Case Report

Contact Angioedema of Male Genitalia after use of Emla Cream Towards Routine Neonatal Circumcision

^{1, 2}Naimer Sody A, ¹Zeldin Yuri

• ¹Department of Family Medicine, Siaal Research Center for Family Medicine and Primary Care Research, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
• ²Elon Moreh Clinic, Clalit Health Services, Shomron district, Lev Shomron, Israel

• Submitted: March 13, 2013;
• Accepted April 28, 2013
• Published: April 29, 2013

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Introduction

Routine neonatal circumcision is commonly performed under topical anesthesia with a eutectic mixture of lidocaine and prilocaine (EMLA). We report that such anesthesia runs the risk of complications that may actually impede the performance of this procedure in the event of a hypersensitivity reaction. We report to our knowledge the first case of contact angioedema in a neonate towards routine circumcision.

Case report

After 30 weeks of gestation, a first born male premature infant weighing 1,230 grams was born with esophageal atresia and duodenal obstruction. At the age of two days a gastrostomy feeding tube was inserted and he was transferred from a local to a major medical center for correction of a tracheo- esophageal fistula and a right inguinal hernia. Following thoracotomy and herniorhaphy, eventually the feeding tube was removed. He gradually improved and at 6 months old the baby was recommended to perform circumcision. Emla cream was applied with polyethylene sheet closure one hour before the procedure. At the ceremony hall, upon exposure the genitalia was revealed an open prepuce with swelling extending towards the proximal shaft precluding any possibility of inserting the guard traditionally used in guillotine circumcision. Subsequently some of the swelling subsided and patiently waiting allowed guard insertion and successful routine circumcision despite the ensuing swelling.

Conclusions

This case stresses the importance of adherence to instructions and appropriate follow up when prescribing medication even for topical use. EMLA cream should be used judiciously due to its possible risk of immediate allergic reaction.

Keywords

Prepuce excision, topical anesthesia, penile hypersensitivity, allergic reaction.

Introduction

Routine neonatal circumcision is the most commonly performed pediatric surgical procedure in the United States, encompassing the majority of male newborns. It is carried out because of a complex array of medical, sociocultural, and religious reasons [1]. With the recognition of the well developed sensory nervous system of the neonate, in attempt to confer a less traumatic experience it is obvious that any of a number of modalities is chosen in order to reduce the inconvenience of the procedure and provide pain alleviation. Reports have been published of the success of various techniques to achieve this goal, from sucrose solution consumption to general anesthesia. A eutectic mixture of lidocaine and prilocaine (EMLA) has been established as a useful agent for pain management in neonatal circumcision [2]. This report discloses that anesthetic establishment may run its risk of complications. The precautions taken to perhaps ease the procedure and enable a more manageable neonate may actually impede or even preclude the performance of this procedure owing to side effects of the anesthetic.

In general, side effects of EMLA cream in popular use are rare. Only twelve years after its first introduction to clinical use was the first case of immediate-type hypersensitivity to EMLA cream published [3]. Since, we have accumulated experience showing that this agent is not totally free of hypersensitivity reactions. We report to our knowledge the first case of contact angioedema in a neonate towards routine circumcision. Fortunately, the phenomenon did not hinder the anatomy to an extent that demanded cancellation of the event to a later date. However, the phenomenon aroused much anxiety in both the circumciser and child's family, all confronted with a surprising unrecognized condition. The baby's parents expressed their will to share this experience with other young parents and delivered their consent to this publication.

Case Report

After 30 weeks of gestation, a first born male premature infant weighing 1,230 grams was born with esophageal atresia and duodenal obstruction. At the age of two days a gastrostomy feeding tube was inserted and he was transferred from a local to a major medical center for correction of a tracheo- esophageal fistula and a right inguinal hernia. Following thoracotomy for correction of the above inborn errors and herniorhaphy, further laparoscopic evaluation revealed an annular pancreas, therefore retrocolic jejenostomy was performed. Esophageal strictures underwent dilation and eventually the feeding tube was removed with satisfactory weight gain and gradual development as expected. Since as Jewish tradition dictates that an unhealthy baby may not undergo circumcision until complete recovery from any ailment, only at this point was he firstly seen fit for the procedure. The baby was 6 months old. The parents were instructed to apply Emla cream with polyethylene sheet closure one hour before the procedure in order to provide topical anesthesia. The parents were told that a decision regarding the necessity of lidocaine infiltration will be taken according to the child's response. Upon arrival at the ceremony hall, the genitalia was exposed and revealed the surprising finding of an open prepuce, extremely swollen, extending towards the proximal shaft precluding any possibility of inserting the routine guard before performing routine guillotine circumcision (Figure 1). There were no previous allergies and no previous exposure to this agent. Subsequently some of the swelling subsided and painstaking efforts to insert the guard normally were deemed successful and allowed him to undergo the procedure as usual uneventfully.

Figure 1

Discussion

Topical eutectic mixture of lidocaine and prilocaine (EMLA: lidocaine 2.5%, prilocaine 2.5%, Astra Zeneca, Wilmington, DE) is used to provide topical anesthesia for various procedures. Immediate hypersensitivity reactions have rarely been reported with local anasthetics [4]. Delayed type hypersensitivity (type IV) reactions to local anaesthetics have been more commonly reported and benzocaine appears to be the most common culprit. It is present in many over the counter products such as suntan lotions, vaginal creams and hemorrhoid alleviation agents. Type IV reactions to EMLA have been shown to occur because of both its constituents and even contact urticaria has been described in one patient [3].

As a class, the topical anesthetic agents are divided into amide and ester groups. Lidocaine-allergic individuals can tolerate ester anesthetics. Evaluating patients with suspected allergic reactions to local anesthetics consists of epicutaneous skin prick testing and serial subcutaneous challenge. In case of suspected delayed type reactions use of patch testing and subcutaneous rechallenges of both at 24 and 48 hours with re-evaluation at 72 hours has been proposed [5].

EMLA most prominently reduces the flare reaction associated with allergic skin reaction [6]. This can explain the appearance of angioedema more likely than urticaria or erythema in our patient. A possible explanation of the mechanism may be through neuropeptide release from sensory nerves (i.e. substance P, VIP, calcitonin generated peptide or nerve growth factor) that can each activate mast cells.

Adverse effects related to the use of EMLA are mild local reactions such as edema, erythema and transient pallor. Hyperpigmentation and contact dermatitis both allergic and irritant have been reported, as well as methmoglobinemia and seizures [7]. Rare non-allergic reactions such as purpura formation may occur probably via a direct toxic effect.

Dermal analgesia is achieved within 1 hour after application and occlusion with a maximal effect at two to three hours, with influence lingering on for one to two hours from removal. In children, recommended EMLA dosing depends on age and body weight, in our case 2 grams applied over a maximal surface area of 20cm² in order to prevent overexposure.

This case stresses the importance of patient and parent instructions and appropriate follow up when prescribing medication even for topical use. Prick and patch tests could not be performed in this case because of lack of consent however; we assume that the swelling reaction was most probably of immediate type allergic origin. Other factors such as prematurity, multiple surgical procedures with possible contact with local anesthetics may play important pathogenetic roles.

A similar case has been reported as localized angioedema of the glans penis as a result of contact allergy to prilocaine in EMLA cream. In this instance the authors proposed a new term: "contact angioedema" for this condition [8] Contact urticaria is a wheal and flare reaction that appears when the cutaneous surface is exposed to certain agents. The reaction may be allergic or irritant. Despite the infrequency of the phenomenon we describe in our case, we really do not know the true incidence of such incidents, especially if the outcome is acceptably benign. In specific relation to the constellation here however, given the immense magnitude of the population performing neonatal circumcision, the impact of even mild reactions and the risk of a much rarer severe hypersensitivity event, these reactions may be perceived as of greater significance and lead us to seek a different approach. The reaction may cause long delays of the procedure, of especially greater importance when the circumcision is performed in the community according to Jewish tradition, sometimes with a large congregation anticipating its completion. The risks of the anesthetic chosen should be carefully weighed against its benefits, seeing as the whole procedure as customarily performed, can be completed in 10-15 seconds under experienced hands. This is what raises debate over the necessity of a transient anesthetic effect.

Conclusions

We suggest judicious use of EMLA cream limiting it to specific indications owing to its possible risk of immediate allergic reaction. If possible its use should be recommended under supervision on the physician's premises for the duration of its application. This is often not feasible due to the lengthened exposure needed in order to induce ample efficacy.

Learning points

In general side effects of EMLA are rare and the preparation is considered a safe agent. However, it should be accepted that allergic reactions may occur even in the event of brief and judicious application before neonatal circumcision. It is wise to take necessary precautions of minimal application under supervision in order to assure that unnecessary complications are prevented.

Conflict of interests

There are no competing interests.

Author’s Contributions

NSA Literature search and preparation of manuscript.

ZYPreparation of manuscript and editing

Ethical Consideration

Written informed consent was obtained from the legal guardian of the patient for publication of this case report

Funding

None

Acknowledgements

None

References

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