Allergic inflammation.
Definition of allergy, intradermal test in the Legal Dictionary. How common are allergies in dogs? Unfortunately, allergies are quite common in dogs of all breeds and backgrounds. Most allergies appear after the pet is six months. An overview of allergy symptoms, allergy diagnosis, allergy treatment and allergy management written and reviewed by leading experts in allergy, asthma and immunology. Sublingual immunotherapy for allergic rhinoconjunctivitis and asthma. Literature review current through. Oct 2. 01. 6. Subcutaneous immunotherapy (SCIT) has proven efficacy in allergic rhinoconjunctivitis and asthma, but it requires regular injections at a clinician's office (typically over a period of three to five years) and carries the risk of potentially serious systemic allergic reactions in response to the treatment itself. The alternate approach of administering allergens orally, and more specifically with a sublingual methodology in which the allergen is given as either a dissolvable tablet (under the tongue) or as an aqueous or liquid extract, has evolved into a viable treatment for allergic respiratory diseases. Sublingual immunotherapy (SLIT) offers several specific advantages over injection immunotherapy. SLIT can be self- administered by patients or caregivers, does not require injections, and carries a much lower risk of anaphylaxis compared with SCIT. This topic will discuss the mechanisms of action, advantages, and limitations of SLIT for allergic rhinitis and the most common methods of administering immunotherapy via an oral route: sublingual immunotherapy tablets (SLIT- tablets) and sublingual aqueous or glycerinated liquid preparations (SLIT- drops). The use of SCIT for the treatment of allergic respiratory diseases is discussed separately. In the 1. 98. 0s, properly designed clinical trials first demonstrated a dose- dependent therapeutic response with specific and well- characterized aeroallergens. In 1. 99. 8, the World Health Organization (WHO) recognized that SLIT was a promising alternate mode of immunotherapy and encouraged continued clinical investigation into this form of treatment . In 2. 00. 9, the World Allergy Organization (WAO) published their opinion that the cumulative evidence showed SLIT represented a viable alternative to SCIT and encouraged continued clinical investigation to characterize optimal techniques . The following forms are most promising. The majority of United States clinical studies have defined a single optimal dose based on prior dose- ranging safety studies. The tablets are self- administered, once daily. The allergen is taken up through the rich vascular lymphoid network of the mouth. Oral solutions that are held in the mouth for a period of time, but then spit out rather than swallowed, have also been evaluated in clinical trials. However, holding the extract under the tongue appears more efficient for delivery of active drug. Other approaches to oral immunotherapy that have been investigated in research trials include administration of the allergen(s) as enteric- coated tablets, liposomal constructs, or microencapsulated polymers. These oral (swallow) delivery systems are intended to protect the allergenic proteins from breakdown in the stomach and then allow a p. H- dependent release in the small intestine for processing by the gut- associated lymphoid tissue (GALT). ![]() However, research studies with these constructs have not, as of yet, demonstrated evidence for effective delivery . There are a smaller number of studies of dust mite immunotherapy. The use of food allergens or latex allergens in oral immunotherapy is discussed separately. Some SLIT- tablets are available in Canada. In April 2. 01. 4, the US Food and Drug Administration (FDA) announced approval of a 5- grass pollen sublingual tablet (Oralair) produced by Stallergenes . These are the first immunotherapy tablets to become available in the United States. The issues regarding this practice are discussed below. ![]() ![]() The normal response of the gut immune system to nonpathogenic proteins is tolerance, a fact which forms the basis for the concept of oral immunization. The gut immune system is comprised of various physical barriers, secretory immunoglobulin A (Ig. A), the gut- associated lymphoid tissue (GALT), and lymphoid organs (mesenteric lymph nodes, spleen, and liver). Within the GALT, two areas of importance for antigen processing are the tonsils and adjacent ring of lymphoid tissue in the posterior pharynx and the Peyer's patches of the duodenum, jejunum, and small intestine. The GALT is essential for normal tolerance to most foreign proteins, as well as in the immunologic response to oral immunotherapy. The role of the GALT in the pathogenesis of food allergy is reviewed elsewhere. Whether the immunologic response to allergens absorbed through the oral mucosa is different from that to allergens absorbed through the intestine is an area of ongoing investigation. Likely mechanisms of action include activation of T regulatory cells and downregulation of mucosal mast cells . Within the oral and sublingual mucosa, effector cells, such as mast cells, are less numerous . This characteristic of the oral mucosa is believed to be an important factor in the lower rates of adverse systemic allergic reactions seen with SLIT. Allergen processing within the GALT is discussed in greater detail separately. Systemic tolerance occurs as a result of a decline in T helper mechanisms or stimulation of T suppressor cells involved in immunoglobulin E (Ig. E) production. Mechanisms of oral tolerance are discussed in more detail separately. Several studies now suggest that Ig. G4 production is under the control of interleukin- 1. IL- 1. 0). As mentioned previously, Ig. G4 production may be regulated by IL- 1. SCIT has been shown to induce T regulatory cells to produce IL- 1. IL- 1. 0 downregulates T helper type 2- dependent inflammation and suppressed B cell isotype switching to Ig. E. Serum ECP is an indicator of activated eosinophils, and reductions in the ECP: eosinophil ratio suggest that a smaller percentage of eosinophils are in an activated state as a result of successful immunotherapy. Furthermore, IL- 1. The immunologic changes observed with SCIT are discussed in more detail elsewhere. Other contraindications include a history of eosinophilic esophagitis and hypersensitivity to any of the inactive ingredients. It is recommended that patients with asthma do not take SLIT- tablets when they are experiencing an acute asthma exacerbation and that they be reassessed after an asthma exacerbation, or if they have recurrent asthma exacerbations on therapy, to determine if it is appropriate to continue treatment. If patients receiving SLIT- tablets develop oral inflammation (eg, thrush, mouth ulcers, oral lichen planus) or oral wounds (eg, following dental surgery or tooth extraction), SLIT therapy should be stopped to allow complete healing of the oral mucosa before resumption. The manufacturers of the SLIT- tablet products available in the United States recommend that patients should be prescribed self- injectable epinephrine and instructed in its proper use . Sensitization to any of the 5- grass species contained in the tablet (Timothy, Orchard, Perennial Rye, Kentucky Blue Grass, Sweet Vernal) should be confirmed by positive skin test or in vitro testing for pollen- specific immunoglobulin E (Ig. E) antibodies to any of the 5- grass species contained in the tablet. The tablet is administered under the tongue and held there for at least one minute or until fully dissolved (table 1). The patient should be instructed not to ingest food or beverage for five minutes following dissolution of the tablet. The first dose is to be taken at the clinician's office under medical supervision, and patients should be observed for at least 3. Subsequent doses are to be administered once a day by the patient (or the patient's caregiver). Dosing is expressed in . For children 1. 0 to 1. IR tablet on day 1, two 1. IR tablets on day 2, one 3. IR tablet daily thereafter, if tolerated). Patients 1. 8 years and older start with the full 3. IR tablet, which contains approximately 2. L of group 5 major allergens. Treatment should be started four months (1. The most common adverse effects were oral pruritus, throat irritation, ear pruritus, and mouth edema (2. Oralair is labeled as contraindicated in patients with severe, unstable, or uncontrolled asthma; a history of any severe systemic allergic reaction; a history of any severe local reaction after taking sublingual allergen immunotherapy; a history of eosinophilic esophagitis; or hypersensitivity to any of the inactive ingredients. Oralair was not studied in patients with moderate or severe asthma or patients requiring daily controller therapy . Prior to considering this therapy, allergy to Timothy or to a cross- reactive grass species (Sweet Vernal, Orchard, Perennial Rye, Kentucky Blue/June Grass, Meadow Fescue, or Redtop) should be confirmed by positive skin test or in vitro testing for pollen- specific immunoglobulin E (Ig. E) to Timothy grass or to one of the cross- reactive grass pollens. Patients living in geographic areas with other grass species that do not cross- react with the temperate family (eg, Bermuda, Bahia) may not have as complete a therapeutic response to the Timothy grass tablet, depending upon the degree to which they are sensitive to these other grasses. In addition, there is some evidence that although grass allergens are highly homologous across species, individual allergens may be differentially recognized by T cells, and therefore a 5- grass tablet may provide a broader array of clinically relevant epitopes . However, there is no evidence at present that the 5- grass tablet provides superior efficacy over the Timothy tablet. The tablet is administered under the tongue and held there until fully dissolved, after which the patient should not ingest food or beverages for five minutes (table 1). The first dose is to be taken at the clinician's office under medical supervision, and patients should be observed for at least 3. Subsequent doses are to be administered once a day by the patient (or the patient's caregiver). Treatment should be started three months (1. It may be taken throughout the year and for three consecutive years, although the optimal schedule of treatment has not been determined.
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