Mucosal Allergy Research Articles

Conditioned Medium of Human Amniotic Epithelial Cells Alleviates Experimental Allergic Conjunctivitis Mainly by IL-1ra and IL-10.

Allergic conjunctivitis (AC) is the most prevalent form of mucosal allergy, and the conditioned medium (CM) from mesenchymal stem cells has been reported to attenuate some allergic diseases. However, the therapeutic effects of CM from different tissue stem cells (TSC-CM) on allergic diseases have not been tested. Here, we studied the effects of topical administration of different human TSC-CM on experimental AC (EAC) mice. Only human amniotic epithelial cell-CM (AECM) significantly attenuated allergic eye symptoms and reduced the infiltration of immune cells and the levels of local inflammatory factors in the conjunctiva compared to EAC mice. In addition, AECM treatment decreased immunoglobulin E (IgE) release, histamine production, and the hyperpermeability of conjunctival vessels. Protein chip assays revealed that the levels of anti-inflammatory factors, interleukin-1 receptor antagonist (IL-1ra) and IL-10, were higher in AECM compared to other TSC-CM. Furthermore, the anti-allergic effects of AECM on EAC mice were abrogated when neutralized with IL-1ra or IL-10 antibody, and the similar phenomenon was for the activation and function of B cells and mast cells. Together, the present study demonstrated that AECM alleviates EAC symptoms by multiple anti-allergic mechanisms mainly via IL-1ra and IL-10. Such topical AECM therapy may represent a novel and feasible strategy for treating AC.

Gastric Enzyme Supplementation Inhibits Food Allergy in a BALB/c Mouse Model.

Impaired gastric digestion due to suppressed gastric acidity enhances the risk for food allergy development. In the current study, we aimed to evaluate the impact of a supported gastric digestion via application of a pharmaceutical gastric enzyme solution (GES) on food allergy development and allergic reactions in a BALB/c mouse model. The ability of the GES to restore hypoacidic conditions was tested in mice treated with gastric acid suppression medication. To evaluate the impact on allergic symptoms, mice were orally sensitized with ovalbumin (OVA) under gastric acid suppression and subjected to oral challenges with or without GES. The immune response was evaluated by measurement of antibody titers, cytokine levels, mucosal allergy effector cell influx and regulatory T-cell counts. Clinical response was objectified by core body temperature measurements after oral OVA challenge. Supplementation of GES transiently restored physiological pH levels in the stomach after pharmaceutical gastric acid suppression. During oral sensitization, supplementation of gastric enzymes significantly reduced systemic IgE, IgG1 and IgG2a levels and allergic symptoms. In food allergic mice, clinical symptoms were reduced by co-administration of the gastric enzyme solution. Support of gastric digestion efficiently prevents food allergy induction and alleviates clinical symptoms in our food allergy model.

Unmet diagnostic needs in contact oral mucosal allergies.

The oral mucosa including the lips is constantly exposed to several noxious stimuli, irritants and allergens. However, oral contact pathologies are not frequently seen because of the relative resistance of the oral mucosa to irritant agents and allergens due to anatomical and physiological factors. The spectrum of signs and symptoms of oral contact allergies (OCA) is broad and a large number of condition can be the clinical expression of OCA such as allergic contact stomatitis, allergic contact cheilitis, geographic tongue, oral lichenoid reactions, burning mouth syndrome. The main etiological factors causing OCA are dental materials, food and oral hygiene products, as they contain flavouring agents and preservatives. The personal medical history of the patient is helpful to perform a diagnosis, as a positive history for recent dental procedures. Sometimes histology is mandatory. When it cannot identify a direct cause of a substance, in both acute and chronic OCA, patch tests can play a pivotal role in the diagnosis. However, patch tests might have several pitfalls. Indeed, the presence of metal ions as haptens and specifically the differences in their concentrations in oral mucosa and in standard preparation for patch testing and in the differences in pH of the medium might result in either false positive/negative reactions or non-specific irritative reactions. Another limitation of patch test results is the difficulty to assess the clinical relevance of haptens contained in dental materials and only the removal of dental materials or the avoidance of other contactant and consequent improvement of the disease may demonstrate the haptens’ responsibility. In conclusion, the wide spectrum of clinical presentations, the broad range of materials and allergens which can cause it, the difficult interpretation of patch-test results, the clinical relevance assessment of haptens found positive at patch test are the main factors that make sometimes difficult the diagnosis and the management of OCA that requires an interdisciplinary approach to the patient.

Disruption of TIM-4 in dendritic cell ameliorates hepatic warm IR injury through the induction of regulatory T cells

Hepatic ischaemia reperfusion (IR) injury results from the infiltration of multiple immune cells especially dendritic cells (DC). T-cell immunoglobulin-domain and mucin-domain 4 (TIM-4) is a type I cell-surface glycoprotein which is extensively expressed on antigen presenting cells (APC) like DC and macrophages. TIM-4 has been demonstrated to be implicated in mucosal allergy, skin allograft rejection and tumour-immune tolerance. However, the role of TIM-4 expressed on DC in hepatic IR injury remains largely unknown. In the present study, we aimed to investigate whether and how DC expressed TIM-4 was involved in hepatic IR injury. With segmental hepatic warm ischaemia mice models, we demonstrated that promoted DC infiltration and increased TIM-4 expression were induced by hepatic IR. Blockade of TIM-4 by anti-TIM-4 mAb (0.35mg/mouse) markedly ameliorated hepatic injury and reduced inflammatory cytokine secretion. Furthermore, in a DC:CD4+ T cell co-culture system, blockade of TIM-4 on DC significantly inhibited T helper-2 cell differentiation and facilitated induced CD4+ CD25+ Foxp3+ T regulatory cell (iTreg) expansion. Interleukin-4 (IL-4)/signal transducer and activator of transcription 6 (Stat 6) signalling was shown to be impeded by TIM-4 blockade and involved in iTreg generation. Additionally, adoptive transfer of iTreg produced by TIM-4 blockade into hepatic IR mice models remarkably attenuated liver injury. We conclude that TIM-4 on DC play a critical role in hepatic IR injury and may be an efficient target for the prevention of liver or other organ IR injury.

Innate stimulatory capacity of high molecular weight transition metals Au (gold) and Hg (mercury)

Nickel, cobalt and palladium ions can induce an innate immune response by triggering Toll-like receptor (TLR)-4 which is present on dendritic cells (DC). Here we studied mechanisms of action for DC immunotoxicity to gold and mercury. Next to gold (Na3Au (S2O3)2⋅2H2O) and mercury (HgCl2), nickel (NiCl2) was included as a positive control. MoDC activation was assessed by release of the pro-inflammatory mediator IL-8. Also PBMC were studied, and THP-1 cells were used as a substitution for DC for evaluation of cytokines and chemokines, as well as phenotypic, alterations in response to gold and mercury. Our results showed that both Na3Au (S2O3)2⋅2H2O and HgCl2 induce substantial release of IL-8, but not IL-6, CCL2 or IL-10, from MoDc, PBMC, or THP-1 cells. Also gold and, to a lesser extent mercury, caused modest dendritic cell maturation as detected by increased membrane expression of CD40 and CD80. Both metals thus show innate immune response capacities, although to a lower extent than reported earlier for NiCl2, CoCl2 and Na2 [PdCl4]. Importantly, the gold-induced response could be ascribed to TLR3 rather than TLR4 triggering, whereas the nature of the innate mercury response remains to be clarified. In conclusion both gold and mercury can induce innate immune responses, which for gold could be ascribed to TLR3 dependent signalling. These responses are likely to contribute to adaptive immune responses to these metals, as reflected by skin and mucosal allergies.

Comparison of the Nasal Release of IL-4, IL-10, IL-17, CCL13/MCP-4, and CCL26/eotaxin-3 in Allergic Rhinitis during Season and after Allergen Challenge

Allergic rhinitis is an inflammatory disease characterized by local overproduction of type 2 cytokines and tissue eosinophilia. Recent research suggests the involvement of additional cytokines such as IL-17, chemokine (C-C motif) ligand (CCL) 26/eotaxin-3, and CCL13/monocyte chemoattractant protein-4 (MCP-4) in its pathophysiology. Furthermore, bronchial epithelial cells treated with IL-17 and type 2 cytokines distinctively up-regulated eotaxin-3 gene expression. In this study we investigated the kinetics of IL-4, IL-10, IL-17, eotaxin-3, and MCP-4 in seasonal allergic rhinitis volunteers after nasal allergen challenge (NAC) and their release during natural pollen exposure. The nasal lavages of 15 symptomatic allergic and 14 nonallergic subjects were collected during the pollination season. Additionally, six allergic subjects underwent a single unilateral nasal allergen and control challenge out of season, and nasal secretions were collected. Levels of IL-4, IL-10, IL-17, eotaxin-3, and MCP-4 in nasal lavages and secretions were measured using an electrochemiluminescent assay. After NAC, allergic subjects had a significant immediate response of nasal symptoms as well as a significant increase at 5 hours of IL-4, IL-10, and IL-17 and at 2, 5, and 24 hours significantly raising levels of eotaxin-3. IL-17 and eotaxin-3 concentrations at 5 hours were correlated (r = 0.94; p = 0.005). During natural pollen exposure, barely detectable levels of IL-17 in allergic subjects were also correlated with eotaxin-3 (r = 0.62; p = 0.01). Eotaxin-3 and MCP-4 levels were significantly elevated 9- or 3.7-fold, respectively, and IL-10 and, unexpectedly, IL-4 were significantly lower in allergic subjects compared with nonallergic subjects. Nasal IL-17, MCP-4, and, possibly, eotaxin-3 may aggravate and IL-10 may alleviate nasal mucosal allergy.

Transgenic rice accumulating modified cedar pollen allergen Cry j 2 derivatives

In order to create a safe tolerogenic antigen with reduced IgE reactivity, we developed transgenic rice that accumulates in the seed endosperm a sufficient amount of Cry j 2, the cedar pollen allergen, in a restructured form of tail-to-head, providing a feasible mucosal allergy vaccine against cedar pollinosis.

Clinical Characteristics and Therapeutic Outcomes of Patients with Localized Mucosal Allergy

Many researchers have focused on the definition and pathophysiology of localized mucosal allergy. However, there are few studies on its clinical characteristics and therapeutic outcomes. The goal of this study was to analyze the prevalence, epidemiology, clinical characteristics, and response to antiallergic medication of localized mucosal allergy patients compared with those in patients with allergic rhinitis. Among 836 patients suspected to have rhinitis, 29 patients with localized mucosal allergy (group A) and 29 patients with allergic rhinitis (group B) were selected. Medical history, family history, symptoms, and their severity were obtained using a questionnaire. The change in minimal cross-sectional area (MCA) after provocation was measured by acoustic rhinometry. After 2 weeks of antihistamine medication, the changes in symptoms were compared between groups. The prevalence of localized mucosal allergy was approximately 3.5%. There were no differences in patient history, symptoms, or symptom severity. The decrease in MCA after provocation was not significantly different. After two weeks of oral antihistamine (ebastine 10 mg once daily), group A reported significantly less symptom improvement than group B. Because patient or family history and clinical picture are very similar in localized mucosal allergy and allergic rhinitis, clinicians should take more care in differentiating them. Based on the reduced effectiveness of an oral antihistamine alone, a combined regimen of oral and topical antihistamine or anti-inflammatory medication is recommended for patients with localized mucosal allergy.

‘Entopy’: local allergy paradigm

Allergy is defined as an immediate hypersensitivity type I immunological disease, which can be IgE or non-IgE driven, and in the latter case may be antibody or cell mediated. Atopy is a term used to describe individuals with a genetic predisposition for developing IgE-mediated allergic disease. But more recently, it has become evident that IgE-mediated disease can occur in non-atopic subjects. While it is now generally accepted that mucosal local IgE has a role in the expression of atopic allergic disease, the concept of 'local allergy' in non-atopic subjects has been proposed, with the term 'entopy' given to this condition. Although there is increasing evidence supporting this paradigm, entopy is only applicable to a proportion of non-atopic patients, suggesting that other disease mechanisms exist to explain non-atopic disease. This review considers the evidence for local mucosal allergy in atopic and non-atopic individuals with an emphasis on diseases affecting the upper airways and eye. Furthermore, the diagnosis, treatment and relationship between local allergy and conventional (systemic) allergy are discussed, and alternative disease mechanisms predominantly involving antibodies or their sub-components (free light chain Igs) are postulated to explain the 'entopy' paradigm. This review is intended to provide an improved understanding of the mechanisms and causes of local mucosal hypersensitivity.

Rethinking the Pathogenesis of Asthma

Asthma research has focused primarily on allergic pathways on the basis that the majority of asthma is associated with atopy, the recruitment of the Th2-type T cell, the cytokines, and the chemokines that are released on exposure to allergens, and the IgE pathway. However, despite considerable investment by industry, targeting these pathways has not resulted in new treatments being developed beyond blockade of cysteinyl leukotrienes and IgE and improvements in inhaled corticosteroids and beta(2)-adrenoceptor bronchodilators. Increasingly, it is recognized that asthma is a heterogeneous disorder, and while important, allergen sensitization is only one component of the disease, with many other environmental and genetic factors playing a role. In addition, these factors act locally on a susceptible airway epithelium that is both structurally and functionally deficient. It may be worthwhile to focus on increasing the resilience of the airways to environmental insults in addition to improving strategies that modify adaptive immunity or suppress inflammation.

Seasonal idiopathic rhinitis with local inflammatory response and specific IgE in absence of systemic response

Patients with idiopathic rhinitis (IR) are considered to be nonallergic because they have a negative skin prick test (SPT) and allergen specific-IgE in serum. The concept of localized mucosal allergy in the absence of atopy has recently been proposed. The immunological mechanisms involved in seasonal IR have not been sufficiently studied. We examined nasal mucosa inflammation, the presence of nasal specific-IgE and the response to nasal allergen provocation test (NAPT) in patients with seasonal IR who presented symptoms only in spring. We evaluated 32 patients with seasonal IR and 35 with persistent allergic rhinitis to pollen (PAR-P) and compared these with healthy controls and persons with PAR to house dust mite during the pollen season, as well as by NAPT out-of-season with grass and Olea europea. We measured the nasal leukocyte-lymphocyte phenotype (CD45, CD33, CD16, CD3, CD4 and CD8), eosinophil-cationic-protein, and total and specific-IgE to grass and olive pollen in serum and nasal lavage and performed NAPT. In the IR group, 62.5% had a positive NAPT (IR-PosNAPT), 20/32 to grass, with four of these having a positive NAPT to olive pollen as well. IR-PosNAPT patients showed a similar nasal leukocyte-lymphocyte profile to the PAR-P patients and different to controls. We detected nasal specific-IgE in 35% of IR-PosNAPT patients. These results support the hypothesis that a subgroup of patients with IR have seasonal symptoms with evidence of a nasal allergic immune reaction in the absence of a positive SPT or serum specific IgE.

Editorial [Hot Topic: CD4+ Regulatory T Cells: Do They Treat Mucosal and Systemic Allergy and Inflammation? (Guest Editor: Noriko M. Tsuji)

Editorial [Hot Topic: CD4+ Regulatory T Cells: Do They Treat Mucosal and Systemic Allergy and Inflammation? (Guest Editor: Noriko M. Tsuji)

Prophylaxis and Therapy of Allergy by Mucosal Tolerance Induction with Recombinant Allergens or Allergen Constructs

The mucosal immune system, present along the respiratory, gastrointestinal and genitourinary tract, has to discriminate between harmful pathogens and innocuous antigens, such as food, airborne antigens or the commensal bacterial flora. Therefore the mucosal immune system has acquired two opposing immunological functions, i.e. the induction of immunity and defence of mucosal pathogens, and the induction and maintenance of tolerance to environmental antigens and bacterial flora. As described for autoimmunity a breakdown or failure of tolerance induction is believed to lead also to allergies and food enteropathies. Based on the physiological role to prevent hypersensitivity reactions, tolerance induction via the mucosa has been proposed as a treatment strategy against inflammatory diseases, such as allergies. The aim of our research is to develop mucosal allergy vaccines based on the induction of mucosal tolerance and/or the induction of counter-regulatory immune responses with or without the use of certain mucosal antigen delivery systems, such as lactic acid bacteria. The use of recombinant allergens instead of allergen extracts with varying allergen content and composition may be essential for improvement of the treatment efficacy. In the present review we give examples of different animal models of type I allergy/asthma. Using these models we demonstrate that recombinant allergens or hypoallergenic variants thereof can be successfully used to induce mucosal tolerance in a prophylactic as well as a therapeutic treatment regime. That the concept of mucosal tolerance induction/mucosal vaccine delivery may in principal also function in humans is supported by recent clinical trials with locally (sublingual) applied immunotherapy.

Mucosal T-cell phenotypes in persistent atopic and nonatopic rhinitis show an association with mast cells.

Allergic rhinitis is characterized by selective expansion of T cell subsets with a CD4+ phenotype. Recently, we identified a subpopulation of nonallergic rhinitis subjects with increased epithelial mast cell and eosinophil populations, suggestive of local mucosal allergy. Previously, T cell subsets have not been characterized in this subselection of nonallergic subjects and furthermore, their relationship to mast cell and basophil effector cells remain unidentified. To determine if a subpopulation of nonallergic subjects with idiopathic rhinitis (IR) have localized allergy confined to their nasal mucosa by comparing the T cell subsets and major histocompatibility complex (MHC) II expressing cells to persistent allergic rhinitis (PAR). Furthermore, the relationship between T cell subsets and mast cells/basophils was investigated. None of the symptomatic patients in this study were clinically allergen-challenged. Nasal turbinate mucosa was removed from patients with PAR, IR and normal controls. Morphometry was performed on immunostained sections for T cell subset populations including CD3+, CD4+, CD8+, CD25+, CD45RA+, CD45RO+, human leucocyte antigen (HLA)-DRalpha (MHC class II), mast cell tryptase and for basophils. Subjects with persistent allergic rhinitis differed to normal controls in showing significantly increased numbers of total (CD3+), activated (CD25+) and allergen-naïve (CD45RA+) T lymphocytes in their nasal mucosa (P < 0.025). The naïve CD45RA+ memory T cells correlated to mucosal mast cells in PAR (P = 0.03). IR patients differ to allergic subjects in showing significantly reduced numbers of epithelial HLA-DRalpha+ cells (P = 0.007), but increased numbers of CD8+ lymphocytes (P = 0.02). The CD8+ T cells correlated with mucosal mast cell numbers (P = 0.02). In both rhinitis groups, basophils were present in very low numbers obviating the need for statistical analysis. PAR is characterized by increased numbers of CD3+, CD25+ and CD45RA+ T lymphocytes compared with normal mucosa. Allergic and nonallergic rhinitis groups can be separated by significant differences in the number of epithelial antigen presenting cells (APCs) (HLA-DRalpha+) and sub-epithelial activated (CD25+) T cells. Moreover, IR patients do not significantly differ to their allergic counterparts with respect to total (CD3+) and naïve (CD45RA+) T cell numbers, or numbers of epithelial activated (CD25+) lymphocytes. IR subjects show significantly increased numbers of CD8+ lymphocytes compared with control mucosa and although our findings suggest that the initiating inflammatory events may differ, both rhinitis groups show a similarity in pathology involving mucosal mast cells with an association to infiltrating T cells.

Immunomodulatory treatment strategies for allergic diseases.

Over the last decades the prevalence of allergic disorders, such as hayfever and asthma has increased worldwide, mostly in westernised countries where up to 20 % of the population are affected. The "hygiene hypothesis" suggests that modernised lifestyles such as improved housing conditions, altered dietary habits and smaller family sizes may be responsible for the decrease in infectious and the increase in allergic diseases. Childhood atopic diseases, like eczema, food allergies and recurrent wheezy bronchitis represent a considerable health problem and a major socioeconomic burden due to the chronicity of these disorders. In recent years, a better understanding of the immunopathogenesis of allergic diseases has evolved, which has contributed to the development of novel more targeted forms of therapy. Allergen injection immunotherapy is the only treatment in current use with the potential for modifying the course of allergic disease. In order to better target mucosal allergies, new approaches of administering allergen, via the sublingual or intranasal route, are being developed. The use of modified allergens, allergen peptides, DNA immunization and the use of novel adjuvants represent alternatives to conventional immunotherapy with potential for improved efficacy with less side effects. For atopic asthma, novel treatment strategies aim at locally targeting inflamed airways. Nebulized monoclonal blocking antibodies and soluble interleukin receptors against "Th(2)-type" cytokines have been designed. An alternative approach has been the administration of "Th(1) -type" cytokines. Although, immunomodulatory strategies provide a promising outlook for the treatment of allergic patients, more studies are needed in the future to address issues of efficacy, safety and long-term effects of altered immune responses.

The role of fungal allergy in bronchial asthma

Fungus is known to be one of the causative allergens inducing bronchial asthma as are housedustmites, pollen and pet dander. Outdoor airborne fungi such as Cladosporium, Alternaria, Penicillium and Aspergillus are important inducing IgE antibody formation. In addition to these common fungi, the indoor fungi Aspergillus restrictus, Neurospora and Eurotium are important allergenic fungi which have recently been identified. The yeast Candida albicans, is a common commensal of the human oral and vaginal mucosae and gastrointestinal tract and part of the normal flora, is known as one of the main allergens causing bronchial asthma. We examined the allergenicity of mannan (Mn) as a cell-wall constituent and acid protease (CAAP) as a secreted enzyme of C. albicans. We previously reported cases of atopic asthma caused by CAAP and stressed the role of CAAP as an important allergen in mucosal allergy to C. albicans 9). The levels of the antibodies to these antigens in the sera of asthmatic patients who showed positive immediate intradermal response to crude C. albicans (n=86) were measured. Anti-Mn IgE and IgG antibody levels were measured by liquid-phase assay (AlaSTAT). Anti-CAAP and anti-crude C. albicans IgE and IgG antibody levels were measured by RAST and AlaSTAT. Anti-Mn A and anti-Mn B IgE antibody titers were strongly correlated (r=0.87), while anti-Mn A and anti-CAAP IgE titers were not correlated. However, all of the anti-Mn A IgE positive sera and all of the anti-CAAP IgE positive sera were positive for IgE to crude-C. albicans. This indicates that both Mn and CAAP are C. albicans-related allergens. Titers of IgG antibodies to Mn A and crude C. albicans were highly correlated (r=0. 90). Results of inhibition assays performed using other fungal antigens as inhibitors showed that Mn is a cross reactive allergen among different fungi and that CAAP is a C. albicans specific allergen causing human mucosal allergic reaction.

Allergenicity of acid protease secreted by Candida albicans

We have previously reported the cases of Candida albicans (C. alb) acid protease (CAAP)-induced atopic asthma. In this study, the allergenicity of the released enzyme CAAP was examined among asthmatic patients with positive immediate skin response to crude C. alb antigen. Among 49 patients with positive skin response to crude C. alb, anti-crude C. alb IgE antibodies were detected in 40 and anti-CAAP IgE antibodies were detected in 18. Moreover, anticrude C. alb IgE antibodies were detected in all of the patients in whom anti-CAAP IgE antibodies were detected. No correlations between IgG antibodies to both antigens or between IgE and IgG antibodies to CAAP were observed. CAAP induced significant T-cell proliferation in 20/28 patients showing positive T-cell proliferation response to crude C. alb antigen. Most of the patients showing positive conjunctival response to crude C. alb antigen also showed positive response to CAAP. Most of the patients showing high levels of serum IgE antibody and positive histamine-release response of peripheral blood leukocytes to CAAP showed positive conjunctival response. The results indicate that CAAP is an important allergen in C. alb-related mucosal allergy.

Allergenicity of acid protease secreted by Candida albicans.

We have previously reported the cases of Candida albicans (C. alb) acid protease (CAAP)-induced atopic asthma. In this study, the allergenicity of the released enzyme CAAP was examined among asthmatic patients with positive immediate skin response to crude C. alb antigen. Among 49 patients with positive skin response to crude C. alb, anti-crude C. alb IgE antibodies were detected in 40 and anti-CAAP IgE antibodies were detected in 18. Moreover, anticrude C. alb IgE antibodies were detected in all of the patients in whom anti-CAAP IgE antibodies were detected. No correlations between IgG antibodies to both antigens or between IgE and IgG antibodies to CAAP were observed. CAAP induced significant T-cell proliferation in 20/28 patients showing positive T-cell proliferation response to crude C. alb antigen. Most of the patients showing positive conjunctival response to crude C. alb antigen also showed positive response to CAAP. Most of the patients showing high levels of serum IgE antibody and positive histamine-release response of peripheral blood leukocytes to CAAP showed positive conjunctival response. The results indicate that CAAP is an important allergen in C. alb-related mucosal allergy.

Aeroallergen patch testing for patients presenting to contact dermatitis clinics

Background: The role of aeroallergens in the production of allergic contact dermatitis or “allergic contact dermatitis-like” atopic dermatitis is controversial. Although techniques and allergens lack standardization, most studies find positive patch test results in 30% to 40% of patients with atopic dermatitis. Objective: Our purpose was to determine the prevalence and clinical significance of positive aeroallergen patch tests in patients undergoing standard patch testing for suspected “nonaeroallergen” allergic contact dermatitis. Methods: One hundred three consecutive patients referred to three university patch test clinics for patch testing were also patch tested with six common aeroallergens in glycerine—dust, mold, cat epithelium, tree, grass, and weed—as well as with a glycerine control. Patches were removed at 48 hours. Readings were performed at this time and at 3 to 7 days after initial application. Results: As determined by history, these 103 patients included 16 patients with both atopic dermatitis and mucosal atopy, 10 patients with atopic dermatitis only, 22 patients with mucosal atopy only, and 55 patients with neither atopic dermatitis nor mucosal atopy. Allergic reactions were seen to one aeroallergen in five patients (three with atopic dermatitis and mucosal allergy, and two with no history of atopy). The prevalence (3 of 16 [18.8%]) of reactions in patients with both atopic dermatitis and mucosal allergy was significantly greater than the prevalence (2 of 87 [2.3%]) in patients with only one or neither of these two atopic disorders ( p = 0.02). None of these aeroallergen contact hypersensitivities were deemed significant in the patients' current dermatitis. However, reactions were of past relevance in two of the three patients with atopic dermatitis and mucosal allergy. Conclusion: In this referral group, none of the six common aeroallergens tested was relevant in the origin of suspected “nonaeroallergen” allergic contact dermatitis. This study suggests that aeroallergen patch testing is of little use in the evaluation of patients referred for routine patch testing for suspected “nonaeroallergen” allergic contact dermatitis. Similar but larger studies inclusive of the assessment of relevance, as well as masked controlled clinical trials assessing the effect of aeroallergen exposure and avoidance, are needed to evaluate this issue more fully.

4 Mucosal allergy: role of mast cells and eosinophil granulocytes in the gut

Despite the progress made in understanding the mechanisms of allergic disease, the pathophysiology and clinical significance of intestinal allergic reactions is largely unclean The intestinal mucosa is pre-destined for allergic reactions against food proteins and other antigens, and a number of studies indicate that allergic reactions occur in the GI tract. However, only a few epidemiological data are available, and the mechanisms are poorly understood. Intestinal allergic reactions may be different to classical IgEmediated reactions because patients with intestinal allergy often have negative skin tests and low levels of serum IgE. There is increasing evidence that, as with the findings in the skin and lung, mast cells and eosinophils play a central role in mediating intestinal allergic reactions. Furthermore, both types of cell are found to be activated in a number of other GI inflammatory diseases such as inflammatory bowel disease, celiac disease and eosinophilic gastroenteritis. However, the relationship between these pathologies and intestinal allergy is largely unclear. A major clinical problem is the lack of appropriate means for confirming the diagnosis of intestinal allergy. However, new test systems have been developed—such as the measurement of eosinophil mediators in stool samples or endoscopic provocation tests performed locally at the intestinal mucosa, which may improve the possibility of identifying afflicted patients on an objective basis. Since symptoms of intestinal allergic reactions are variable and nonspecific, the diagnosis requires the use of multiple tests and the exclusion of other pathologies such as infectious disease or non-immunological intolerance reactions. The preferred therapeutic option is avoidance of the allergens of relevance; however, this approach can be realized only in some patients, whereas others require additional treatment, for example, with oral cromoglycate or corticosteroids. Although we do not yet know to what extent intestinal allergic reactions may be an aetiological factor in GI diseases, such reactions should be considered in the differential diagnosis of unclear intestinal inflammation and irritable bowel syndrome.