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 [Figures11 and and2].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.

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.
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Diagnostic Test
The various tests which can be used to confirm the
allergic reactions to chlorhexidine are as follows:
1. Prick tests.
2. Intradermal reactions.
3. Sulfidoleukotriene Stimulation test (CAST: cellular
antigen stimulation test).
4. Patch test.
In the present case report the confirmatory test used
was the skin prick test.
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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:
1. The inner forearm of the patient was cleaned with
soap and water.
2. The forearm was coded with a skin marker pen.

3. A drop of allergen (chlorhexidine) was then placed

besides the mark.
4. A small prick through the drop was made to the
skin using a sterile prick lancet.
5. 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.
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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 postoperative 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.
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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.
Case 1
Jack is a 26 month old male who returns to your clinic
after an ER visit for food allergy. He ate a piece of a
granola bar that was produced on a line with peanut
and tree nuts. Fifteen minutes later he developed hives
on his arms, legs, and trunk. His mother next noticed
periorbital edema and wheezing. He was taken to a
nearby ER and was treated with IM epinephrine,
diphenhydramine, steroids, and one albuterol nebulized
treatment. He was observed in the ER and then
discharged home that evening. He was sent home with
a prescription for an epinephrine auto-injector.
Jack has a history of eczema that is well controlled with
topical emollients and occasional topical steroid use.

He has no prior history of wheezing. His parents do not

report any previous exposure to peanuts. He eats eggs,
milk, soy and wheat with no symptoms of food allergy.
He has never eaten tree nuts, fish, or shellfish.
The parents are concerned about other potential signs
of food allergy. Other signs may include:
A. Atopic dermatitis
B. Chronic nasal congestion
C. Acute Urticaria
D. Both A and C

ANSWER:
There is a wide range of manifestations of food allergy.
Food allergy has been reported in up to 35% of patients
referred to an allergist or dermatologist for atopic
dermatitis. Evaluation should be considered in infants
and children with moderate to severe atopic dermatitis
or if there is a history of exacerbation when eating
specific foods. If food allergy is diagnosed, the atopic
dermatitis often improves after dietary elimination of
that particular food. The causes of acute urticaria vary
and include infection, drug reaction, and food allergy.
Acute urticaria is a common symptom present with food
allergy. In contrast, chronic urticaria is very rarely
related to food allergy. Food allergy testing is rarely
indicated for chronic urticaria since most cases are
idiopathic.
Multiple nasopharyngeal symptoms occur with food
allergy, including acute rhinitis, but the rhinitis is

typically associated with other oropharyngeal

symptoms such as pruritus of the throat and
angioedema. However, chronic rhinitis is not a
manifestation of food allergy.
The correct answer is D, both atopic dermatitis
and acute urticaria may be signs of food allergy.

Jack is referred to an allergist for further evaluation.

What is the most appropriate testing at this time?
A: Atopy patch testing
B: Serum specific IgE testing or skin prick testing
C: Oral food challenge

ANSWER
Skin prick testing involves introduction of allergen
extracts into the skin. A positive reaction is defined as a
wheal at least 3mm greater than the negative control.
The negative predictive value is > 95% while the
positive predictive value is <50%; therefore, there are
many false positive results. Antihistamines should be
discontinued prior to testing. Testing cannot be
performed on skin with extensive eczema/rash or in
patients with dermatographia. In these patients, serum
specific IgE testing may be of use. Serum specific IgE
testing is the detection of the serum specific IgE to
specific allergens. All positive and negative tests need
to be correlated with the patients clinical history. A
positive test alone does not make the diagnosis of
clinical food allergy. Rather, it provides evidence of
sensitization, i.e., an immunological response.

A double-blind, placebo controlled food challenge is the

gold standard for diagnosis of food allergy, though open
challenges are generally used in most clinical settings.
The patient is given gradually increasing amounts of
the suspected food allergen over a time period of hours
to a day. The process requires close physician
supervision. Patients may benefit from an oral food
challenge if they have borderline test results or if a
false positive or false negative is suspected based on
clinical history. Oral food challenges may prevent
unjustified food elimination from the diet.
Atopy patch tests are currently used to diagnose
delayed hypersensitivity T-cell mediated reactions such
as contact dermatitis. Atopy patch testing for IgEmediated food allergy is not recommended.
The correct answer is B, serum specific IgE
testing or skin prick testing are appropriate
initial tests for food allergy.

Of the following, which is the proper anticipatory

guidance regarding recognition and appropriate
management of anaphylaxis?

A: A dose of anti-histamine can prevent food-induced

anaphylaxis
B. Epinephrine is the primary treatment for anaphylaxis
C. Fatal anaphylactic reactions occur most often in
individuals with unknown food allergy

ANSWER:
Fatal and near-fatal anaphylaxis typically occurs in people with
known food allergy at locations away from home (such as
school). Of note, persons with asthma and teenagers are at a
higher risk for fatal reactions. Many people with food allergy do
not carry self-injectable epinephrine with them. Food antigens
may not be apparent in foods such as cookies or cakes, and
even trace amounts of the food or handling of the food can
induce anaphylaxis.
Common symptoms of anaphylaxis include dyspnea, urticaria,
angioedema, flushing, pruritus, GI symptoms, syncope, and
hypotension. Cutaneous symptoms are the most common and
occur in over 90% of reported cases but are less common in
cases of fatal anaphylaxis. Signs of anaphylaxis typically occur
within seconds to minutes after exposure to the allergen,
although, rarely, symptoms may occur a few hours later. A late
phase reaction may also occur several hours after the initial
reaction. Parents should be advised that any child with signs of
anaphylaxis needs observation in a healthcare setting for a
minimum of 4-6 hours.
Epinephrine should be given at the first sign of anaphylaxis.
Epinephrine acts by decreasing vasodilation, edema, and
bronchoconstriction. In addition, it suppresses the release of
inflammatory mediators from mast cells and basophils. Patients
should be taken to the closest hospital even if the symptoms
have resolved as they may recur and the patient would then
require additional doses of epinephrine.
Antihistamines may control urticaria or other symptoms of
anaphylaxis but its use should not be substituted for

intramuscular epinephrine. Diphenhydramine and cetirizine can

be used in addition to epinephrine but both medications have a
slower onset of action and should never be used alone for the
treatment of anaphylaxis.
All patients with food allergy should wear a MedicAlert bracelet
listing the foods that cause allergic reactions.
The correct answer is B, epinephrine is the primary
treatment for anaphylaxis.