Allergic urticaria: a case report of rare skin allergy with a common mouthwash.

Chlorhexidine is a widely used antiseptic and disinfectant in medical and non-medical environments. Compared to its ubiquitous use, allergic contact dermatitis from chlorhexidine has rarely been reported and so its sensitization rate seems to be low. Chlorhexidine has been used for more than 50 years but it was only in the last two decades, that reports of immediate- type reactions to chlorhexidine were seen. Reactions ranging from localized urticaria to anaphylactic shock and hypersensitivity reactions, including delayed hypersensitivity reactions such as contact dermatitis, fixed drug eruptions, and photosensitivity reactions, began to appear more frequently. However the prevalence of contact urticaria and anaphylaxis due to chlorhexidine remains to be unknown. In this case report we have reported a case of urticaria due to oral use of chlorhexidine. The adverse reaction was confirmed by a skin prick test.

What was known?

Chlorhexidine mouthwash is one of the safest mouthwashes and allergy to it is rarely reported. The component of the mouthwash responsible for the allergy is still unknown and the research for the same is still going on.

Introduction

Chlorhexidine gluconate is a cationic bis-biguanide, with a very broad anti-microbial spectrum. Chlorhexidine's antimicrobial effects are associated with the attractions between chlorhexidine (cation) and negatively charged bacterial cells. After chlorhexidine is absorbed onto the organism's cell wall, it disrupts the integrity of the cell membrane and causes the leakage of intracellular components of the organisms. The first report of its anti anti-plaque activity was provided by Loe and Schiott.[1]

The major advantage of chlorhexidine over most of the other compounds lies in its substantivity. It binds to hard and soft tissues in the mouth enabling it to act over a long period after use. Bacterial counts in saliva consistently drop to between 10 to and 20% of baseline after single rinses and remain at this level for at least 7 hours[2] and probably more than 12 hours.[3]

Chlorhexidine is known to occasionally cause brown staining of the teeth especially when used on long- term basis. These stains can be removed by oral prophylaxis.

Other minor subjective reactions include, an objectionable taste with altered taste sensations, feeling of soreness, and dryness in the mouth. Chlorhexidine mouthwashes can also effect the oral mucosa. In a study reported by Flotra et al.,[4] a few cases of desquamation of the mucosa were also reported.

Immediate hypersensitivity reactions to chlorhexidine (urticaria or anaphylaxis), though rare, have been documented previously.

This paper presents a case report of urticaria due to oral rinsing (topical application) of chlorhexidine gluconate mouthwash. (Rexidine mouthwash).

Case Report

A 19- year- old female patient with the major complaint of bleeding from the gums reported to the Department of Periodontics at Subharti Dental College, Meerut. After her thorough oral examination she was advised oral prophylaxis and was prescribed chlorhexidine mouthrinse (by the trade name: Rexidine), twice daily for a period of 3 weeks.

Next day the patient presented with urticaria on her forehead and face, the front of the elbow and forearms, side and upper back region of the neck, and on the lower abdomen. No oral changes were observed.

On questioning, the patient reported using chlorhexidine mouthwash (Rexidin). She used the formulation in a 1:1 concentration and rinsed with it for at least 1 minute. The patient had never used any chlorhexidine formulation before. On rinsing with it for the first time she noticed reddening on her forehead, face, and side of the neck (after about 12 hours of using it) [Figures 1 and 2]. On waking up the next morning she felt some burning sensation on the red spots, which she had noticed the previous night. Upon using the formulation again on waking up the next day, after a couple of hours she observed marked redness on her upper back [Figure 3] neck region, lower abdomen, and on the front of the elbow and forearms [Figure 4]. This was accompanied with irritation.

Figure 1

Redness on forehead and face after first time use of chlorhexidine formulation

Figure 2

Redness on the side of the neck after the use of chlorhexidine formulation

Figure 3

Marked redness on the upper back neck region as a result of chlorhexidine allergy

Figure 4

Redness on forearm and and elbow as a result of chlorhexidine allergy

A thorough case history of the patient was taken, including the history of recent drug use or allergy to food intake. History of any previous such allergic reactions were also recorded. The patient was also questioned about any accidental ingestion of the chlorhexidine formulation.

Diagnostic Test

The various tests which can be used to confirm the allergic reactions to chlorhexidine are as follows:

Prick tests.

Intradermal reactions.

Sulfidoleukotriene Stimulation test (CAST: cellular antigen stimulation test).

Patch test.

In the present case report the confirmatory test used was the skin prick test.

Skin Prick Test

The allergy was from mouthwash only. Patient was not on antihistamines as the allergy subsided with restriction of mouthwash. No control was used in this case report. The adverse reaction of chlorhexidine mouthwash was confirmed by the skin prick test.

It was performed in the following way:

The inner forearm of the patient was cleaned with soap and water.

The forearm was coded with a skin marker pen.

A drop of allergen (chlorhexidine) was then placed besides the mark.

A small prick through the drop was made to the skin using a sterile prick lancet.

The excess allergen solution was dabbed off with a tissue.

A reaction was seen within 30 minutes of performing the test. The skin under the drop of the chlorhexidine solution had become red and itchy and this was surrounded by a white raised wheal.

Discussion

The result of the skin prick test confirmed that the urticaria with which the patient reported was caused by the topical use of the chlorhexidine mouthwash in a 1:1 concentration. Thus, though rare but as reported earlier chlorhexidine can cause immediate hypersensitivity, sometimes taking the form of acute urticaria that may result in anaphylactic shock which is even rarer.[5]

In a similar study, six patients were reported who developed urticaria, dyspnea, and anaphylactic shock due to topical application of chlorhexidine. Chlorhexidine was confirmed as the causative agent of type I hypersensitivity by intradermal and scratch test.[6]

In a similar case report, Yoneyama et al.,[7] reported a case of a 25- year- old female, with pemphigus almost on her whole body except face ten minutes after using mouthwash containing chlorhexidine gluconate.

The mouthwash used in this case is Rexidine (by BRASSICA PHARMACEUTICALS and CHEMICALS) which basically comprises of chlorhexidine gluconate along with chlorhexidine hydrochloride and out of these chlorhexidine is the main constituent. Minute proportion of thymol and eucalyptol oil is also present but the percentage of their volume is not known to cause any side effect effect to the patients using it. Rexidine is a transparent solution without any colarants dyes added to it.

Urticaria was suspected to be caused by the mouthwash, and a skin test was conducted. The intradermal test was positive with the mouthwash and its component chlorhexidine gluconate. A scratch test showed positive result with chlorhexidine gluconate and chlorhexidine hydrochloride.

Similar reactions have also been reported after the use of chlorhexidine as a spray or as pre- and post- operative antiseptic solutions. Goon et al.,[8], reported five cases of allergic contact dermatitis from chlorhexidine, out of which three had positive patch test reactions to chlorhexidine.

A literature review of 66 case reports was done by Heinemann et al.[9] Twenty reactions occurred when chlorhexidine was applied to damaged skin surfaces and 27 patients showed an immediate type reaction when chlorhexidine was applied to mucous membranes. Similarly two cases of mucosal sensitivity to contact with chlorhexidine were reported by Yusof and Khoo.[10]

Kenrad,[11] also reported major changes in the oral mucosa after an overdose of mouthrinse with chlorhexidine gluconate, which included a thickening of the mucosa resembling leukoplakia but disappeared when the dose was reduced.

In a case report similar to the present one, anaphylaxis due to topical skin application of chlorhexidine was reported. This was confirmed by skin testing and CAST. Thus the application of chlorhexidine especially to mucous membranes was discouraged as it could cause anaphylaxis.[12]

Hypersensitivity and other adverse reactions to chlorhexidine are rare, but its potential to cause anaphylactic shock is probably underestimated.

Conclusion

Chlorhexidine is the most effective and widely used anti plaque agent to date.

It is hoped that with continued research and trials more would be known about the adverse effects of chlorhexidine would be known.

Nevertheless, the present case report would remind the clinicians of an important potential risk of this widely used antiseptic and make them cautious before prescribing any chlorhexidine formulation as it may lead to local symptoms or even severe attacks.

What is new?

Since very less cases have been reported of Chlorhexidine allergy and not much of literature is available against the same, it remains as a universally accepted mouthwash till date.