The management of allergic patients; the role of the internist

There has been an increasing trend in the United States toward intensive specialization in allergic diseases. Whereas the tendency toward specialization has led to greater knowledge of the scientific aspects of allergic phenomena, it has somewhat diverted the specialists' attention from the many clinical problems that await solution. Effective treatment of the allergic patient depends in no small measure on the broad viewpoint and clinical experience of the internist. This fact has been reemphasized by the growing awareness of the significance of the secondary or precipitating causes, such as climatic, nutritional, hormonal and psychogenic factors which influence allergic manifestations. Overemphasis on specialization in allergic diseases with their wide ramifications may defeat the main objective-a successful therapeutic result. To meet this challenge, the internist should be trained in allergy and yet retain a broad approach to the more basic problems of internal medicine. This objective may be attained by certain modifications in undergraduate medical instruction in allergy. Postgraduate training sponsored by our national allergy societies affords internists an excellent opportunity to advance their knowledge of clinical allergy.     

Radioimmunologic tests in children with pruritus and with a combination of pruritus and allergic respiratory disease

Radioimmunological tests were carried out in 180 children with pruritus and 167 children with pruritus and allergic respiratory diseases. Difference between these groups was statistically insignificant in case of food allergy. Results of RAST were more often positive in case of respiratory allergy in the patients with pruritus and coexisting allergic respiratory diseases than in patients with skin involvement only. Reaction was more intense and allergy polyvalence measured with RAST was higher. All differences were statistically significant (p less than 0.001 or 0.01). Mean IgE levels was higher in children of all age groups in case of pruritus coexisting with allergic respiratory diseases.     

THE MANAGEMENT OF ALLERGIC PATIENTS—The Role of the Internist

There has been an increasing trend in the United States toward intensive specialization in allergic diseases. Whereas the tendency toward specialization has led to greater knowledge of the scientific aspects of allergic phenomena, it has somewhat diverted the specialists'' attention from the many clinical problems that await solution.Effective treatment of the allergic patient depends in no small measure on the broad viewpoint and clinical experience of the internist. This fact has been reemphasized by the growing awareness of the significance of the secondary or precipitating causes, such as climatic, nutritional, hormonal and psychogenic factors which influence allergic manifestations. Overemphasis on specialization in allergic diseases with their wide ramifications may defeat the main objective—a successful therapeutic result.To meet this challenge, the internist should be trained in allergy and yet retain a broad approach to the more basic problems of internal medicine. This objective may be attained by certain modifications in undergraduate medical instruction in allergy. Postgraduate training sponsored by our national allergy societies affords internists an excellent opportunity to advance their knowledge of clinical allergy.     

Allergy as a systemic disease

The prevalence of allergic diseases has shown an increase in the last few years. Allergic diseases develop in persons with a genetic background, this genetic trait being known as atopy. The main pathophysiological characteristic of allergy is inflammation. The inflammatory process may explain the diversity of symptoms and signs of allergy. The early sensitization increases the risk of developing different symptomatic forms of allergy, and one person may present different symptoms and signs of allergy. But some persons can become allergic without atopy trait in conditions of a higher and longer exposure to allergens (e.g. occupational allergy). In the last years new allergens have induced symptoms, sometimes with a life-threatening evolution. The load of allergen in public areas is also increasing. In this context, allergy must be understood as a unique systemic disease with various forms of presentation.     

Antigen-fixed leukocytes tolerize Th2 responses in mouse models of allergy

Allergic diseases, including asthma and food allergies, are an increasing health concern. Immunotherapy is an effective therapeutic approach for many allergic diseases but requires long dose escalation periods and has a high risk of adverse reactions, particularly in food allergy. New methods to safely induce Ag-specific tolerance could improve the clinical approach to allergic disease. We hypothesized that Ag-specific tolerance induced by the i.v. injection of Ags attached to the surface of syngeneic splenic leukocytes (Ag-coupled splenocytes [Ag-SPs]) with the chemical cross-linking agent ethylene-carbodiimide, which effectively modulate Th1/Th17 diseases, may also safely and efficiently induce tolerance in Th2-mediated mouse models of allergic asthma and food allergy. Mice were tolerized with Ag-SP before or after initiation of OVA/alum-induced allergic airway inflammation or peanut-induced food allergy. The effects on disease pathology and Th2-directed cytokine and Ab responses were studied. Ag-SP tolerance prevented disease development in both models and safely tolerized T cell responses in an Ag-specific manner in presensitized animals. Prophylactically, Ag-SP efficiently decreased local and systemic Th2 responses, eosinophilia, and Ag-specific IgE. Interestingly, Ag-SP induced Th2 tolerance was found to be partially dependent on the function of CD25(+) regulatory T cells in the food allergy model, but was regulatory T cell independent in the model of allergic airway inflammation. We demonstrate that Ag-SP tolerance can be rapidly, safely, and efficiently induced in murine models of allergic disease, highlighting a potential new Ag-specific tolerance immunotherapy for Th2-associated allergic diseases.     

肠道微生物与过敏性疾病关系研究进展

目前,过敏性疾病的防治主要依赖于使用抗生素,然而抗生素的滥用已造成了严重的危害。近年来随着肠道微生物相关研究的不断深入以及人们对过敏性疾病的日益关注与重视,肠道微生物与过敏性疾病间的关系逐渐受到科学家们的关注。调整肠道菌群结构可能为过敏性疾病的防治提供新的思路。目前对肠道微生物与过敏性疾病间的相关性报道相对较少且未有深层次的剖析。本文总结了关于肠道微生物与过敏性疾病关系的研究起源、发展与现状,旨在为过敏性疾病的防治提供新策略。     

Difference in the Breast Milk Proteome between Allergic and Non-Allergic Mothers

Background

Breastfeeding has been linked to a reduction in the prevalence of allergy and asthma. However, studies on this relationship vary in outcome, which may partly be related to differences in breast milk composition. In particular breast milk composition may differ between allergic and non-allergic mothers. Important components that may be involved are breast milk proteins, as these are known to regulate immune development in the newborn. The objective of this study was therefore to explore differences in the proteins of breast milk from 20 allergic and non-allergic mothers. The results from this comparison may then be used to generate hypotheses on proteins associated with allergy in their offspring.

Methods

Milk samples from allergic and non-allergic mothers were obtained from the PIAMA project, a prospective birth cohort study on incidence, risk factors, and prevention of asthma and inhalant allergy. Non-targeted proteomics technology, based on liquid chromatography and mass spectrometry, was used to compare breast milk from allergic and non-allergic mothers.

Results

Nineteen proteins, out of a total of 364 proteins identified in both groups, differed significantly in concentration between the breast milk of allergic and non-allergic mothers. Protease inhibitors and apolipoproteins were present in much higher concentrations in breast milk of allergic than non-allergic mothers. These proteins have been suggested to be linked to allergy and asthma.

Conclusions

The non-targeted milk proteomic analysis employed has provided new targets for future studies on the relation between breast milk composition and allergy.     

Clinical study of peanut and nut allergy in 62 consecutive patients: new features and associations.

OBJECTIVE--To investigate clinical features of acute allergic reactions to peanuts and other nuts. DESIGN--Analysis of data from consecutive patients seen by one doctor over one year in an allergy clinic at a regional referral centre. SUBJECTS--62 patients aged 11 months to 53 years seen between October 1993 and September 1994. MAIN OUTCOME MEASURES--Type and severity of allergic reactions, age at onset of symptoms, type of nut causing allergy, results of skin prick tests, and incidence of other allergic diseases and associated allergies. RESULTS--Peanuts were the commonest cause of allergy (47) followed by Brazil nut (18), almond (14), and hazelnut (13). Onset of allergic symptoms occurred by the age of 2 years in 33/60 and by the age of 7 in 55/60. Peanuts accounted for all allergies in children sensitised in the first year of life and for 82% (27/33) of allergies in children sensitised by the third year of life. Multiple allergies appeared progressively with age. The commonest symptom was facial angioedema, and the major feature accounting for life threatening reactions was laryngeal oedema. Hypotension was uncommon. Of 55 patients, 53 were atopic--that is, had positive skin results of tests to common inhaled allergens--and all 53 had other allergic disorders (asthma, rhinitis, eczema) due to several inhaled allergens and other foods. CONCLUSIONS--Sensitisation, mainly to peanuts, is occurring in very young children, and multiple peanut/nut allergies appear progressively. Peanut and nut allergy is becoming common and can cause life threatening reactions. The main danger is laryngeal oedema. Young atopic children should avoid peanuts and nuts to prevent the development of this allergy.     

A novel DC therapy with manipulation of MKK6 gene on nickel allergy in mice

BACKGROUND: Although the activation of dermal dendritic cells (DCs) or Langerhans cells (LCs) via p38 mitogen-activated protein kinase (MAPK) plays a crucial role in the pathogenesis of metal allergy, the in vivo molecular mechanisms have not been identified and a possible therapeutic strategy using the control of dermal DCs or LCs has not been established. In this study, we focused on dermal DCs to define the in vivo mechanisms of metal allergy pathogenesis in a mouse nickel (Ni) allergy model. The effects of DC therapy on Ni allergic responses were also investigated. METHODS AND FINDING: The activation of dermal DCs via p38 MAPK triggered a T cell-mediated allergic immune response in this model. In the MAPK signaling cascade in DCs, Ni potently phosphorylated MAP kinase kinase 6 (MKK6) following increased DC activation. Ni-stimulated DCs could prime T cell activation to induce Ni allergy. Interestingly, when MKK6 gene-transfected DCs were transferred into the model mice, a more pronounced allergic reaction was observed. In addition, injection of short interfering (si) RNA targeting the MKK6 gene protected against a hypersensitivity reaction after Ni immunization. The cooperative action between T cell activation and MKK6-mediated DC activation by Ni played an important role in the development of Ni allergy. CONCLUSIONS: DC activation by Ni played an important role in the development of Ni allergy. Manipulating the MKK6 gene in DCs may be a good therapeutic strategy for dermal Ni allergy.     

Mechanism and epidemiology of laboratory animal allergy

Laboratory animal allergy (LAA) is a form of occupational allergic disease. The development of laboratory animal allergy is due to the presence of IgE antibodies directed against animal proteins. The process of sensitization (development of IgE antibodies) is a complex process which involves interaction of antigen presenting cells and lymphocytes of the Th-2 cell type. These cells generate a host of cytokines and other factors which lead to immediate hypersensitivity reactions and other factors which lead to immediate hypersensitivity reactions and the generation of allergic inflammation. Typical symptoms of laboratory animal allergy include nasal symptoms, such as sneezing, watery discharge, and congestion. Skin rashes are also common. Asthma, which produces symptoms of cough, wheezing, and shortness of breath, may affect 20-38% of workers who are sensitized to laboratory animal allergens. Rarely a generalized, life-threatening allergic reaction (anaphylaxis) may occur. The estimated prevalence of laboratory animal allergy is variable depending on the method used for diagnosis, but nonetheless may affect up to 46% of exposed workers. The presence of pre-existing allergies to non-work place allergens (e.g., dust mite, pollens, molds), exposure to laboratory animal allergens, and possibly tobacco smoking are risk factors for the development of laboratory animal allergy. Progress in the understanding of the mechanism and epidemiology of laboratory animal allergy will lead to improved methods for its prevention.     

Allergy to penicillin: fable or fact?

OBJECTIVE--To assess whether, on the basis of one blood test, penicillin allergy might be excluded sufficiently for general practitioners to give oral penicillin to patients claiming a history of penicillin allergy. DESIGN--Prospective study of patients referred by general practitioners. SETTING--Outpatient allergy clinic in a district general hospital. PATIENTS--175 referred patients who gave a history of immediate type reaction to penicillin, of whom 144 attended as requested and 132 completed the investigations. MAIN OUTCOME MEASURES--History and examination, serum radioallergosorbent test to phenoxymethylpenicillin and benzylpenicillin, and oral challenge with penicillin. RESULTS--Of 132 patients, four were confirmed to have penicillin allergy by the radioallergosorbent test and 128 had an oral penicillin challenge without ill effect. CONCLUSIONS--Most patients who gave a history of penicillin allergy are not so allergic, and their actual allergic state should be substantiated whenever feasible. For patients reporting minor or vague reactions negative findings with a radioallergosorbent test to phenoxymethylpenicillin and benzylpenicillin provide sufficient evidence to give oral penicillin safely.     

No Adjuvant Effect of Bacillus thuringiensis-Maize on Allergic Responses in Mice

Genetically modified (GM) foods are evaluated carefully for their ability to induce allergic disease. However, few studies have tested the capacity of a GM food to act as an adjuvant, i.e. influencing allergic responses to other unrelated allergens at acute onset and in individuals with pre-existing allergy. We sought to evaluate the effect of short-term feeding of GM Bacillus thuringiensis (Bt)-maize (MON810) on the initiation and relapse of allergic asthma in mice. BALB/c mice were provided a diet containing 33% GM or non-GM maize for up to 34 days either before ovalbumin (OVA)-induced experimental allergic asthma or disease relapse in mice with pre-existing allergy. We observed that GM-maize feeding did not affect OVA-induced eosinophilic airway and lung inflammation, mucus hypersecretion or OVA-specific antibody production at initiation or relapse of allergic asthma. There was no adjuvant effect upon GM-maize consumption on the onset or severity of allergic responses in a mouse model of allergic asthma.     

IgE against food and respiratory allergens in healthy and allergic mothers and their children

IgE against mixtures of common food or respiratory allergens were determined by ELISA in healthy (n = 38) and allergic (n = 62) mothers and their children. Significantly higher level of IgE against respiratory allergens was found in sera of allergic mothers and in cord blood of their children. No correlation between antibody level in maternal and newborn's sera was found; this argues against the transfer of IgE from mother to fetus and points rather to offspring's intrauterine sensitization. Specific IgE level in cord blood was higher in children who developed later allergy than in children who did not. Specific IgE level in colostrum was low both in healthy and allergic mothers; there was no correlation between high concentration of IgE against respiratory allergens in sera of allergic mothers and their colostrum, which does not support the idea of IgE transport from blood to mammary gland. Only slightly increased colostral IgE was detected in allergic mothers whose children manifested allergy later. Allergy of the mother and high level of anti-allergen IgE in her serum and in cord blood are the main predictive factors of future occurrence of allergy in the offspring. A combination of several predictive factors could have higher prognostic value.     

支气管扩张合并支气管哮喘患者的病原菌检测及危险因素分析

目的分析支气管扩张合并支气管哮喘患者的病原菌及危险因素。方法选取湖州市中心医院115例支气管扩张合并支气管哮喘患者作为观察组,另选取同期110例健康体检者作为对照组。分析患者病原菌的组成、耐药性及发病危险因素。结果观察组患者送检痰样本经痰培养,阳性检出者68例,阳性率为59.13%(68/115)。全部样本共分离出104株病原菌,其中革兰阴性菌92株(以铜绿假单胞菌最多,占54.81%),革兰阳性菌8株,真菌4株。药敏试验结果表明革兰阴性菌对复方新诺明、头孢曲松、左旋左氧氟沙星和阿莫西林/克拉维酸等药物的耐药性均较高,对妥布霉素、亚胺培南、头孢哌酮/舒巴坦和哌拉西林的耐药性较低。Logistic回归分析显示,吸烟史、药物过敏史、食物过敏史、过敏性鼻炎、哮喘、过敏性肺炎、慢性支气管炎及慢性阻塞性肺疾病均是支气管扩张伴支气管哮喘发生的危险因素。结论支气管扩张合并支气管哮喘患者其病原菌以革兰阴性菌为主,吸烟史、药物过敏史、食物过敏史、过敏性鼻炎等是支气管扩张伴支气管哮喘发生的危险因素。     

Focus: Allergic Diseases and Type II Immunity: Allergy Prevention: An Overview of Current Evidence

Background: There has been a rapid rise in allergic disorders across the globe. This has increased research into the determinants of allergy development, to identify factors that may be manipulated to mitigate risk. An opportune window in immunological development appears to exist in early life whereby certain exposures may promote or prevent the development of an allergic disposition. Furthermore, factors that affect the composition and diversity of the microbiome in early life have been explored. In this review, we discuss current literature and recommendations relating to exposures that may prevent allergy development or promote tolerance. Risk factors and recommendations: Delivery by caesarean section, omission of breastfeeding, vitamin D insufficiency, and environmental exposures, such as cigarette smoke exposure, all increase the risk of an allergic predisposition. Dietary diversity during pregnancy, lactation, and in infancy is protective. Breastfeeding for at least 4 months reduces the risk of eczema. Recommendations for food-allergen exposure has shifted from delayed introduction to early introduction as a tolerance-inducing strategy. Supplements such as probiotics and vitamins during pregnancy and infancy have yet to produce conclusive results for allergy prevention. Emollient use in infancy has not been shown to be protective against eczema or food allergy.     

The Anisakis allergy debate: does an evolutionary approach help?

Allergic phenomena share common pathways with the immune response against helminth parasites. The definitions regarding allergens and their related concepts have their roots in the area of allergy research. The experience with the fish parasite Anisakis simplex-associated allergic features still nurtures an open debate on the necessity of larvae being alive to induce allergic reactions such as urticaria or anaphylaxis. Conceptual definitions of allergen, major allergen, as well as putatively crossreacting antibodies, as are used in food allergy, depend on the clinical relevance of specific IgE and deserve careful interpretation in the various forms of A. simplex-associated allergic features. Conversely, an evolutionary based interpretation of the presence of specific IgE depends on the viability of A. simplex.     

Asthma,allergy and the risk of prostate cancer: Results from the Montreal PROtEuS study

BackgroundThe few previous studies examining the association between asthma or allergy and prostate cancer (PCa) risk were inconclusive. This study aimed to evaluate these associations, and to explore in details the possible influence of current versus former allergic condition, age at onset, time since onset, and duration of each allergic condition.MethodsDetailed information on self-reported asthma and allergy was collected in the context of a large population-based case–control study conducted in Montreal, Canada. Study subjects included 1936 cases, diagnosed between 2005 and 2009, and 1995 population controls. Unconditional multivariate logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) adjusting for age, ancestry and familial history of prostate cancer.ResultsThe ORs were 1.11 (95% CI: 0.89–1.40) and 0.98 (95% CI: 0.84–1.14) for ever reporting of asthma and allergy, respectively. These ORs did not substantially vary according to status (former or current), age at onset, time since onset, and duration of each allergic condition. PCa screening was not associated with allergic diseases reporting.ConclusionsOverall, our findings are in line with the absence of an association between a history of asthma or allergy, and PCa risk.     

Elevation of soluble interleukin-2 receptor levels in nasal allergy

To investigate soluble IL-2 receptor (sIL-2R) levels in nasal allergy, the sera and nasal secretions from patients with nasal allergy and from healthy subjects were subjected to a double-epitope enzyme-linked immunosorbent assay. Significant elevation of sIL-2R concentrations in the sera and nasal secretions was observed in the allergy patients (n = 26) compared with those of healthy subjects (n = 9). IL-2R-positive (CD25(+)) cells were observed in the crust formed in an allergic nasal mucosa. The concentration of sIL-2R in the sera correlated neither with the eosinophil count of the peripheral blood count nor with clinical severity. The concentration of sIL-2R in the nasal secretions was significantly higher compared with that in the sera from allergic patients (p < 0.01), whereas no significant difference was observed between sIL-2R levels in the sera and nasal sections from normal subjects. These findings indicate that sIL-2R plays an essential role in allergic processes by regulating IL-2R-positive cells recruited into the nasal mucosa.     

Primary structure, recombinant expression, and molecular characterization of Phl p 4, a major allergen of timothy grass (Phleum pratense)

Grass pollen allergy is one of the most important allergic diseases world-wide. Several meadow grasses, like timothy grass and rye grass, contribute to allergic sensitizations, but also allergens from extensively cultivated cereals, especially rye, make a profound contribution. The group 4 allergens are well known as important major allergens of grasses. We have cloned for the first time group 4 sequences from Phleum pratense, Lolium perenne, Secale cereale, Triticum aestivum, and Hordeum vulgare, and investigated the IgE-reactivity of recombinant Phl p 4 as a candidate for allergy diagnostic and therapeutic applications.     

Association of Allergic Symptoms with Dengue Infection and Severity: A Systematic Review and Meta-analysis

The relationship between the severity of dengue infection and allergy is still obscure. We conducted an electronic search across 12 databases for relevant articles reporting allergic symptoms, dengue infection, and dengue classification. These studies were categorized according to dengue severity and allergy symptoms, and a meta-analysis was performed by pooling the studies in each category. Among the included 57 articles, pruritus was the most common allergic sign followed by non-specified allergy and asthma(28.6%, 13%, and 6.5%, respectively). Despite the reported significant association of dengue with pruritus and total Ig E level(P \ 0.05), in comparison with non-dengue cases and healthy controls, there was no association between the different severe dengue group with pruritus, skin allergy, food allergy or asthma. However,removing the largest study revealed a significant association between asthma with dengue hemorrhagic fever(DHF) rather than dengue fever(DF). In comparison with DF, DHF was associated with Ig E positivity. Furthermore, specific-Ig E level was higher in secondary DF rather than primary DF. There was a possible association between allergy symptoms and dengue severity progression. Further studies are needed to clarify this association.