Caterina Pronzato

Randomised controlled trial of local allergoid immunotherapy on allergic inflammation in mite-induced rhinoconjunctivitis

BACKGROUND Non-injective routes of immunotherapy are thought to be valuable therapeutic options for respiratory allergy. We investigated the clinical efficacy and the effects of sublingual/oral immunotherapy on conjunctival allergic inflammation in patients with mite-induced respiratory allergy. METHODS We used a double-blind placebo-controlled design. 20 patients with mite-induced rhinoconjunctivitis (six of whom also had mild asthma) were randomly assigned sublingual/oral immunotherapy (n=10) or placebo (n=10) for 2 years. We assessed symptom score by diary cards and inflammatory-cell infiltrate, and expression of intercellular adhesion molecule 1 (ICAM-1) in the conjunctiva after specific allergen challenge at enrollment and after 12 and 24 months of treatment. FINDINGS We found significantly lower symptom scores in the immunotherapy group than in the placebo group in most of the winter months (p=0.05). Compared with the placebo group, inflammatory-cell infiltration after conjunctival challenge, and ICAM-1 expression on conjunctival epithelium decreased significantly in the first year of treatment in the immunotherapy group (p=0.04 and p=0.02, respectively). These effects were also seen for the minimum persistent inflammation, in symptom-free patients exposed constantly to allergens (p=0.02). Serum concentrations of eosinophil cationic protein decreased significantly (p=0.04). Immunotherapy was well tolerated and compliance was good. INTERPRETATION Our results suggest that this immunotherapy is clinically effective in rhinoconjunctivitis and that it decreases the immune-mediated inflammatory responses to the allergen.

Minimal persistent inflammation is present at mucosal level in patients with asymptomatic rhinitis and mite allergy

The natural exposure to house dust mites causes sensitization in genetically susceptible patients. Persistent exposure of sensitized patients causes chronic inflammation, and consequently, hyperreactivity, thus promoting the development of clinical features. Recently, intercellular adhesion molecule-1 (ICAM-1)/CD54 expression on epithelial cells triggered by allergen has been demonstrated and related to the inflammation caused by the allergic reaction. Therefore we evaluated the possible presence of inflammation (i.e., inflammatory cell infiltrate and ICAM-1/CD54 expression on epithelium) at conjunctival and nasal levels in patients with asymptomatic allergic rhinitis caused by mites, in their relatives living in the same environment, and in healthy volunteers. In addition, the possible relationship between inflammation and house dust mite allergen exposure was evaluated. Conjunctival and nasal scrapings of allergic subjects enrolled in the study showed many inflammatory cells. A mild ICAM-1/CD54 expression on conjunctival and nasal epithelium was detectable in allergic subjects, whereas relatives and healthy volunteers showed few inflammatory cells and no ICAM-1/CD54 expression on epithelial cells. A detectable level of house dust mite, sufficient to cause sensitization, was found in all houses. This study demonstrates a minimal persistent inflammation at conjunctival and nasal levels constantly detectable in patients without symptoms who are sensitized to mites and continuously exposed to the natural allergens.

Topical azelastine reduces eosinophil activation and intercellular adhesion molecule-1 expression on nasal epithelial cells: An antiallergic activity

BACKGROUND It is well known that allergen-specific nasal challenge (ASNC) is a fruitful tool with which to evaluate antiallergic activity exerted by a drug. Azelastine is a new antihistamine also available in topical form (i.e., nasal spray). OBJECTIVE The aim of the study was to evaluate the effects of azelastine nasal spray on inflammatory changes after ASNC in both the early-phase reaction and the late-phase reaction. METHODS The study had a double-blind, placebo-controlled, randomized, and parallel-group design. Twenty patients with pollen allergy were enrolled out of pollen season. ASNC was performed at baseline (TO) and after 1 week of washout (T7). At T7, 10 patients sprayed azelastine (1 puff) into their nostrils, and 10 patients used placebo. ASNC was performed after 30 minutes. The considered parameters (evaluated during early- and late-phase reactions) were: (1) clinical signs and symptoms, (2) cytologic assessment (neutrophils and eosinophils), (3) assay-of mediators (eosinophil cationic protein and myeloperoxidase), and (4) expression of intercellular adhesion molecule-1 (ICAM-1) on nasal epithelial cells. We focused our attention on ICAM-1 because it is the natural ligand of leukocyte functional associated antigen-1 and Mac-1, expressed on eosinophils. In addition, ICAM-1 is expressed on epithelial cells only on allergen exposure (both natural and experimental). RESULTS Placebo did not exert any modification on the considered parameters. After azelastine administration, significant decreases in total symptom score, eosinophilic and neutrophilic infiltration, and ICAM-1 expression were observed during both early- and late-phase reactions. Furthermore, serum eosinophil cationic protein levels decreased during the late-phase reaction, whereas myeloperoxidase was not affected by the treatment. These findings were confirmed by the powerful Kochs split-plot statistical analysis. CONCLUSION Azelastine exerts antiallergic activity, mainly affecting eosinophil function and downregulating ICAM-1 expression, on nasal epithelial cells.

Evidence of intercellular adhesion molecule-1 expression on nasal epithelial cells in acute rhinoconjunctivitis caused by pollen exposure

Rhinoconjunctivitis caused by pollen allergy is characterized by typical signs and symptoms and mucosal infiltration by inflammatory cells during pollen season. It has been recently demonstrated that the adhesion molecule system is deeply involved in cell-to-cell interaction during inflammatory response consequent to allergic reactions. The aim of this study was to evaluate the expression of intercellular adhesion molecule-1 (ICAM-1 or CD54) on nasal epithelial cells, before and during natural seasonal exposure, in 10 allergic patients (Parietaria judaica-sensitized) and in 10 healthy volunteers, correlating this parameter with clinical and cytologic involvement. Nasal epithelial cells of allergic subjects showed a significant expression of CD54 during pollen season (p < 0.001). On the contrary, no CD54 expression was observed out of pollen season. In healthy volunteers no CD54 expression was observed both before and during pollen season. Cytologic evaluation demonstrated an infiltration by eosinophils (mainly activated [EG2+]), (p < 0.001), neutrophils (p < 0.001), and metachromatic cells (p < 0.001) during pollen season only in allergic subjects. Therefore results indicate that seasonal allergic rhinitis is characterized by an infiltration of inflammatory cells correlated with CD54 expression on nasal epithelial cells. This phenomenon is specific, being restricted only to allergic patients during pollen season.

Effective long-term α-interferon treatment for hypereosinophilic syndrome

cially available. In our case, the drug that induced the reaction and the compound that was well tolerated were paraben-free. The exact mechanism that produces fixed drug eruptions is not well known. The short interval of initiation of the symptoms is not common; usually in fixed drug eruptions, symptoms appear after an interval of 6 hours or later, although the maximum expression of skin lesions takes a period of 24 to 48 hours or longer after administration of the drug. However, unreported evidence from our group indicates that with other drugs, such as sulfonamides and erythromycin, initiation of itching and erythema may occur as early as 20 minutes after drug intake. Quantitation of histamine in blood and urine has not shown evidence of the release of this mediator. We believe this to be the first reported case of a fixed drug eruption induced by mepivacaine in a patient with good tolerance to lidocaine.

Fibrous invasive (Riedel's) thyroiditis with critical response to steroid treatment.

The Riedel’s thyroiditis is an uncommon form of chronic thyroiditis characterized by an invasive fibrosclerosis of the gland, often involving the surrounding tissues. Usually, the only possible treatment is the surgical decompression of the tissues. We describe a case of aggressive Riedel’s thyroiditis with severe compression and dislocation of thrachea and esophagus. The surgical approach was uneffective, while an “ex juvantibus” steroid treatment, resulted in a dramatic regression of fibrosclerosis and a complete clinical remission. This report points out the possible effectiveness of corticosteroids in the treatment of selective disorders involving increased fibrogenesis.

Functional involvement of the LFA-1/ICAM-1 adhesion system in the autologous mixed lymphocyte reaction

The integrin surface molecule termed lymphocyte functional antigen-1 (LFA-1), and its physiological ligand intercellular adhesion molecule-1 (ICAM-1), have been proven to play a relevant role in several immune reactions where cell-to-cell contact is required: these reactions include allogeneic mixed lymphocyte reaction (MLR) and direct cytotoxicity. In the present study, we show that monoclonal antibodies (mAbs) directed to LFA-1 as well as to ICAM-1 molecules are able to inhibit T cell proliferation in autologous MLR (AMLR). Such an in vitro reaction is generally considered a functional model of Ia-mediated immunocompetent cell cooperation, and is impaired in several pathological conditions. It is noteworthy that the LFA-1 molecule is largely represented on the T cell surface, whereas ICAM-1 is poorly expressed on resting T cells: autologous stimulation slightly increases ICAM-1 expression. Pretreatment studies indicate that the inhibitory effect of anti-ICAM-1 mAb on T cell proliferation in AMLR is exerted on responder T cells.