Case Report
Received: June 11, 2001
A Case of Cutaneous Delayed-Type Allergy to
Oral Dexamethasone and to Betamethasone
Eleonora Nucera Alessandro Buonomo Emanuela Pollastrini Tiziana De Pasquale
Massimiliano Del Ninno Chiara Roncallo Domenico Schiavino Giampiero Patriarca
Department of Allergology, Policlinico ‘A. Gemelli’, Università Cattolica del Sacro Cuore, Roma, Italia
Key Words
Delayed-type allergy W Betamethasone W
Dexamethasone
Abstract
Corticosteroids are drugs that may cause
allergic contact dermatitis, but systemic al-
lergic reactions to these drugs are rare. A 29-
year-old man developed a maculopapular
rash during an oral therapy with betametha-
sone. Patch tests demonstrated a delayed-
type allergy to dexamethasone, betametha-
sone and fluocortolone. Oral, intramuscular
or topical provocation tests with other corti-
costeroids – deflazacort, hydrocortisone,
methylprednisolone, fluticasone dipropion-
ate, triamcinolone and prednisone – were all
negative. This demonstrates that a patient
with a systemic allergy to a group of cortico-
steroids can tolerate those of other groups.
Copyright © 2002 S. Karger AG, Basel
Introduction
It is well known that corticosteroids are
drugs that may cause allergic contact derma-
titis.
Contact allergy to topical corticosteroids
occurs in about 0.2–5% of patients attending
a contact dermatitis clinic; these patients
show positive patch tests for one or more
corticosteroids [1–3].
© 2002 S. Karger AG, Basel
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Dermatology 2002;204:248–250
Corticosteroids can seldom cause sys-
temic allergic reactions when administered
via the oral or parenteral route [4–7]. The
corticosteroids that more often cause ad-
verse systemic reactions are prednisolone
and prednisone [6], while triamcinolone, hy-
drocortisone, dexamethasone and betame-
thasone are rarely involved [7–10].
Case Report
We present the case of a 29-year-old
man, without any signs or symptoms of ato-
py, contact dermatitis or skin allergy in his
history, who had well tolerated steroids in
his past until the episode described in this
paper. He was treated with oral spiramycin
and betamethasone for bacterial infection of
the middle ear – otitis – and developed a
maculopapular rash 24 h after the beginning
of the therapy, first localized to the scalp,
and after 2 h with the involvement of the legs
and of the abdomen. The symptoms wor-
sened with discontinuation of spiramicyn
but gradually disappeared over 1 month af-
ter discontinuation of betamethasone. Eo-
sinophilia was not present.
Prick, intradermal and patch tests with
the suspected drugs and with other cortico-
steroids were then performed (table 1).
Prick and intradermal tests were consid-
ered as positive with a wheal reaction of 3
and 5 mm, respectively, together with a posi-
Prof. Giampiero Patriarca
Department of Allergology, Policlinico ‘A. Gemelli’, Università Cattolica del Sacro Cuore
Largo F. Vito, 1
I–00168 Rome (Italy)
Tel. +39 06 30154965, Fax +39 06 3051343, E-Mail giapatr@tin.it
Accepted: October 4, 2001
tive control with histamine and a negative
control with saline.
Patch tests were read after 2 and 4 days,
and reactions were scored as recommended
by the ICDRG. For the patch tests we used
all the corticosteroids dissolved in ethanol
1%.
Prick and intradermal tests were all nega-
tive, while patch tests with betamethasone,
dexamethasone and fluocortolone were posi-
tive (++).
This result clearly showed a delayed-type
allergy to betamethasone, dexamethasone
and fluocortolone.
Thus, we decided to perform further test-
ing using challenges with some alternative
corticosteroids.
Informed consent and a favourable opin-
ion by the local Ethical Committee were
obtained, and the patient underwent oral
provocation tests with triamcinolone (4 mg),
prednisone (5 mg), deflazacort (6 mg), meth-
ylprednisolone (4 mg), a nasal provocation
test with fluticasone dipropionate (100 Ìg)
and an intramuscular challenge with hydro-
cortisone (100 mg). Each test was performed
with a 10-day interval from each other.
In all cases, the patient did not show any
symptom and could also tolerate a 5-day oral
therapy with methylprednisolone (4 mg a
day) and with fluticasone dipropionate (100
Ìg a day) by inhalation.
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 Discussion

Our patient had a type IV cell-mediated

immunoreaction as demonstrated by patch
tests. Other studies [11–13] have previously
demonstrated the usefulness of patch tests in
the diagnosis of allergy to ß-lactams and to
other drugs. Prick and intradermal tests,
which put in evidence just type I, IgE-
mediated immunoreactions, were all nega-
tive.
It is widely accepted that patients allergic
to one corticosteroid also show cross-reactiv-
ity to other molecules because they often
have common chemical structures.
In fact, as it has already been demon-
strated for allergy to ß-lactams [14], the mo-
lecular model is very useful to explain the
cross-reactivity among the various molecules
[15]. Fig. 1. Chemical structure of some corticosteroids. Methylpredniso-
The C16/17 substitutions on the D ring lone belongs to group A, triamcinolone to group B and betametha-
of the molecules (fig. 1) seem to be very sone and dexamethasone to group C.
important to determine the patterns of cross-
reactivity [16–18].
Dexamethasone, betamethasone and Table 1. Results of skin, patch and provocation tests
fluocortolone are corticosteroids that belong
to group C according to the classification of Drug Skin tests Patch tests OCT NCT ICT
Coopman et al. [19] (table 2) and they differ
just for the position in the space of the C16 Betamethasone neg. ++ n.d. n.d. n.d.
methyl group on the D ring; this substitution Dexamethasone neg. ++ n.d. n.d. n.d.
is responsible for the cross-reaction of the Fluocortolone neg. ++ n.d. n.d. n.d.
three molecules (fig. 1). Prednisone neg. neg. neg. n.d. n.d.
Recent studies suggest that corticoste- Methylprednisolone neg. neg. neg. n.d. n.d.
roids are not allergens themselves; cortico- Hydrocortisone neg. neg. n.d. n.d. neg.
steroids are degraded to a corticosteroid Beclomethasone dipropionate neg. neg. n.d. n.d. n.d.
glyoxal that then reacts with arginine mole- Flunisolide neg. neg. n.d. n.d. n.d.
cules of proteins to form the complete anti- Budesonide neg. neg. n.d. n.d. n.d.
gen; so, the immune system can recognize Triamcinolone neg. neg. neg. n.d. n.d.
the allergen [20, 21]. Momethasone furoate neg. neg. n.d. n.d. n.d.
It has also been shown that positive patch Deflazacort neg. neg. neg. n.d. n.d.
tests with corticosteroids are correlated to Fluticasone dipropionate neg. neg. n.d. neg. n.d.
positive reactions with the same corticoste-
roid glyoxal [22, 23]. OCT = Oral challenge test; NCT = nasal challenge test; ICT = intramuscular challenge
It is possible that also in our case the test; n.d. = not done. Skin tests: prick and intradermal tests.
reaction occurred with the same mechanism,

Table 2. Classification of corticosteroids according to Coopman et al. [19]

Group A Group B Group C Group D

Hydrocortisone Triamcinolone Betamethasone Hydrocortisone-17-butyrate

Hydrocortisone acetate
Prednisolone
Prednisolone acetate
Methylprednisolone acetate
Prednisone
Tixocortol pivalate
Triamcinolone acetonide Dexamethasone Hydrocortisone-17-valerate
Amcinonide Fluocortolone Clobetasone-17-butyrate
Budesonide Fluocortolone caproate
Fluocinonide Fluocortolone pivalate
Betamethasone valerate
Betamethasone dipropionate

Cutaneous Delayed-Type Allergy Dermatology 2002;204:248–250 249

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since even when betamethasone was admin-
istered orally, the patient had a cutaneous
reaction.
In patients allergic to one or more corti-
costeroids, it is very important to establish
which the patients can tolerate because these
drugs are widely used for the treatment of
several diseases (autoimmune, allergic and
neoplastic diseases). This is possible after an
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