Andrea Nardelli, Hugo Degreef, An
Goossens
Department of Dermatology
University Hospital, Katholieke
Universiteit Leuven
Leuven, Belgium
Correspondence to:
Prof An Goossens
Department of Dermatology
Contact Allergy Unit
University Hospitals Leuven
Kapucijnenvoer 33, B-3000, Leuven
Belgium
Tel: +32 16 337860
Fax: +32 16 337012
E-mail: An.Goossens@uz.kuleuven.ac.be
Contact Allergic Reactions
of the Vulva: A 14-year review
Abstract
Background:
In women with vulval complaints, irritant contact dermatitis is more
common than allergic contact dermatitis, but secondary sensitization has to be
taken into consideration since these patients often use several topical
medications.
Objective: The aims of this retrospective study were to establish the
prevalence of allergic contact dermatitis in patients with vulval complaints
and to verify how many patients with allergic contact dermatitis suffered from
a previous pathology.
Methods: We reviewed the results of patch and prick tests obtained from
92 women. They had all been
administered a European Standard series and most had also been tested for other
allergens such as ingredients of topical pharmaceutical products and cosmetics.
Results: Thirty-five patients (38%) presented with one or more positive
allergic reactions. For 15 of them,
these reactions were considered to be relevant to their clinical condition and
were most often due to contact dermatitis from topical pharmaceutical
products. Three patients presented with
a positive and relevant Contact Urticaria Syndrome to latex and two patients
with Protein Contact Dermatitis to human seminal plasma.
Conclusions: Patients with vulval dermatitis are at risk of developing
contact sensitivities, particularly to topical pharmaceutical products, so
attention should be paid to this problem when they are prescribed.
Introduction
The exact prevalence of vulval
dermatitis is unknown. Etiological
factors are poorly understood and are not always guided by clinical signs. They may vary from pruritus, mild erythema,
eczema, to gross lichenification and be limited to a small area or spread onto
the adjacent skin. When vulval
involvement occurs as part of a generalized dermatitis, there is usually no
difficulty in diagnosing it, but it often occurs in isolation or with minimal
involvement of other sites. A careful
personal and family history must then be taken to determine if there is a
background of, for example, atopic or seborrheic dermatitis (endogenous) as well
as to establish details of exposure to potential irritants and allergens
(exogenous). Iron deficiency, a known
cause of generalized pruritus has also been implicated in lichen simplex
chronicus of the vulva.1 In
the vulval area, irritant contact dermatitis (ICD) is more common than allergic
contact dermatitis (ACD), but secondary sensitization may occur.2 Those who receive long–term topical
treatment are especially at risk.3,4,5
This study
was conducted to establish the prevalence of ACD in patients with chronic
vulval complaints and to verify how many of the patients with ACD suffered from
a previous pathology that could predispose them to develop the disease.
We retrospectively
investigated 92 women who suffered from vulval complaints and who were referred
for patch testing to our Contact Allergy Unit between 1990 and 2003. They were
attendees at our outpatient clinic in whom response to treatment for a
particular dermatitis was less successful than expected or those in whom
diagnostic difficulty arose. Their mean
age was 49 years old (range 7-92 years).
They were patch tested to a European Standard series (Hermal, Reinbek,
Germany) with Belgian additions (Table 1) and, when indicated, to other
allergens, including ingredients of the cosmetics and topical pharmaceutical
products they had used. The patch test
readings were performed according to the international guidelines after 2 days,
3 days (exceptionally), and / or 4 days, and, if necessary, as with suspicion
of corticosteroid contact allergy, also after 6 or 7 days. For practical purposes here, ACD reactions
were only indicated as being positive or negative. If indicated from the history, prick testing with latex and/or
human seminal plasma was also administered.
These tests were read immediately and also after Days 2 and 4 since the
patch tests were also read at that time.
Irritant dermatitis was considered
when the results of patch testing were negative and when the patient‘s clinical
signs corresponded to those of an irritancy reaction.
The allergens that
produced at least one positive patch test result are listed in Tables 1-4 along
with their test concentrations and vehicles.
Table 5 gives all of the positive test results along with their relevance. Thirty-five patients (38%) had one or more
positive reactions. Thirteen patients,
of whom eight were nickel sensitive, had one positive response; the remaining
22 had multiple positive responses.
Including all the positive reactions, 11 patients (12%) had 23 reactions
to topical pharmaceutical products or to one or more of its constituents that
were considered definitely relevant and four (4.5 %) had five positive
reactions that were probably relevant to their clinical condition (Table 1-4).
The clinical diagnoses following
skin testing are given in Table 6. The
vast majority of the patients tested had suffered from pre-existing vulval
lesions prior to patch testing. Chronic
eczema was the most common primary diagnosis, and six of these patients had one
or more relevant sensitivities.
Similarly, three of the patients with lichen sclerosus, two of the
patients with candidiasis, two with seborrheic dermatitis, one with
neurodermatitis, and one with hemorrhoids were contact allergic to topical
drugs.
Three patients who received prick
tests had a positive and relevant Contact Urticaria Syndrome (CUS) to
latex. Two, of whom one was also latex
positive, showed Protein Contact Dermatitis (PCD) to human seminal plasma.
ICD was considered to be an
important factor in 15 patients with different vulval dermatoses, i.e. lichen
planus, seborrheic dermatitis, seborrheic psoriasis, and in one patient with
Crohn’s disease, a recto-vaginal fistula, and urine incontinence. There are five patients in the category
diagnosis unknown/unclassified.
In the vulval area,
many dermatoses mimic each other.
Besides ICD and ACD, psoriasis, atopic eczema, seborrheic dermatitis,
infections (bacterial, mycotic or viral), blistering diseases, inflammatory
diseases such as lichen planus, lichen sclerosus et atrophicus, and adverse
drug reactions need to be considered.2 These conditions may be complicated by irritant and/or allergic
contact dermatitis, so these patients should be investigated for contact
allergy if the lesions do not respond to topical therapy.
Patients with vulvodynia (to be
differentiated from those suffering from pruritus vulvae) or vulval
vestibulitis seem to be at low risk of developing ACD, possibly because topical
pharmaceutical products are ineffective and are therefore applied less.2,6,7,8
The vulval area is more easily
severely affected by irritants 9,10,11 than, for example, the
forearms, although secondary sensitization is possible. The vulval skin is exposed to foreign
proteins during sexual intercourse and is said to be more resistant to
sensitizers than perianal skin.12
Fecal incontinence should be considered in patients complaining of
vulval burning, particularly in the presence of eczema. Indeed, enzymes in feces may contribute to
perianal and vulval problems, as is encountered in patients who require
pancreatic enzyme supplements (pancreatin), which contains protease, lipase,
and amylase.13.
The cumulative use of quaternary
ammonium antiseptic agents such as benzalkonium chloride 9 and
methyl benzethonium chloride14 has been reported to cause irritancy
in this region. Even “Indian God
Lotion”, a popular herbal spray containing Herba Asari and isopropyl alcohol
that is used in Hong Kong for enhancing sexual potency, has been described as
an irritant.15
With regard to the allergens
observed in our study, nickel tested positively 15 times, but these reactions
were not considered relevant. Indeed,
the relevance of nickel in vulval dermatoses has been debated,16,17 and
it is unclear whether direct transfer of nickel by the hands or exposure to
nickel at remote sites may be the cause.
Even gold sodium thiosulfate has been put forward as a likely
significant allergen producing perianal or perivulval rash.18
Topical pharmaceutical products,
which, according to some studies, may be the cause of vulval dermatitis in up
to 29% of the patients,5 were considered relevant in 12% of our
cases.
The most common relevant active
principles were found to be corticosteroids: triamcinolone acetonide (three
times), hydrocortisone acetate and hydrocortisone-17-butyrate (both
twice). In the literature, other
corticosteroids, i.e. clobetasol propionate, an effective and usually
recommended treatment for lichen sclerosis (one positive but not relevant
reaction in our group), and both mometasone furoate and methylprednisolone
aceponate have also been implicated in vulval dermatitis.19 Therefore, the importance of corticosteroids
as causes of secondary sensitization and the need for testing with them must be
emphasized.20
Aminoglycosides such as neomycin are
the most common allergenic antibacterial agents reported,5 and three
of our patients reacted to it. One of
them was relevant for Mycolog cream, which also contains ethylenediamine.5 Moreover, the perfume component of this
cream can also be the cause of ACD.21
In this regard, other active agents
reported in the literature are nifuratel, which is used as an antitrichomonal
and antimycotic agent and as an antiseptic in antihaemorrhoidal ointments and
suppositories, and usnic acid.22,23
In one of our patients, positive and relevant reactions to both
cinchocaine and lidocaine with cross-reactions to bupivacaine and mepivacaine
were observed.
Besides ethylenediamine, other
non-active ingredients that were deemed to be relevant allergens in topical
pharmaceutical products were the following:
benzoic acid, a preservative agent (twice) and butylhydroxyanisole, an
antioxidant (twice), both present in antifungal creams; wool alcohols (once);
chlorocresol, a preservative agent in a corticosteroid cream (once); paraben
mix (once), which, among other preservatives such as formaldehyde,
Quaternium-15, and methyl chloroisothiazolinone, have been reported as causes
of vulval dermatitis.5 The
actually rather high sensitization rate of the preservative agents methyl
(cloro) isothiazolinone and the methyldibromo-glutaronitrile/2-phenoxyethanol
mixture (Euxyl K400) has been attributed to their widespread use in cosmetics
and toiletries, including moistened toilet paper to which one of our patients reacted
because of sensitization to both methyl chloroisothiazolinone and
bromonitropropanediol (a formaldehyde releaser) present in them.2 Moreover, chlorhexidine, a common
preservative in cosmetics, toothpastes, lubricants and contraceptive gels for
which irritant contact dermatitis is more common than the allergic type, has
been reported as the cause of connubial allergic contact balanitis.24 Last but not least, reactions to fragrance
components and balsam of Peru may be relevant because of contact with perfumed
soaps, bath additives, and toiletries,5 an example being lavender
oil as the cause of chronic vulvovaginitis.25 In one of our cases, balsam of Peru
(Myroxeilon Pereirae resin) was present in a topical pharmaceutical product the
patient had used.
Resins are also allergens reported
as culprits in vulval dermatitis, such as acrylates in incontinency pads: one
woman had been primarily sensitized by sculpture acrylic nails and had also
reacted to a dental crown.26 One patient, who used colophony rosin
when playing the cello, developed pruritus vulvae, which condition definitely
improved when the rosin was avoided.27 We observed a patient with a severe reaction to colophony but who
remained negative when tested with extracts of the suspected sanitary pads.28 Nail polish29,30 proved to be
relevant in one case due to transfer by the hands of the
tosylamide/formaldehyde resin it contained.
Textile dyes such as Disperse Orange
3 (an azo dye) and Disperse Blue 35 and 153 (anthraquinone dyes) present in underwear
have been described as the causes of a pigmented and purpuric dermatitis. After changing to white underwear, the
condition of the patient cleared completely within four months.31 Among 6 patients in our study who had been
sensitized to paraphenylendiamine, one similar case (the patient also reacted
to para-aminoazobenzene) was observed.
Contact allergy to rubber mixes,
such as naphtyl mix and thiuram mix might be relevant to leggings, elastic
underwear, and rubber condoms,32 the last of which was also involved
in latex-contact urticaria although primary sensitization by condoms still
needs to be confirmed.33,34
One of our latex-allergic patients who had Apert’s Syndrome presented
postoperative vulval swelling due to contact with natural rubber gloves worn by
the medical personnel. The spermicides
used both in condoms and topical products (even causing a connubial dermatitis)
may also cause allergic reactions.35,36
Human seminal plasma (HSP)
hypersensitivity is a poorly known immunologically mediated disorder that
occurs mainly in younger atopic women.
It may be characterized by local (vulvovaginal) and also by systemic
(anaphylactic) symptoms. We have
observed 2 such patients, one of whom was also latex-allergic, who presented
with a combined Type I and also Type IV allergy to HSP (a so-called protein
contact dermatitis that presented clinically as an urticarial reaction followed
by the development of eczema).37,38
In our experience, avoidance of the
offending allergen by these patients generally led to an improvement of the
condition.
Vulval pruritus and/or dermatitis
are common, chronic and embarrassing conditions that have a negative impact on
most aspects of life. Such patients
risk developing contact sensitivities, particularly to topical pharmaceutical
products. Patch testing is useful in
their management and significant benefits ensue if the offending allergens are
avoided. Patch testing should be used
early in the therapeutic process rather than being reserved for those patients
who do not respond to treatment.5, 39
Andrea Nardelli, Hugo Degreef, An Goossens
Department of Dermatology
University Hospital, Katholieke Universiteit Leuven
Leuven, Belgium
Table 1: Results of the patch testing with standard series (n=92).
|
European Standard Series |
N
|
R |
|
Potassium dichromate |
1 |
0 |
|
Neomycin sulphate |
3 |
1 |
|
Thiuram mix |
1 |
0 |
|
Paraphenylenediamine free base |
6 |
0 (+2**) |
|
Cobalt Chloride |
2 |
0 |
|
Benzocaine |
3 |
0 |
|
Colophony |
3 |
0 (+1**) |
|
Balsam of Peru |
4 |
1 |
|
Isopropyl phenyl
paraphenylendiamine |
1 |
0 |
|
Wool alcohols |
1 |
1 |
|
Mercapto mix |
1 |
0 |
|
Epoxy resin |
2 |
0 |
|
Paraben mix |
2 |
1 |
|
Fragance mix |
4 |
0 |
|
Nickel sulphate |
15 |
0 |
|
Primin |
2 |
0 |
|
Propylene glycol 10% aq.* |
1 |
1 |
|
Euxyl k 400 1.5 %pet.* |
3 |
0 |
|
Methyl (chloro) isothiazolinone
0.01%aq. |
1 |
1 |
|
Tosyl/formaldehyde resin 10% pet.* |
1 |
1 |
|
Tixocortol-21- pivalate 0.1%
pet.*** |
2 |
0 |
|
Budesonide 0,01% pet.*** |
4 |
0 |
|
Total |
63 |
10 |
* Belgian additions
N = number of positive reactions
R = number of relevant (** probably
relevant) positive reactions
*** Not relevant as such but as markes for
sensitivity to the other corticosteroids (see Table 2)
Table 2: Results of the patch
testing to topical drugs (n=15).
|
Tested substances |
N
|
R |
|
Clobetasol prop. 1% alc. |
1 |
0 |
|
Hydrocortisone ac. 1% alc. |
4 |
2 |
|
Hydrocortisone-17-but. 1% alc. |
3 |
2 |
|
Triamcinolone acetonide 1% alc. |
4 |
3 |
|
Prednisolone Caproate 0.1% alc. |
1 |
1 |
|
Econazole nitrate 2% pet. |
1 |
1 |
|
Miconazole
2 % pet. |
1 |
1 |
|
Isoconazole 2% pet. |
1 |
1 |
|
Etofenamate 2% pet. |
1 |
0 |
|
Testosterone 1% alc. |
1 |
1 |
|
Benzoyl peroxide 1% pet. |
1 |
0 |
|
Butoform 5% pet. |
1 |
0 |
|
Sulfanilamide 2% alc. |
1 |
0 |
|
Estradiol 0.5% pet. |
1 |
1 |
|
Lidocaine 5 + pet. |
1 |
1 |
|
Cinchocaine 2.5% pet. |
1 |
1 |
|
Bupivacaine hydrochloride 1% aq. |
1 |
0 |
|
Mepivacaine hydrochloride 0.5% aq. |
1 |
0 |
|
Total |
26 |
15 |
N = number of positive reactions
R = number of relevant positive
reactions
Table 3: Results of the patch testing to other cosmetic and/or pharmaceutical vehicle components and preservatives (n=7).
|
Tested substances |
N
|
R |
|
Benzoic acid 5% pet. |
2 |
2 |
|
Butylhydroxyanisole 2% pet. |
2 |
2 |
|
Ethylenediamine dihydrochloride
1%pet. |
1 |
1 |
|
Bromonitropropanediol 0.5% pet. |
1 |
1 |
|
Chlorocresol 1%pet. |
1 |
1 |
N = number of positive reactions
R = number of relevant positive
reactions
Table 4: Results of the patch (n=9) and prick testing (n= 3).
|
Tested substances |
N
|
R |
|
Para-amino-azobenzene 0.25% pet. |
1 |
0 (+ 1**) |
|
Naphtyl mix 1% pet. |
1 |
0 (+ 1**) |
|
Carba mix 3% pet. |
1 |
0 |
|
Diphenylthiourea 1% pet. |
1 |
0 |
|
Disperse Orange 1 1% pet. |
1 |
0 |
|
Disperse Blue 153 1% pet. |
1 |
0 |
|
Limonene ox. 2% pet. |
1 |
0 |
|
Palladium Chloride 1% pet. |
1 |
0 |
|
Diaminodiphenyl Methane 0.1% pet. |
2 |
0 |
|
Isoeugenol 2% pet. |
1 |
0 |
|
HSP*** |
2 |
2 |
|
Latex*** |
2 |
2 |
N = of
positive reactions
R = number
of relevant (** probably relevant) positive reactions
*** = Protein Contact
Dermatitis/Contact Urticaria Syndrom
Table 5: Allergic vulval dermatitis: summary of the test results.
|
Summary of the test results |
N°
|
(%) |
|
Patients tested |
92 |
100 |
|
Patients with +
reactions in total |
35 |
38 |
|
Patients with multiple
+ reactions |
22 |
24 |
|
Total number of
implicated allergic reactions |
58 |
|
|
Patients with relevant
(11 definite/ 4 probable) + patch tests |
15 |
16.5 |
|
Total number of
relevant implicated allergens |
28 |
|
|
Patients with relevant
medicament-related reactions |
11 |
12 |
+ = Positive reactions.
Table 6: Clinical diagnosis of patient with vulval dermatoses (n= 92).
|
Diagnosis |
Number of patients |
Positive and relevant patch tests |
|
Allergic Contact Dermatitis |
34 |
15 |
|
Irritative Contact Dermatitis |
15 |
0 |
|
Contact Urticaria Syndrom (Latex) |
2 |
2 |
|
Protein Contact Dermatitis (Sperm) |
2 |
2 |
|
Candidiasis |
10 |
2 |
|
Chronic eczema |
15 |
6 (3 probably relevant) |
|
Lichen planus |
8 |
0 |
|
Lichen sclerosus |
6 |
3 |
|
Seborrheic dermatitis |
7 |
2 (1 probably relevant) |
|
Psoriasis |
6 |
0 |
|
Neurodermitis |
7 |
1 |
|
Drug eruption |
1 |
0 |
|
Fixed drug eruption |
1 |
0 |
|
Prurigo |
1 |
0 |
|
Atopic dermatitis |
3 |
0 |
|
Diabetic vulvovaginitis |
2 |
0 |
|
Intertrigo |
2 |
0 |
|
Vulvodynia |
2 |
0 |
|
Hemorrhoids |
1 |
1 |
|
Diagnosis unknown/unclassified |
5 |
0 |