A brief history of allergen immunotherapy.

Allergen immunotherapy has its roots in the immunologic treatment of contagious disease. The idea, beginning in the 18th century, that one could be protected against certain illnesses was successfully extended to the field of allergy in 1911. This review presents highlights of the advances by some of the individuals who have contributed to the science of allergen immunotherapy.

Rhinitis 2020: A practice parameter update.

This comprehensive practice parameter for allergic rhinitis (AR) and nonallergic rhinitis (NAR) provides updated guidance on diagnosis, assessment, selection of monotherapy and combination pharmacologic options, and allergen immunotherapy for AR. Newer information about local AR is reviewed. Cough is emphasized as a common symptom in both AR and NAR. Food allergy testing is not recommended in the routine evaluation of rhinitis. Intranasal corticosteroids (INCS) remain the preferred monotherapy for persistent AR, but additional studies support the additive benefit of combination treatment with INCS and intranasal antihistamines in both AR and NAR. Either intranasal antihistamines or INCS may be offered as first-line monotherapy for NAR. Montelukast should only be used for AR if there has been an inadequate response or intolerance to alternative therapies. Depot parenteral corticosteroids are not recommended for treatment of AR due to potential risks. While intranasal decongestants generally should be limited to short-term use to prevent rebound congestion, in limited circumstances, patients receiving regimens that include an INCS may be offered, in addition, an intranasal decongestant for up to 4 weeks. Neither acupuncture nor herbal products have adequate studies to support their use for AR. Oral decongestants should be avoided during the first trimester of pregnancy. Recommendations for use of subcutaneous and sublingual tablet allergen immunotherapy in AR are provided. Algorithms based on a combination of evidence and expert opinion are provided to guide in the selection of pharmacologic options for intermittent and persistent AR and NAR.

SIT beyond respiratory diseases.

OBJECTIVE: The goal was to assess the effectiveness of specific immunotherapy (SIT) in reduction of symptoms and medication score in patients with immunoglobulin E (IgE) mediated extrinsic form of atopic dermatitis (AD); and to assess the effectiveness of oral immunotherapy (OIT) as "active" treatment to achieving tolerance for food(s) in patients with IgE mediated food allergy. DATA SOURCES: Computerized bibliographic searches of MEDLINE (1998-2010) were supplemented by hand searches of reference lists. Studies were included if they were double-blind randomized controlled trials comparing subcutaneous immunotherapy (SCIT) or sublingual immunotherapy (SLIT) or OIT with placebo. However uncontrolled studies and case reports were also included. STUDY SELECTIONS: Thirty-two studies were analyzed. Because of the high heterogeneity of the AD studied only results of 2 placebo controlled studies 1-SCIT and 1-SLIT respectively were comparable. Among OIT studies: 4 carried out with control groups were analyzed. RESULTS: From 36% to 92% of patients treated with OIT reached tolerance to cow's milk or egg; a rate of 8% to 53% reached partial tolerance. The patients had either clinical history of severe systemic reactions to foods: anaphylaxis, or mild to moderate reactions. Regarding SIT for AD: 72% of patients treated with house dust mite SCIT and 54% treated with SLIT had a significant improvement of SCORAD-Index. CONCLUSIONS: This review found that OIT with cow's milk or egg is effective in achieving full tolerance or partial tolerance in the majority of patients with IgE mediated food allergy. SIT may represent an additional therapeutic tool for the treatment of extrinsic AD in properly selected patients.

Immunotherapy throughout the decades: from Noon to now.

OBJECTIVE: To review major milestones in the development of subcutaneous allergen immunotherapy in 20-year segments. DATA SOURCES: Review of the literature available in textbooks and journals. STUDY SELECTION: Articles and books addressing major achievements in the development of subcutaneous allergy immunotherapy were selected for inclusion in this review. RESULTS: Immunotherapy administration has improved the lives of possibly millions of patients with hay fever. Asthmatic symptoms have been relieved if not ablated in millions as well. Insect venom hypersensitivity became treatable and highly effective. In the beginning years of immunotherapy, it was clear that immunotherapy worked; in the later years, the mechanisms for this efficacy were discovered. In this case, the therapy preceded its validation. Methods, materials, and safety have vastly improved. Postulated mechanisms explain much but not everything. CONCLUSIONS: There is still research to be accomplished, improvements to be made, and, of course, patients to be made well.

American Academy of Allergy, Asthma & Immunology/American College of Allergy, Asthma and Immunology Joint Task Force Report on omalizumab-associated anaphylaxis.

The American Academy of Allergy, Asthma & Immunology and the American College of Allergy, Asthma and Immunology Executive Committees formed the Omalizumab Joint Task Force with the purpose of reviewing the Genentech Xolair (omalizumab) clinical trials and postmarketing surveillance data on anaphylaxis and anaphylactoid reactions. Using the definition of anaphylaxis proposed at a 2005 multidisciplinary symposia, the Omalizumab Joint Task Force concluded that 35 patients had 41 episodes of anaphylaxis associated with Xolair (omalizumab) administration between June 1, 2003, and December 31, 2005. With 39,510 patients receiving Xolair (omalizumab) during the same period of time, this would correspond to an anaphylaxis-reporting rate of 0.09% of patients. Of those 36 events for which the time of reaction was known, 22 (61%) reactions occurred in the first 2 hours after one of the first 3 doses. Five (14%) of the events after the fourth or later doses occurred within 30 minutes. Considering the timing of these 36 events, an observation period of 2 hours for the first 3 injections and 30 minutes for subsequent injections would have captured 75% of the anaphylactic reactions. The OJTF report provides recommendations for physicians who prescribe Xolair (omalizumab) on (1) the suggested wait periods after administration and (2) patient education regarding anaphylaxis.

Efficacy and response with olopatadine versus epinastine in ocular allergic symptoms: a post hoc analysis of data from a conjunctival allergen challenge study.

OBJECTIVES: This post hoc analysis used data from a previous study to more precisely evaluate the efficacy of olopatadine hydrochloride and epinastine hydrochloride in alleviating various levels of severity of ocular itching and conjunctival redness and to determine whether there were any significant differences in the number of responders to treatment. METHODS: The original study was a randomized, double-masked allergen challenge comparison assessment. Adult patients with allergic conjunctivitis were screened (visits 1 and 2); those who exhibited positive allergic reactions at both visits were randomized to 1 of 3 groups. olopatadine/epinastine, olopatadine/placebo, or epinastine/placebo. At visit 3, each eye was treated with study medication, and then challenged with allergen. Itching, redness, and chemosis assessments were recorded. For the present post hoc analysis, each eye in the olopatadine/epinastine group was separately classified at each time point, based on the pretreatment severity of their symptom (itching) and sign (conjunctival redness) scores, as moderate, moderate/severe, or severe. Data were analyzed to determine responders (eyes with itching and/or conjunctival redness scores of 0 [none]). RESULTS: Of 96 patients screened, 66 were randomized to treatment (36 women, 30 men; mean age, 44.38 years [range, 20-71 years]). Olopatadine-treated eyes exhibited lower mean itching scores than epinastine-treated eyes in the moderate/severe and severe groups at all 3 time points (3, 5, and 7 minutes), with significance in the moderate/severe group at 5 minutes (P = 0.05) and in the severe group at 5 and 7 minutes (P = 0.017 and P = 0.02, respectively). Olopatadine-treated eyes had mean conjunctival redness scores similar to epinastine-treated eyes in all severity groups at all time points (10, 15, and 20 minutes) except in the severe group at 10 minutes (P = 0.03). On response analysis, for itching, the proportion of responders was significantly greater in the olopatadine group versus the epinastine group 7 minutes after challenge (27 [50.9%] vs 14 [26.4%]; P = 0.016). For conjunctival redness, the proportion of responders was significantly greater with olopatadine treatment versus epinastine treatment at 15 and 20 minutes after challenge (15 minutes, 12 [22.6%] vs 1 [1.9%] [P = 0.002]; 20 minutes, 10 [18.9%] vs 1 [1.9%] [P = 0.008]).

Is immunotherapy effective in allergic disease?

PURPOSE OF REVIEW: The purpose of this review is to summarize the basic principles of effective immunotherapy, and to highlight some of the advances that have been published in the past year. RECENT FINDINGS: Recent findings show that immunotherapy, when performed appropriately and properly, not only causes a decrease in symptoms, use of medication and an improved quality of life, but also that the shift from allergic rhinitis to asthma is substantially decreased and the development of new allergies is diminished. In addition, laboratory studies continue to demonstrate significant changes in the immune system moving the patient towards a non-allergic immune function T helper type 2 cell to T helper type 1 cell shift. SUMMARY: In summary, recent research clearly continues to demonstrate the efficacy of immunotherapy not only as a therapeutic agent but as a preventive one as well.

Immunotherapy in the age of anti-IgE.

Recent results of allergen immunotherapy research have continued to validate efficacy and have also demonstrated a truly preventive aspect for this treatment. This review summarizes the basic principles of effective allergen immunotherapy and highlights some of the advances that have been published in the past year. These studies show that allergen immunotherapy, when done appropriately and properly, not only causes a decrease in symptoms and use of medication as well as an improved quality of life, but that the progression of disease from allergic rhinitis to asthma is substantially decreased and the development of new allergies is diminished. In addition, laboratory studies continue to demonstrate significant changes in the immune system with a shift in the immune pathway from TH2 toward a TH1 response. The impact of anti-IgE as a therapeutic agent with allergen immunotherapy is also be reviewed.

Clinical efficacy of olopatadine vs epinastine ophthalmic solution in the conjunctival allergen challenge model.

BACKGROUND: Olopatadine hydrochloride 0.1% ophthalmic solution (Patanol) and epinastine hydrochloride 0.05% ophthalmic solution (Elestat) are two topical antiallergic agents. Olopatadine is indicated for the treatment of the signs and symptoms of allergic conjunctivitis that include itching, redness, tearing, lid swelling, and chemosis. Epinastine is indicated for the prevention of itching associated with allergic conjunctivitis. OBJECTIVE: This study compared the clinical efficacy of olopatadine and epinastine in the prevention of itching and conjunctival redness in the conjunctival allergen challenge (CAC) model. RESEARCH DESIGN AND METHODS: This was a prospective, randomized, double-masked, contralaterally-controlled, single center allergen challenge study. Ninety-six subjects with a history of allergic conjunctivitis were screened, and the 66 who responded to conjunctival allergen challenge at visits 1 and 2 were randomized into 1 of 3 treatment groups at visit 3 to receive one drop of study medication in each eye: (1) olopatadine in one eye and epinastine in the fellow eye, (2) olopatadine in one eye and placebo in the fellow eye, and (3) epinastine in one eye and placebo in the fellow eye. Five minutes after study drop instillation, subjects were bilaterally challenged with the allergen concentration that had elicited a positive conjunctival allergic response at Visits 1 and 2. Subjective itching assessments were given at 3 min, 5 min, and 7 min post challenge. Objective redness and chemosis assessments were made at 10 min, 15 min, and 20 min post challenge. Paired sample two-tailed t-tests were performed on the mean scores at each time point to assess statistical significance in the differences between treatments. MAIN OUTCOME MEASURES; RESULTS: Fifty-three subjects were randomized into the olopatadine/epinastine treatment group, the primary analysis group. Olopatadine treated eyes exhibited significantly lower mean itching and conjunctival redness scores than the contralateral epinastine treated eyes, -0.19 (p = 0.003) and -0.52 (p < 0.001), respectively. Olopatadine treated eyes also exhibited significantly less chemosis -0.24 (p < 0.001), ciliary redness -0.55 (p < 0.001), and episcleral redness -0.58 (p < 0.001) than epinastine treated eyes. CONCLUSION: Olopatadine is significantly more effective than epinastine in controlling itching, redness and chemosis associated with allergic conjunctivitis in the CAC model.

Conference scene: recent advancements in immunotherapy.

Immunotherapy was a prominent part of the program at the Annual Meeting of the American College of Allergy, Asthma and Immunology in Boston, MA, USA, 3-8 November 2011. New advances in immunotherapy as well as mechanisms were featured. Recent updates of the immunotherapy practice parameters were discussed as well. The report on the safety of immunotherapy highlighted the data demonstrating that there have been no fatalities from this treatment during the past 4 years. The last speaker dealt with economic issues, presenting data that show that subcutaneous immunotherapy led to improved clinical outcomes and reduced costs in children and adults with allergic rhinitis.

Nontuberculous mycobacterial infection in the differential diagnosis of chronic cough.

Patients presenting with chronic coughs are seen frequently by allergists/immunologists. When the usual diagnostic and therapeutic maneuvers do not control symptoms, it is worthwhile to consider whether a non-tuberculous mycobacterial (NTM) infection might be playing a role in the pathogenesis of the coughing. Sputum culture should be considered along with a pulmonary computerized axial tomography scan. NTM infection should be added to the differential diagnosis list for patients with chronic coughs unresponsive to conventional therapy.

Issues in stinging insect allergy immunotherapy: a review.

PURPOSE OF REVIEW: The treatment of insect allergy by desensitization still continues to present with some unanswered questions. This review will focus mainly on articles that have dealt with these issues in the past 2 years. RECENT FINDINGS: With the publication in 2007 of Allergen Immunotherapy: a practice parameter second update, many of the key issues were reviewed and summarized. Other recent studies deal with omalizumab pretreatment of patients with systemic mastocytosis and very severe allergic reactions to immunotherapy. It would appear that venom immunotherapy is somewhat unique compared to inhalant allergen immunotherapy in that premedication prior to rush protocols may not be necessary and that intervals of therapy may be longer than with allergen immunotherapy. The use of concomitant medications such as beta-blockers may be indicated in special situations. Angiotensin-converting enzyme inhibitors can be stopped temporarily before venom injections to prevent reactions. The issue of when to discontinue immunotherapy remains unsettled and should be individualized to patient requirements. SUMMARY: The newest revision of the Immunotherapy Parameters provides much needed information concerning successful treatment with immunotherapy of Hymenoptera-sensitive patients.