Antihistamines and Steroids in
Pediatric Dermatology
ELECTRA NICOLAIDOU, MD, PhD
ANDREAS D. KATSAMBAS, MD, PhD
B
oth antihistamines and corticosteroids are very
widely prescribed in dermatologic practice. In
this chapter, we review their use in pediatric
dermatology.
Antihistamines
Histamine-receptor antagonists, or antihistamines,
compete with histamine for receptors in various tissues
and are classified into H1- and H2-antihistamines. The
principal actions of H1-antihistamines are on vasodila-
tation and increased vascular permeability. They re-
duce whealing and suppress the wheal-and-flare reac-
tion of the axon reflex in acute urticaria as well as the
associated itching. H2-antihistamines are mainly used
in peptic ulcer disease, but the presence of H2-receptors
in the cutaneous microvasculature has prompted their
use in dermatology, too. It seems that an H2-antihista-
mine given concurrently with an H1-antihistamine may
modestly improve itching and wheal formation in some
patients with urticaria refractory to treatment with an
H1-antihistamine alone, but the available evidence does
not justify the routine use of H2-antihistamines in urti-
caria management.1
H1-antihistamines are further classified into first-
and second-generation agents. First-generation antihis-
tamines include diphenhydramine, chlorpheniramine,
and hydroxyzine and may cause sedation due to their
property of crossing the blood-brain barrier. Second-
generation, or low-sedating, H1-antihistamines include
terfenadine, astemizole, cetirizine, loratadine, fexofena-
dine, and mizolastine.
Indications
H1-antihistamines are widely used in children for the
management of allergic disorders.2 In pediatric derma-
tology, they are most commonly used in urticaria2–5
and atopic dermatitis.6 – 8 Other less common indica-
tions for their use include anaphylaxis9 and mastocyto-
sis.10 There are also reports of their use in varicella,11 in
From the Department of Dermatology, University of Athens School of
Medicine, A. Sygros Hospital, Athens, Greece
Address for correspondence: A.D. Katsambas, MD, PhD, 35 Skoufa
Street, GR-10673 Athens, Greece.
E-mail address: katsabas@compulink.gr
© 2003 by Elsevier Inc. All rights reserved.
360 Park Avenue South, New York, NY 10010
mosquito bite reactions,12 and in eosinophilic celluli-
tis.13
Urticaria
Urticaria is a common disease in childhood. Acute ur-
ticaria usually responds well to oral H1-antihistamines.3
Chronic urticaria may sometimes require the combined
use of both H1- and H2-antagonists.5 Nevertheless, rec-
ommendations for the treatment of urticaria in the pe-
diatric population are based on extrapolation from ev-
idence obtained in clinical trials in adults and on clinical
experience. Until recently, no prospective, randomized,
double-blind, placebo-controlled clinical trial of H1-an-
tihistamines in the treatment of urticaria in pediatric
patients had been published.
There is, however, a very recent prospective, ran-
domized, double-blind, placebo-controlled study con-
cerning not the treatment but the prevention of acute
episodes of urticaria in young children with atopic
dermatitis.4 Acute urticaria is often associated with
atopy. In one study of acute urticaria in infancy and
early childhood,3 atopy in the patient or his/her family
was found in 58% of cases. So during the Early Treat-
ment of the Atopic Child (ETAC) study, 0.25 mg/kg
cetirizine or matching placebo was given randomly to
817 children with atopic dermatitis for 18 months.
Acute urticaria occurred in 16.2% of the placebo-treated
children but in only 5.8% of the children treated with
cetirizine (P ⬍ 0.001). The protective effect of cetirizine
disappeared when the treatment was stopped.
Atopic Dermatitis
Histamine is an important pruritogen in atopic derma-
titis, and H1-antihistamines are often given to atopic
children to decrease itching and scratching.2 Anecdot-
ally, sedating first-generation H1-antihistamines have
sometimes been useful at bedtime because of their so-
porific effect, when the itching is so intense that it
disturbs nocturnal sleep. In a recent evidence-based
review of the efficacy of antihistamines in relieving
pruritus in atopic dermatitis, no large, randomized,
double-blind, placebo-controlled clinical trial with def-
inite conclusions was available for analysis.6 In the
subsequently published ETAC study, however, cetiriz-
ine significantly reduced requirements for application
of high-potency topical corticosteroids in young chil-
0738-081X/03/$–see front matter
doi:10.1016/S0738-081X(03)00047-6
322 NICOLAIDOU AND KATSAMBAS
dren with the most severe atopic dermatitis.7 During
the same study, cetrizine compared with placebo de-
layed or in some cases, prevented the development of
asthma in a subgroup of infants with atopic dermatitis
sensitized to grass pollen and, to a lesser extent, the
house dust mite.8 There was no difference, however, in
the prevalence of asthma between the treated and pla-
cebo groups as a whole.
Anaphylaxis
In anaphylaxis, an H1-antagonist such as diphenhydra-
mine 1–5 mg/kg by intravascular injection or intrave-
nous infusion may be a helpful adjunctive treatment to
epinephrine for hypotension as well as urticaria.2,9 The
combined use of an H1- and an H2-antagonist such as
cimetidine 4 mg/kg infused intravenously may be
more helpful than diphenhydramine alone.9
Pediatric Mastocytosis
In pediatric mastocytosis, plasma histamine levels may
be elevated. This is another disorder that is usually
treated with antihistamines. A combination of H1- and
H2-antihistamines is usually needed for relief of symp-
toms.10
Adverse Effects
First-generation H1-antihistamines cause objective im-
pairment of cognitive functioning and school perfor-
mance in children.11,12 In infants and young children,
they may also have stimulatory effects on the central
nervous system and cause irritability, hyperactivity,
and seizures.13 They also have some anticholinergic
effects, such as blurred vision, urinary retention, and
dry mouth.14
Second-generation H1-antihistamines minimally
cross the blood-brain barrier and appear to be relatively
free from adverse central nervous system effects in
children.2 Astemizole and terfenadine, which are no
longer available in most countries, have been reported
to cause cardiac toxicity in children, including ventric-
ular arrhythmias and torsades de pointes.15,16 Never-
theless, the potential cardiac toxicity of cetirizine,17 lo-
ratadine,18 and fexofenadine19 has been thoroughly
studied prospectively in many children and proved to
be negligible.
According to the aforementioned safety profile, it
seems that the use of first-generation H1-antagonists
should be restricted to 2 situations: children with urti-
caria or atopic dermatitis whose pruritus is so severe
that the sedation produced by an H1-antagonist is a
benefit and children with anaphylaxis who require in-
travenous diphenhydramine as adjunctive treatment to
epinephrine.2 Apart from these 2 situations, second-
generation H1-antihistamines are clearly the medication
of choice. Table 1 presents the recommended pediatric
doses of some representative H1-antihistamines.
Clinics in Dermatology Y 2003;21:321–324
Table 1. Recommended pediatric doses of H1-antihistamines
First generation
Diphenhydramine 1–5 mg/kg/24 h; parenterally, as an adjunct
treatment to epinephrine in anaphylaxis2,9
Hydroxyzine 2 mg/kg/24 h parenterally as an adjunct
treatment to epinephrine in anaphylaxis
and orally for itching unresponsive to
other H1-antihistamines2
Second generation
Cetirizine 2–5 years: 2.5 mg once or twice daily or 5
mg once daily
6–11 years: 5–10 mg/d
⬎12 years: 5–10 mg/d2
Loratadine 2–12 years: 5 mg/d
⬎12 years and ⬎30 kg: 10 mg/d2
Fexofenadine 6–11 years: 30 mg twice daily
⬎12 years: 60 mg twice daily or 180 mg
once daily2
Steroids
The introduction of glucocorticoids (corticosteroids) in
dermatology revolutionized the treatment of many skin
diseases, because they have potent anti-inflammatory
and immunosuppressive actions. They increase the syn-
thesis of lipocortin, which reduces phospholipase A2
activity and thus, reduce the concentration of arachi-
donic acid, a precursor of the prostaglandins and leu-
kotrienes, which take part in the inflammatory re-
sponse. They also inhibit the production and release of
cytokines, such as interleukin-1, interleukin-6, tumor
necrosis factor-␣, and ␥-interferon from macrophages,
Langerhans cells, and monocytes, which are involved in
the activation of T cells and in triggering the entire
immunoreactive cascade. In addition, they cause lym-
phocytopenia and vasoconstriction, so that various
blood cells have less access to the tissues.
Indications
Glucocorticoids are used in children both topically and
systemically.
Topical Use
Topical glucocorticoids are used successfully in a wide
variety of skin conditions, including atopic and contact
dermatitis, psoriasis, lichen planus, alopecia areata, and
vitiligo.20 Among them, atopic dermatitis is by far the
most common.
Atopic Dermatitis
Aggressive corticosteroid therapy is crucial in the man-
agement of atopic dermatitis during flaring. A mid-
strength corticosteroid should be applied twice daily,
ideally after bathing. As inflammation subsides, the
frequency of applications can be reduced to alternate
days. The goal for chronic management of atopic der-
matitis is twice-weekly applications to reduce the side
effects of topical steroid use.21
Clinics in Dermatology Y 2003;21:321–324 ANTIHISTAMINES AND STEROIDS IN PEDIATRIC DERMATOLOGY
Systemic Use
Autoimmune Blistering Diseases and Connective
Tissue disorders
Systemic corticosteroids are a cornerstone of treatment
for autoimmune blistering diseases such as pemphi-
gus22–25 and bullous pemphigoid26 and for connective
tissue disorders such as moderate to severe systemic
lupus erythematosus27 and dermatomyositis.28,29 They
are used alone or in combination with adjuvant immu-
nosuppressive therapy. The starting dose is usually 1 to
2 mg/kg/day, but higher doses may be needed to
control the disease. Steroid pulse therapy in the form of
15 mg/kg/day of methylprednisolone for 3–5 days or
alternate-day, small-quantity (8 –10 mg/kg) bolus infu-
sion over 16 –20 days for pemphigus25 and at a dose of
20 –30 mg/kg/day infused over 0.5 to 3 hours for sys-
temic lupus erythematosus and dermatomyositis29 may
be valuable for severely affected patients.
Acne Fulminans
Acne fulminans is an uncommon complication of acne
that affects predominantly adolescent males. According
to a recent review,30 the preferred treatment of acne
fulminans is oral prednisolone 0.5 to 1 mg/kg daily for
4 to 6 weeks (thereafter slowly reduced to zero), with
oral isotretinoin being added at the fourth week at 0.5
mg/kg daily and gradually increased to achieve com-
plete clearance.
Alopecia Areata
The efficacy of systemic corticosteroids as a therapeutic
modality for severe alopecia areata remains debatable.
In one study of severely affected patients,31 15– 40 mg/
day of oral prednisone induced satisfactory hair re-
growth in 38.9% of patients, which was not, however,
maintained off therapy. More encouraging results have
been obtained with a 300-mg monthly oral pred-
nisolone pulse.32
Other Disorders
Pyoderma gangrenosum is usually managed with sys-
temic corticosteroids.33 Short courses of systemic corti-
costeroids are also given in exceptional cases of atopic
dermatitis and allergic contact dermatitis, when other
treatment modalities have failed.
Adverse Effects
Adverse local effects of topical corticosteroids include
cutaneous atrophy, striae, telangiectasia, hypopigmen-
tation, and increased hair growth.20 If used in large
amounts, percutaneous absorption may occur, leading
to systemic adverse affects.
Systemic adverse effects are usually caused by long-
term systemic use of corticosteroids. They include
growth retardation, hypertension, osteoporosis, cushin-
goid facies, and cataracts.29 Suppression of the pitu-
itary-adrenal axis is managed with tapering of the dos-
323
age. Pulse corticosteroid therapy leads to a shorter
overall course of steroid therapy and fewer long-term
complications, such as growth retardation and osteopo-
rosis. Myocardial infarction, cardiac arrhythmias, and
even sudden death have been reported with pulse ste-
roid therapy in adults, warranting further studies of its
safety in children.29
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