Tolerability of sublingual versus vestibular allergy immunotherapy tablet administration: A randomized pilot study.

BACKGROUND: Local application site reactions are common with sublingual allergy immunotherapy (AIT)-tablets for the treatment of allergic rhinitis/conjunctivitis (AR/C) and occasionally lead to treatment discontinuation. Because of the lower mast cell density in the vestibular mucosa than the sublingual area, vestibular AIT-tablet administration may result in fewer adverse events (AEs). This pilot study evaluated the tolerability of the vestibular administration route of AIT-tablets compared with the sublingual route in adult subjects with AR/C. METHODS: Adults (n = 164) aged 18-65 years with AR/C treated with daily birch pollen, grass pollen, ragweed pollen or house dust mite AIT in tablet form were randomized 1:1 to vestibular or sublingual administration for 28 days, followed by 28 days of sublingual administration only. The primary endpoint was the severity (mild, moderate, severe) of local treatment-related adverse events (TRAEs) during the first 28 days of treatment. RESULTS: During the first 28 days, the percentage of subjects in the vestibular and sublingual groups reporting mild TRAEs were 55.6% versus 50.6%, respectively; moderate TRAEs were 27.2% versus 30.1%; and severe TRAEs were 12.3% versus 6.0% (p = .16). In the vestibular group, 95.1% of the subjects experienced at least one TRAE during the first period versus 81.9% in the sublingual group (p = .01) and discontinuation rates due to AEs were higher (12.3% vs. 3.6%). CONCLUSION: The frequencies of subjects experiencing severe TRAEs, at least one TRAE, and discontinuations due to AEs at the initiation of AIT-tablets were numerically higher with vestibular administration than sublingual administration. Sublingual administration should remain the standard of care for subjects treated with AIT-tablets for AR/C.

Thresholds in nasal histamine challenge in patients with allergic rhinitis, patients with hyperreflectory rhinopathy, and healthy volunteers.

BACKGROUND: Characteristic symptoms of hyperreflectory rhinopathy include recurrent sneezing, nasal obstruction, and nasal secretion without an allergic background. The diagnosis can only be made if all differential diagnoses have been excluded. So far no clinical test has been established to reliably diagnose hyperreactivity of the nasal mucosa. The present study aimed to investigate whether nasal provocation with histamine allows identification of patients with hyperreflectory rhinopathy. MATERIALS AND METHODS: One-sided nasal challenge with histamine was applied to 13 patients with allergic rhinitis, 13 patients with hyperreflectory rhinitis, and 12 healthy volunteers. Histamine concentrations used were 0.25, 0.5, 1.0, 2.0, 4.0, 8.0, and 16.0 mg/mL. Test results were quantified using a symptom score (positive at values above 3) and active anterior rhinomanometry (positive at a reduction of airflow of 40% or more in comparison to challenge with solvent). RESULTS: While there was a significant difference between controls and patients with allergic rhinitis or hyperreflectory rhinopathy, respectively, no significant difference was observed between the two groups of patients. Results indicated that one-sided nasal provocation with histamine at a concentration of 1 mg/mL is sufficient to separate healthy subjects from patients with hyperreactivity of the nasal mucosa. In terms of the differentiation between subjects with hyperreactivity of the nasal mucosa and healthy controls, the sensitivity of one-sided nasal histamine provocation with 1 mg/mL was found to be 100%; its specificity was 83% if it was evaluated by rhinomanometry and symptom score. CONCLUSION: The present results indicate that one-sided nasal challenge with histamine at a concentration of 1 mg/mL is sufficient to separate healthy subjects from patients with hyperreactivity of the nasal mucosa. However, the test does not differentiate between patients with allergic rhinitis and patients with hyperreflectory rhinitis.