Allergen Immunotherapy

Specific allergen immunotherapy provides a 50% reduction in medication and symptoms if sufficient doses of the major allergens are administered to significantly (epicutaneous or percutaneous positive skin tests) allergic subjects. This improvement is confirmed by the majority of controlled trials with immunotherapy in both seasonal and perennial allergic rhinitis. Laboratory tests and challenge studies, in general, correlate with the clinical findings. The most consistent humoral change is an increase in specific IgG, with some studies showing a switch from specific IgG1 to IgG4 (Table 10). However, the many exceptions indicate that there is not a specific confir­matory test to

Table 8

Stepwise Approach to the Treatment of Seasonal Allergic Rhinitis

Allergen avoidance and pharmacological therapy

Mild disease or with occasional symptoms

Moderate disease with prominent nasal symptoms Moderate disease with prominent eye symptoms

If above ineffective

Perennial allergic rhinitis in adults Intermittent disease

1 Oral nonsedating Hj-antihistamine when symptomatic (desloratidine, fexofenadine, loratidine, or possibly cetirizine)a OR

1 Topical nasal azelastine when symptomatic or sodium cromoglycate to eyes, nose, or both/alternative for intermittent eye symptoms is topical ocular antihistamine or topical nonsteroidal antiinflammatory (ketoroloac tromethamine )b

1 Intranasal corticosteroid daily (start early in season) PLUS

1 Antihstamine or topical eye therapy with sodium cromoglycate or lodoxamide tromethamine or olopatadine hydrocholorideb

1 Oral nonsedating Hj-antihistamine daily3 OR

1 Intranasal corticosteroid and topical eye therapy with sodium cromoglycate or lodoxamide tromethamine or olopatadine hydrocholoride/topical nonsteroidal antiinflammatory (ketoroloac tromethamine) additional therapy for exacerbationsb

1 Review possibility of coexisting disease or complications (e.g., sinusitis)

1 Consider immunotherapy

1 Systemic corticosteroid therapy for a few days for severe symptoms

1 Topical ipratropium bromide if rhinorrhea a major problem

1 Allergen avoidance

1 Intranasal corticosteroids if long-term exposure

1 Oral nonsedating Hj-antihistamine therapy'

1 Oral decongestants

  • Sedating, traditional (first-generation) antihistamine therapy is a consideration because of cost of second-generation antihistamines. However, functional impairment occurs with first-generation antihistamine therapy even if treated subjects do not perceive impairment. Therefore, it is difficult to evaluate the risk-benefit ratio, and a treating physician may be at legal risk if any accident occurs while a patient is being treated with a sedating antihistamine without first trying nonsedating antihistamine therapy. Fexofenadine, loratidine, and desloratidine are safe, effective, nonsedating antihistamine therapies that have almost no side effects. There is no concern with combining these treatments with other therapies, including macrolide antibiotics and azole antifungals. Cetirizine is mildly sedating, with clinical trial results variable as to the importance of this sedation. Oral antihistamine therapy achieves approx 30% improvement in 50% of treated subjects. Azelastine (a topical antihistamine therapy for rhinitis) is also mildly sedating, but some authorities debate the clinical significance of this effect. Azelastine topical is indicated for nonallergic rhinitis, an indication not shared by any oral antihistamine. This point supports a mechanism of action that may be unique for azelastine topical.
  • Topical ocular therapy is not recommended with contact lens use.

Table 9 Allergen Avoidance Measures

Avoidance measures for mite allergen

Bedrooms

  • Cover mattresses and pillows with impermeable covers
  • Wash bedding regularly at 130° F
  • Remove carpets, stuffed animals, and clutter from bedrooms
  • Eliminate wall-to-wall carpet
  • Vacuum clean weekly (wear a mask or use a high-efficiency particulate air (HEPA)

filtered vacuum cleaner

Rest of house

  • Minimize carpets and upholstered furniture (particularly in basements or overlying concrete)
  • Reduce humidity below 45% relative humidity or 6 g/kg (may not be feasible in many climates)
  • Consider treatment of carpets with benzyl benzoate powder or tannic acid spray
  • questionable efficacy)

Avoidance measures for cat allergen

Remove cat from the house (allergen reduction sufficient to affect symptoms may take >12-16 wk)

Measures to reduce allergen if cat remains in home (limited if any efficacy)

  • Minimize cat contact with carpets, upholstered furniture, and bedding
  • Use vacuum cleaners with an effective filtration system
  • Increase ventilation
  • Consider a HEPA system to remove small airborne particles
  • Consider washing cat every 2 wk demonstrate clinical benefit. Symptom improvement remains the standard response variable.

Advantages of allergen immunotherapy in addition to symptom improvement are that the treatment may reduce the future development of additional sensitivities and minimize the occurrence of asthma in subjects with allergic rhinitis. Pharmacotherapy is not likely to achieve these goals. Finally, immunotherapy offers the potential of treating allergic airway disease beyond the nose with improvement in allergic conjunctivitis and/or asthma. Duration of allergen immunotherapy is based on clinical experience and limited evidence. In general, 3-5 yr of maintenance treatment, usually administered every 3-4 wk, is necessary to minimize reoccurrence of symptoms after discontinuation.

The major impediments to allergen immunotherapy are the inconvenience and cost of the therapy and risk of anaphylaxis. Analyses have shown that high-dose allergen immunotherapy is cost-effective because of the reduction of regular medication use. Anaphylaxis following immunotherapy occurs in 0.1-3% of treated subjects. This risk, which is minimized by identification and treatment of anaphylaxis, requires that allergen immunotherapy be administered under the immediate supervision of a physician or provider trained in the treatment of anaphylaxis. Treated subjects should remain under

Table 10

Mechanisms of Action of Immunotherapy

  • Increase in T-suppressor activity
  • Modulation of T-regulatory cells
  • Decrease in histamine-releasing factors
  • Increase in specific IgG
  • Decrease in specific IgE
  • Decrease in mediator release from basophils observation for 20-30 min after receiving subcutaneous allergen immunotherapy to minimize risk after departure.

The indications for allergen immunotherapy include severe symptoms, poor response to medications, intolerance to, or side effects from medications or reluctance to take medications (Fig. 6). Relative contraindications include uncontrolled asthma, p-blocker therapy, autoimmune disease, and malignancy. Immunotherapy should be initiated and supervised by a trained specialist but can be administered by any physician who is prepared to treat anaphylaxis, the most serious adverse effect of the treatment.

The risk and inconvenience of allergen immunotherapy have stimulated the study of oral allergen immunotherapy. This technique has been utilized in the past but the dose of allergen administered was inadequate for double-blind, controlled trials to demonstrate efficacy. In the past 10 yr, a series of investigations have shown clinical improvement with high-dose oral immunotherapy. Side effects do occur, but these tend to be less severe than with injection immunotherapy and localized to the mouth and gastrointestinal tract. The advantages of home administration, the minimized risk of anaphylaxis, and the relatively rapid attainment of the maintenance dose and clinical improvement make this treatment attractive. The disadvantages are the requirement for a very large dose of allergen vaccine, probable reduced efficacy compared to injection treatment, less evidence of efficacy in children, and limited evidence for long-term disease modification. Nevertheless, sublingual allergen immunotherapy may be a consideration for select patients at risk for anaphylaxis or in circumstances not permitting regular visitation with a physician to administer immunotherapy. This treatment is not currently approved in the United States.

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