Efficacy and safety of birch pollen immunotherapy for local allergic rhinitis

Background

Local allergic rhinitis (LAR) is a relatively new disease.

Dynamic changes in conjunctival dendritic cell numbers, anatomical position and phenotype during experimental allergic conjunctivitis

Dendritic cells (DCs) are a subset of antigen-presenting cells (APCs) that are involved in the initiation and control of the immune response to antigens present at the interface with the environment. A limited number of groups have studied DCs in human and animal conjunctiva but no data is available concerning the different DC subsets present in the conjunctival tissue. The aims of this study are to characterize the phenotypes and numbers of DCs present in the murine model of allergic conjunctivitis using the technique of immunohistochemistry so as to aid the understanding of the mechanisms involved in allergic eye disease. A double immunofluorescence method was used to analyze the phenotypic distribution and density of DC subsets in the mouse conjunctival tissues of the allergic model using a panel of antibodies: CD11c, as a general marker of DCs, coupled with another DC subset marker such as Langerin for Langerhans cells (LCs), CD11b for myeloid DCs (mDCs) and mPDCA-1 for plasmacytoid DCs (pDCs). In the na?ve conjunctiva, mDCs were consistently detected in the subepithelial layer and substantia propria. In the epithelium and the subepithelial layer, very few LCs and virtually no pDCs were observed. Following allergen challenge, there was a marked influx of mDCs and pDCs, but no LCs, into the subepithelial layer and throughout the substantia propria. These results indicate that conjunctival DC subsets may play an important role in the immune-regulatory processes involved in the inflammatory component of allergic conjunctivitis.     

Expression of ICAM-1 on conjunctival epithelium and ECP in tears and serum from children with allergic conjunctivitis.

BACKGROUND: Conjunctival eosinophilia may be considered to be an indicator of conjunctival allergic disease. The absence of eosinophils on conjunctival scraping, however, cannot rule out the diagnosis of allergic conjunctivitis because eosinophil infiltration may be deeper in conjunctival tissue. Eosinophil cationic protein (ECP) is a toxic product secreted by activated eosinophil as a marker of eosinophil activation. Eosinophil cationic protein concentrations in body fluids correlate with the severity of some allergic diseases. ICAM-1 promotes adhesion of leukocytes to epithelium, endothelium, and upregulates inflammation. Expression of adhesion can be modified by many extracellular and intracellular variables such as proinflammatory cytokines, extracellular matrix proteins, and viral infection. OBJECTIVE: We investigated whether local eosinophils are only activated in conjunctival epithelium or circulating activated eosinophils are involved in peripheral blood during allergic reaction of the eye. We also demonstrated the possible expression of ICAM-1 on epithelial cells from conjunctival scraping and compared them with soluble ICAM-1 values of serum and tears in children with allergic conjunctivitis and healthy children. METHODS: Seventeen subjects were selected on the basis of clinical manifestations, history, skin prick test, and total serum IgE. A microcapillary tube was used to collect the tears from the inner canthus. Conjunctival epithelia were obtained by scraping the upper tarsal conjunctiva. The level of ECP was measured by the CAP system, soluble ICAM-1 was measured by ELISA, and ICAM-1 on conjunctival epithelial cells were expressed by the avidine-biotin peroxide complex procedure. RESULTS: Serum IgE and the eosinophil count were increased in 10 out of 17 patients, positive skin prick tests were positive in 11 patients (Dermatophagoides pternyssinus; 9, Dermatophagoides farinae: 8), and eosinophilia in conjunctival epithelium was in 11 patients (4 patients: >3/HPF, 7 patients: 1-3/HPF). The ECP levels in tears were significantly increased in the patient group (12.0+/-8.0 versus 3.9+/-3.8 microg/mL, P = .01), but not in serum (52.5+/-43.1 versus 28.3+/-25.9 microg/mL). There is significant correlation between the eosinophil count in peripheral blood and on conjunctival epithelium (P = .007, r = .62; n = 25). The ICAM-1 expression score on conjunctival epithelial cells was significantly different between the patient group and controls (patient group: 1.77+/-1.25 versus control: 0.13+/-0.35 ng/mL, P = .002). There was a significant correlation between ICAM-1 expression on conjunctival epithelial cells and the ECP levels of tears (P = .01, r = .58; n = 25). Soluble ICAM-1 levels in serum and tears showed no significant difference between the patient group and controls, and also, there was no correlation between sICAM-1 levels in the serum and tears. CONCLUSION: Eosinophil cationic protein in tears and ICAM-1 expression scores on conjunctival epithelium showed a significant difference between children with allergic conjunctivitis and the healthy controls, but circulating ECP and sICAM-1 in serum were not significantly different between the two groups. These results may suggest that ICAM-1 is locally upregulated in inflammation, mediating eosinophil activation and migration to conjunctival epithelium, but is not involved as inflammatory mediators in peripheral blood during allergic response in children with allergic conjunctivitis.     

Cromolyn sodium in seasonal allergic conjunctivitis

A formulation of 2% cromolyn sodium (CS) ophthalmic solution without the preservative, 2-phenylethanol, was compared with placebo in 58 patients with seasonal allergic conjunctivitis. Selection was based on history and positive skin tests. Neither immunotherapy nor use of antihistamines was allowed. This study was double-blinded and stratified by RAST scores to assure comparable groups. Either CS or placebo was used six times daily. Patients were observed weekly for 5 weeks during the peak of the fall weed-pollen exposure. Nasal symptoms were treated as required with beclomethasone nasal spray, and uncontrolled ocular symptoms were treated with boric acid and ephedrine solution. Nasal and ocular symptoms were recorded. There was a significant suppression of eye symptoms in the group receiving CS ophthalmic solution (p less than 0.02) during weeks 2, 4, and 5. There was a trend for nasal symptoms and the requirement for nasal beclomethasone to be less in patients receiving CS.     

Efficacy of mequitazine in comparison with placebo assessed by ocular challenge with allergen in allergic conjunctivitis

Pharmacologic intervention in the management of allergic conjunctivitis was evaluated with different topical ocular agents in man. Their effect can be precisely assessed with the conjunctival provocation test (CPT). A potent specific H₁-receptor antagonist, 0.05% mequitazine eye-drops, was tested in a double-blind, randomized, placebo-controlled study using CPT with grass pollen allergens. Twenty healthy subjects allergic to grass pollen were included outside the pollen season after a positive CPT screening. They received one drop of 0.05% mequitazine in one eye and the vehicle in the contralateral eye in a random order, four times daily for 5 days. CPT was performed 15 min after the last instillation, and the threshold dose inducing a positive reaction was determined. Results were given by Abelson's composite score including redness, chemosis, tearing, and itching. Topical 0.05% mequitazine significantly reduced the composite score compared to placebo. The allergen threshold concentration which induced the positive conjunctival reaction was higher in mequitazine pretreated eyes. No side effect was reported. These data clearly suggest that mequitazine has potential to treat allergic conjunctivitis.     

Low-dose local nasal immunotherapy in children with perennial allergic rhinitis due to Dermatophagoides

BACKGROUND: Allergen specific immunotherapy was known to be useful in the treatment of respiratory allergic disease. Local nasal immunotherapy (LNIT) offers advantages such as a good efficacy/safety ratio and a more convenient allergen delivery. The aim of this study was to assess the safety and clinical efficacy of a modified scheduling of LNIT in 32 children with allergic rhinitis due to Dermatophagoides. METHODS: A multicentre, randomized, double-blind placebo controlled study carried out for two years, with a modified schedule of LNIT treatment: a build-up phase at increasing dosages from 2.5 AU to 80 AU and a maintenance period at low dosage (80 AU) once a week. Symptom and medication scores. threshold dose with specific nasal provocation test (NPT) and immunological parameters (IgE and IgG4) were evaluated. RESULTS: No important local or systemic side-effects were observed in children who completed the study. Compared to placebo, the active treatment group showed significant improvement in rhinitis symptoms and a reduction of drug consumption after 18 months of LNIT. These results were confirmed by a significant reduction of allergen specific nasal reactivity. Serum and nasal specific IgE and IgG4 did not show any difference in the two groups. CONCLUSIONS: The safety and clinical efficacy of low-dose LNIT suggests that this therapy may be useful in the treatment of allergic rhinitis disease in children.     

Cytological evaluation of conjunctival scrape smears in cases of conjunctivitis.

The present study was conducted on 130 cases of untreated conjunctivitis and 25 control cases to assess the diagnostic value of cytology. Conjunctival scrapings from all cases were stained with Giemsa and Papanicoloau's stain and categorized cytologically and later correlated with the clinical profile. Normal cytologic profile was obtained in 7 cases (5.4%) of the study group and 14 cases (56%) of the control group. Cytologic diagnosis of trachoma was made in 63 cases (48.5%) including 48 out of 51 clinically diagnosed cases of trachoma, 9 cases of allergic conjunctivitis and 6 cases of acute follicular conjunctivitis, positive clinico cytologic correlation being 76.2%. Mucopurulent conjunctivitis was diagnosed in 24 cases (18.5%) both clinically as well as by cytological technique. Viral conjunctivitis was diagnosed in 24 cases (18.5%) including 19 cases (14.6%) of clinically diagnosed viral conjunctivitis and 5 cases (3.9%) of acute follicular conjunctivitis, positive correlation being 79.2%. Only 2 cases (1.5%) out of 15 clinically diagnosed cases of allergic conjunctivitis were confirmed cytologically. In all the 4 cases (3.1%) of spring catarrh and 6 cases (4.6%) of phlyctenular conjunctivitis the cytologic features were found to be consistent with the clinical diagnosis.     

Allergen-specific immunotherapy in allergic rhinitis

The scope of this review is to highlight important and interesting articles in the field of allergen-specific immunotherapy in allergic rhinitis published within the past year. The review is not intended to give a full overview of published literature but rather to focus on some subjects that I find significant in relation to the understanding of the specific treatment of allergies and to the selection of different treatment modalities. The most important aspects are how to define the most suitable candidates for the specific treatment, the mechanisms of action of immunotherapy and how to optimize treatment, and finally I include some reflections on the optimal presentation of the allergen to the immune system.     

Human conjunctival mast cells: distribution of MCT and MCTC in vernal conjunctivitis and giant papillary conjunctivitis

The distribution and concentration of human tryptase-positive, chymase-negative mast cells (MCTS) and tryptase-positive, chymase-positive mast cells (MCTCS) were examined in conjunctival biopsy specimens from subjects with active vernal conjunctivitis (VC; n = 7), giant papillary conjunctivitis (GPC; n = 6), and allergic conjunctivitis (AC; n = 5), and from asymptomatic soft-contact lens wearers (SCL; n = 6) and normal control individuals (n = 19). Carnoy's fixed tissue sections were stained by a double immunohistochemical method using a biotinylated mouse monoclonal antichymase antibody with immunoperoxidase, followed by an alkaline phosphatase-conjugated mouse monoclonal antitryptase antibody. Epithelial mast cells (MCs) were found in all VC specimens (96% MCTCs) and in three GPC specimens (100% MCTCS) but in none of the other groups. In the substantia propria, MCTCS were the predominant type of MC observed in all specimens, accounting for 95% of the total MCs in the normal control group and 100% of the total MCs in the subjects with GPC, AC, and SCL. No significant differences were found in the total MC concentration of the substantia propria among the normal control subjects (11,054 +/- 6327 MCs per cubic millimeter), subjects in the SCL group (13,168 +/- 4685 MCs per cubic millimeter), subjects with GPC (17,313 +/- 8500 MCs per cubic millimeter), and subjects with AC (15,380 +/- 5660 MCs per cubic millimeter). In subjects with VC, the percentage of MCTs (18% +/- 13%) and the total MC concentration (24,689 +/- 18,978 MCs per cubic millimeter) in the substantia propria were significantly increased as compared to the normal control group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Tear tryptase levels and allergic conjunctivitis

We measured tryptase, a neutral protease stored in the secretory granules of mast cells, by solid-phase radioimmunoassay in tears of 12 subjects with vernal keratoconjunctivitis (VKC) during remission phases, nine subjects with seasonal or perennial allergic conjunctivitis, and eight healthy controls. Mean values of tear tryptase levels were significantly ( P < 0.02) increased in VKC patients (14.5 ± 13 μg/1) when compared to those measured in patients with seasonal or perennial allergic conjunctivitis (0.6 ±0.1 μg/1) and in controls (3.3 ± 3.2 μg/1). In subjects with allergic conjunctivitis, the levels of tryptase, almost undetectable before allergen conjunctival challenge, showed a significant increase in the challenged eye 20 min - but not 6 h - after provocation in 5/9 cases. Our results indicate that VKC, a severe ocular disease characterized by an increased number and abnormal distribution of mast cells in the conjunctiva, also shows elevated levels of tryptase in tears even during remission phases. Evidence of mast-cell activation, as revealed by a significant increase of tryptase levels in tears, is documented during the early-phase reaction, but not during the late-phase reaction, of allergic conjunctivitis patients challenged topically by specific allergen.