Perennial Allergic Rhinoconjunctivitis Research Articles

English

Background: Bilastine is a second-generation antihistamine for the symptomatic treatment of allergic rhinoconjunctivitis (ARC) and urticaria in adults, adolescents, and children. The pharmacokinetics and safety of oral bilastine 10 mg/d in children aged 2 to 5 years were evaluated. Methods: This was a multicenter, open-label clinical trial in children aged 2 to 5 years with seasonal or perennial ARC or urticaria treated once daily with bilastine 10 mg orodispersible tablets. The safety evaluation included treatment-emergent adverse events (TEAEs), vital signs, and physical examination. Pharmacokinetic data were pooled with data from a prior pediatric study, and pharmacokinetic modeling was performed to assess consistency. Results: A total of 37 children with ARC (81.1%), urticaria (8.1%), or both (10.8%) were included in the study, with a mean (SD) age of 3.7 (1.2) years. The highest plasma concentrations of bilastine were observed 1 hour after administration (634.91 ng/mL). Eight patients (21.6%) experienced 1 TEAE each, none of which was severe. Body weight and age were not covariates of variation in either systemic clearance or the volume of distribution in children aged 2 to 5 years and did not affect the pharmacokinetic parameters of bilastine. Conclusions: The pharmacokinetics of bilastine was linear and consistent with data from a previous trial, suggesting that a 10-mg dose may be used in children (2 to <12 years). No dose adjustments are deemed necessary. Oral once-daily bilastine 10 mg presented a good safety profile in children aged 2 to 5.

ELEVATED BASELINE SERUM TRYPTASE AND HEREDITARY ALPHA TRYPTASEMIA (HAT)

<h3>Introduction</h3> Hereditary alpha tryptasemia (HaT) is an autosomal dominant genetic trait characterized by elevated basal serum tryptase levels due to extra allelic copies of the tryptase alpha/beta 1 (TPSAB1) gene. HaT has been associated with multisystem complaints and as a modifier of mast cell-associated disorders and anaphylaxis. <h3>Case Description</h3> A 38-year-old male presented for evaluation of food and environmental allergies. He had severe oropharyngeal symptoms and a throat-closing sensation immediately after ingesting raw fruits and tree nuts. He also had symptoms of perennial allergic rhinoconjunctivitis with seasonal variation. Allergy skin testing showed IgE sensitivities to tree, grass and weed pollens, dust mites, mold spores, cat, dog, and cockroach. He had no IgE sensitivities to any of the fruits tested. He had IgE sensitivities to walnut, hazelnut, and almond. Given the severity of his oropharyngeal symptoms a baseline serum tryptase was checked, which was elevated at 20.3 mcg/L. Repeat determinations again showed baseline serum tryptase above 20 mcg/L. CBC with differential and CMP were within normal limits. 24-hour urinary histamine and N-methylhistamine were both within normal. Kit D16 mutation analysis was negative. TPSAB1 copy number analysis showed extra allelic alpha-tryptase copies, consistent with hereditary alpha tryptasemia (HaT). The patient received counseling and standard treatment for environmental/food allergies and tolerates allergen-specific immunotherapy. <h3>Discussion</h3> HaT is an inherited condition considered a biochemical trait and can be present in around 5% of the general population. Patients with elevated baseline serum tryptase may benefit from testing for extra allelic copies of TPSAB1.

Dupilumab elicits a favorable response in type-2 inflammatory comorbidities of severe atopic dermatitis

BackgroundThis case is the first report describing rapid, successful treatment of severe atopic dermatitis (AD) and comorbid type-2 inflammatory diseases in the same patient, with dupilumab treatment, with no side-effects.Case presentationWe report on effects of dupilumab in a patient with severe AD, a long-standing history of a mild, perennial allergic rhino-conjunctivitis, moderate asthma and chronic rhinosinusitis with nasal polyps (CRSwNP).ConclusionsPatients suffering from AD, asthma, allergic rhinitis and CRSwNP may be eligible for dupilumab single treatment that is possibly advantageous also from the pharmaco-economic standpoint.

Efficacy of dupilumab in atopic comorbidities associated with moderate-to-severe adult atopic dermatitis.

Dupilumab is an anti-IL-4Rα antibody used in the treatment of patients with moderate-to-severe atopic dermatitis (msAD). This study explored the potential benefit of dupilumab in perennial allergic rhinoconjunctivitis (PAR) and perennial allergic asthma (PAA) caused by indoor allergens in adults with msAD. This multicentric, prospective, observational, real-life study included adult patients with msAD who had been treated with dupilumab in 16 Italian care centres. Efficacy outcomes regarding AD, PAR and PAA were collected at baseline and 16weeks. Safety was also assessed. We enrolled 123 patients with msAD. Between baseline and 16weeks of treatment, the following measurements decreased statistically significantly: Eczema Area and Severity Index, SCOring AD, Patient-Oriented Eczema Measure, pruritus score, sleep score, Dermatology Life Quality Index and IgE. Dupilumab treatment in patients with comorbid PAR (n=41) was associated with significant improvements in PAR disease control (measured using a Rhinitis Control Scoring System) and in PAR Quality of life (QoL) (measured using the Rhinoconjunctivitis QoL Questionnaire scores). In 32 patients with comorbid PAA, dupilumab significantly improved PAA control (measured using the Asthma Control Test and five-item Asthma Control Questionnaire scores) and disease-related QoL (measured using the Asthma QoL Questionnaire scores). Thirty-five patients (28.5%) developed conjunctivitis during the study period. These results support the benefits of dupilumab for adult patients with PAR and/or PAA associated with msAD.

The efficiency of hypoallergenic space created with LG Puricare™ air purifier in the complex therapy of seasonal and perennial allergic rhinitis and bronchial asthma

Background. To evaluate the efficacy and tolerability of a hypoallergenic space created with the LG Puricare air purifier, in a closed hospital ward and at home in the complex treatment of patients with exacerbation of perennial and seasonal allergic rhinoconjunctivitis with or without asthma. Materials and methods. 70 patients with seasonal and perennial allergic rhinoconjunctivitis with or without asthma were involved in the open comparative, randomized, placebo-controlled study conducted in 2 stages. At the 1st stage, an assessment of the efficacy and tolerability of hypoallergenic space created with LG Puricare™ air purifier in the hospital was performed. At the 2nd stage, the same study was performed at home space. The primary endpoint of the study was the evaluation of the total symptoms score. Secondary endpoints were changes in the parameters of peripheral blood, eye, and nasal secretion eosinophilia, external respiration function, peak flowmetry parameters. An assessment of indoor allergens, pollen and mold spores concentration, determination of the number of particle matter and evaluation of microbial and fungal air contamination in the environment were also carried out. Results. A significant reduction of the concentration of airborne particles and mold spores was demonstrated. Disease severity score showed significant clinical improvement but no changes in the parameters of the external respiration function, eosinophilia of blood, eyes and nasal secretions. Conclusion. The use of LG Puricare™ air purifier is recommended as a part of complex therapy of patients with various allergic diseases.

EAACI Guidelines on Allergen Immunotherapy: Allergic rhinoconjunctivitis.

Allergic rhinoconjunctivitis (AR) is an allergic disorder of the nose and eyes affecting about a fifth of the general population. Symptoms of AR can be controlled with allergen avoidance measures and pharmacotherapy. However, many patients continue to have ongoing symptoms and an impaired quality of life; pharmacotherapy may also induce some side-effects. Allergen immunotherapy (AIT) represents the only currently available treatment that targets the underlying pathophysiology, and it may have a disease-modifying effect. Either the subcutaneous (SCIT) or sublingual (SLIT) routes may be used. This Guideline has been prepared by the European Academy of Allergy and Clinical Immunology's (EAACI) Taskforce on AIT for AR and is part of the EAACI presidential project "EAACI Guidelines on Allergen Immunotherapy." It aims to provide evidence-based clinical recommendations and has been informed by a formal systematic review and meta-analysis. Its generation has followed the Appraisal of Guidelines for Research and Evaluation (AGREE II) approach. The process included involvement of the full range of stakeholders. In general, broad evidence for the clinical efficacy of AIT for AR exists but a product-specific evaluation of evidence is recommended. In general, SCIT and SLIT are recommended for both seasonal and perennial AR for its short-term benefit. The strongest evidence for long-term benefit is documented for grass AIT (especially for the grass tablets) where long-term benefit is seen. To achieve long-term efficacy, it is recommended that a minimum of 3years of therapy is used. Many gaps in the evidence base exist, particularly around long-term benefit and use in children.

Allergen Immunotherapy Clinical Trial Outcomes and Design: Working Toward Harmonization of Methods and Principles.

Progress has been made in the harmonization of efficacy and safety outcome measures for allergen immunotherapy (AIT) trials, but unresolved issues still remain. Furthermore, there are discrepancies in recommendations from professional medical societies and regulatory agencies regarding requirements for AIT trials. In this article, we reviewed published recommendations and current data from recent clinical trials, as well as the criteria applied by regulatory authorities for approval of AIT products, to provide updated considerations for conducting phase 3 AIT trials. Topics discussed include analysis of outcomes and trial designs for pediatric and asthma indications, as well as trial designs for perennial allergic rhinoconjunctivitis. In addition, the need for harmonization of safety reporting is emphasized. Considerations presented in this article may further effort to find common ground among professional medical societies and government agencies in developing future recommendations for AIT trial design.

Bilastine in symptomatic allergic rhinoconjunctivitis and urticaria: a guide to its use

Bilastine, a non-sedating and long-acting second-generation antihistamine, is indicated for the symptomatic treatment of seasonal or perennial allergic rhinoconjunctivitis and urticaria in >90 countries worldwide. It has a favourable pharmacological profile, with a rapid onset of action and sustained efficacy over the 24-h dosing interval period, as well as a lack of CNS and cardiotoxic effects and clinically relevant drug interactions. In clinical trials, the efficacy of bilastine in treating rhinoconjunctivitis and urticaria was greater than that with placebo and generally similar to that of other second-generation antihistamines, and the overall tolerability profile of bilastine was similar to that of placebo.

The relative clinical impact of sublingual immunotherapy with carbamylated monomeric allergoids on allergic respiratory symptoms

Background To assess the cumulative and allergen-specific magnitude of effect, and its relative clinical impact, of sublingual allergy immunotherapy with carbamylated monomeric allergoids for allergic rhinoconjunctivitis. Carbamylated allergoids are hypoallergenic extracts with enhanced bioavailability, consequent to a partial resistance to enzymatic degradation, providing efficient dose-tuning. Methods Literature was searched for double-blind placebo-controlled randomized trials administering this treatment, without any restrictions. Pooled analysis of the effects on total symptoms scores (TSSs) during the first season of treatment was performed and for each selected trial the relative clinical impact (RCI) was calculated as the percentage reduction in TSSs obtained with active treatment compared to placebo. The effect size (SMD), the overall and allergen-related RCI were used to estimate an indirect comparison with pharmacotherapy (based on summary data recently extracted from literature). Results Eight studies (4 in grass, 2 in mites, 1 in pellitory, 1 in ragweed allergy) met inclusion criteria and were pooled, comparing overall 180 patients treated with active and 155 with placebo. The overall SMD for TSSs resulted [-0.99 (IC -1.41 to -0.57) p<0.001] with a significant interstudy heterogeneity (I 2 = 68%). SMD for grass pollen tablets was [-0.58 (IC -0.89 to -0.27) p<0.001], for mite tablets was [-1.54 (IC -2.07 to -1.02) p<0.001]. The weighted mean RCI was overall -31.69%, for grass pollen tablets -32.14%, for mite tablets -24.27%. Conclusions Indirectly compared to the relative clinical impact of standard pharmacotherapy (antihistamines RCI: -15.0%; antileukotrienes RCI: -6.5%; nasal corticosteroids RCI: -23.5%), carbamylated monomeric allergoids result highly effective in providing symptoms relief in seasonal and perennial allergic rhinoconjunctivitis. This estimation is most likely conservative and apparently reduced by the numerous methodological aspects that differentiate clinical trials on drugs and allergen immunotherapy.

Critical appraisal of bilastine for the treatment of allergic rhinoconjunctivitis and urticaria

Bilastine is a second generation antihistamine indicated for the treatment of seasonal or perennial allergic rhinoconjunctivitis and chronic urticaria with a daily dose of 20 mg, in adults and children over 12 years of age. The efficacy of bilastine has been shown to be similar to that of the comparator drugs for the control of the nasal and nonnasal symptoms of allergic rhinoconjunctivitis, while also showing a subjective improvement in the quality of life and in overall clinical impression. For chronic urticaria the symptoms (itching and the development of papules) lessens from the second day of treatment onwards, in a similar way to other antihistamines used as comparators. Bilastine should not be administered at meal times to avoid interference with the absorption process. It is not distributed to the central nervous system, is scarcely metabolized, and elimination is through the kidneys and feces, with a 14-hour elimination half-life. It has no effect on cytochrome P450. During clinical development, bilastine was shown to be a drug that is adequately tolerated, with a similar effect to placebo with regard to drowsiness and changes in heart rate. In relation to its use, headaches were the most frequent adverse effect to be reported. No cardiotoxic effects have been observed, and the therapeutic dose does not alter the state of alertness.

Bilastine: a guide to its use in the treatment of symptomatic allergic rhinoconjunctivitis and urticaria

Bilastine, a new antihistamine, is indicated for the symptomatic treatment of seasonal or perennial allergic rhinoconjunctivitis and urticaria in many European countries. In clinical trials, the efficacy of bilastine in these indications was similar to that of other second-generation antihistamines. Bilastine is well tolerated, with an overall tolerability profile similar to that of placebo.

Bilastine

Bilastine is an orally administered, second-generation antihistamine used in the symptomatic treatment of seasonal or perennial allergic rhinoconjunctivitis and urticaria. In two well designed phase III trials, 14 days' treatment with bilastine was associated with a significantly lower area under the effect curve (AUEC) for the reflective total symptom score (TSS) than placebo in patients with symptomatic seasonal allergic rhinitis. Additionally, reflective nasal symptom scores were significantly lower in bilastine than placebo recipients in patients with a history of seasonal allergic rhinitis who were challenged with grass pollen allergen in a single-centre, phase II study. Neither bilastine nor cetirizine was effective in the treatment of perennial allergic rhinitis with regard to the mean AUEC for reflective TSS in another well designed phase III trial. However, results may have been altered by differences in some baseline characteristics and placebo responses between study countries. In another well designed phase III trial, compared with placebo, bilastine was associated with a significantly greater change from baseline to day 28 in the mean reflective daily urticaria symptom score in patients with chronic urticaria. There were no significant differences in primary endpoint results between bilastine and any of the active comparators used in these trials (i.e. cetirizine, levocetirizine and desloratadine). Bilastine was generally well tolerated, with a tolerability profile that was generally similar to that of the other second-generation antihistamines included in phase III clinical trials.

Efficacy of a novel air filtration pillow for avoidance of perennial allergens in symptomatic adults

Nighttime allergen exposures are a primary contributor to the development of allergic and asthmatic morbidities. Disease management guidelines recommend the use of environmental control measures to reduce these exposures, but clinically relevant reductions are difficult to achieve because most measures control only 1 allergen source among many in the bedroom environment. To determine whether a novel localized approach to nighttime allergen avoidance provides effective exposure reductions and clinical benefits. Thirty-five adults with perennial allergic rhinoconjunctivitis (dog, cat, or dust mite sensitivity) were randomized to receive PureZone, a combination therapy involving localized air filtration and pillow encasement, or placebo in a crossover trial with two 2-week treatment periods separated by a 1-week washout. Nasal and ocular allergy symptoms, quality of life, and breathing zone particulate exposure were assessed. Bedroom allergen dust samples were collected in the sleeping environment. Reductions (>99.99%) in allergen-sized particulate (> or = 0.3 microm) in the breathing zone led to significant improvements in nocturnal nasal and ocular allergy symptoms (P < .001) and quality of life (P = .02) for the active vs placebo device. Significant nocturnal symptom reductions vs placebo occurred the second night of use and were maintained for the duration of treatment; these reductions improved sleep problems in particular (P = .02). Allergens were detected in 100% of bedrooms, of which 44% had levels that exceeded sensitizing thresholds. The combination therapy of pillow encasement and localized air filtration provided effective nighttime allergen exposure reductions and clinical benefits without the use of adjunctive therapy.

Efficacy of PUREZONE ™, a Novel Local High Efficiency Particulate Air (HEPA) Filtration Pillow Device, in Patients With Perennial Allergic Rhinoconjunctivitis (PARC): A Double-Blind, Placebo-Controlled Randomized Clinical Trial (RCT)

Efficacy of PUREZONE ™, a Novel Local High Efficiency Particulate Air (HEPA) Filtration Pillow Device, in Patients With Perennial Allergic Rhinoconjunctivitis (PARC): A Double-Blind, Placebo-Controlled Randomized Clinical Trial (RCT)

Use of Antihistamines in Ocular Therapy

Approximately 20% of the general population have allergic symptoms of various forms. One third of these people have also ocular symptoms. Some forms of ocular allergy can cause severe symptoms and result in significant ocular morbidity. Allergic ocular disease consists of allergic conjunctivitis (including seasonal hay fever and perennial allergic rhinoconjunctivitis and acute anaphylaxis), giant papillary conjunctivitis (including vernalis, atopic keratoconjunctivitis and contact lens induced conjunctivitis), contact dermatokeratoconjunctivitis and microbioallergic disease. Histamine is the most prominent mediator in allergic ocular disease and causes increased vasopermeability, vasodilation, and bronchoconstriction, mediated through histamine receptors. Both H1 and H2 receptors have been identified on the ocular surface. Oral H1-receptor blockers can be given to relieve symptoms in the allergic ocular disease, but side effects such as sedation and systemic anticholinergic reactions are possible. Newer oral antihistamines such as astemizole and terfenadine supposedly have lesser side effects. Topical H1-receptor blocking antihistamine drugs are now available. Levocabastine is an agent with proven efficacy. There are no topical H2-receptor antagonists presently available for ocular use, but such agents have theoretic potential, especially in combination with an H1-receptor blocker Keywords: ocular allergic disease, hay fever, allergic conjunctivitis, seasonal conjunctivitis, vernal conjunctivitis, atopic conjunctivitis, antihistamine, h receptor antagonist

Influence in the quality of life of the respiratory patients by environmental control and the acaricide FrontacÆÊ

The present prospective, open, observational study assessed the effect of the use of standard environmental control measures together with the application of an acaricide-containing aerosol of esbiol/benzyl benzoate/piperonyl butoxide/2-phenylphenol (Frontac) on several clinical and environmental parameters in patients suffering from perennial allergic rhinoconjunctivitis related to house dust mites (HDM). Fifty-five patients were enrolled and studied for one year. Both symptoms and the patients' quality of life (evaluated by the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ)) were assessed at several clinic visits. The amount of HDM antigen was semi-quantitatively estimated using the guanine test. We found a significant decrease (p < 0.001) in most nasal symptoms scores: sneezing, runny nose, stuffy nose and itching. The overall quality of life (QoL) score also showed a significant improvement during the study period; the mean score decrease found was 0.86 (CI 95 %, 0.54-1.17) (p < 0.001). Five of the seven domains included in the questionnaire decreased significantly: non-hayfever symptoms; practical problems; nasal symptoms; eye symptoms, and emotions. These QoL score decreases were found during the first 3 months and later remained stable at lower levels than at baseline. The content of guanine in dust samples decreased significantly from 2.17 0.75 to 1.43 0.68 (p < 0.001). No toxic adverse events were recorded. In conclusion, these results show an improvement in the quality of life and a clinical benefit of the long-term use of the new chemical acaricide tested, together with environmental measures, in the home of patients suffering from allergic respiratory pathology.

Marked Peripheral Edema Associated with Montelukast and Prednisone

Letters6 June 2000Marked Peripheral Edema Associated with Montelukast and PrednisoneMario Geller, MDMario Geller, MDRua Visconde de Pirajá; 22410-001 Rio de Janeiro, Brazil (Geller)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-132-11-200006060-00022 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Cysteinyl leukotriene-receptor antagonists are new drugs for the treatment of persistent asthma (1). They may be used as alternatives to corticosteroids or adjuncts to corticosteroids in some patients with asthma. They are available orally and provide safe and effective therapy as long as compliance is good (2).A 23-year-old man with persistent severe perennial allergic asthma and rhinoconjunctivitis was evaluated for acute respiratory symptoms. He also had exercise-induced asthma and was sensitive to house dust mites, Dermatophagoides pteronyssinus, D. farinae, and Blomia tropicalis. From age 1 to 7 years, he had minimal-change nephrotic syndrome that completely resolved ...

Rapid symptom relief in rhinitis

In some patients, symptoms of allergic rhinitis can be severe and therefore rapid relief is required. There are many treatment options for allergic rhinitis but histamine H1 blockers and topical corticosteroids represent the first-line treatment. Although the latter drugs are usually very effective on nasal symptoms, their onset of action is around 24 h. Thus drugs that are more rapidly effective are of interest. Recently 400 French specialists (in Allergy, ENT and Pneumology) met together to define the criteria for selecting a drug for the treatment of rhinitis. Twelve criteria were proposed and rapid onset of action (less than 24 h) was among the foremost designated criteria. In the first trial, a comparison of mizolastine (10 mg once daily [od]) with cetirizine (10 mg od) and placebo was carried out in the management of seasonal allergic rhino-conjunctivitis (SAR) with special focus on onset of action. A total of 375 patients were included in this European multicentric, randomized, parallel group and placebo-controlled study. By comparison to placebo, both cetirizine and mizolastine reduced significantly nasal and ocular symptoms during the 28-day follow-up trial. The percentage of responders ranged from 40% in the placebo group to 55% in the mizolastine group and 53% in the cetirizine group. Both active drugs were effective from the first intake with a rapid onset within 2 h. However, mizolastine was more rapidly and more profoundly effective than cetirizine during the first 12 h. A second trial included 257 patients suffering from perennial allergic rhino-conjunctivitis (PAR) in a 4-week double-blind placebo-controlled multicentric study. During the study, patients recorded, using a diary card, ocular and nasal symptoms, including nasal blockage. The mean values of nasal score between day 1, 14 and 28 in the mizolastine group were statistically significantly lower than those in the placebo group. The mean values of ocular score showed a statistical difference in recordings between day 1 and day 14 in favour of the mizolastine group. Mizolastine was an effective drug both in SAR and PAR with a rapid onset of action. Mizolastine relieved symptoms more effectively than cetirizine (SAR) and placebo (SAR and PAR) at the beginning of treatment.

Faster onset of action with topical levocabastine than with oral cetirizine

This international multicentre, open-label, parallel-group trial was undertaken to compare the therapeutic efficacy and tolerability of topical levocabastine and oral cetirizine in patients with perennial allergic rhinoconjunctivitis, with particular reference to the comparative onset of action of the two drugs. A total of 207 patients were randomized to receive either levocabastine nasal spray (0.5 mg/ml, two sprays in each nostril twice daily) plus levocabastine eye drops as required (0.5 mg/ml, one drop in each eye twice daily p.r.n.) or cetirizine orally (10 mg once daily) with a treatment duration of 2 weeks. Onset of action was found to be significantly more rapid with levocabastine than with cetirizine for both nasal and ocular symptoms (p < 0.001). Within 15 min of study drug administration, 36% of levocabastine-treated patients reported relief from nasal symptoms and 32% relief from ocular symptoms compared with 10% and 17% of patients on cetirizine, respectively. At 1 h, the percentages of patients reporting relief were 76% and 38% for nasal symptoms, and 81% and 48% for ocular symptoms in the levocabastine and cetirizine treatment groups, respectively. At 8 h there were no differences between the two treatments. Overall therapeutic efficacy was found to be comparable in the two treatment groups over the 2-week study period with no significant intergroup differences in symptom severity or global therapeutic efficacy. Both drugs were well tolerated with no significant differences in the incidence or type of adverse reactions between the two groups. In conclusion, levocabastine eye drops and nasal spray are as effective and well tolerated as oral cetirizine for the treatment of perennial allergic rhinoconjunctivitis with the advantage of a significantly faster onset of action for both nasal and ocular symptoms.

Effects of immunotherapy with a purified standardized allergen preparation of Dermatophagoides farinae in adults with perennial allergic rhinoconjunctivitis

Immunotherapy (IT) was performed for 12 months with a purified and standardized preparation of Dermatophagoides farinae. Twenty adults with rhinoconjunctivitis sensitive to house-dust mite were given IT, and a similar group of 11 patients served as open controls. A total of 512 injections were given. Twenty-eight episodes of allergic side-effects occurred, 13 general and 15 local, most of them during the initial incremental dose period. No severe reactions started later than 30 min after the injection. One patient suffered anaphylactic shock. In this patient, specific antibodies fell immediately, followed by an increase within 1 week. The therapy group improved significantly in relation to the open controls in patients' subjective evaluation of symptoms (P < 0.028) and skin (P < 0.0001) and conjunctival (P < 0.001) sensitivity. Specific IgE increased in controls (P < 0.0001) but not in IT-treated patients during the "mite season"; that is, there was a significant difference in change during the observation period (P < 0.0001). There was also a difference in change of specific IgG between the groups during the first 4-5 months and the whole year (P < 0.0001), but not from 4-5 months to 12 months. In contrast to changes in antibody titers (IgG, P = 0.04), changes in conjunctival (P < 0.01) and especially skin sensitivity (P < 0.005) correlated well with subjective improvement. This implies that the skin prick test and the conjunctival test can be recommended for follow-up of IT.(ABSTRACT TRUNCATED AT 250 WORDS)