VA, Fowler JG Jr, et al. North American contact dermatitis group patch-test results, 1998 to 2000. Am J Contact Dermat 2003;14:59–62. 35. Koay J, Orengo I. Application of local anesthetics in dermatologic surgery. Dermatol Surg 2002;28:143–8. 36. Beck MH, Holden A. Benzocaine—an unsatisfactory indicator of topical local anaesthetic sensitization for the UK. Br J Dermatol 1988; 118:91–4. 37. Wilkinson JD, Andersen KE, Lahti A, Rycroft RJ, et al. Preliminary patch testing with 25% and 15% “caine”-mixes. The EECDRG. Contact Dermatitis 1990;22:244–5. 38. Suhonen R, Kanerva L. Contact allergy and cross-reactions caused by prilocaine. Am J Contact Dermat 1997;8:231–5. 39. Hardwick N, King CM. Contact allergy to lignocaine with crossreaction to bupivacaine. Contact Dermatitis 1994;30:245–6. 40. Garcia F, Iparraguirre A, Blanco J, Alloza P, et al. Contact dermatitis from prilocaine with cross-sensitivity to pramocaine and bupivacaine. Contact Dermatitis 2007;56:120–1. 41. Sanchez-Morillas L, Martinez JJ, Martos MR, Gomez-Tembleque P, et al. Delayed-type hypersensitivity to mepivacaine with cross-reaction to lidocaine. Contact Dermatitis 2005;53:352–3. 42. Curley RK, Macfarlane AW, King CM. Contact sensitivity to the amide anesthetics lidocaine, prilocaine, and mepivacaine. Case report and review of the literature. Arch Dermatol 1986;122:924–6. 43. Ramirez P, Sendagorta E, Floristan U, Feltes RA, et al. Allergic contact dermatitis from antihemorrhoidal ointments: concomitant sensitization to both amide and ester local anesthetics. Dermatitis 2010;21:176–7. 44. Gunson TH, Greig DE. Allergic contact dermatitis to all three classes of local anaesthetic. Contact Dermatitis 2008;59:126–7. 45. Bernardini R, Catania P, Caffarelli C, Cardinale F, et al. Perioperative latex allergy. Int J Immunopathol Pharmacol 2011;24(Suppl 3):S55–60. 46. Thyssen JP, Linneberg A, Menne T, Johansen JD. The epidemiology of contact allergy in the general population – prevalence and main findings. Contact Dermatitis 2007;57:287–99. 47. Amado A, Sood A, Taylor JS. Contact allergy to lidocaine: a report of sixteen cases. Dermatitis 2007;18:215–20.
Address correspondence and reprint requests to: Derek To, c/o Gillian de Gannes, Department of Dermatology and Skin Science, The Skin Care Center, 835 West 10th Avenue, Vancouver, BC V5Z 4E8, Canada, or e-mail: [email protected]
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