Page 656 - Clinical Immunology_ Principles and Practice ( PDFDrive )

630 ParT FIVE Allergic Diseases

of potentially deficient nutrients in the diet of the patient with Few studies have compared SLIT with OIT; current evidence
a food allergy. Allergen-specific immunotherapies are currently indicates that SLIT has fewer side effects compared with OIT,
under investigation utilizing the oral, sublingual, and epicutaneous but SLIT does not appear to induce a similar level of desensitiza-
routes for the application of the allergen. Although currently no tion or achieve SU as often as OIT. Ongoing compliance with
therapies have been approved by the US Food and Drug Admin- SLIT has also been reported as challenging. Additional studies
istration for the treatment of food allergy, several of those being are needed to reveal whether adjuvant therapy with SLIT increases
investigated are promising. efficacy and to understand whether SLIT could be combined
with OIT to improve its safety.
Oral Immunotherapy
Oral immunotherapy (OIT) is accomplished by mixing the THEraPEUTIC PrINCIPLES
allergenic food into a vehicle food, initially giving doses below avoidance
the level that would trigger reactions in an allergic individual Read ingredient labels closely. The eight most common food allergens
and gradually increasing the amount of protein ingested over are required to be disclosed on ingredient labels of foods manufactured
time. The buildup phase of therapy typically lasts several months; and sold in the United States.
once a maintenance dose of allergen is achieved, the patient Minimize cross-contact with food allergens during meal preparation.
has to ingest the allergen for a certain period (typically ≥1 years, Use utensils, cutting boards, and pans that have been thoroughly
washed with soap and water.
possibly indefinitely) to maintain a protected, desensitized state. If you are preparing several foods, make the allergy-safe food first.
Most studies have focused on achievement of desensitization, Wash hands with soap and water before touching anything else if
which refers to a temporary increase in the threshold of allergen you have handled a food allergen.
required to elicit a reaction and is dependent on regular exposure Wash counters and table with soap and water after making meals.
to the allergen. When eating at a restaurant, inform the waiter and cooking staff about
OIT will induce significant desensitization in most patients food allergens.
who are able to tolerate therapy. However, sustained protection Avoid buffets.
against an allergic reaction independent of ongoing allergen Treatment
exposure (sustained unresponsiveness [SU]) has not been Advise patients at risk of anaphylaxis to carry two autoinjectable epi-
adequately measured; only a minority of individuals achieved nephrine devices at all times.
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SU in the few studies measuring this outcome. Most indi- Recommend a medical identification bracelet.
viduals undergoing OIT will experience adverse reactions. Oral Provide an anaphylaxis emergency plan, and review indications for
pruritus and transient abdominal pain are the most common administration of autoinjectable epinephrine.
problems; reactions are typically mild and do not require any Demonstrate the appropriate use of autoinjectable epinephrine with a
treatment. Severe reactions, such as anaphylaxis, may develop trainer device at the physician’s clinic visits.
during therapy; predisposing factors include infection, exercise,
and allergen coexposure. GI symptoms are the most common Epicutaneous Immunotherapy
reason for participants withdrawing from OIT trials, and EoE Epicutaneous immunotherapy (EPIT) delivers allergen to the
has occasionally been documented. Further work is needed to skin through application of an allergen-containing patch.
determine which patients are most likely to develop SU, who Langerhans cells in the skin are activated and effector cell
will tolerate OIT with few dose-limiting adverse events, and responses are downregulated. Peer-reviewed published data are
the mechanisms underlying the development of desensitization currently lacking, but preclinical studies have demonstrated
and SU. potential for clinical efficacy. The only published trial utilizing
The initial immune response detected in desensitization EPIT has reported an increased threshold of reactivity after 3
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includes an increase in food-specific IgG4, decreased basophil months of therapy in children with milk allergy. Anaphylaxis
and mast cell responsiveness, and an initial increase in allergen- has not been reported with EPIT; the most common side effect
specific IgE. Allergen-specific IgE then decreases gradually over appears to be an eczematous response at the site of patch
time. After 6–12 months of therapy there appears to be a shift application.
away from Th2 cytokine production in response to allergen
toward a Th1 profile. Treg upregulation occurs later in the course CONCLUSIONS
of OIT, with studies showing increased function of antigen-specific
+
+
+
CD4 CD25 FOXP3 Tregs. Epitope mapping typically changes
over time indicating different antigen-specific responsiveness. ON THE HOrIZON
Unfortunately, there are no biomarkers that consistently predict Allergen-specific desensitization therapies are currently investigational
successful desensitization or sustained unresponsiveness. but may be available for clinical use in the near future.
Oral immunotherapy (OIT) exposes the allergic patient to progressively
Sublingual Immunotherapy larger doses of ingested allergen in an effort to induce a desensitized
state. Gram quantities of allergen are typically administered.
Sublingual immunotherapy (SLIT) utilizes a food protein dis- Epicutaneous immunotherapy (EPIT) applies microgram amounts of
solved in a liquid medium and delivered beneath the tongue. allergen directly to the allergic patient’s skin, resulting in an effort
The oral mucosa contains tolerogenic APCs: SLIT is thought to to increase the threshold of reactivity. EPIT patch is typically kept
rely on these cells to induce a desensitized state. SLIT dosing on skin for up to 24 hours at a time, and a new patch is applied
utilizes microgram to milligram quantities of protein, whereas daily. Few published studies to date have reported its efficacy.
OIT protocols utilize gram quantities of protein. Increasing Sublingual immunotherapy (SLIT) involves sublingual administration
the amount of allergen given is limited by the concentration of milligram quantities of allergen solubilized in a liquid formulation.
of available extracts and the volume of liquid that can be held Systemic reactions are rare; however, studies to date have not
consistently shown benefit in tested subjects.
sublingually.