++
With the exception of subcutaneous immunotherapy, which has a
proven record of success in the treatment of allergic rhinoconjunctivitis and
bee sting allergy, presumably by inducing a long-lasting tolerance,
most therapeutic modalities for allergic diseases are geared toward ameliorating
the symptoms of the affected patients and, at the same time, to
prevent possible complications or involvement of other organs. This
is not to say that the available therapies are not effective, and
compliance with these treatments can certainly improve the quality
of life of these patients.
++
The proper management of the allergic child requires a multipronged
approach that includes minimizing the exposure to the allergic trigger(s)
as well as using a cohort of medications that can revert or control
an established allergic reaction (eg, antihistaminics, epinephrine)
or limit its development (eg, glucocorticoids, leukotriene inhibitors,
and others).10
++
Exclusion of the allergenic food from a child’s diet
clearly reduces the likelihood of developing an allergic reaction
to this food and should always be recommended.8 Although
there have been isolated reports of nondietary exposures to food
allergens (eg, through the skin or inhalation) resulting in systemic
reactions, these are rare occurrences. Minimizing the exposure to allergens
that act primarily on the respiratory tract has been shown to decrease
symptoms and improve control in children with respiratory allergies
and asthma.9 Environmental control measures directed
at decreasing the levels of indoor allergens such as dust mites,
mold, and pet dander usually result in a tangible relief in allergic
symptoms, particularly in children with perennial allergic rhinoconjunctivitis
and/or asthma. Removal of the pet from the home should
be recommended but is not always an acceptable option for the family.
In those cases, limiting the access of the animal to the child’s bedroom
and placing an air purifier (especially useful for cat allergens)
can be helpful. Measures to prevent exposure to pollens are largely ineffective
because the distribution of these allergens is widespread and they
can travel airborne over large distances.
+++
Pharmacological Agents
++
Corticosteroids are pleiotropic anti-inflammatory drugs with
proven efficacy in the management of various aspects of the allergic inflammation.
The development of highly effective topical preparations (intranasal,
inhaled, or dermatological creams) with minimal systemic effects
has revolutionized the therapy of common disorders such as allergic
rhinitis, allergic asthma, and atopic dermatitis. Inhaled corticosteroids
are the first line of treatment for patients with persistent asthma,
and they provide relief in children even when used on an as-needed
schedule (see Chapter 512). As monotherapy, intranasal
corticosteroids are more efficacious than either leukotriene receptor
antagonists or antihistamines, or their combination, in the management
of the both nasal and ocular symptoms of allergic rhinoconjunctivitis.
When used at the recommended doses, most intranasal corticosteroid
preparations are not generally associated with clinically significant
effects on the hypothalamic-pituitary-adrenal axis, ocular pressure
or cataract formation, or bone density.
++
Histamine is a primary amine produced by mast cells and basophils
that orchestrates many aspects of the allergic response by binding
to specific receptors present on the surface of its target cells. So
far, four types of histamine receptors belonging to the G protein–coupled
receptor family have been identified: H1, H2, H3, and H4. Signals
transduced via the H1 (and to a lesser extent H2) receptor mediate
many of the acute symptoms and signs of allergic disease in the
skin, airway, and gastrointestinal tract, whereas H1 and H4 appear
to promote the accumulation of inflammatory cells at sites of allergic
inflammation.
++
Histamine receptor antagonists are widely prescribed for the
treatment of allergic disorders. Pretreatment with an oral H1 antihistamine
reduces early responses to allergen in the conjunctiva, nose, lower
airway, and skin, and administering the drug during the course of
an allergic response curbs the symptoms triggered by acute allergic
inflammation. Onset of action occurs within 1 to 3 hours. Newer
H1-antihistamines have a prolonged half-life and need to be administered
only once or twice daily, whereas others have to be administered
several times a day to maintain efficacy. Tolerance to doses that
achieve clinical efficacy does not develop, but symptom relief may
be insufficient when other mediators (leukotrienes, neuropeptides, etc)
are involved. This is often the case in the pruritus of atopic dermatitis,
which, by and large, is resistant to antihistamines.
++
There are more than 40 H1 antagonists available worldwide. These
agents, which have diverse chemical structures, are in general effective
and safe to use in infants and children.11 However,
they are not interchangeable, and the safety profile varies from
agent to agent. First-generation H1 blockers (eg, brompheniramine, cyproheptadine,
chlorpheniramine, hydroxyzine, and promethazine) are lipophilic
and penetrate the CNS readily, causing sedation or, in some patients,
paradoxical excitation. These drugs are excreted in breast milk
and have been reported to induce drowsiness or respiratory depression
in nursing infants. Thus, unless sedation is a primary goal, second-generation
H1 antihistamines (eg, loratadine, cetirizine, and fexofenadine),
which penetrate the CNS poorly, are preferable.
+++
Leukotriene
Receptor Antagonists
++
Leukotrienes are products of the 5-lipoxygenase pathway synthesized
by white cells in response to a variety of inflammatory stimuli. Within
this family, the cysteinyl leukotrienes (LTC4, LTD4, and LTE4) account
for the biologic activity known as slow-reacting substance of anaphylaxis.
Leukotriene receptors (BLT1 and 2, CysLT1 and 2) are expressed in several
tissues, including hemopoietic cells, smooth muscle cells, and epithelia,
where they mediate a myriad of biological functions. Pertinent to
allergic disease, leukotrienes induce the migration and activation
of virtually all white cells involved in allergic inflammation as
well as smooth muscle and asthma.
++
Several studies have demonstrated the efficacy of leukotriene
receptor antagonists (LTRA) in the treatment of asthma. The best studied
in this group is montelukast, which is now approved for the treatment
of asthma in children 12 months and older and for relief of symptoms
of perennial allergic rhinitis in infants from 6 months on.12 As
single drugs, LTRA are less effective than nasal or inhaled corticosteroids
in the treatment of allergic rhinitis or asthma. Furthermore, the
clinical response to LTRA is somewhat unpredictable, which may be
due in part to genetic factors. Yet, the safety profile of leukotriene
receptor antagonists makes them a suitable alternative for those
patients who cannot receive steroids or who are wary of their side
effects. The efficacy of LTRA in other allergic disorders such as
atopic dermatitis and urticaria has been suggested but not demonstrated.
+++
Allergen-Specific Immunotherapy
++
Allergen-specific subcutaneous immunotherapy
(SCIT) has been practiced since the late 1950s and has proven to
be clearly effective therapy for allergic airway diseases and insect venom
allergy. Currently, SCIT is the only treatment that can potentially
modify the course of allergic rhinoconjunctivitis by redirecting
the immune response toward a tolerant state, and its clinical benefits
may be sustained years after discontinuation of treatment.13 Allergen
immunotherapy for allergic rhinitis diminishes the risk of new allergen sensitizations
in monosensitized children and has reduced the risk of asthma in children
with allergic rhinitis.
++
While the cost of SCIT is comparable to that of pharmacotherapy,
it is a time- and resource-consuming therapy that requires long-term
(minimum of 2 years) commitment on the part of the patient. In children,
usually fearful of shots, there is the added drawback that it implies
subcutaneous injections. Noninjection routes (sublingual immunotherapy) have
been in use for years in Europe and are effective in the treatment
of allergic rhinoconjunctivitis in adults, although the evidence
in children is promising but still inconclusive.14