Ocular allergies

Ocular allergic disease affects not only the conjunctivae but also surrounding structures including the eyelids. Allergic diseases of the eyelid include atopic dermatitis, contact dermatitis, and urticaria/angioedema. They must be differentiated from nonallergic eyelid diseases. Allergic diseases of the conjunctivae comprise a spectrum of disorders from common, non-sight-threatening conditions such as seasonal allergic conjunctivitis, perennial allergic conjunctivitis, and giant papillary conjunctivitis to less common and potentially sight-threatening diseases such as vernal keratoconjunctivitis and atopic keratoconjunctivitis. Each of these conditions is mediated primarily by type I hypersensitivity reactions. The clinical manifestations, differential diagnosis, and treatment of these conditions are reviewed in this article.     

Prevalence and associated factors of allergic rhinitis and atopic dermatitis in children

Allergic disorders are the chronic diseases of greatest pediatric morbidity, affecting over 25 % of the pediatric population. Indeed, this situation has been referred to as an "allergic epidemic". In comparison with asthma, atopic dermatitis and allergic rhinitis have been less extensively investigated, although this does not mean that they should be regarded as minor disorders but rather as alterations that affect the quality of life of the patients and their families, which generate considerable direct and indirect costs. Despite an important research effort, the reason for this allergic epidemic is not well known. These are multifactor disorders without a single causal agent, in which the most important component is the genetic predisposition of the patient (atopy), modulated by environmental factors, exposure to allergens, infections and irritants, among others. A confounding element is the fact that the concept of allergic diseases encompasses phenotypes of rhinitis, atopic dermatitis or asthma in which no IgE-mediated atopic mechanism is demonstrated, and which can manifest in a way similar to true allergic phenotypes. Differentiation between the two is difficult to establish on the basis of self-administered questionnaires alone, in the absence of a precise etiological diagnosis. The present article reviews the numerous factors suggested to be responsible for the increase in allergic diseases recorded in the last few decades, and for the differences in prevalence observed among centres. For most of these factors the results published in the literature are contradictory, in some cases due to a lack of control of the associated interacting or confounding factors. Consensus exists for only some of these causal factors, such as the established parallelism between the increase in allergic diseases and the reduction in infectious processes on one hand, and the increase in particles generated by diesel fuel combustion on the other. In addition, the implicated factors could act differently (and in some cases even antagonically) upon atopy and on the different disease phenotypes, thereby complicating the study of these interactions even further.     

Eosinophils and allergic diseases of the gastrointestinal tract

The association between increased tissue eosinophilia and allergic disease is particularly striking in the case of the gastrointestinal tract. About 80% of individuals with eosinophilic gastrointestinal disorders (EGIDs) are atopic, while half of the patients with gastrointestinal allergy show tissue eosinophilia. The function of eosinophils in gastrointestinal allergic disorders is unclear; however, a proinflammatory action is most likely. Cytokines (interleukins 5 and 3, granulocyte-monocyte colony-stimulating factor) and chemokines (eotaxin, RANTES, etc.) released by Th2 lymphocytes, mast cells and other tissue cells have been identified as major regulators of eosinophil chemotaxis and activation, but a convincing mechanism by which eosinophils are activated in an allergen-dependent manner is still lacking. The diagnostic approach comprises both histological and laboratory methods to assess eosinophilia and eosinophil activation, as well as tools to assess the allergic disease while excluding other gastrointestinal diseases such as food intolerances, infections and tumours. Treatment of allergic EGIDs includes elimination or elemental diets and drug therapy using classical anti-allergic agents such as topical corticosteroids and new approaches such as LTD4 receptor antagonists or antibodies against IL-5 or eotaxin.     

Les échinococcoses : un modèle parasitaire pour la compréhension des maladies allergiques ?

Relationship between parasitic and allergic diseases has often been stressed. Parasitic diseases do offer a model to study the role of those events that may determine the final outcome of immune responses and the type of their effector stage. At first glance, the pathophysiological mechanisms involved in Echinococcus sp infections, hydatid cyst (cystic echinococcosis) and alveolar echinococcosis, appear quite different: IgE-dependent responses seem to be involved in the former and cell-mediated immunity in the latter. However, an analysis of the cytokine profile in these two cestodoses shows that, in both cases, Th1 responses are protective, and are present in “abortive” forms of infection; conversely, Th2 responses characterised by IL-5 and especially IL-10 synthesis are the hallmarks of the “progressive” forms of infection, leading to the disease and its clinical complications. In patients, it seems that all known actors of the effector cell-mediated responses actually surround the parasitic cells but are somehow “paralysed”, at least partially, by anti-inflammatory cytokines and other mediators such as nitric oxide; hence the chronic evolution of the disease and all complications related to fibrosis and necrosis. Both are the results of an inefficient immune response deviated by the parasite and favoured by immunogenetic characteristics of the host. The IgE synthesis that results from the Th2 immune response also participate in the occurrence of clinical complications. The comparison between parasitic and allergic diseases, through the “echinococcosis model” may be used to better understand the immune mechanisms involved both in the increase in allergic disorders in developed countries and in “mixed-type allergic lesions” which associate cellular immunity and IgE-dependent responses, such as atopic dermatitis.     

The bidirectional capacity of bacterial antigens to modulate allergy and asthma.

In recent decades, the prevalence of allergic diseases including bronchial asthma, hay fever and atopic dermatitis, has risen steadily in high-income countries. The underlying mechanisms for this phenomenon remain largely unknown. Since the natural mutation rate is low, altered environmental and lifestyle conditions are thought to play an important role. Epidemiological and clinical studies have provided indirect evidence that infections may prevent the development of atopy and atopic disease. This is referred to as the "hygiene hypothesis". According to the hygiene hypothesis, viral and/or bacterial infections could inhibit the T-helper (Th)-2 immune response associated with atopic reactions by stimulating a Th-1 response involved in defence of bacterial infections and delayed-type hypersensitivity reactions. In particular, the prenatal period and early childhood are considered to be critical for the establishment and maintenance of a normal Th-1/Th-2 balance. On the other hand, several studies suggested that infections exacerbate established allergic diseases, e.g. bronchial asthma, airway hyperresponsiveness and atopic dermatitis. Therefore, viral and/or microbial infections and/or their products may have bidirectional effects on the development of allergy and asthma. This review will focus on recent findings related to the interaction between allergic disorders and infectious diseases, with the main emphasis on bacterial infections.     

Eosinophil granule proteins in serum and urine of patients with helminth infections and atopic dermatitis

Eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EPX) are cytotoxic molecules involved in helminth infections and allergic reactions. Hitherto most clinical chemical studies have been concerned with the analysis of serum ECP in allergic diseases. The aim of this study was to examine whether serum as well as urine levels of these proteins are useful clinical chemical parameters in helminthiases and allergic diseases such as atopic dermatitis. Comparing these diseases under the same methodological conditions, levels of ECP and EPX were generally higher in helminthiases than in atopic dermatitis and non-helminth, non-allergic diseases. The highest levels of both proteins occurred in tropical worm diseases, in particular hookworm disease and onchocerciasis. When comparing helminthiases with allergic disorder, only hookworm disease (ECP and EPX) and onchocerciasis (EPX) exhibited significantly higher eosinophil cationic protein serum levels than atopic dermatitis. In patients with schistosomiasis mansoni and egg loads of > 1000-10 000 eggs/g stool (epg) EPX serum levels were significantly higher than in patients exhibiting loads < 1000 epg. Urinary analyses revealed only EPX to be present in measurable amounts. Levels of this protein were much higher in urine of patients with hookworm disease and onchocerciasis than in those with atopic dermatitis and in healthy controls. The results suggest that besides serum EPX, urinary EPX may be a useful clinical chemical parameter in eosinophilia of helminth and allergic aetiology.     

Infektionen unter immunsuppressiver Therapie nach Organtransplantation

The risk to acquire opportunistic infections is clearly increased in patients receiving immunosuppressive therapeutic regimens following organ transplantation or during treatment of autoimmune disorders. The modulation of the immune system can alter the clinical symptoms and the course of infectious diseases, including diagnostic signs such as fever or pathological changes in radiographs or blood cell counts. However, a rapid diagnosis and start of treatment is essential in these patients. Thus, a correct interpretation of even mild symptoms in the initial phase of an infectious disease is essential for establishing a diagnosis and initiation of a therapy at an early stage. Therefore, it is necessary that the clinical hallmarks of these diseases are widely known and that physicians treating these patients cooperate closely with transplant centers.     

Dendritic cells: importance in allergy.

In this review we discuss the role of dendritic cells (DC) in the pathogenesis of allergic contact hypersensitivity (ACH) and atopic disorders, such as asthma and atopic eczema. In ACH patients, DC recognize the invasion of simple chemicals such as haptens, and trigger antigen-specific T cell responses leading to the characteristic histological and clinical changes such as spongiosis and papulovesicular eruptions. During atopic disorders, it is well known that the Th2-deviated immune response plays a crucial role in their pathogenesis. DC provide T cells with antigen and costimulatory signals (signals 1 and 2, respectively), as well as with a polarizing signal (signal 3). When studying ACH, it is important to understand how simple chemicals induce the activation of DC and their migration to the draining lymph nodes where they supply signals 1 and 2 to naive T cells. The mechanisms by which DC induce the Th2-deviated immune response, namely via the Th2-deviated signal 3, are central topics in the pathogenesis of atopic disorders.     

The impact of age on prevalence of positive skin prick tests and specific IgE tests

Aging is associated with modifications of the immune system, defined as immunosenescence. This could contribute to a reduced prevalence of allergic disease in the elderly population. In this regard, atopy has rarely been considered in the clinical assessment of the geriatric respiratory patient. This article is a review of the available literature assessing the impact of age on atopy. In the majority of papers, we found a lower prevalence of atopy in the most advanced ages, both in healthy subjects and in individuals affected by allergic respiratory diseases. Unfortunately, no large, longitudinal studies performed in the general population have been conducted to further explore this observation. Although available data seem to favor the decline of allergen sensitization with age, the prevalence of allergic sensitizations in the elderly population with respiratory symptoms is substantial enough to warrant evaluation of the atopic condition. From a clinical perspective, allergic reactions in older adults can have the same or even worse manifestations compared to young people. For this reasons, the evaluation of the atopic condition also in the geriatric patient is recommended. Thus, the role of atopy as it pertains to the diagnosis, therapy (adoption of preventive measure such as removal of environmental allergen or immunotherapy), and prognosis (influence on morbidity and mortality) of chronic respiratory illnesses in the elderly is addressed.     

Eosinophilic disorders in children

Many pediatric diseases demonstrate blood or tissue eosinophilia. Included among these disorders are common atopic diatheses such as asthma as well as the rarer conditions of hypereosinophilic syndrome and eosinophilic gastrointestinal disorders. Eosinophil trafficking and activation in target organs leads to tissue damage and ongoing reparative attempts that can ultimately result in changes in organ structure and function. Recent treatment with biologic agents such as tyrosine kinase inhibitors and anti-interleukin-5 has offered new therapeutic options in certain eosinophilic disorders. Eosinophilic disorders such as eosinophilic esophagitis are increasingly being diagnosed in children, but many lessons in disease pathogenesis, diagnosis, optimal treatment, and natural history continue to be learned.     

Atopy and neural damage

The occurrence of myelitis with atopic diathesis (atopic myelitis) affecting young adults has recently been noted in Japan. The disease preferentially affects the posterior column of the cervical spinal cord, as shown clinically and by MRI. It is characterized by hyperIgEaemia and the presence of mite antigen-specific IgE. The spinal cord lesions have been shown to be eosinophilic inflammation on biopsy and thus an allergic mechanism is thought to be operative in this condition. In addition, we also found that Hirayama disease, juvenile muscular atrophy of the distal upper extremity, is also associated with airway allergy such as allergic rhinitis and atopic asthma. In children, poliomyelitislike illness after acute asthma attacks is well known as Hopkins syndrome. Moreover, by the prospective study of the history of allergic disorders in common neurologic diseases, an association between spinal progressive muscular atrophy (SPMA) and asthma as well as between myelitis and atopic dermatitis has been demonstrated. These observations strongly suggest a link between atopic diathesis and spinal cord damage. Central nervous system damage associated with atopic diathesis may be classified into two types; eosinophilic myelitis preferentially affecting the cervical spinal cord and lower motor neuron damage, such as Hopkins syndrome, Hirayama disease and SPMA. The former is typically associated with atopic dermatitis while the latter, with airway allergy.     

Sweat is a most efficient natural moisturizer providing protective immunity at points of allergen entry

Although there is a growing acceptance that sweat could play a detrimental role in various allergic skin diseases, the possibility that sweat is also involved in maintenance of skin hydration and skin-specific immune responses has not been acknowledged. We initially describe physiological role of sweat in both maintaining skin hydration and thermoregulation. The purpose of this article is to provide the reader with objective evidence that sweating is intimately linked to vital stratum corneum barrier function and usefulness of application of moisturizers in clinical care of allergic skin diseases. This review also covers how sweating disturbance would leave the skin vulnerable to the development of various allergic skin diseases, such as atopic dermatitis. New therapeutic approaches would specifically target such sweating disturbance in these allergic skin diseases.     

Immunological pathogenesis of main age-related diseases and frailty: Role of immunosenescence

Nowadays, it is well known that with advancing age individuals are at an increased susceptibility to develop diseases such as Alzheimer's disease, infectious diseases, cancer, and osteoporosis. Ageing is associated with various changes in immune parameters; therefore many authors have postulated that these age-related diseases could be explained, at least in part, by an overall deregulation of the function of the immune system. Immunosenescence is the term usually used to describe the acquired dysfunctional immunity within the ageing population affecting both innate and adaptive immunity. The present review examines the close involvement of the immunosenescence in the pathogenesis of these main age-related clinical outcomes, insulin resistance and the frailty process.     

Conference scene: Parasites to treat immune-mediated diseases?

A growing number of childhood diseases, such as allergic disorders (e.g., allergic rhinitis, atopic dermatitis and asthma) and other immune-mediated diseases (e.g., Type 1 diabetes), have been linked to environmental exposures during prenatal and early postnatal life, along with genetic determinants. Immunological mechanisms, diagnosis, treatment, prevention and management of allergies and other immune-mediated diseases were discussed at the 2012 Annual Meeting of the American Academy of Allergy, Asthma & Immunology in Orlando, FL, USA, 2-6 March 2012.     

细胞焦亡在过敏性疾病发病中的作用及机制

过敏性疾病是由IgE介导的慢性炎症,包括一系列常见疾病,如哮喘、过敏性鼻炎、特应性皮炎、荨麻疹等。近年来过敏性疾病发病率呈明显上升趋势,但目前的治疗手段尚不能满足其治疗需求,深入研究过敏性疾病的发生机制并开辟新的治疗策略十分迫切。细胞焦亡是一种新型的炎症相关的细胞程序性死亡方式,它与细胞凋亡、程序性坏死等其他死亡形式共同调控细胞命运,决定疾病进程。研究表明细胞焦亡参与了感染性疾病、动脉粥样硬化、痛风等多种疾病的发生、发展,其与过敏性疾病的发病关系也陆续被报道。本综述主要阐述细胞焦亡发生过程中的关键蛋白和关键细胞因子在过敏性疾病发病中的作用及机制,总结导致发病的共同病因和一般规律,期望能为深入认识过敏性疾病并开辟全新的治疗方式提供帮助。     

Barrier Dysfunction Caused by Environmental Proteases in the Pathogenesis of Allergic Diseases

Skin barrier dysfunction has emerged as a critical driving force in the initiation and exacerbation of atopic dermatitis and the "atopic march" in allergic diseases. The genetically determined barrier deficiency and barrier disruption by environmental and endogenous proteases in skin and epithelium are considered to increase the risk of sensitization to allergens and contribute to the exacerbation of allergic diseases. Sources of allergens such as mites, cockroaches, fungi, and pollen, produce or contain proteases, which are frequently themselves allergens. Staphylococcus aureus, which heavily colonizes the lesions of atopic dermatitis patients and is known to trigger a worsening of the disease, also produces extracellular proteases. Environmental proteases can cause barrier breakdown in the skin, not only in the epithelium, and stimulate various types of cells through IgE-independent mechanisms. Endogenous protease inhibitors control the functions of environmental and endogenous proteases. In this review, we focus on the barrier dysfunction caused by environmental proteases and roles of endogenous protease inhibitors in the pathogenesis of allergic diseases. Additionally, we examine the subsequent innate response to Th2-skewed adaptive immune reactions.     

Quelles raisons pour un traitement probiotique chez les nourrissons allergiques ?

The underlying denominators in allergic disease may be outlined as genetic susceptibility, aberrant barrier functions of skin epithelium and the gastrointestinal and respiratory tracts, and dysregulation of the immune response to ubiquitous environmental antigens. The prevalence of atopic diseases has been progressively increasing in Western societies. Genetic factors are unlikely to explain the emergence of the atopic type of immune responsiveness to antigens such as those deriving from food, food allergy being frequently its first manifestation. Two candidate explanatory factors include altered hygiene and nutrition. The hygiene hypothesis conceives the rapid increase in atopy to be related to reduced exposure to microbes at an early age. The earliest and most massive source of microbial exposure is associated with the establishment of the gut microflora. Diet can also have a major effect on the composition and activity of the gut microflora. In infants, it is thought that those who are breast-fed have a natural predominance of bifidobacteria while the formula-fed have a profile which is more complex and similar to the adult microflora. Since the gut microflora directs the regulation of systemic and local immune responsiveness, including hyporesponsiveness to antigens derived from microorganisms and food, modulation of the gut microflora has been taken as a treatment target in allergic disease. Indeed, differences in the neonatal gut microflora were shown to precede the development of atopy, suggesting a crucial role of the balance of indigenous intestinal bacteria for the maturation of human immunity to a nonatopic mode. Probiotics are live microbial food supplements or components of bacteria, which have been demonstrated to have beneficial effects on human health. Probiotics may create optimal conditions to redirect the allergic immune responsiveness to a healthy balance, and to control local and systemic allergic inflammation before altered structure and function in the target organ develops.     

Acute autoimmune hepatitis presenting with peripheral blood eosinophilia

Peripheral blood eosinophilia has been described in a broad variety of allergic, infectious, neoplastic and autoimmune diseases. To the best of our knowledge blood eosinophilia has never previously been reported in association with isolated autoimmune hepatitis (AIH) in the absence of other autoimmune conditions. Herein we report an interesting case of an 18 year old man who presented to our hospital with an acute autoimmune hepatitis diagnosed on the basis of clinical features, serology and histopathology. He was noted to have a moderate peripheral eosinophilia at diagnosis which resolved within days of initiation of corticosteroids for treatment of the AIH. Given the absence of other systemic conditions or drugs which may have produced the eosinophilia and its rapid resolution with treatment of the underlying liver disease, we wished to highlight this rather novel presentation of AIH.     

变态反应疾病的自然进程及干预

变态反应疾病的发生和发展一直备受关注，其变态反应症状可表现在胃肠道、皮肤、鼻腔、支气管等不同部位，流行病学研究发现婴儿或儿童早期出现的某种变态反应症状常常预示着未来其他变态反应疾病的发生，这种现象被称为变态反应疾病的自然进程。本文就变态反应疾病的自然进程的相关研究进行综述，以为变态反应疾病的预防和治疗提供线索。     

Trained innate lymphoid cells in allergic diseases

Group 2 innate lymphoid cells (ILC2s) reside in peripheral tissues such as the lungs, skin, nasal cavity, and gut and provoke innate type 2 immunity against allergen exposure, parasitic worm infection, and respiratory virus infection by producing T_H2 cytokines. Recent advances in understanding ILC2 biology revealed that ILC2s can be trained by IL-33 or allergic inflammation, are long-lived, and mount memory-like type 2 immune responses to any other allergens afterwards. In contrast, IL-33, together with retinoic acid, induces IL-10-producing immunosuppressive ILC2s. In this review, we discuss how the allergic cytokine milieu and other immune cells direct the generation of trained ILC2s with immunostimulatory or immunosuppressive recall capability in allergic diseases and infections associated with type 2 immunity. The molecular mechanisms of trained immunity by ILCs and the physiological relevance of trained ILC2s are also discussed.