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Cholinergic urticaria (CU) has clinically characteristic features, and has been frequently described in the literature. However, despite its comparatively old history, the pathogenesis and classification remains to be clarified. CU patients are occasionally complicated by anhidrosis and/or hypohidrosis. This reduced-sweat type should be included in the classification because the therapeutic approaches are different from the ordinary CU. It is also well-known that autologous sweat is involved in the occurrence of CU. More than half of CU patients may have sweat hypersensitivity. We attempt to classify CU and address the underlying mechanisms of CU based on the published data and our findings. The first step for classification of CU seems to discriminate the presence or absence of hypersensitivity to autologous sweat. The second step is proposed to determine whether the patients can sweat normally or not. With these data, the patients could be categorized into three subtypes: (1) CU with sweat hypersensitivity; (2) CU with acquired anhidrosis and/or hypohidrosis; (3) idiopathic CU. The pathogenesis of each subtype is also discussed in this review.

Wheat-dependent exercise-induced anaphylaxis (WDEIA) is a specific form of wheat allergy typically induced by exercise after ingestion of wheat products. Wheat ω-5 gliadin is a major allergen associated with conventional WDEIA, and detection of serum immunoglobulin E (IgE) specific to recombinant ω-5 gliadin is a reliable method for its diagnosis. Recently, an increased incidence of a new subtype of WDEIA, which is likely to be sensitized via a percutaneous and/or rhinoconjunctival route to hydrolyzed wheat protein (HWP), has been observed. All of the patients with this new subtype had used the same brand of soap, which contained HWP. Approximately half of these patients developed contact allergy several months later and subsequently developed WDEIA. In each of these patients, contact allergy with soap exposure preceded food ingestion-induced reactions. Other patients directly developed generalized symptoms upon ingestion of wheat products. The predominant observed symptom of the new WDEIA subtype was angioedema of the eyelids; a number of patients developed anaphylaxis. This new subtype of WDEIA has little serum ω-5 gliadin-specific serum IgE.

Several guidelines for urticaria and angioedema have been published in Europe and United States since 1997. General principles for diagnosis and treatments of them are similar. However, each guideline has its own characteristics and shows differences in areas such as the coverage of urticaria subtypes, nomenclatures, and hierarchy of the medications. In Japan, the Japanese Dermatological Association (JDA) published its first guideline for urticaria and angioedema in 2005. It established a new classification of urticaria and angioedema together with the definition of each subtype. It emphasized the importance of discriminating idiopathic urticaria, consisting of acute urticaria and chronic urticaria from inducible urticaria, such as allergic urticaria, physical urticaria and cholinergic urticaria. It contains several unique algorithms for diagnosis and treatment of urticaria from a view point of clinical practices, and was further enforced by a style of EBM in 2011. Nevertheless, these guidelines have not been recognized outside of Japan, because of a language barrier. In this article, the outline of the newest guidelines by JDA are introduced and compared with the guidelines in other countries published in English.

Angioedema is the end result of deep dermal, subcutaneous and/or mucosal swelling, and is potentially a life-threatening condition in cases where the pharynx or larynx is involved. Drug-induced angioedema has been reported to occur in response to a wide range of drugs and vaccines. Drug-induced angioedema, like other cutaneous drug reactions, has been reported to be most frequently elicited by beta-lactam antibiotics and non-steroidal anti-inflammatory drugs, although reliable data from epidemiologic studies are scarce. Recent reports suggested an increasing role of angiotensin-converting enzyme inhibitors (ACEIs) in the causation of life-threatening angioedema. ACEI-related angioedema is never accompanied by urticaria and occurs via a kinin-dependent mechanism. ACEI-related angioedema not only can start years after beginning the treatment, but it can then recur irregularly while under that treatment. Furthermore, allergy tests are unreliable for the diagnosis of ACEI-related angioedema, and so the relationship between angioedema and ACEIs is often missed and consequently quite underestimated. Accordingly, better understanding of the kinin-dependent mechanism, which is particular to angioedema, is necessary for the appropriate management of drug-induced angioedema.

Background: Allergic rhinitis represents a worldwide health problem. The prevalence is increasing. The aim of this study was to analyse the correlation between the severity of allergic rhinitis and an adequate treatment dose of modern oral antihistamines. Methods: From a comprehensive databank containing data from ten different open-label prospective observational studies including raw data of 140,853 patients with allergic rhinitis, symptomatology variables were analysed and scored to study the effects of treatment with four antihistamines (Desloratadine, Ebastine, Fexofenadine, Levocetirizine) alone or in combination with intranasal corticosteroids. The patient data were collected in 23,606 study centres from Germany, mostly medical specialist and some primary care physicians in private practice. The analyses were performed via individual patient data meta-analysis techniques. Results: Finally 92,900 patient data from nine of ten studies could be analysed. One study with data of 47,953 patients was excluded due to incomplete treatment documentation. Both monotherapy analysis subgroups (Total Symptom Score and Total Nasal Symptom Score) were significantly better than those of their combinations with intranasal steroids. Monotherapy with levocetirizine was determined to be significantly more effective in lowering the Total Symptom Score (p < 0.001) and the Total Nasal Symptom Score (p < 0.05) than the other antihistamines. In the next stage, a greater positive effect of levocetirizine was demonstrated in relation to the severity of the clinical symptoms of allergic rhinitis (Total Nasal Symptom Score in cases with severe symptomatology [effect size = -0.09]). Conclusions: Levocetirizine asserted itself as the only antihistamine compared with the others as significant in this analysis. The study authors recommend monotherapy with the new-generation antihistamine levocetirizine, especially in severe cases of allergic rhinitis.

We previously identified MGL_1304 secreted by Malassezia globosa as a sweat antigen for patients with atopic dermatitis (AD) and cholinergic urticaria (ChU). However, purifying native MGL_1304 from human sweat or culture supernatant of M. globosa (sup-MGL_1304) is costly and time-consuming. Moreover, recombinant MGL_1304 expressed by using Escherichia coli (TF-rMGL_1304) needs a large chaperon protein and lacks the original glycosylation of yeasts. Thus, we generated a recombinant MGL_1304 by Pichia pastoris (P-rMGL_1304) and investigated its characteristic features.

Atopic dermatitis (AD) is a chronic inflammatory skin disease that is often associated with the development of food allergy and asthma. New insights into AD reveals an important role for structural abnormalities in the epidermis resulting in a leaky epithelial barrier as well as chronic immune activation that contribute to the pathophysiology of this common skin disease. Patients with AD have a predisposition to colonization or infection by microbial organisms, most notably Staphylococcus aureus and herpes simplex virus (HSV). Measures directed at healing and protecting the skin barrier and controlling the immune activation are needed for effective management of AD. Early intervention may improve outcomes for AD as well as reduce the systemic allergen sensitization that may lead to associated allergic diseases in other organs.

Large-scale biodiversity loss and complex changes in social behaviors are altering human microbial ecology. This is increasingly implicated in the global rise in inflammatory diseases, most notably the “allergy epidemic” in very early life. Colonization of human ecological niches, particularly the gastrointestinal tract, is critical for normal local and systemic immune development and regulation. Disturbances in composition, diversity and timing of microbial colonization have been associated with increased allergy risk, indicating the importance of strategies to restore a dysbiotic gut microbiota in the primary prevention of allergic diseases, including the administration of probiotics, prebiotics and synbiotics. Here, we summarize and discuss findings of randomized clinical trials that have examined the effects of these microbiome-related strategies on short and long-term allergy preventative effects - including new guidelines from the World Allergy Organization which now recommend probiotics and prebiotics for allergy prevention under certain conditions. The relatively low quality evidence, limited comparative studies and large heterogeneity between studies, have collectively hampered recommendations on specific probiotic strains, specific timing and specific conditions for the most effective preventive management. At the same time the risk of using available products is low. While further research is needed before specific practice guidelines on supplement probiotics and prebiotics, it is equally important that the underlying dietary and lifestyle factors of dysbiosis are addressed at both the individual and societal levels.

Poly(γ-glutamic acid) (PGA) is an allergen in natto, fermented soybeans, which causes late-onset anaphylaxis. We hypothesized that jellyfish stings sensitize adults to PGA because a surfer had allergies to both natto and jellyfish, whose sting contains PGA. The aim of the study was to identify behavioral factors, such as marine sports, associated with PGA sensitization.

Gut microbial ecology and function are dynamic in infancy, but are stabilized in childhood. The ‘new friends’ have a great impact on the development of the digestive tract and host immune system. In the first year of life, especially, the gut microbiota dramatically changes through interactions with the developing immune system in the gut. The process of establishing the gut microbiota is affected by various environmental factors, with the potential to be a main determinant of life-long health. In this review, we summarize recent findings regarding gut microbiota establishment, including the importance of various factors related to the development of the immune system and allergic diseases later in life.