The effect of desloratadine on patch test reactions in Chinese patients.

BACKGROUND: Few data on the effect of antihistamines on patch test results in Chinese patients are currently available. OBJECTIVES: To evaluate the effect of desloratadine on patch test reactions. METHODS: Patients known to have at least one strongly positive (+ +) test with an allergen were re-patch tested after 14 to 70 days (average time interval 26.3 days) of administering oral desloratadine 5 mg twice a day for 5 days before and during the test. Patch testing was performed with the previously recognized allergen according to the guidelines of the ICDRG. The -to + + + system was converted into numeric values (0, 1, 2, 3, 4) for statistic evaluation. RESULTS: Of the 58 chambers (47 patients), which were all strongly positive (+ +) during the 1st patch test, the situation was unchanged in 51 chambers; 4 + reactions and 2 + + + reactions were observed; and 1 chamber was negative. There was no statistically significant difference when comparing the scores of the 1st assessment with those of the 2nd (p = 0.206). If the patch test reaction of the patient who dropped out of the trial had changed from strongly positive (+ +) to negative, there would still have been no statistically significant difference between the score of the 1st assessment with those of the 2nd ( p = 0.107). CONCLUSIONS: The reaction of a patch test is not hampered by doubling dose of desloratadine. The anti-inflammatory effects of desloratadine on patch test reaction may be limited.

Allergic rhinitis: continuous or on demand antihistamine therapy?

Allergic rhinitis is an inflammatory disease of the nasal mucosa, caused by an IgE-mediated reaction after exposure to the allergen to which the patient is sensitized. Histamine is the most important preformed mediator released in the early stage of the allergic reaction, and also contributes to the late phase of the latter, exhibiting proinflammatory effects. Minimal persistent inflammation is a physiopathological phenomenon induced by the presence of an inflammatory cell infiltrate, together with ICAM-1 expression in the epithelial cells of the mucosa exposed to the allergen to which they are sensitized, in the absence of clinical symptoms. This molecule is considered to be an allergic inflammatory marker. The priming effect first described by Connell in 1968 consists of the reduction in the allergen concentration required to elicit a nasal hyper-response when performing a daily nasal exposure test. This implies that with natural exposure to inhaled allergens, small amounts of environmental allergen will maintain the patient symptoms, and thus of course minimal persistent inflammation. Considering the above, it is questionable whether antihistamines should be administered on a continuous basis or upon demand. The antihistamines, and fundamentally the second-generation drugs, have been shown to exert an antiinflammatory effect, and this effect is greater when the drug is administered continuously than when administered upon demand. Likewise, a reduction in treatment cost and an improvement in quality of life among patients treated on a continuous basis has been documented. However, no studies have been specifically designed to clarify the indication of treatment on a continuous basis or upon demand, as occurs in the GINA. As a result, the individualization of treatment according to the concrete characteristics of each patient seems to be the best approach, at least for the time being.

Use of antihistamines in pediatrics.

Drugs with antihistamine action are among the most commonly prescribed medicines in pediatrics. According to the International Medical Statistics (IMS), almost two million antihistamine units (in solution) for pediatric use were sold in Spain during 2006--at a cost of nearly 6 million euros. Of this amount, 34% corresponded to first-generation (or sedating) antihistamines. The difficulties inherent to research for drug development increase considerably when the pediatric age range is involved. The use of any medication in this age group must adhere to the strictest safety criteria, and must offer the maximum guarantees of efficacy. For this reason, detailed knowledge of the best scientific evidence available in relation to these aspects is essential for warranting drug use. The first-generation antihistamines have never been adequately studied for pediatric age groups, though they are still widely used in application to such patients. In contrast, studies in children have been made with the second-generation antihistamines, allowing us to know their safety profile, and such medicines are available at pediatric dosages that have been well documented from the pharmacological perspective. The present review affords an update to our most recent knowledge on antihistamine use in children, based on the best scientific evidence available.

Antihistamines in the treatment of chronic urticaria.

Chronic urticaria is highly prevalent in the general population, and while there are multiple treatments for the disorder, the results obtained are not completely satisfactory. The second-generation H1 antihistamines remain the symptomatic treatment option of choice. Depending on the different pharmacokinetics and H1 receptor affinity of each drug substance, different concentrations in skin can be expected, together with different efficacy in relation to the histamine-induced wheal inhibition test--though this does not necessarily have repercussions upon clinical response. The antiinflammatory properties of the H1 antihistamines could be of relevance in chronic urticaria, though it is not clear to what degree they influence the final therapeutic result. Before moving on to another therapeutic level, the advisability of antihistamine dose escalation should be considered, involving increments even above those approved in the Summary of Product Characteristics. Physical urticaria, when manifesting isolatedly, tends to respond well to H1 antihistamines, with the exception of genuine solar urticaria and delayed pressure urticaria. In some cases of chronic urticaria, the combination of H2 antihistamines may prove effective--though only with common liver metabolism (CYP3A4 isoenzyme-mediated) H1 antihistamines, due to the existence of mutual metabolic interferences. The role of leukotriene antagonists associated to antihistamines in application to chronic urticaria remains to be clearly defined.

Hypersensitivity reaction to mizolastine: study of cross reactions.

A 26-year-old male suffering from acute rhinitis took the first dose of Zolistan (mizolastine, 10 mg), orally, and 15 minutes later he developed intense generalized pruritus, cutaneous rash, oropharyngeal pruritus, edema on his face, difficulty in swallowing, and mild dyspnea. He was treated with methylprednisolone and epinephrine and improved within 30 minutes. The patient had not taken mizolastine before and he has avoided it since the reaction. Cutaneous tests with Zolistan and its excipients proved negative. Simple-blind oral challenge tests with the excipients and then with Zolistan were positive only with Zolistan. In order to confirm the absence of cross-reactivity between mizolastine and other benzimidazoles, we tested omeprazole, domperidone and mebendazole, all of which yielded negative results. To our knowledge, this is the second case of immediate hypersensitivity to mizolastine documented to date. In our case, the clinical history, physical examination and provocation tests allow us to establish the diagnosis of hypersensitivity to mizolastine and exclude the cross reactivity with other benzimidazole derivatives.

A new antihistamine levocetirizine inhibits eosinophil adhesion to vascular cell adhesion molecule-1 under flow conditions.

BACKGROUND: We previously demonstrated that low concentrations of a new antihistamine levocetirizine inhibited eosinophil transmigration through human microvascular endothelial cells. OBJECTIVE: Here, the inhibitory effect of levocetirizine on eosinophil adhesion to recombinant human vascular cell adhesion molecule-1 (rhVCAM)-1 was examined under conditions of shear stress using an in vitro model of the post-capillary venules. METHODS: Eosinophils isolated from normal subjects were pre-incubated with a concentration range of levocetirizine (10(-6)-10(-10) m) or negative dilution control. Resting or granulocyte macrophage-colony stimulating factor (GM-CSF)-stimulated cells were pumped through rhVCAM-1 (10 microg/mL) coated capillary tubes using a microfluidic syringe pump at a precise and constant flow rate (1 dyn/cm(2)). Images of rolling and firmly adherent eosinophils were captured using real-time video microscopy. RESULTS: Levocetirizine significantly inhibited resting eosinophil adhesion to rhVCAM-1 with maximal effect at 10(-8) M with an EC(50) of 10(-9) m. Levocetirizine almost abolished resting eosinophil adhesion by the 15 min time-point. GM-CSF significantly enhanced eosinophil adhesion and their ability to flatten on rhVCAM-1. Both phenomena were inhibited by levocetirizine in a dose-dependent manner, at both 5 and 15 min (optimal concentration of 10(-8) m with an EC(50) of 10(-9) m). Real-time imaging revealed that the effect of levocetirizine on post-adhesion behaviour (detachment, flatness) contributed to its inhibitory action on eosinophil adhesion to rhVCAM-1. In contrast, very late antigen (VLA)-4 mAb inhibited eosinophil adhesion to rhVCAM-1 from the earliest time-points. CONCLUSION: Physiologically relevant concentrations of levocetirizine inhibit resting and GM-CSF-stimulated firm eosinophil adhesion to rhVCAM-1 under flow conditions.

Persistent skin colonization with Staphylococcus aureus in atopic dermatitis: relationship to clinical and immunological parameters.

BACKGROUND: Staphylococcus aureus has important implications for the pathogenesis of atopic dermatitis (AD). In some patients S. aureus can be eradicated from the skin during anti-inflammatory treatment, while in others bacterial colonization is persistent. Potential mechanisms and features of these two distinct groups of patients are not known. OBJECTIVE: Accordingly, we studied relationships between the ability to eliminate S. aureus during an anti-inflammatory treatment and selected clinical and immunological features. METHODS: Quantitative assessment of S. aureus on the skin, in nasal vestibule and throat, serum IgE levels, CD4/CD8 T-cell ratio, lymphocyte proliferation and phagocyte oxidative burst were determined during the exacerbation and after 4 and 12 weeks of the treatment using topical steroid and oral antihistamine in 34 patients with AD. RESULTS: S. aureus was found on the skin of all 34 patients during exacerbation. Disease severity scoring of atopic dermatitis (SCORAD) correlated with the density of bacteria. Treatment with oral antihistamine and topical steroid resulted in a significant alleviation of symptoms, which correlated with the elimination of S. aureus from the skin in 70% of patients. In the remaining 30% of patients, dense (more than 10(10)/cm2) S. aureus skin colonization, persisted despite the treatment. Patients with persistent S. aureus presented with higher serum IgE levels, lower lymphocyte proliferation in response to staphylococcal enterotoxin B, phytohaemagluttinin and anti-CD3. Persistence of S. aureus was more common in men. CONCLUSIONS: Patients with AD differ in the ability to clear S. aureus from the skin during anti-inflammatory treatment, which appears to be related to the abnormalities in immunological parameters. Local antibiotic therapy should be considered only in patients with persistent S. aureus colonization.

Anti-inflammatory properties of desloratadine.

BACKGROUND: Allergic rhinitis (AR) is associated with robust infiltration of immune cells and mediators that may contribute to clinical manifestations of the disease. OBJECTIVE: To review the complex immune effector mechanisms involved in the allergic response and discuss their effects on the pathophysiological and clinical manifestations of AR. Desloratadine, a novel antihistamine, was used as a probe with the goal of attaining a better understanding of the inflammatory processes underlying the allergic response. METHODS: Data were obtained from abstracts and peer-reviewed journals. The pathophysiology of the allergic response has been extensively studied. This paper presents only data from studies that used desloratadine at physiologically relevant concentrations. RESULTS: Key mediators involved in the allergic response and in pathophysiological and clinical manifestations of the immune response were reviewed. Desloratadine was used as a probe to further elucidate the mechanisms involved during an allergic response. CONCLUSIONS: Some have proposed a link between the pathophysiology of AR and the clinical manifestation of symptoms. Desloratadine, a new-generation antihistamine, has demonstrated anti-inflammatory effects in vitro; indeed, desloratadine is capable of intervening at various points in the immune cascade. Although in vitro results do not necessarily correlate with clinical efficacy, the anti-inflammatory properties of desloratadine may contribute to its efficacy in patients with AR, allergy-induced asthma, and other related allergic conditions. Antihistamines that modulate in the immune system at various stages may optimize treatment of allergic disease.