Drug hypersensitivity reactions in Asia: regional issues and challenges

There are geographical, regional, and ethnic differences in the phenotypes and endotypes of patients with drug hypersensitivity reactions (DHRs) in different parts of the world. In Asia, aspects of drug hypersensitivity of regional importance include IgE-mediated allergies and T-cell-mediated reactions, including severe cutaneous adverse reactions (SCARs), to beta-lactam antibiotics, antituberculous drugs, nonsteroidal anti-inflammatory drugs (NSAIDs) and radiocontrast agents. Delabeling of low-risk penicillin allergy using direct oral provocation tests without skin tests have been found to be useful where the drug plausibility of the index reaction is low. Genetic risk associations of relevance to Asia include human leucocyte antigen (HLA)-B*1502 with carbamazepine SCAR, and HLA-B*5801 with allopurinol SCAR in some Asian ethnic groups. There remains a lack of safe and accurate diagnostic tests for antituberculous drug allergy, other than relatively high-risk desensitization regimes to first-line antituberculous therapy. NSAID hypersensitivity is common among both adults and children in Asia, with regional differences in phenotype especially among adults. Low dose aspirin desensitization is an important therapeutic modality in individuals with cross-reactive NSAID hypersensitivity and coronary artery disease following percutaneous coronary intervention. Skin testing allows patients with radiocontrast media hypersensitivity to confirm the suspected agent and test for alternatives, especially when contrasted scans are needed for future monitoring of disease relapse or progression, especially cancers.

Asia Pacific Association of Allergy Asthma and Clinical Immunology White Paper 2020 on climate change, air pollution, and biodiversity in Asia-Pacific and impact on allergic diseases

Air pollution, climate change, and reduced biodiversity are major threats to human health with detrimental effects on a variety of chronic noncommunicable diseases in particular respiratory and cardiovascular diseases. The extent of air pollution both outdoor and indoor air pollution and climate change including global warming is increasing-to alarming proportions particularly in the developing world especially rapidly industrializing countries worldwide. In recent years, Asia has experienced rapid economic growth and a deteriorating environment and increase in allergic diseases to epidemic proportions. Air pollutant levels in many Asian countries especially in China and India are substantially higher than are those in developed countries. Moreover, industrial, traffic-related, and household biomass combustion, indoor pollutants from chemicals and tobacco are major sources of air pollutants, with increasing burden on respiratory allergies. Here we highlight the major components of outdoor and indoor air pollutants and their impacts on respiratory allergies associated with asthma and allergic rhinitis in the Asia-Pacific region. With Asia-Pacific comprising more than half of the world's population there is an urgent need to increase public awareness, highlight targets for interventions, public advocacy and a call to action to policy makers to implement policy changes towards reducing air pollution with interventions at a population-based level.

Climate change, air pollution, and biodiversity in Asia Pacific: impact on allergic diseases

No abstract available.

A case of anhidrotic ectodermal dysplasia presenting with pyrexia, atopic eczema, and food allergy

Anhidrotic ectodermal dysplasia (AED) is a rare hereditary disorder with a triad of sparse hair, dental hypoplasia, and anhidrosis. Here we report a case of AED with food allergy and atopic eczema. The patient was a 11-month-old boy admitted to our hospital with pyrexia for 2 weeks. He presented with a history of dry skin, eczema, and food allergy to egg. On clinical examination, his body temperature was 38.8°C, with dry skin and eczema almost all over the body, sparse eyebrows, and scalp hair. Laboratory investigations and physical examination did not show any evidence of infection. Radioallergosorbent test was positive to egg yolk, egg white, ovomucoid, milk, house dust, and house dust mite. As the child did not sweat despite the high fever, we performed the sweat test which revealed a total lack of sweat glands. Genetic examination revealed a mutation of the EDA gene and he was diagnosed as AED. His pyrexia improved upon cooling with ice and fan. His mother had lost 8 teeth and her sweat test demonstrated low sweating, suggestive of her being a carrier of AED. Atopy and immune deficiencies have been shown to have a higher prevalence in patients with AED. Disruption of the skin barrier in patients with AED make them more prone to allergic diseases such as atopic eczema, bronchial asthma, allergic rhinitis and food allergy. Careful assessment of the familial history is essential to differentiate AED when examining patients with pyrexia of unknown origin and comorbid allergic diseases.

Optimal control of asthma improved eosinophilic otitis media

BACKGROUND: Eosinophilic otitis media (EOM) is often associated with comorbid asthma. The middle ear cavity is part of the upper airway. Therefore, EOM and asthma can be considered to be a crucial part of the “one airway, one disease” phenomenon. Based on the concept of one airway, one disease in the context of allergic rhinitis and asthma, optimal level of inhalation therapy for better asthma control leads to improvement in allergic rhinitis. OBJECTIVE: We conducted a pilot study to determine whether appropriate strengthening of inhalation therapy for asthma is effective for EOM. METHODS: Fifteen patients with EOM and comorbid asthma were enrolled in this study. Eight patients were randomly selected and administered appropriately strengthened inhalation therapy for asthma (strengthened group). The effect of the therapy on EOM was assessed by comparing a questionnaire for ear symptoms, clinical characteristic score, pure tone audiometry, blood tests and temporal bone computed tomography (CT) examination before and after the therapy. Seven other EOM + asthma patients without the above mentioned therapy were included as controls. RESULTS: In the strengthened group, the score of ear symptoms, clinical characteristics score, peripheral blood eosinophil count, CT score, and air conduction hearing level improved significantly after strengthening the inhalation therapy, but not in the control group. The lung function tests (forced vital capacity [%predicted], forced expiratory volume in 1 second [FEV₁] [L], and FEV₁ [%predicted]) significantly increased in the strengthened group after the therapy, but not in the control group. CONCLUSION: In this study we demonstrated that EOM improved along with improved lung function when appropriately optimal inhalation therapy was implemented in patients with EOM and asthma. Administration of optimizing therapy for asthma might be effective for concomitant EOM.

Basophils are increased and express increased levels of interleukin-4 in the parotid lesions of Kimura disease

BACKGROUND: Kimura disease (KD) is a systemic soft-tissue disease that leads to formation of painless masses in lymph nodes, with the highest predilection for the head and neck and especially the parotid gland. KD lesions are characterized by marked eosinophil infiltration, production of IgE and increased expression of T-helper type 2 (Th2) cytokines (interleukin [IL]-4, IL-5, etc.). Skewing to a Th2 inflammation is also demonstrated in the peripheral blood, with elevated eosinophils and high IgE levels. It is thought that basophils may play important roles in orchestrating this Th2 inflammation via IL-4 production leading to the induction of IgE synthesis as well as eosinophil infiltration. However, there are no reports as yet on the role of basophils in KD. OBJECTIVE: The present study was performed to investigate the potential role of basophils in the pathogenesis of KD. In this context we also examined the expression of IL-4 in basophils in the KD lesions. METHODS: By immunohistochemistry using a monoclonal antibody against a basophil marker ProMBP1 we investigated the number and distribution of basophils in the KD lesions. By double immunohistochemistry we analyzed the colocalization of IL-4 in basophils. RESULTS: There was an increased number of basophils infiltrating the KD parotid gland lesions as compared to that in normal control parotid tissue. By double-immunofluorescence we found that approximately 7% of IL-4-positive cells in KD patients' parotid glands were basophils. CONCLUSION: Basophils may also play a role in the pathogenesis of KD, leading to the induction of IgE synthesis and eosinophil infiltration.

Climate Change and Air Pollution: Effects on Respiratory Allergy

A body of evidence suggests that major changes involving the atmosphere and the climate, including global warming induced by anthropogenic factors, have impact on the biosphere and human environment. Studies on the effects of climate change on respiratory allergy are still lacking and current knowledge is provided by epidemiological and experimental studies on the relationship between allergic respiratory diseases, asthma and environmental factors, such as meteorological variables, airborne allergens, and air pollution. Urbanization with its high levels of vehicle emissions, and a westernized lifestyle are linked to the rising frequency of respiratory allergic diseases and bronchial asthma observed over recent decades in most industrialized countries. However, it is not easy to evaluate the impact of climate changes and air pollution on the prevalence of asthma in the general population and on the timing of asthma exacerbations, although the global rise in asthma prevalence and severity could also be an effect of air pollution and climate change. Since airborne allergens and air pollutants are frequently increased contemporaneously in the atmosphere, an enhanced IgE-mediated response to aeroallergens and enhanced airway inflammation could account for the increasing frequency of respiratory allergy and asthma in atopic subjects in the last 5 decades. Pollen allergy is frequently used to study the relationship between air pollution and respiratory allergic diseases, such as rhinitis and bronchial asthma. Epidemiologic studies have demonstrated that urbanization, high levels of vehicle emissions, and westernized lifestyle are correlated with an increased frequency of respiratory allergy prevalently in people who live in urban areas in comparison with people living in rural areas. Climatic factors (temperature, wind speed, humidity, thunderstorms, etc.) can affect both components (biological and chemical) of this interaction.

Improvement of Eosinophilic Otitis Media by Optimized Asthma Treatment

Eosinophilic otitis media (EOM) shows a very high rate of association with asthma, and intractable otitis media involves marked eosinophil infiltration into the middle ear. The middle ear space is connected to the nasopharynx by the Eustachian tube, and it is considered a part of the upper respiratory tract. Allergic rhinitis and asthma often coexist as chronic inflammatory diseases of the upper and lower airways, respectively, and have an impact on each other. In fact, inhaled corticosteroids reduce seasonal eosinophilia systemically in the circulation and locally in the nasal mucosa, as well as attenuate seasonal nasal symptoms. We report a case of EOM associated with adult-onset asthma that improved following optimal asthma therapy after changing the treatment from inhaled fluticasone propionate (FP) (200 microg b.i.d.) to a combination of FP/salmeterol (250/50 microg b.i.d.). This result supports the hypothesis that EOM and asthma are closely linked, presenting as different manifestations of a similar disease syndrome.

Expression and Roles of MMP-2, MMP-9, MMP-13, TIMP-1, and TIMP-2 in Allergic Nasal Mucosa

PURPOSE: Allergic rhinitis (AR) and asthma share many characteristics, but structural changes are observed far less often in AR. Matrix metalloproteinases (MMPs) constitute a family of Zn-dependent endopeptidases that can decompose the extracellular matrix and basement membrane, and regulate cell infiltration. We analyzed the expression of MMPs and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs), in allergic nasal mucosa after nasal allergen challenge (NAC) and determined their relationship to inflammatory cells. METHODS: Nasal mucosa specimens were obtained at surgery performed for hypertrophied turbinates. We performed NAC with house dust mite (HDM) allergen disks and control disks, and took biopsies at 30 minutes, 6 hours, and 12 hours after NAC. Cells expressing MMP-2, MMP-9, MMP-13, TIMP-1, and TIMP-2, as well as eosinophils and mast cells, were analyzed immunohistochemically. The MMPs and TIMPs in allergic nasal mucosa were quantified using enzyme-linked immunosorbent assays. RESULTS: At 30 minutes post-NAC, HDM-exposed nasal mucosa exhibited significantly more MMP-2+, MMP-9+, MMP-13+, TIMP-1+, and TIMP-2+ cells compared with control mucosa, and the numbers of MMP-9+ and TIMP-1+ cells correlated strongly with the number of mast cells. At 6 hours post-NAC, the numbers of MMP+ and TIMP+ cells did not differ significantly between HDM-exposed mucosa and control mucosa, but the ratios of MMP+ cells to TIMP+ cells were higher in HDM-exposed mucosa. At 12 hours post-NAC, the number of MMP-13+ cells tended to be higher in HDM-exposed mucosa and was strongly correlated with the number of eosinophils. Quantitatively, the levels of MMP-2 and MMP-13 were significantly higher than the MMP-9 level, and the TIMP-2 level was significantly higher than the TIMP-1 level in allergic nasal mucosa. CONCLUSIONS: We demonstrated increased expression of MMP-2, MMP-9, and MMP-13 in allergic nasal mucosa, high MMPs-to-TIMP-1 ratios, and a strong correlation between MMP-9 and mast cells and between MMP-13 and eosinophils. The imbalance between MMPs and TIMPs may contribute to the migration of inflammatory cells such as eosinophils and mast cells to the nasal mucosa of AR patients, suggesting a possible active role of MMPs in AR.

Decreased Expression of FOXP3 in Nasal Polyposis

PURPOSE: The pathogenesis of nasal polyposis (NP) is unclear. Eosinophils and mast cells are considered to play important roles in this process. In addition, the levels of Th2-type cells are increased, irrespective of the atopic status of the patient with NP. In this context, we and others have shown high levels of thymus and activation-related chemokine/CCL17, macrophage-derived chemokine, eotaxin, and RANTES in patients with NP. Forkhead box P3 (FOXP3) plays a key role in CD4+CD25+ regulatory T-cell function and represents a specific marker for regulatory T cells (Tregs). Decreased expression of FOXP3 has been reported in allergic diseases. The present study was designed to evaluate the presence and potential roles of Tregs, defined by the expression of FOXP3 protein, in NP. METHODS: Using immunohistochemistry, we estimated the numbers of FOXP3+ cells in the epithelium and lamina propria of the NPs of 17 patients with chronic rhinosinusitis with NP and the nasal mucosa of 15 patients with allergic rhinitis (AR). The number of FOXP3+ cells in NPs was compared with that in the nasal mucosa of patients with AR, and the numbers of FOXP3+ cells in atopic and non-atopic NP were also compared. RESULTS: The number of FOXP3+ cells in the lamina propria of patients with NP was significantly lower than that in the nasal mucosa of the AR patients (2.79 vs. 5.99, P=0.008). There was no statistically significant difference noted for the numbers of FOXP3+ cells between the epithelium of the NP and the nasal mucosa (3.60 vs. 2.39, P=0.180). Furthermore, the numbers of CD4+FOXP3+ cells were lower in NPs than in the allergic nasal mucosa. There was no difference in the number of FOXP3+ cells between the atopic and non-atopic NP patients. CONCLUSIONS: Fewer Tregs (i.e., decreased FOXP3 expression) are found in NPs than in the nasal mucosa of AR patients. As the severity of eosinophilic, Th2-type inflammation and the levels of inflammatory mediators are much higher in NPs than in the nasal mucosa of AR patients, an inverse co-relationship may exist between these parameters and the number of Tregs. The deficiency of Tregs in NP may account for the more pronounced Th2-type inflammation seen in these patients.

Increased Expression and Role of Thymic Stromal Lymphopoietin in Nasal Polyposis

PURPOSE: Nasal polyposis is a chronic inflammatory disease of the upper airways often associated with asthma and characterized by markedly increased numbers of eosinophils, Th2 type lymphocytes, fibroblasts, goblet cells and mast cells. Previous studies have shown elevated levels of thymic stromal lymphopoietin (TSLP) in atopic diseases like asthma, atopic dermatitis and mainly in animal models of allergic rhinitis (AR). Here, we investigated the expression of TSLP in nasal polyps from atopics and non-atopics in comparison with the nasal mucosa and its potential role in nasal polyposis. METHODS: Messenger RNA expression for TSLP, thymus and activation-regulated chemokine (TARC) and macrophage derived chemokine (MDC) in nasal polyps and nasal mucosa of atopics and non-atopics was analyzed by real time PCR. Immunoreactivity for TSLP in nasal polyps and in the nasal mucosa of patients with AR and non-allergic rhinitis (NAR) was analyzed by immunohistochemistry. Eosinophil counts was analyzed by Wright-Giemsa staining and nasal polyp tissue IgE, by ELISA. RESULTS: Messenger RNA expression for TSLP,TARC and MDC was markedly higher in nasal polyps as compared to the allergic nasal mucosa. Immunoreactivity for TSLP was detected in epithelial cells, endothelial cells, fibroblasts and inflammatory cells of the nasal mucosa and nasal polyps. The number of TSLP+ cells was significantly greater in the nasal mucosa of AR than NAR patients. The number of TSLP+ cells in nasal polyps from atopics was significantly greater than that of non-atopics and that in the allergic nasal mucosa. The number of TSLP+ cells correlated well with the number of eosinophils and the levels of IgE in nasal polyps. CONCLUSIONS: The high expression of TSLP in nasal polyps and its strong correlation to eosinophils and IgE suggest a potential role for TSLP in the pathogenesis of nasal polyps by regulating the Th2 type and eosinophilic inflammation.

Overview on the pathomechanisms of allergic rhinitis

Allergic rhinitis a chronic inflammatory disease of the upper airways that has a major impact on the quality of life of patients and is a socio-economic burden. Understanding the underlying immune mechanisms is central to developing better and more targeted therapies. The inflammatory response in the nasal mucosa includes an immediate IgE-mediated mast cell response as well as a latephase response characterized by recruitment of eosinophils, basophils, and T cells expressing Th2 cytokines including interleukin (IL)-4, a switch factor for IgE synthesis, and IL-5, an eosinophil growth factor and on-going allergic inflammation. Recent advances have suggested new pathways like local synthesis of IgE, the IgE-IgE receptor mast cell cascade in on-going allergic inflammation and the epithelial expression of cytokines that regulate Th2 cytokine responses (i.e., thymic stromal lymphopoietin, IL-25, and IL-33). In this review, we briefly review the conventional pathways in the pathophysiology of allergic rhinitis and then elaborate on the recent advances in the pathophysiology of allergic rhinitis. An improved understanding of the immune mechanisms of allergic rhinitis can provide a better insight on novel therapeutic targets.

Asthma insights and reality in the United Arab Emirates

The burden of asthma in the United Arab Emirates [UAE] and the extent to which guidelines are being followed for optimum asthma control are largely unknown. This survey assessed the current level of asthma control, the burden of the disease, and adherence to asthma guidelines by patients. A face-to-face interview of 200 asthmatics in the UAE was conducted. In addition to the questionnaire administered by expert interviewers, each respondent self-completed an Asthma Control Test. The sample was stratified by region within the country and sampled proportionately. Sudden severe attacks of asthma were reported by 64% in the past year. Day time symptoms and night time symptoms were reported by 57.5% and 35.5%, respectively, in the past 4 weeks. Overall, 52.8% of the children and 17.1% of the adults missed school and work in the past year, respectively. The percentage of asthmatics that had emergency room visits within the past year was 27.5%, and 4% were hospitalized. Only 5.5% used inhaled corticosteroids in the past year and 47.5% were on short-acting beta-2 agonists. Only 17.8% ever owned a peak flow meter and only 30% ever had a lung function test. Only 17% had scheduled follow-up and 66% were followed-up by general practitioners. This survey shows that the current level of asthma control in the UAE is far from optimal. Therefore, it is necessary to increase the awareness among patients and update doctors about asthma control guidelines for attaining optimal asthma control, and thus reducing the burden of the disease