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Allergic contact dermatitis to chlorhexidine

ARTICLE in AUSTRALASIAN JOURNAL OF DERMATOLOGY JUNE 2013

Impact Factor: 0.98 DOI: 10.1111/ajd.12087 Source: PubMed

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Australasian Journal of Dermatology (2013) 54, 303306
SMALL CASE SERIES
Allergic contact dermatitis to chlorhexidine
Ryan Toholka and Rosemary Nixon
Occupational Dermatology Research and Education Centre, Skin and Cancer Foundation, Melbourne,
Victoria, Australia
ABSTRACT
Chlorhexidine is a commonly used antiseptic agent
in the health-care setting. Although exposure to
chlorhexidine is very common, allergic contact der-
matitis (ACD) is rarely reported. We report a case
series of ACD to chlorhexidine in health-care workers
and discuss our rates of allergy to chlorhexidine, from
patch-testing performed at the Skin and Cancer Foun-
dation, Melbourne, Australia. Of 7890 patients patch-
tested, 840 patients were tested to 0.5% chlorhexidine
diacetate with 28 (3%) positive reactions, 13 (2%)
of which relevant to their presenting dermati-
tis. Altogether 1565 patients were tested to 0.5%
chlorhexidine digluconate, with 47 (3%) positive
reactions, 16 (1%) of which were relevant. We esti-
mate our rate of relevant chlorhexidine ACD from our
total clinic patients, non-occupational and occupa-
tional, to be at least 19/7890 (0.24%). Our rate of
relevant chlorhexidine ACD in health-care workers is
10/541 (2%). Interestingly, our rates of chlorhexidine
allergy are slightly higher than documented else-
where. This raises the possibility that chlorhexidine is
underestimated as an allergen worldwide, and should
be tested for in health-care workers where there is a
history of exposure.
Key words: alcohol rub, doctors, hand eczema,
hand rub, hand wash, health-care worker, nurse,
occupation, scrub.
INTRODUCTION
Chlorhexidine is a commonly used antiseptic agent in
health care, yet allergic contact dermatitis (ACD) is seldom
reported.1 Chlorhexidine is typically present as either a
Correspondence: Dr Ryan Toholka, Occupational Dermatology
Research and Education Centre, Skin and Cancer Foundation,
80 Drummond Street, Carlton. Victoria 3053, Australia. Email:
ryantoholka@hotmail.com
Ryan Toholka, MBBS(Hons). Rosemary Nixon, FACD.
Conflict of interest: none
Submitted 26 March 2013; accepted 7 May 2013.
2013 The Authors
Australasian Journal of Dermatology 2013 The Australasian College of Dermatologists
doi: 10.1111/ajd.12087
diacetate or digluconate salt and is effective against a wide
variety of bacteria, viruses and fungi.2 It is used both as a
skin and mucosal disinfectant and as an agent to reduce
bacterial colonisation of medical devices, such as central
venous catheters and orthopaedic metal wear. It is also used
as a preservative in a variety of personal-care products such
as toothpaste, cosmetics and lubricants.1
The following case series highlights our experience of
ACD to chlorhexidine in health-care workers. In the first
three cases the same patch-test protocol was followed.
Allergens (supplied by Chemotechnique Diagnostics, Vel-
linge, Sweden) were applied to the patients back, using
Finn chambers on Scanpor tape (SmartPractice, Phoenix,
AZ, USA), for 48 h. Patch-test readings were performed on
days 2 and 4 post-application of the tests. Positive reactions
were classified in terms of relevance: relevant, if there was
a recent history of exposure to chlorhexidine and a pattern
of dermatitis that would be consistent with exposure to a
chlorhexidine-containing product; old, if there was a history
of chlorhexidine exposure but the presenting dermatitis
was not explained by exposure to chlorhexidine; and
unknown, where there was no history of exposure to
chlorhexidine and the presenting dermatitis was not
explained by exposure to chlorhexidine.
CASE SERIES
Case 1
A 21-year-old graduate nurse presented with a 3-year
history of episodic skin problems particularly involving her
hands, starting when she began her clinical placements.
She had also developed an erythematous, pruritic eruption
of her face with localised oedema on two occasions. These
reactions took days to settle, with the second episode
requiring a course of oral corticosteroids. She suspected the
cause to be chlorhexidine, as her dermatitis did not recur
after she avoided chlorhexidine-containing skin cleansers.
No reactions were evident on day 2. However, on day 4 a
strong positive reaction (2+) to chlorhexidine diacetate was
evident, as were weak positive reactions to chlorhexidine
digluconate and three chlorhexidine-containing products
Abbreviation:
ACD allergic contact dermatitis
304 R Toholka and R Nixon

Table 1 Chlorhexidine-containing products

Chlorhexidine Concentration
Products Manufacturer Salt (%)

Antiseptic skin cleansers

Avagard Antiseptic Hand Rub 3M, Sydney, New South Wales Gluconate 0.5
Avagard Antiseptic Surgical Hand Scrub 3M, Sydney, New South Wales Gluconate 4.0
Debug Hand Hygiene Solution Orion Laboratories, Perth, Western Australia Gluconate 0.5
Microshield 2 Johnson and Johnson, Sydney, New South Wales Gluconate 2.0
Microshield 4 Johnson and Johnson, Sydney, New South Wales Gluconate 4.0
Microshield 5 Johnson and Johnson, Sydney, New South Wales Gluconate 5.0
Microshield Hand Rub Johnson and Johnson, Sydney, New South Wales Gluconate 0.5
Other chlorhexidine containing products
Acnederm Foaming Wash Ego Pharmaceuticals, Melbourne, Victoria Gluconate 0.5
Bactigrass Dressing Smith and Nephew, Sydney, New South Wales Acetate 0.5
Difflam-C Anti-inflammatory Antiseptic Solution iNova Pharmaceuticals, Sydney, New South Wales Gluconate 0.1
Hemocane Key Pharmaceuticals, Sydney, New South Wales Acetate 0.1
Lignocaine-chlorhexidine lubricating gel Pfizer, Sydney, New South Wales Gluconate 0.1
Nasalate Nose Cream Care Pharmaceuticals, Sydney, New South Wales Gluconate 0.3
Obstetric Care Lotion Orion Laboratories, Perth, Western Australia Gluconate 1.0
Paraderm Plus Wyeth Consumer Healthcare, Melbourne, Victoria Gluconate 0.1
Savacol Original Mouthwash Colgate-Palmolive, Sydney, New South Wales Gluconate 0.2
Savlon Antiseptic Cream Reckitt Benckiser, Sydney, New South Wales Hydrochloride 0.1
Silvazine Smith and Nephew, Sydney, New South Wales Gluconate 0.2

(1+) to which she had been exposed to during her place-
ments. Given the temporal relationship of exposure to
chlorhexidine-containing cleansers and the development of
her dermatitis, the positive patch tests and the resolution
of her dermatitis when she avoided skin contact with
chlorhexidine, she was diagnosed with occupational ACD to
chlorhexidine in skin cleansers.
Case 2
A 20-year-old nursing student presented with a papular
eruption on the dorsal aspect of her hands, her chin and
nose, which occurred while on a clinical placement. She
suspected that she had a reaction to the alcohol-based hand
rub, Debug (Orion Laboratories, Perth, Western Australia)
(Table 1), provided on the ward.
No reactions were evident on day 2. However, on day 4
weak positive reactions (1+) to chlorhexidine diacetate,
chlorhexidine digluconate and Debug were evident, as
were weak and doubtful (1+ and +/) reactions to 5 other
chlorhexidine containing products. Debug includes 0.5%
chlorhexidine digluconate. In addition to patch-testing, the
patient applied Debug to her hands during the course of the
testing, which produced a marked papular reaction on the
dorsal aspects of her hands. A diagnosis of occupational
ACD to chlorhexidine in Debug was made.
Case 3
A 21-year-old nursing student presented for investigation of
recurrent episodes of dermatitis occurring on the dorsal
aspects of her hands, which had, on occasion, spread to
involve her arms, occurring with each clinical placement.
Her past history included atopic eczema as a child, which
resolved at the age of 9 years. She recalled a previous reac-
tion to Savlon (Reckitt Benckiser, Sydney, New South Wales)
(Table 1) cream as a child.
On days 2 and 4 weak positive reactions (1+) to
chlorhexidine diacetate and digluconate were evident,
as were doubtful (+/) reactions to four chlorhexidine-
containing products. She was diagnosed with occupational
ACD to chlorhexidine in skin cleansers. Interestingly,
Savlon (Table 1) also contains chlorhexidine hydrochloride
0.1% and was likely to have been the cause of her initial
sensitisation.
Case 4
A 28-year-old intensive-care nurse re-presented as part of a
follow-up study. At this re-assessment a significant deterio-
ration in her hand dermatitis was observed. She had been
diagnosed with irritant contact dermatitis following patch-
testing 5 years previously, at which time all tests were nega-
tive. It was decided to repeat patch-testing.
This patient was only able to present for patch-test read-
ings on day 3. She developed a strong positive reaction
(2+) to chlorhexidine diacetate, a doubtful reaction (+/)
to chlorhexidine digluconate and a variety of reactions
ranging from +/ to 2+ to 8 chlorhexidine-containing prod-
ucts. Given the recent deterioration of her hand dermatitis
and patch-test reactions to chlorhexidine, it appeared that
she had become sensitised to chlorhexidine from skin
cleansers at work. She was now diagnosed with occupa-
tional ACD to chlorhexidine, as well as occupational irritant
contact dermatitis.
DISCUSSION
Data from patch-testing for chlorhexidine from our total
clinic population, including our contact dermatitis clinics

2013 The Authors

Australasian Journal of Dermatology 2013 The Australasian College of Dermatologists
 ACD to chlorhexidine
and occupational dermatology clinics, has been collated
from 1 January 1993 to 31 December 2012. Chlorhexidine
diacetate and chlorhexidine digluconate are not tested as
part of our baseline series but are included in our medica-
ment and nurses series, and are tested in all health-care
workers, as many hospital skin cleansers used in Australia
contain chlorhexidine (Table 1).
We tested 840 patients to 0.5% chlorhexidine diacetate. In
all, 28 (3%) tests were positive, of which 13 (2%) were of
current relevance. The number of reactions that were
either of old or unknown relevance was 15. In total 1565
patients were tested to 0.5% chlorhexidine digluconate,
with 47 (3%) positive tests, of which 16 (1%) were relevant
and 31 were of old or unknown relevance. The total number
of patients patch tested over this period was 7890, of whom
19 patients had relevant reactions to either or both
chlorhexidine digluconate and chlorhexidine diacetate.
Thus, we estimate our rate of relevant chlorhexidine ACD
for our clinic population to be at least 19/7890 (0.24%),
although chlorhexidine was tested only in patients in whom
a history of exposure was obtained. This estimate is likely to
underestimate the true rate of chlorhexidine allergy in our
clinic population, as it assumes that patients not tested to
chlorhexidine would not be allergic to it. Given the ubiqui-
tous exposure of chlorhexidine, this is unlikely to be the
case. Altogether 549 health-care workers were patch tested
during this time, of whom 10 (2%) had relevant positive
reactions to either or both chlorhexidine digluconate and
chlorhexidine diacetate.
A number of publications have described type I and
IV allergic reactions to chlorhexidine, including allergic
contact dermatitis, contact urticaria and anaphylaxis.1,37
Most of the recent literature has focused on immediate
reactions.
In a Danish study, 104 health-care workers without der-
matitis but with regular exposure to chlorhexidine under-
went patch and skin-prick testing to chlorhexidine. No
positive reactions were recorded and it was concluded that
sensitisation to chlorhexidine was likely to be rare.8 By con-
trast, a French group reported that sensitisation to antisep-
tics including chlorhexidine was not so uncommon and
their study included 14 cases of chlorhexidine allergy.
However the total number of patients in this study is not
known.9
A study of Polish health-care workers showed that 8/333
(2%) nurses and 3/167 (2%) doctors had positive patch tests
to chlorhexidine, of which all of the reactions were deemed
to be irritant in the nurses cohort, and only one (0.6%) of
the doctors cohort was deemed to be relevant.10 It was not
clear whether these workers had dermatitis or not.
At St Johns Institute of Dermatology in the UK, only
5/4733 (0.1%) of patients tested to chlorhexidine as part of
the medicament, nurses and contact lens allergen series
had positive and relevant patch tests to chlorhexidine.1 In
the patch test clinic at Turku University Hospital, Finland,
36/7610 (1%) of consecutive clinic patients tested to
chlorhexidine had a positive reaction, of which 14 (0.18%)
were classified as relevant.2 This rate is similar to our esti-
mate of relevant reactions to chlorhexidine in the total
Australasian Journal of Dermatology 2013 The Australasian College of Dermatologists
305
clinic patients (0.24%). However, given that we did not test
all our clinic patients, and that exposure to chlorhexidine,
such as from topical antiseptics, in non-health care workers
is not uncommon it is likely that our rate of allergy is higher
than in Finland.
A paediatric study from Toulouse, France, quotes a much
higher rate of chlorhexidine allergy in a selected population
of 641 children with atopic dermatitis.11 The median age
of the study population was 3.4 years (interquartile range
1.36.9). They were patch tested to seven common
topical agents used in their treatment, including 0.5%
chlorhexidine digluconate. Of this group, 17/641 (3%) had
positive patch-test reactions to chlorhexidine digluconate
on day 3. They did not perform a day 4 reading. Clinical
relevance is quoted in eight cases, (1%) in that there was
history of exposure to chlorhexidine. Only one patient
(0.2%) had a current exposure to a chlorhexidine-
containing product. It is unclear whether this was a con-
tributing factor to their dermatitis. According to our
classification, the seven other patients from whom a history
of previous exposure to chlorhexidine-containing products
was obtained appear to be of old, not current, relevance. In
addition, a Danish study has cast doubt on the accuracy of
patch-testing in young children.12 Only two of 21 children
(10%) who tested positive to nickel at 12 and 18 months, had
reproducible reactions at 3 and 6 years of age. In adult
groups, studies have determined optimum concentrations
to minimise irritancy yet maximise yield of detecting aller-
gic reactions. This has not been done for the paediatric
population. Given the young age of the participants in the
French study and that all patients had atopic dermatitis,
which is known to result in more easily irritated skin, we
suspect that many of these day 3 reactions to chlorhexidine
were in fact irritant, rather than allergic.
While ACD to chlorhexidine is clearly uncommon, our
rates of both allergy and ACD appear to be slightly higher
than reported elsewhere in the general patch-test popula-
tion. It would appear that chlorhexidine is an important
allergen in health-care workers and should not be over-
looked when they present with hand dermatitis. In addition,
patients may become sensitised through other exposures to
chlorhexidine which may be non-occupational, such as in
case 3 in this study where there was a history of a reaction
to an antiseptic cream. It is important for practitioners to
consider the diagnosis of ACD to chlorhexidine in health-
care workers presenting with hand dermatitis, who are
exposed to chlorhexidine-containing skin cleansers.
REFERENCES
1. Goon AT, White IR, Rycroft RJ et al. Allergic contact dermatitis
from chlorhexidine. Dermatitis 2004; 15: 457.
2. Liippo J, Kousa P, Lammintausa K. The relevance of
chlorhexidine contact allergy. Contact Dermatitis 2011; 64:
22934.
3. Bergqvist-Karlsson A. Delayed and immediate-type hypersen-
sitivity to chlorhexidine. Contact Dermatitis 1988; 18: 848.
4. Lauerma A. Simultaneous immediate and delayed hypersensi-
tivity to chlorhexidine digluconate. Contact Dermatitis 2001;
44: 59.
2013 The Authors
306 R Toholka and R Nixon

5. Chopra V, Chopra H, Sharma A. Allergic urticarial: a case
report of rare skin allergy with a common mouthwash. Indian
J. Dermatol. Venereol. Leprol. 2013; 58: 85.
6. De Waard-van der Spek FB, Oranje AP. Allergic contact der-
matitis to chlorhexidine and para-amino compounds in a
4-year-old boy: a very rare observation. Contact Dermatitis
2008; 58: 23941.
7. Ebo DG, Stevens WJ, Bridts CH et al. Contact allergic derma-
titis and life threatening anaphylaxis to chlorhexidine. J.
Allergy Clin. Immunol. 1998; 101: 1289.
8. Garvey LH, Roed-Petersen J, Husum B. Is there a risk of
sensitization and allergy to chlorhexidine in healthcare
workers? Acta Anaesthesiol. Scand. 2003; 47: 7204.
9. Barbaud A, Vigan M, Delrous J. Contact allergy to antiseptics:
75 cases analysed by the dermato-allergovigilance network.
Ann. Dermatol. Venereol. 2005; 132: 9625.
10. Rudzki E, Rebandel P, Grzywa Z. Patch tests with occupational
contactants in nurses, doctors and dentists. Contact Dermatitis
1989; 20: 24750.
11. Mailhol C, Lauwers-Cances V, Ranc F et al. Prevalence and
risk factors for allergic contact dermatitis to topical treatment
in atopic dermatitis: a study in 641 children. Allergy 2009; 64:
8016.
12. Mortz CG, Kjaer HF, Eller E et al. Positive nickel patch tests in
infants are of low clinical relevance and rarely reproducible.
Pediatr. Allergy Immunol. 2013; 24: 847.

2013 The Authors

Australasian Journal of Dermatology 2013 The Australasian College of Dermatologists