Efficacy and safety of on-demand versus daily rupatadine in chronic spontaneous urticaria: A randomized trial.

BACKGROUND: Non-sedating H1 -antihistamines (nsAH) are the most commonly used treatment for chronic spontaneous urticaria (CSU). Many patients use them as on-demand (OD) therapy rather than a maintenance treatment. Here, we compared OD versus daily maintenance treatment with the nsAH rupatadine, assessed the efficacy of rupatadine updosing, and investigated potential long-term disease-modifying effects. METHODS: This multicenter, randomized study consisted of 2 weeks of screening, 8 weeks of double-blind treatment, and 6 weeks of treatment-free follow-up (OD allowed). Adult patients were randomized to 10 mg rupatadine OD or 10 mg rupatadine daily. At Week 4, if patients did not have a complete response, they switched from 10 to 20 mg rupatadine daily or underwent sham updosing (patients on 10 mg rupatadine OD). The primary aim was to compare CSU disease activity at the end of follow-up between daily versus OD. Additionally, we assessed the efficacy of rupatadine updosing. Major outcomes were disease activity, CSU-related quality of life (QoL), and disease control. RESULTS: At Week 4, disease activity and QoL significantly improved in daily versus OD-treated patients. Updosing of rupatadine did not improve the mean disease activity, but the number of complete responders increased during updosing from 5% to 22%. At the end of follow-up, the disease activity of patients treated OD versus daily was not significantly different. CONCLUSIONS: Daily rupatadine treatment significantly improved CSU disease activity and QoL during treatment versus OD treatment but not after discontinuation of rupatadine, indicating the benefits of a daily maintenance nsAH schedule.

Occupational sensitization to lactase in the dietary supplement industry.

Aerogen lactase exposure carries a risk for the development of allergic asthma and rhinitis; only a few occupationally affected patients have been reported. The authors report the results of allergy testing with employees of a lactase tablets manufacturing plant. The survey involved 13 workers, including a questionnaire, spirometry, basophil activation test (BAT), and skin prick tests (SPTs) with lactase and a panel of common aeroallergens. Furthermore, lactase-specific immunoglobulin E (IgE) antibodies were analyzed. Sensitization to lactase could be proven for 9 workers by SPT and BAT; specific IgE antibodies could be detected in serum samples of all sensitized. However, IgE levels ≥0.35 kU/L were only found in 4 sera. These data confirm that occupational exposure to lactase can induce IgE-mediated respiratory sensitization resulting in allergic diseases. Protective measures should thus be obligatory when working with lactase.

Allergy--current insights into prevention and diagnostic workup of immediate-type allergy and treatment of allergic rhinoconjunctivitis.

In recent decades, the incidence of allergic diseases has dramatically increased, by now affecting a large percentage of the population. For a long time, allergen avoidance was considered the most crucial measure in primary allergy prevention. However, studies have increasingly shown that exposure to allergens is an essential prerequisite for the development of immunological tolerance. Diagnostic workup is based on patient history, skin tests, and measurement of specific IgE antibodies. The introduction of component-based diagnostic workup offer an option to differentiate between primary sensitization and cross-reactivity caused by sensitization to panallergens or sensitization to cross-reactive carbohydrate epitopes. Symptomatic treatment only leads to temporary relief of allergic symptoms. By contrast, specific immunotherapy (SIT) may have long-lasting therapeutic effects and potentially even result in a complete cure. The selection of allergens for SIT is guided by the principle of major allergens. It is recommended to use those preparations that have been proven safe and effective in controlled clinical studies. With respect to subcutaneous immunotherapy, a host of tested and approved extracts are available for a wide range of different allergens. Large clinical trials have also confirmed the efficacy of sublingual immunotherapy with grass and also birch pollen extracts, which has led to the official approval of some preparations containing these allergens.

Cross-reacting carbohydrate determinants and hymenoptera venom allergy.

PURPOSE OF REVIEW: Insect venom allergy is an important cause of anaphylaxis. Venom immunotherapy assume the clear identification of the culprit insect, but this is impeded by Immunoglobulin E (IgE) antibodies to cross reactive carbohydrate determinant (CCD) epitopes of common glycoproteins. Here we give an overview about inducers, importance, and relevance of anti-N-Glycan CCD IgE antibodies. RECENT FINDINGS: Pollen exposure and insect stings induce anti-CCD IgE antibodies interfering with in-vitro tests for allergy diagnosis due to extensive IgE cross-reactivity. Instead of being biologically active these antibodies are irrelevant for allergic reactions due to hymenoptera stings. The general response of the immune system to the ubiquitous exposure to N-glycan containing glycoproteins is still a matter of debate. CCD specific IgG antibodies in sera of bee keepers suggest tolerance induction due to high-dose exposure. Tolerance induction by pollen and food glycoproteins has not been proved. SUMMARY: Hymenoptera stings and pollen exposure induce anti-CCD IgE. In regard to anaphylaxis due to Hymenoptera stings these antibodies are not clinically relevant, but they are important for the specificity of in-vitro tests proving insect venom allergy. The introduction of component based diagnostic IgE testing improves the specificity of in-vitro tests if proteins devoid of CCD epitopes are used.

Modern aspects of phototherapy for atopic dermatitis.

Phototherapy has still great importance in the treatment of atopic dermatitis, though costs, compliance, and long-term risks narrow its relevance. In spite of its long history, up to now, the therapeutic regimes are mostly empirical. Narrowband UVB und UVA1 are the most frequently applied regimens in atopic dermatitis with proven efficacy. However, even for these modalities randomized prospective and controlled studies are still pending. Advances in photoimmunology and molecular biology had demonstrated that phototherapy targets inflammatory cells, alters cytokine production, and has a significant antimicrobial effect within atopic skin. This paper summarizes the current literature on the different regimes of phototherapy and also discusses therapeutic modalities like photochemotherapy and extracorporeal photopheresis. These more complex regimes should be restricted to severe cases of atopic dermatitis, which are refractory to topical treatment.

Lactase deficiency: a potential novel aetiological factor in chronic pruritus of unknown origin.

Chronic pruritus, which is associated with a wide variety of underlying diseases, represents a challenge in diagnostics and treatment in dermatology and general medicine. The cause of pruritus remains unknown in up to 45% of patients. In this study, 718 patients with chronic pruritus were analysed concerning lactase deficiency, demographic data, aetiology, duration and intensity of pruritus. A total of 154 patients were tested positive for lactase deficiency and 38.3% showed a significant anti-pruritic response to a lactose-free diet (minimum 4 weeks). The best results were observed in patients with pruritus of mixed or unknown origin (n = 91; 64% response). Age, sex, localization or duration had no significant influence on the anti-pruritic effect of a lactose-free diet. Lactase deficiency might be an independent causal factor in the elicitation of chronic pruritus. Thus, screening for lactase deficiency represents a rational step in the diagnostic work-up of chronic pruritus. In case of a positive test result, a lactose-free diet offers a low-cost, efficient and specific therapy in patients with chronic pruritus.

Delayed pressure urticaria - dapsone heading for first-line therapy?

BACKGROUND: Pressure urticaria as a subform of physical urticaria is rare and treatment is often difficult. Established therapeutic regimes include antihistamines (generally exceeding approved dosages in order to achieve a therapeutic benefit) or antihistamines combined with montelukast. Complete relief of symptoms is difficult. PATIENTS AND METHODS: We used dapsone as an early therapeutic alternative in the event of treatment failure and established a standardized therapeutic regime at our clinic. We surveyed 31 patients retrospectively who had received dapsone between 2003-2009. RESULTS: In 74 % of patients in whom symptoms persisted despite established therapies, the results of treatment with dapsone were good or very good. Longer-term pressure urticaria and the co-existence of a chronic spontaneous urticaria were associated with a smaller benefit (p<0.05). No significant effects were found related to age, gender, duration of therapy, side-effects, or Met-Hb elevation (a tendency toward a decreased benefit was associated with middle-age, male sex, shorter duration of therapy, observed side-effects, and Met-Hb elevation). CONCLUSIONS: Therapy is well tolerated and results in a good therapeutic benefit which lasts after termination of therapy. With adequate monitoring, the use of dapsone in patients with pressure urticaria has such a good risk-benefit ratio that we support early treatment initiation.

Chronic pruritus: clinics and treatment.

Chronic pruritus, one of the main symptoms in dermatology, is often intractable and has a high impact on patient's quality of life. Beyond dermatologic disorders, chronic pruritus is associated with systemic, neurologic as well as psychologic diseases. The pathogenesis of acute and chronic (>6 weeks duration) pruritus is complex and involves in the skin a network of resident (e.g., sensory neurons) and transient inflammatory cells (e.g., lymphocytes). In the skin, several classes of histamine-sensitive or histamine-insensitve C-fibers are involved in itch transmission. Specific receptors have been discovered on cutaneous and spinal neurons to be exclusively involved in the processing of pruritic signals. Chronic pruritus is notoriously difficult to treat. Newer insights into the underlying pathogenesis of pruritus have enabled novel treatment approaches that target the pruritus-specific pathophysiological mechanism. For example, neurokinin-1 antagonists have been found to relieve chronic pruritus.

Pruritus: an overview of current concepts.

Pruritus is an integral part of the patient's symptoms in numerous dermatological and systemic diseases in humans and animals. Comparable to chronic pain, pruritus can have a dramatic impact on the quality of life of the patient. In recent years, pruritus has been defined as an autonomous, pain-independent sensation, and itch-specific neurons, mediators, spinal neurons and cortical areas have been identified. These observations have not only improved our understanding of the neurobiology of itch but will also lead to improved diagnosis and to the development of new and more efficient therapeutic options. This article reviews the role of itch fibres and their response to various mediators of pruritus including histamine, vasoactive intestinal peptide (VIP), calcitonin gene-related peptide (CGRP), and substance P (SP), and opioids. Substances that may be involved in the induction or modulation of itch may be termed pruritogenic mediators and examples discussed include proteases, lipid mediators, neuropeptides, opioids and various cytokines. There is no single, generally accepted clinical classification of chronic pruritus. In the past pruritus has been classified on the basis of the neuroanatomical origin and on the potential underlying disease. Therapeutic options for the management of pruritus are discussed including topical and systemic therapies, assuming that trigger factors have been eliminated where possible. Topical agents may include capsaicin, the calcineurin inhibitors tacrolimus and pimecrolimus, and cannabinoid agonists such as N-palmitoyl ethanolamine. Systemic therapies may include antihistamines, anticonvulsants, opiate receptor antagonist or agonists, antidepressants, ciclosporin, and UV light.

Regulation of cellular immunity by Photo(chemo)therapy.

Phototherapy and photochemotherapy are important treatment regimens for inflammatory as well as malignant diseases in dermatology. Both treatment modalities have been developed already three decades ago and therefore profound knowledge exists on the use, efficacy, and long-term side effects. Since the development of new mmunosuppressive medications, biologics, and changes in medical reimbursement policies, phototherapy is currently less frequently used compared to previous years to treat psoriasis or atopic dermatitis. However, cost-effectiveness analysis demonstrated that phototherapy can significantly induce therapeutic beneficial effects on a large number of inflammatory and malignant skin disorders at a low cost of treatment rate. Since many chronic skin disorders require rotational treatment regimens to decrease the development of (long-term) adverse events, phototherapy will play an important role in dermatology in future years. In the following the molecular as well as cellular mechanisms of phototherapy are described and discussed in light of the fact that photobiology is a very active field in biomedical research.