Showing papers in "Current Opinion in Allergy and Clinical Immunology in 2003"

Nasal polyposis: an update: editorial review.

Abstract: Purpose of review Nasal polyposis is a chronic inflammatory disease of the upper airway characterized histologically by the infiltration of inflammatory cells like eosinophils or neutrophils. Several hypotheses have been put forward regarding the underlying mechanisms including chronic infection, aspirin intolerance, alteration in aerodynamics with trapping of pollutants, epithelial disruptions, epithelial cell defects/gene deletions (CFTR gene), inhalant or food allergies. The present review is an update on the pathomechanisms of nasal polyposis. Recent findings In the majority of nasal polyps, eosinophils comprise more than 60% of the cell population. Besides eosinophils, mast cells and activated T cells are also increased. An increased production of cytokines/chemokines like granulocyte/macrophage colony-stimulating factor, IL-5, RANTES and eotaxin contribute to eosinophil migration and survival. Increased levels of IL-8 can induce neutrophil infiltration. Increased expression of vascular endothelial growth factor and its upregulation by transforming growth factor-beta can contribute to the edema and increased angiogenesis in nasal polyps. Again, transforming growth factor-beta can modulate fibroblast function and thus contribute to eosinophil infiltration and stromal fibrosis. Other mediators like albumin, histamine and immunoglobulins IgE and IgG are also increased in nasal polyps. In addition, the local production of IgE in nasal polyps can contribute to the increased recurrence of nasal polyps via the IgE-mast cell-FcepsilonRI cascade. Finally, mast cell/T cell-epithelial cell/fibroblast interactions can contribute to the persistent eosinophilic inflammation seen in polyps. Summary Thus although nasal polyposis is a multifactorial disease with several different etiological factors, chronic persistent inflammation is undoubtedly a major factor irrespective of the etiology.

Role of intestinal flora in the development of allergy.

Abstract: Purpose of review The frequency of allergic diseases is increasing worldwide. Experimental and clinical studies have linked a reduced number of early infections to this trend. The gastrointestinal system, which comprises the largest lymphoid tissue and microbial reservoir of the body, has received more attention during the last few years as a potential determiner in the development of atopic disease. Recent findings Alterations in intestinal microbiota have been detected both in infants suffering from allergic disease and in those later developing the disorder. Delay in the compositional development of and in gut microflora was a general finding in allergic children. In a subsequent study, perinatal administration of lactobacilli halved the later development of atopic eczema during the first 2 years of life. Specific strains of the healthy gut microbiota have been shown to induce the production of IL-10 and transforming growth factor-beta, which possess an important regulative role in the development of allergic type immune response. Probiotics also strengthen gut defence barrier mechanisms and reduce antigen load in the gut. Pattern recognition receptors in intestinal epithelial and antigen-presenting cells have been demonstrated to mediate a continuing dialogue between host and gut microbiota. Summary Despite several promising findings, the exact role of gut normal microbiota in the development of allergy remains to be elucidated. For successful interventions, more data concerning a communication between host and specific microbial species are needed.

Primary immunodeficiencies associated with pneumococcal disease.

Abstract: Purpose of reviewStreptococcus pneumoniae may cause disease in patients with a variety of primary immunodeficiencies. However, no previous review has dealt with the issue of which primary immunodeficiencies predispose affected individuals to pneumococcal disease. We thus reviewed the medical literat

Chronic idiopathic urticaria.

Abstract: PURPOSE OF REVIEW Chronic idiopathic urticaria has long been a demoralizing disease, baffling allergists and dermatologists alike, to the detriment of the patient. Recent findings, however, have shed light on causation in many, though not all, of these patients. The purpose of this review is to bring the reader up to date on the current position regarding aetiology and pathogenesis and the strength of the evidence. The review also seeks to point up rational approaches to diagnosis and treatment in the light of these developments. RECENT FINDINGS Chronic idiopathic urticaria encompasses at least two subgroups. One of these is the now well-established entity of autoimmune chronic urticaria, due to autoantibodies against either the high-affinity IgE receptor Fc epsilon R1 or, less commonly, IgE. These patients, who co-segregate with chronic idiopathic urticaria patients having an increased frequency of antithyroid autoantibodies, represent 30-50% of the patients previously designated as having chronic idiopathic urticaria. Convenient routine diagnostic tests for this subset remain elusive. The remaining 50% of patients with chronic idiopathic urticaria remain truly 'idiopathic', although the condition in some may have an autoimmune basis, autoantibodies having eluded current techniques for detection. Selected patients with autoimmune urticaria may benefit from immunotherapy. SUMMARY It is now known that in 30-50% of patients with chronic idiopathic urticaria, the condition has an autoimmune basis, although confirmation of the diagnosis in these patients is not straightforward. In selected patients, attempts to establish this diagnosis are worthwhile since there are important therapeutic implications.

Early origins of allergic disease: a review of processes and influences during early immune development.

Abstract: Purpose of review With the disturbing increase in allergic disease, there is a pressing need to determine the causes, pathogenesis and safe avenues for disease prevention. Although events in early life appear important, no causal pathways have been identified. This review examines new developments in the area of foetal and early postnatal immune maturation. It secondly addresses early predisposing influences and protective factors that may have a future role in allergy prevention. Recent findings New developments in the understanding of the ontogeny of allergen-specific immune responses in atopic infants are discussed, including the role of early type 1 and 2 immune responses, and how these are influenced by perinatal antigen presenting cell and T-cell immaturity. The controversial role of early dietary exposures including breastfeeding, food allergens, hydrolyzed formulae and other dietary factors including omega-3 fatty acids are discussed in the context of the most recent literature. Equally contentious, the role of early house dust and pet allergen exposure is discussed in light of new epidemiological studies and disappointing early results of multicentre allergen avoidance studies. Finally, a number of studies in animals and humans suggest that bacterial products can influence early immune development, providing a new potential therapeutic avenue for disease treatment and prevention. Summary Complex multifactorial genetic and environmental interactions make research in this area difficult and apparent associations with allergic disease may not be causal in nature. Many current targets for prevention, such as early allergen exposure and infant feeding practices, are proving to be ineffective and may not be directly implicated in rising rates of disease.

Update on wheat hypersensitivity.

Abstract: Purpose of reviewWheat is among the six foods responsible for approximately90% of food allergies in children, and in recent years wheat hasbeen increasingly recognized as a cause of food-dependent,exercise-induced anaphylaxis. Wheat flour is an important causeof baker’s asthma, a well-known occupational respiratory allergyto inhaled flour. This review outlines the diverse clinicalmanifestations of IgE-mediated wheat hypersensitivity andsummarizes recent advances in characterization of clinicallysignificant allergens.Recent findingsOnly a few of the numerous wheat proteins recognized by IgEof sensitized individuals have been characterized at themolecular level. Characterized allergens causing baker’sasthma include several water/salt-soluble wheat proteins,however sensitization patterns show a great degree of individualvariation. The insoluble gliadins have been implicated in IgE-mediated allergy to ingested wheat, and o-5 gliadin has beenidentified as a major allergen in wheat-dependent, exercise-induced anaphylaxis. The presence of IgE to purified o-5 gliadinin children was highly predictive of immediate clinical symptomson oral wheat challenge.SummaryDiagnostic skin prick and in-vitro tests measuring sensitizationagainst water/salt-soluble wheat proteins have poor predictivevalues. Quantification of gliadin-specific IgE in serum or skinprick testing with gliadin could serve as an additional tool in thediagnostic work-up of allergy to ingested wheat.Keywordswheat allergy, gliadin, IgE, allergen

Human herpesvirus 6 and drug allergy.

Abstract: Purpose of review The similarity between viral skin eruption and drug-induced rash has inspired many researchers to seek an association between viral infection and drug allergy. Hypersensitivity syndrome (referred to in this review as drug-induced hypersensitivity syndrome) is one of the severe adverse reactions to drugs and was reported more than 50 years ago. However, the mechanism of drug-induced hypersensitivity syndrome has not been fully elucidated. Several groups reported the association between human herpesvirus 6 reactivation and drug-induced hypersensitivity syndrome 5 years ago. Recently, similar case reports have accumulated. Recent findings concerning human herpesvirus 6 and drug-induced hypersensitivity syndrome are reviewed here. Recent findings In drug-induced hypersensitivity syndrome, examination of serial serum samples revealed a marked and sudden increase in anti-human herpesvirus 6 IgG titers in the third or fourth week after the onset of clinical manifestations. In addition, active human herpesvirus 6 replication precedes the rise in antibody titers. Furthermore, the recurrence or worsening of signs and symptoms was observed concurrently with human herpesvirus 6 reactivation. In encephalitis associated with drug-induced hypersensitivity syndrome, human herpesvirus 6 DNA was detected in cerebrospinal fluid. This strongly indicates the involvement of reactivated human herpesvirus 6 in the pathogenesis of encephalitis. Similarly, reactivation of human herpesvirus 6 was observed in fulminant type 1 diabetes mellitus associated with drug-induced hypersensitivity syndrome caused by carbamazepine. Summary The reactivation of human herpesvirus 6 in drug-induced hypersensitivity syndrome is not a coincidental phenomenon. Human herpesvirus 6 reactivation plays an important role in the pathogenesis of drug-induced hypersensitivity syndrome, especially in the latter half of the clinical symptoms. Reactivated human herpesvirus 6 sometimes leads to the severe complications of drug-induced hypersensitivity syndrome, such as encephalitis and type 1 diabetes mellitus. In conclusion, drug-induced hypersensitivity syndrome is a complex disease composed of drug allergy and human herpesvirus 6.

Environmental exposure to endotoxin and other microbial products and the decreased risk of childhood atopy: evaluating developments since April 2002.

Abstract: Purpose of review The hygiene hypothesis proposes an association between the change in exposure to microbes and the increased incidence of atopic diseases in recent decades. Exposure to microbes and childhood infections and their association with atopy has thus attracted much scientific interest. This review focuses on new developments in the field of epidemiology. Recent findings Studies in adults confirm that exposure to orofaecal pathogens are associated with less asthma and allergies. In seropositive individuals, no increase in allergy prevalence over time was noted. Similarly, the generational increase in atopy and allergic rhinitis was not observed in individuals who were exposed to a farming environment in childhood. More than 20 studies have been published examining the effect of exposure to a farm environment in children and adults. Most consistently, the 'protective' farm effect was related to livestock farming and thus to microbial exposure. A dose-dependent inverse relationship between exposure to endotoxin in the mattress dust of children and the occurrence of atopic diseases was shown in rural environments in Europe. In addition, the blood cells of farmers' children were shown to express higher amounts of innate immunity receptors. Only a few farm studies have so far included an objective measure of the microbial environment. The examined exposure to endotoxin might partly be a surrogate measure of a much broader spectrum of immunomodulatory microbial compounds present in a rural environment. Summary The 'hygiene hypothesis' has gained much credibility, but the results should be balanced against the benefits of established hygiene standards.

Innate immune responses to mycobacteria and the downregulation of atopic responses.

Abstract: Purpose of reviewExposure to certain environmental microorganisms can promote the induction of T regulatory cells via the innate immune system. This review explores the possibility that reduced exposure to such organisms is leading to increased immunoregulatory disorders in a subset of individuals i

WASP (Wiskott-Aldrich syndrome protein) gene mutations and phenotype.

Abstract: Purpose of review Wiskott-Aldrich syndrome (WAS) and X-linked thrombocytopenia (XLT), characterized by chronic microthrombocytopenia with and without immunodeficiency, are caused by mutations of the WAS protein (WASP) gene. WASP has been reported to interact with many cytoplasmic molecules linking cellular signaling to the actin cytoskeleton. In this review we will focus on recent molecular findings that provide a better understanding of the pathogenesis of this complex disease and explore the correlation of genotype and clinical phenotype. Recent findings Recent investigations have provided evidence that WASP and several related proteins are involved in the reorganization of the actin cytoskeleton by activating Arp2/3-mediated actin polymerization. This function is controlled mainly by a small GTPase Cdc42. Activated GTP-bound Cdc42 dissociates the intramolecular autoinhibitory loop formation of WASP. In addition, WASP is involved in cytoplasmic signaling by its interaction with a variety of adaptor molecules or kinases and serves as a link to actin reorganization, which is important for immunological synapse formation, cell trafficking and motility. Tyrosine or serine phosphorylation of WASP increases the actin polymerization activity of WASP via Arp2/3. Mutation analysis of WAS/XLT patients has provided evidence for a strong correlation between phenotype and genotype. Gene therapy for WASP-deficient human lymphocytes and Wasp-deficient mice was performed successfully. Summary The study of WASP and its mutations has led to a better understanding of the pathogenesis of the syndrome (thrombocytopenia, immunodeficiency, atopic dermatitis, autoimmune and malignant diseases) and the mechanisms required for cell mobility, cell-cell interaction and cytoplasmic signaling, as well as thrombopoiesis and maintenance of the number of platelets.

Chemokine regulation of inflammation during acute viral infection.

Abstract: Purpose of reviewChemokines are important inflammatory mediators, and regulate disease due to viral infection. This article will discuss scientific papers published primarily since June 2002 that have introduced new concepts in how chemokines regulate the inflammatory response to specific viruses.Re

The role of the mast cell in asthma: a reassessment.

Abstract: Purpose of reviewInterest in the role of the mast cell in bronchial asthma has waxed and waned over several decades, but there is now compelling evidence that mast cells make an important contribution to the pathophysiology of this disease. This review will discuss current advances in this field.Rec

Use of epinephrine in the treatment of anaphylaxis.

Abstract: Purpose of review This paper is intended to review recent literature that impacts the use of epinephrine in the therapy of anaphylaxis. Recent findings The most important recent finding regarding the administration of epinephrine is that the intramuscular route of administration is the route of choice for the treatment of anaphylaxis, and the lateral aspect of the thigh is the site of choice. In addition, recent research emphasizes the fact that epinephrine is grossly underused in the management of anaphylaxis, which accentuates the need for further education of both physician and patient in this regard. Summary Several major themes have emerged from this review of the recent literature. The finding that the intramuscular route of administration for epinephrine is superior has now been recognized by the guidelines, and because the site of choice has been found to be the lateral aspect of the thigh, the needle used for injection must be long enough to penetrate the vastus lateralis muscle. The reasons for the underutilization of epinephrine in the treatment of anaphylaxis are also discussed. Other important findings include the fact that outdated EpiPens can usually be administered safely, and alternative routes of administration, which may be more acceptable to patients, may be on the horizon as a result of preliminary studies assessing the administration of sublingual epinephrine by wafer. Finally, it is now understood that epinephrine prescription data may be one of our best tools to study the epidemiology and incidence of anaphylactic episodes.

Allergic chronic inflammation of the ocular surface in vernal keratoconjunctivitis.

Abstract: Purpose of review The purpose of this review is to describe the new immunopathologic features of vernal keratoconjunctivitis: the involvement of cytokines, growth factors, cells, mediators and neurotransmitters, as well as the mechanism leading to tissue remodelling. Recent findings Vernal keratoconjunctivitis is an allergic eye disease affecting young boys living in a warm climate. It is characterized by conjunctival giant papillae, hyperemia and frequent involvement of the cornea. Approximately 50% of the patients with vernal keratoconjunctivitis do not have a family or medical history of atopic diseases, and do not show IgE sensitization, suggesting that this disease is not solely IgE mediated. Vernal keratoconjunctivitis is a Th2 lymphocyte driven disease with a Th2 cytokine derived pattern, increased levels of mRNA for IL-3, IL-4, IL-5 and IL-13. Th2 lymphocytes induce IgE hyperproduction, activation of mast cells, eosinophils, neutrophils and their toxic products. An overexpression of adhesion molecules, RANTES, eotaxin and metalloproteinases contribute to chronic inflammation. A role for substance P and nerve growth factor has been postulated, as well as for other growth factors (epidermal growth factor, fibroblast growth factor and transforming growth factor beta 1) that induce fibroblast growth and new collagen production. Recent studies have also pointed out the role of resident conjunctival cells, such as epithelial cells and fibroblasts, in the inflammatory and remodelling process of vernal keratoconjunctivitis. The pathogenesis of the condition is probably multifactorial, with the interaction of the immune, nervous and endocrine systems. Summary Vernal keratoconjunctivitis is a chronic inflammatory and potentially blinding disease. Understanding of the complex interactions and cross talk between cells, cytokines and other mediators is relevant for new therapeutic approaches.

The relationships between atopy, rhinitis and asthma: pathophysiological considerations.

Abstract: Purpose of reviewA close relationship has been described between atopy, allergic rhinitis and asthma. The purpose of this work was to review recent data that have become available on the interactions between these conditions and the ways in which they influence one another.Recent findingsRecent find

Nitric oxide in allergic airway inflammation.

Abstract: Purpose of review Exhaled nitric oxide has been proposed as a useful noninvasive marker of airway inflammation in asthma. Great efforts have been made to standardize the methodology for exhaled nitric oxide measurement in both children and adults. As a consequence there is now an opportunity to establish the precise relationship between exhaled nitric oxide, atopy and airway inflammation, and to investigate whether or not there is a role for the measurement of exhaled nitric oxide in the management of patients with asthma. Recent findings A number of recent studies have investigated the relationship between exhaled nitric oxide and airway inflammation in asthma measured directly, using sputum induction, bronchoalveolar lavage and endobronchial biopsy. These measurements suggest that exhaled nitric oxide reflects eosinophilic airway inflammation in asthma, although there is no evidence for any relationship between exhaled nitric oxide and other airway inflammatory cells. Exhaled nitric oxide levels were found to be higher in atopic compared with nonatopic groups. These levels, however, are further elevated in atopic patients with asthma, suggesting that exhaled nitric oxide is not simply a marker of atopy. Although there is little evidence to support the routine use of measurement of exhaled nitric oxide in the management of patients with asthma, it may prove to be useful in assessing adherence to treatment with inhaled corticosteroids, or in the identification of patients in whom respiratory symptoms are associated with eosinophilic airway inflammation. Summary There is good evidence that exhaled nitric oxide reflects eosinophilic airway inflammation in asthma. Well designed, long-term studies are needed to evaluate whether the addition of exhaled nitric oxide measurements to clinical and lung function assessment results in improved asthma control.

WHIM syndrome: a genetic disorder of leukocyte trafficking.

Abstract: Purpose of reviewWHIM syndrome (the association of warts, hypogammaglobulinemia, recurrent bacterial infections, and ‘myelokathexis’) is a rare congenital form of neutropenia associated with an unusual immune disorder involving hypogammaglonulinemia and abnormal susceptibility to warts. In this revi

Gene therapy for adenosine deaminase deficiency.

Abstract: Purpose of review Gene therapy for severe combined immunodeficiency due to adenosine deaminase deficiency has moved from the early trials of safety and feasibility to recent studies demonstrating efficacy and clinical benefit. This review describes the latest advances in gene therapy trials for this condition using peripheral blood lymphocytes or hematopoietic progenitors. Recent findings In the first patients with severe combined immunodeficiency due to adenosine deaminase deficiency treated with peripheral blood lymphocytes, transduced T cells have been shown to persist for over 10 years, expressing transgenic adenosine deaminase, but the therapeutic effect of gene therapy remained difficult to assess because of the concomitant treatment with bovine adenosine deaminase conjugated to polyethylene-glycol (PEG-ADA). A recent report showed that discontinuation of PEG-ADA resulted in a strong selective advantage of gene corrected T cells associated with restoration of T cell functions and antibody responses to neoantigen, but incomplete correction of the metabolic defect. Follow-up studies in patients treated with engineered hematopoietic progenitors in the early trials revealed low marking levels of long-term living progenitors and limited clinical effect. Recently, an improved gene transfer protocol in bone marrow CD34+ cells combined with low-dose busulfan resulted in multilineage, stable engraftment of transduced progenitors at substantial levels, restoration of immune functions, correction of the adenosine deaminase metabolic defect, and proven clinical benefit, in the absence of PEG-ADA. Overall, no adverse effect or toxicity has been observed in patients treated with adenosine deaminase gene transfer in mature lymphocytes or hematopoietic progenitors. Summary Gene transfer in hematopoietic stem cells combined with nonmyeloablative conditioning is efficacious and might be extended to the treatment of other inherited and acquired disorders of the hematopoietic system.

The development of asthma in patients with allergic rhinitis.

Abstract: Purpose of reviewWe will review data supporting the link between allergic rhinitis and asthma, examine recent progress made towards understanding the influence of allergic rhinitis on asthma regarding future development or progression of asthma, and discuss possible mechanisms through which this occ

Unproved diagnostic and therapeutic approaches to food allergy and intolerance.

Abstract: Purpose of reviewAlternative and complementary medicine approaches to allergic disorders are commonly used by patients. Not all have been subjected to experimental analysis to support or refute their validity in the armamentarium of a practitioner. This review covers some of the most common unproved

The immunological synapse for B-cell memory: the role of the ICOS and its ligand for the longevity of humoral immunity.

Abstract: Recent findingsThe ICOS is one of the many costimulatory molecules of T cells. Recently, the authors discovered that the homozygous loss of the ICOS in humans presents as common variable immunodeficiency, the most prevalent treated primary immunodeficiency in man. Therefore, the ICOS is after CD40 a

Early pet exposure: friend or foe?

Abstract: PURPOSE OF REVIEW: Sensitization to pets is a risk factor for asthma and it was assumed that pet ownership was a risk factor for sensitization.Epidemiological studies failed to confirm this, some even suggesting thatkeeping pets decreased the risk of sensitization and asthma. In the lastyear, 10 studies have been published which have, at least in part,attempted to address the question. The results, however, are heterogeneousand it is still not clear how we should advise our patients on this issueof pet ownership. RECENT FINDINGS: Results of studies of the associationbetween exposure to cat or cat allergen and the development ofsensitization are such that almost any view on the relationship could besupported by evidence from the literature. For dogs, there are fewer data,but there is little to suggest that keeping a dog increases the risk ofsensitization to dog. The majority of studies reviewed find either noassociation or a reduced risk of asthma amongst pet owners, but only oneof these selectively excludes those who deliberately avoid pets from theanalysis. There is evidence to suggest that amongst non-pet owners, therisk of sensitization and of asthma increases in areas with a highproportion of pet owners. There is evidence emerging that the effect ofexposure to pets may be different in different relative risk groups, basedon parental allergy. There is also evidence that asthma is more severeamongst pet sensitized pet owners. SUMMARY: There are several large birthcohort studies being conducted around the world designed to measure thedevelopment of asthma and allergies in children with prospective andobjective measures of environmental exposures. The results of such studiesare required before the association between pets and asthma can bedetermined.

Quality of life in insect venom allergic patients

Abstract: Purpose of reviewAs re-sting rates and mortality in Hymenoptera allergy are generally low, health related quality of life is an important therapeutic target in the treatment of allergic patients. This review focuses on the impact of anaphylactic reactions and the effect of interventions in health re

Relevance of inhalational exposure to food allergens.

Abstract: Purpose of review: This review discusses the inhalational route as a clinically important route of exposure to food allergens. Recent findings: In childhood, we have recently demonstrated that food allergens can induce both early and late phase bronchial reactions within blinded, placebo-controlled challenges. Additionally, clinically important levels of food allergens have been measured in environmental air samples. Summary: It is well known that the ingestion of food allergens frequently causes respiratory symptoms and that the mechanism of death in fatal anaphylaxis is usually profound bronchospasm. The mechanism by which ingested food allergens induce bronchial reactions is unclear. There are many case reports of bronchial reactions to aerosolized food allergens. Within the food industry the problems have been examined more systematically. From such work it is possible to gain an impression of the potential prevalence of the problem. With 10% of adult asthma being occupational and 10% of occupational asthma being induced by aerosolized food, inhalational exposure to food allergens plays a major role in at least 1% of adult asthma. For a patient with co-existent food allergy and asthma it is important that both dietary and environmental avoidance be practised. The similar pathophysiology of allergic and occupational asthma and the ability of inhaled food allergens to cause the latter raises the question as to whether aerosolized food could play a role in the pathogenesis of childhood asthma.

Does exposure to dogs and cats in the first year of life influence the development of allergic sensitization

Abstract: Purpose of review The goal of the review is to place studies published after 1 June 2002, concerning the relationship between early life exposure to cats and dogs and the later development of allergy, within the context of the effects of other environmental exposures on allergic disease. Recent findings Most of the recent studies have shown that exposure to cats and dogs early in infancy reduces the prevalence of allergic sensitization or allergic disease later in childhood. While this general trend is relatively consistent, there are differences in specific findings between studies, such as the effect of parental allergies. Other studies suggest that the association between cat and dog exposure and a lower risk of allergy is due to either differences in other environmental exposures or to genetic differences between exposed and non-exposed children. It is impossible to directly compare the results from all of these studies since there are often important differences in racial/ethnic backgrounds of the children, climate, housing conditions, and the family and social customs of those enrolled in different studies. Summary The risk of a child developing any form of allergy appears to depend upon many factors including a child's genetic constitution, early environmental exposure to allergens and to other agents which interact with the immune system, and to allergen exposure later in life. It appears that exposure to something that is increased in homes with cats or dogs reduces the risk of allergic sensitization.

Recent developments and future strategies for immunotherapy of insect venom allergy.

Abstract: Purpose of review Hymenoptera venom allergy may cause life-threatening, sometimes even fatal, allergic reactions and thus may be associated with a serious reduction in the quality of life Venom immunotherapy is effective in the majority of patients with this allergy Treatment failures do however occur and immunotherapy may cause frequent systemic allergic side effects, especially in honeybee venom-allergic patients New strategies to improve safety and efficacy of this treatment are therefore of general interest Recent findings Among these new strategies are premedication with antihistamines: this definitely reduces side effects and based on recent in-vitro experiments and one clinical controlled study may even improve efficacy by modulating the T-cell response through interference with histamine receptors on these cells Furthermore, during recent years the cDNA of most major allergens of bee and vespid venoms has been cloned and these allergens have been expressed in recombinant form This allows for the preparation of patient-tailored extracts, with or without reduction of their allergenicity, for example by using unrefolded or point-mutated recombinant allergens Yet another approach is the use of non IgE binding peptide fragments of the allergen with preserved T-cell epitopes for immunotherapy Such preparations of bee venom phospholipase A2 have been used successfully in pilot studies Finally, DNA vaccination with phospholipase A2 sequence plasmids has proved effective in one experimental study in sensitized mice Summary A number of new strategies for venom immunotherapy, mostly based on genetic engineering, have been described and we await their use in clinical medicine

Characterization of allergenic food proteins for improved diagnostic methods.

Abstract: Purpose of review Diagnostic decision points for food allergen-specific serum IgE concentration and for skin prick test results have been established for several foods, reducing the requirement for food challenges in a number of patients. Many patients, however, still need to undergo oral food challenges because their food-specific IgE level is in the undefined range. In addition, diagnostic decision points could not be established for several foods. It appears that measurement of serum specific IgE concentrations to individual allergens is superior to determination of specific IgE to the crude food extract containing allergenic and nonallergenic proteins. This review will outline recent advantages in characterization of food allergens as well as the relevance of this knowledge for use in recently developed protein microarray technology. Recent findings Protein microarrays have been developed to profile allergen-specific IgE antibodies from human serum with the advantage of screening hundreds of allergens in parallel using minute amounts of blood. This technology, however, requires prior knowledge of the proteins to be studied. The identification and characterization of clinically relevant allergens have increased dramatically within the last several years. Relevant new allergens have been identified, especially in tree nuts and seeds. Interestingly, most of these allergens belong to the same family of seed storage proteins. In addition, known food allergens have been further characterized and IgE-binding sites have been determined. Moreover, 'informative' peptides shown to be predictive for the persistence of food allergy have been identified. Summary The combination of food allergen characterization and protein or peptide microarray technology will enable us to develop improved diagnostic tools in food allergy.

The effect of treatment of allergic rhinitis on asthma morbidity, including emergency department visits.

Abstract: Purpose of review It has been hypothesized that asthma and allergic rhinitis are both manifestations of a single inflammatory process present throughout the airway and that control of the inflammatory response associated with allergic rhinitis may help to reduce inflammation throughout the airway and improve control of asthma. Although previous evidence has documented that therapy directed at allergic rhinitis can improve asthma symptoms and bronchial responsiveness, until recently, there was no evidence that the use of medication targeted at the upper airway can also reduce utilization of acute health care services due to asthma. Recent findings We identified studies published between August 2001 and July 2002 that examined the therapeutic link between allergic rhinitis and asthma. In particular, we concentrated on investigations that evaluated whether, among patients diagnosed with allergic rhinitis and asthma, treatment of the former resulted in significantly fewer asthma-related emergency department visits or inpatient hospitalizations. Two such studies were identified. Using observational study designs, both investigations established that among a population with asthma and allergic rhinitis, treatment for allergic rhinitis was associated with a decrease in the risk of subsequent asthma-related events by one-third to one-half compared with persons who did not receive treatment for this disorder. Summary Effective management of allergic rhinitis with nasal steroids and possibly oral antihistamines reduces utilization of acute health care services due to asthma among persons with co-existent asthma.

A current review of idiopathic anaphylaxis.

Abstract: Purpose of review Idiopathic anaphylaxis is a well established entity that can lead to unnecessary morbidity and costs if not diagnosed and managed properly. To ensure that more patients benefit from proper care, the medical community needs to be better informed of this rare disease. Recent findings The classification and treatment of idiopathic anaphylaxis have been fine-tuned over the past 25 years without knowledge of the disease's underlying mechanism, despite much research dedicated towards this end. The observation that idiopathic anaphylaxis is a steroid-responsive disease has led to a more recent view that its underlying mechanism may be autoimmune in nature. Summary Although the underlying pathogenesis of idiopathic anaphylaxis remains unknown, thousands of patients in the United States have been successfully treated with the currently recommended regimen of steroids and antihistamines. If diagnosed and treated properly, approximately 85% of patients will have a sustained remission after being tapered off corticosteroids.

Relationship between quality of life and disease severity in atopic dermatitis/eczema syndrome during childhood.

Abstract: Purpose of reviewAtopic dermatitis is a chronic relapsing itchy disease that has an effect on children and families' quality of life. The purpose of this review is to give workers in the field an easy-to-read, up-to-date and accessible summary of recent advances in the relationship between quality o