Showing papers in "Current Allergy and Asthma Reports in 2014"

Role of “Western Diet” in Inflammatory Autoimmune Diseases

Abstract: Developed societies, although having successfully reduced the burden of infectious disease, constitute an environment where metabolic, cardiovascular, and autoimmune diseases thrive. Living in westernized countries has not fundamentally changed the genetic basis on which these diseases emerge, but has strong impact on lifestyle and pathogen exposure. In particular, nutritional patterns collectively termed the “Western diet”, including high-fat and cholesterol, high-protein, high-sugar, and excess salt intake, as well as frequent consumption of processed and ‘fast foods’, promote obesity, metabolic syndrome, and cardiovascular disease. These factors have also gained high interest as possible promoters of autoimmune diseases. Underlying metabolic and immunologic mechanisms are currently being intensively explored. This review discusses the current knowledge relative to the association of “Western diet” with autoimmunity, and highlights the role of T cells as central players linking dietary influences to autoimmune pathology.

Penicillin and Beta-Lactam Allergy: Epidemiology and Diagnosis

Abstract: Penicillin is the most common beta-lactam antibiotic allergy and the most common drug class allergy, reported in about 8 % of individuals using health care in the USA. Only about 1 % of individuals using health care in the USA have a cephalosporin allergy noted in their medical record, and other specific non-penicillin, non-cephalosporin beta-lactam allergies are even rarer. Most reported penicillin allergy is not associated with clinically significant IgE-mediated reactions after penicillin rechallenge. Un-verified penicillin allergy is a significant and growing public health problem. Clinically significant IgE-mediated penicillin allergy can be safely confirmed or refuted using skin testing with penicilloyl-poly-lysine and native penicillin G and, if skin test is negative, an oral amoxicillin challenge. Acute tolerance of an oral therapeutic dose of a penicillin class antibiotic is the current gold standard test for a lack of clinically significant IgE-mediated penicillin allergy. Cephalosporins and other non-penicillin beta-lactams are widely, safely, and appropriately used in individuals, even with confirmed penicillin allergy. There is little, if any, clinically significant immunologic cross-reactivity between penicillins and other beta-lactams. Routine cephalosporin skin testing should be restricted to research settings. It is rarely needed clinically to safely manage patients and has unclear predictive value at this time. The use of alternative cephalosporins, with different side chains, is acceptable in the setting of a specific cephalosporin allergy. Carbapenems and monobactams are also safely used in individuals with confirmed penicillin allergy. A certain predictable, but low, rate of adverse reactions will occur with all beta-lactam antibiotic use both pre- and post-beta-lactam allergy evaluations.

Skin Barrier Defects in Atopic Dermatitis

Abstract: Atopic dermatitis (AD) is a chronic inflammatory skin condition with complex etiology that is dependent upon interactions between the host and the environment. Acute skin lesions exhibit the features of a Th2-driven inflammatory disorder, and many patients are highly atopic. The skin barrier plays key roles in immune surveillance and homeostasis, and in preventing penetration of microbial products and allergens. Defects that compromise the structural integrity or else the immune function of the skin barrier play a pivotal role in the pathogenesis of AD. This article provides an overview of the array of molecular building blocks that are essential to maintaining healthy skin. The basis for structural defects in the skin is discussed in relation to AD, with an emphasis on filaggrin and its genetic underpinnings. Aspects of innate immunity, including the role of antimicrobial peptides and proteases, are also discussed.

Skin testing and patch testing in non-IgE-mediated drug allergy.

Abstract: Drug skin tests can reproduce delayed hypersensitivity to drugs and entail a moderate reexposure of patients to offending drugs. Drug patch tests (DPTs) and prick tests can be done with any commercialized form of a drug. In non-severe delayed non-IgE-mediated reactions to drugs, intradermal tests (IDT) with delayed readings have a greater value, but their techniques lack standardization. A negative drug skin test does not exclude the responsibility of a drug, and the drug must be rechallenged in non-severe cases. DPTs are useful in maculopapular rashes, flexural exanthemas, and if done in situ, also in fixed drug eruption. Their best indication is in acute generalized exanthematous pustulosis or drug reaction with eosinophilia and systemic symptoms (DRESS). They should be carried out cautiously, following strict guidelines. Prick tests have a low value but they can sometimes be positive on delayed readings. In non-severe delayed reactions to drugs, intradermal tests with delayed readings are the most sensitive skin tests especially for beta-lactam antibiotics, radiocontrast media, heparins but also some biological agents. The value of patch testing varies according to the implicated drug and the non-immediate adverse drug reaction. In DRESS, DPTs have a good value in testing carbamazepine or proton pump inhibitors but remain negative in testing with allopurinol or salazopyrin. In toxic epidermal necrolysis, DPTs are safe but positive in only 9 to 23 % of the reported cases.

Cross-Reactivity of Peanut Allergens

Abstract: Peanut seeds are currently widely used as source of human food ingredients in the United States of America and in European countries due to their high quality protein and oil content. This article describes the classification and molecular biology of peanut seed allergens with particular reference to their cross-reactivities. Currently, the IUIS allergen nomenclature subcommittee accepts 12 peanut allergens. Two allergens belong to the cupin and four to the prolamin superfamily, and six are distributed among profilins, Bet v 1-like proteins, oleosins, and defensins. Clinical observations frequently report an association of peanut allergy with allergies to legumes, tree nuts, seeds, fruits and pollen. Molecular cross-reactivity has been described between members of the Bet v 1-like proteins, the non-specific lipid transfer proteins, and the profilins. This review also addresses the less well-studied cross-reactivity between cupin and prolamin allergens of peanuts and of other plant food sources and the recently discovered cross-reactivity between peanut allergens of unrelated protein families.

Complexities in the Relationship Between Infection and Autoimmunity

Abstract: The possible role of infections in driving autoimmune disease (AD) has long been debated. Many theories have emerged including release of hidden antigens, epitope spread, anti-idiotypes, molecular mimicry, the adjuvant effect, antigenic complementarity, or simply that AD could be a direct consequence of activation or subversion of the immune response by microbes. A number of issues are not adequately addressed by current theories, including why animal models of AD require adjuvants containing microbial peptides in addition to self tissue to induce disease, and why ADs occur more often in one sex than the other. Reviews published in the past 3 years have focused on the role of the innate immune response in driving AD and the possible role of persistent infections in altering immune responses. Overall, recent evidence suggests that microbes activating specific innate immune responses are critical, while antigenic cross-reactivity may perpetuate immune responses leading to chronic autoinflammatory disease.

Allergic contact dermatitis in children: review of the past decade.

Abstract: Allergic contact dermatitis (ACD) is a type IV delayed hypersensitivity reaction. During the last decade, there has been a heightened awareness of this disease in the pediatric population. The gold standard for diagnosis is patch testing. The prevalence of positive patch tests in referred children with suspected ACD ranges from 27 to 95.6 %. The most common allergens in children in North America are nickel, neomycin, cobalt, fragrance, Myroxylon pereirae, gold, formaldehyde, lanolin/wool alcohols, thimerosal, and potassium dichromate. The relationship between ACD and atopic dermatitis (AD) is complicated with conflicting reports of prevalence in the literature; however, in a patient with dermatitis not responding to traditional therapies, or with new areas of involvement, ACD should be considered as part of the work-up.

The nasal and sinus microbiome in health and disease.

Abstract: There has been great interest in unraveling the complex inter-relationships between microbes and humans as they relate to human health and disease. This review will focus on recent advances in the appreciation and understanding of these relationships in terms of the upper respiratory tract, specifically the nose and paranasal sinuses.

MicroRNAs in Allergy and Asthma

Abstract: microRNAs (miRNAs) are short, single-stranded RNA molecules that function together with the partner proteins and cause degradation of target mRNAs or inhibit their translation. A particular miRNA can have hundreds of targets; therefore, miRNAs cumulatively influence the expression of a large proportion of genes. The functions of miRNAs in human diseases have been studied since their discovery in mammalian cells approximately 12 years ago. However, the role of miRNAs in allergic disease has only very recently begun to be uncovered. The purpose of this review is to provide an overview of the functions of miRNAs involved in the development of allergic diseases. We describe here the functions of miRNAs that regulate Th2 polarization and influence general inflammatory and tissue responses. In addition, we will highlight findings about the functions of extracellular miRNAs as possible noninvasive biomarkers of diseases with heterogeneous phenotypes and complex mechanisms and briefly discuss advances in the development of miRNA-based therapeutics.

Interleukin-31: A Novel Diagnostic Marker of Allergic Diseases

Abstract: Interleukin-31 (IL-31) is a newly discovered cytokine associated with chronic skin inflammation and pruritus. Patients with atopic dermatitis, chronic spontaneous urticaria, allergic contact dermatitis, prurigo nodularis, primary cutaneous lymphoma and mastocytosis exhibit increased serum levels of IL-31 protein and elevated IL-31 mRNA in the skin. Interestingly, in some of these diseases, IL-31 serum levels correlate with disease activity. In the present review, we particularly focus on studies investigating IL-31 as a novel diagnostic biomarker indicating the severity of allergic diseases. We highlight a recent study on IL-31 in mastocytosis, which reports on elevated serum levels of IL-31 in adults correlating with the severity of disease categories, tryptase levels and percentage of bone marrow infiltration. We conclude that growing knowledge about IL-31, its receptors and signaling pathways serves to better understand the pathogenesis of allergic diseases and may lead to the development of novel treatment approaches.

Autoimmune lymphoproliferative syndrome: an update and review of the literature.

Abstract: Autoimmune lymphoproliferative syndrome (ALPS) is characterized by immune dysregulation due to a defect in lymphocyte apoptosis. The clinical manifestations may be noted in multiple family members and include lymphadenopathy, splenomegaly, increased risk of lymphoma, and autoimmune disease, which typically involves hematopoietic cell lines manifesting as multilineage cytopenias. Since the disease was first characterized in the early 1990s, there have been many advances in the diagnosis and management of this syndrome. The inherited genetic defect of many ALPS patients has involved (FAS) pathway signaling proteins, but there remain those patients who carry undefined genetic defects. Despite ALPS having historically been considered a primary immune defect presenting in early childhood, adult onset presentation is increasingly becoming recognized and more so in genetically undefined patients and those with somatic FAS mutations. Thus, future research may identify novel pathways and/or regulatory proteins important in lymphocyte activation and apoptosis.

Cytokine profiles in allergic rhinitis.

Abstract: Allergic rhinitis, particularly seasonal allergic rhinitis, is considered a classic Th2-mediated disease, with important contributions to pathology by interleukins 4, 5 and 13. As such, allergic rhinitis is an excellent model for studying allergic inflammation, with findings potentially relevant to the mechanism of lower airways inflammation seen in allergic asthma. However, recent evidence has revealed roles for additional non-Th2 cytokines in asthma, including IL-17 family cytokines and epithelial-derived cytokines. Additionally, putative roles for epithelial-derived cytokines and innate lymphoid cells have been described in chronic rhinosinusitis with nasal polyps. Here, evidence for the involvement of different cytokines and cytokine groups in allergic rhinitis is considered.

Microbiome Diversity and Asthma and Allergy Risk

Abstract: The prevalence of asthma and allergy has been constantly increasing in Westernized countries in the last decades. Asthma and allergies are complex diseases with a local tissue inflammation that are determined by genetic and environmental factors. Because the commensal microflora is crucial to maintain inflammatory homeostasis and to induce immune regulation, the microbiome may play an important role for the development of allergic conditions. New techniques such as next-generation sequencing methods give the opportunity to explore the microbial community structure of the human body comprehensively. In this review, we will discuss the available literature concerning the human microbiota and asthma and allergy development and occurrence. The focus is on studies of the local microbiome of the place of inflammation, the gastrointestinal microbiome, and the influence of intrinsic factors relating to the host and extrinsic factors relating to the external environment on the microbiome.

Allergic reactions to Anisakis found in fish.

Abstract: The food-borne parasite Anisakis is an important hidden food allergen. Anisakis is a parasitic nematode which has a third-stage larval form that infects mainly fish, and ingestion of contaminated seafood can result in severe allergic reactions. Symptoms experienced due to exposure to this parasite include gastrointestinal disorders, urticaria, dermatitis, asthma and even anaphylaxis. Accurate prevalence data of allergic sensitisation to Anisakis are difficult to estimate due to the lack of well-designed population-based studies. Current diagnostic approaches rely on the detection of serum IgE antibodies to allergenic proteins, which however demonstrate considerable immunological cross-reactivity to other invertebrate allergens. While exposure to this parasite seems to increase due to the increasing consumption of seafood worldwide, the immunology of infection and allergic sensitization is not fully understood.

The Molecular Basis of Peanut Allergy

Abstract: Peanut allergens can trigger a potent and sometimes dangerous immune response in an increasing number of people. The molecular structures of these allergens form the basis for understanding this response. This review describes the currently known peanut allergen structures and discusses how modifications both enzymatic and non-enzymatic affect digestion, innate immune recognition, and IgE interactions. The allergen structures help explain cross-reactivity among allergens from different sources, which is useful in improving patient diagnostics. Surprisingly, it was recently noted that similar short peptide sequences among unrelated peanut allergens could also be a source of cross-reactivity. The molecular features of peanut allergens continue to inform predictions and provide new research directions in the study of allergic disease.

Etiology and Pathogenesis of Late-Onset Alzheimer’s Disease

Abstract: Alzheimer’s disease (AD) is a neurodegenerative condition that occurs in two forms, an early-onset form that is genetically determined and a far more common late-onset form that is not. In both cases, the disease results in severe cognitive dysfunction, among other problems, and the late-onset form of the disease is now considered to be the most common cause of dementia among the elderly. While a good deal of research has been focused on elucidating the etiology of the late-onset form for more than two decades, results to date have been modest and have not yet engendered useful therapeutic strategies for cure of the disease. In this review, we discuss the prevalent ideas that have governed this research for several years, and we challenge these ideas with alternative findings suggesting a multifactorial etiology. We review promising newer ideas that may prove effective as therapeutic interventions for late-onset AD, as well as providing reliable means of earlier and more specific diagnosis of the disease process. In the discussions included here, we reference relevant clinical and basic science literature underlying research into disease etiology and pathogenesis, and we highlight current reviews on the various topics addressed.

Skin testing versus serum-specific IgE testing: which is better for diagnosing aeroallergen sensitization and predicting clinical allergy?

Abstract: An accurate diagnosis of aeroallergen sensitization is pivotal to clinical practice and research. Given the recent technological advances in analyzing serum allergen-specific IgE, the question of which testing method, skin or serum testing, is superior in diagnosing allergic sensitization must be readdressed, as well as their value in predicting clinical disease. This review article provides a detailed summary of recent studies addressing these questions. Conclusively, most studies show substantial discordance between serum-specific IgE and skin testing results, suggesting that the two testing methods compliment each other and cannot be used interchangeably. On average, using only one testing method may misdiagnose every fourth allergically sensitized patient as non-sensitized. In addition, depending on the allergen tested, skin prick testing and serum-specific IgE testing appear to be the methods of choice in predicting outcomes of experimental allergen challenge, while intradermal testing is less contributory.

B cell biology: an overview.

Abstract: In this review we summarize recent insights into the development of human B cells primarily by studying immunodeficiencies. Development and differentiation of B cells can be considered as a paradigm for many other developmental processes in cell biology. However, it differs from the development of many other cell types by phases of extremely rapid cell division and by defined series of somatic recombination and mutation events required to assemble and refine the B cell antigen receptors. Both somatic DNA alteration and proliferation phases take place in defined sites but in different organs. Thus, cell migration and timely arrival at defined sites are additional features of B cell development. By comparing experimental mouse models with insights gained from studying defined genetic defects leading to primary immunodeficiencies and hypogammaglobulinemia, we address important features that are characteristic for human B cells. We also summarize recent advances made by developing improved in vitro and in vivo systems allowing the development of human B cells from hematopoietic stem cells. Combined with genetic and functional studies of immunodeficiencies, these models will contribute not only to a better understanding of disease affecting the B lymphocyte compartment, but also to designing better and safer novel B cell-targeted therapies in autoimmunity and allergy.

Noninfectious immune-mediated uveitis and ocular inflammation.

Abstract: Noninfectious uveitis encompasses a diverse group of ocular inflammatory disorders that share an underlying immune etiology and may be associated with systemic disease or confined primarily to the eye. Uveitis is commonly classified by anatomical location of inflammation into anterior, intermediate, posterior, and panuveitis. The treatment of noninfectious uveitis consists of corticosteroids, immunosuppressive agents, and surgically placed steroid implants. We review the epidemiology, immunopathology, and clinical features of several noninfectious immune-mediated uveitides, including HLA-B27 acute anterior uveitis, juvenile idiopathic arthritis, intermediate uveitis, sarcoidosis, Behcet’s disease, Vogt-Koyanagi-Harada syndrome, sympathetic ophthalmia, and white dot syndromes. We also discuss the stepwise approach to medical treatment of immune-mediated uveitis as well as the characteristics, safety, and efficacy of immunosuppressive agents used to treat ocular inflammatory disease.

The Common Cold: Potential for Future Prevention or Cure

Abstract: The common cold is the most frequent, although generally mild, human disease. Human Rhinoviruses are the prevalent causative agents, but other viruses are also implicated. Being so common, viral colds, have significant implications on public health and quality of life, but may also be life-threatening for vulnerable groups of patients. Specific diagnosis and treatment of the common cold still remain unmet needs. Molecular diagnostic techniques allow specific detection of known pathogens as well as the identification of newly emerging viruses. Although a number of medications or natural treatments have been shown to have some effect, either on the number or on the severity of common colds, no single agent is considerably effective. Virus-specific management remains in most cases a challenging potential as many factors have to be taken into account, including the diversity of the viral genomes, the heterogeneity of affected individuals, as well as the complexity of this long standing host-virus relationship.

Evidence-based Surgery for Chronic Rhinosinusitis with and without Nasal Polyps

Abstract: Meta-analysis of both large outcome studies as well as cohort studies support the safety and efficacy of Endoscopic Sinus Surgery for Chronic Rhinosinusitis. The efficacy of endoscopic sinus surgery is demonstrated in the improvement of both disease-specific and generic QOL as well as objective measures. However, this must be interpreted together with a well-recognized long-term 15–20 % revision rate, seen more often in patients with ASA trias and cystic fibrosis as well as osteitis and previous surgery. The effect of surgery is higher in managing nasal obstruction (effect size 1.7) and less so hyposmia (effect size 0.8). Allergy has an additive role on the symptomatology of CRS; however, its role if any on the outcome of ESS for CRS is unclear. The concurrent presence of aspiring sensitivity and asthma is associated with increased disease burden and more revision surgeries. Improved phenotyping of CRS may lead in the future to better tailoring of surgical treatments.

Complement Deficiencies in Systemic Lupus Erythematosus

Abstract: The complement system is a major, multifunctional part of innate immunity and serves as a bridge between the innate and adaptive immune systems. It consists of more than 30 distinct proteins that interact with one another in a specific sequence. There are three pathways of complement activation: the classical, the lectin, and the alternative pathways. The three pathways are initiated by distinct mechanisms, but they all generate the same core set of effector molecules. Inherited complete deficiencies in complement components are generally very rare and predispose to infections and autoimmune disease. One of the better described associations is between deficiencies in early classical pathway components and the development of systemic lupus erythematosus. The goal of this review will be to discuss the associations between and the causal mechanisms of complement deficiencies and systemic lupus erythematosus.

Recombinant Allergens for Diagnosis of Cockroach Allergy

Abstract: Molecular cloning of cockroach allergens and their expression as recombinant proteins have allowed a better understanding of the mechanisms of cockroach allergic disease. Recombinant cockroach allergens have been used for skin testing or in vitro methods to measure IgE antibody levels in serum. Early studies evaluating selected U.S. patients revealed that a cocktail of four cockroach allergens, Bla g 1, Bla g 2, Bla g 4, and Bla g 5, would identify 95 % of cockroach allergic patients. More recent studies pointed to an important role of sensitization to tropomyosin among certain populations, and suggested that a cocktail of five allergens Bla g 1 and/or Per a 1, Bla g 2, Bla g 4, Bla g 5, and Bla g 7, and/or Per a 7, would be expected to diagnose 50– 64 % of cockroach-allergic patients worldwide. Variation in IgE reactivity profiles could be in part due to IgE responses to cross-reactive homologous allergens from different origins. The availability of purified natural or recombinant cockroach allergens provides the capacity to improve diagnosis of cockroach allergy and to develop novel forms of immunotherapy for cockroach-allergic patients.

Genotyping for Severe Drug Hypersensitivity

Abstract: Over the past decade, there have been significant advances in our understanding of the immunopathogenesis and pharmacogenomics of severe immunologically-mediated adverse drug reactions. Such T-cell-mediated adverse drug reactions such as Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), drug-induced liver disease (DILI) and other drug hypersensitivity syndromes have more recently been shown to be mediated through interactions with various class I and II HLA alleles. Key examples have included the associations of HLA-B*15:02 and carbamazepine induced SJS/TEN in Southeast Asian populations and HLA-B*57:01 and abacavir hypersensitivity. HLA-B*57:01 screening to prevent abacavir hypersensitivity exemplifies a successful translational roadmap from pharmacogenomic discovery through to widespread clinical implementation. Ultimately, our increased understanding of the interaction between drugs and the MHC could be used to inform drug design and drive pre-clinical toxicity programs to improve drug safety.

Anaphylaxis as a Clinical Manifestation of Clonal Mast Cell Disorders

Abstract: Clonal mast cell disorders comprise a heterogeneous group of disorders characterized by the presence of gain of function KIT mutations and a constitutively altered activation-associated mast cell immunophenotype frequently associated with clinical manifestations related to the release of mast cells mediators. These disorders do not always fulfil the World Health Organization (WHO)-proposed criteria for mastocytosis, particularly when low-sensitive diagnostic approaches are performed. Anaphylaxis is a frequent presentation of clonal mast cell disorders, particularly in mastocytosis patients without typical skin lesions. The presence of cardiovascular symptoms, e.g., hypotension, occurring after a hymenoptera sting or spontaneously in the absence of cutaneous manifestations such as urticaria is characteristic and differs from the presentation of anaphylaxis in the general population without mastocytosis.

Emerging Role of Human Basophil Biology in Health and Disease

Abstract: Basophils have emerged in recent years as a small but potent subpopulation of leukocytes capable of bridging innate and adaptive immunity. They can be activated through IgE-dependent and IgE-independent mechanisms to release preformed mediators and to produce Th2 cytokines. In addition to their role in protective immunity to helminths, basophils are major participants in allergic reactions as diverse as anaphylaxis and immediate hypersensitivity reactions, late-phase hypersensitivity reactions, and delayed hypersensitivity reactions. Additionally, basophils have been implicated in the pathophysiology of autoimmune diseases such as lupus nephritis and rheumatoid arthritis, and the modulation of immune responses to bacterial infections, as well as being a feature of myelogenous leukemias. Distinct signals for activation, degranulation, transendothelial migration, and immune regulation are being defined, and demonstrate the important role of basophils in promoting a Th2 microenvironment. These mechanistic insights are driving innovative approaches for diagnostic testing and therapeutic targeting of basophils.

Immune Mechanisms of Sublingual Immunotherapy

Abstract: Sublingual immunotherapy (SLIT) is a well-established allergen-specific immunotherapy and a safe and effective strategy to reorient inappropriate immune responses in allergic patients. SLIT takes advantage of the tolerogenic environment of the oral mucosa to promote tolerance to the allergen. Several clinical studies have investigated the complex interplay of innate and adaptive immune responses that SLIT exploits. The oral immune system is composed of tolerogenic dendritic cells that, following uptake of allergen during SLIT, support the differentiation of T helper cell type 1 (Th1) and the induction of IL-10-producing regulatory T cells. Following SLIT, allergic disease-promoting T helper cell type 2 (Th2) responses shift to a Th1 inflammatory response, and IL-10 and transforming growth factor (TGF)-β production by regulatory T cells and tolerogenic dendritic cells suppress allergen-specific T cell responses. These immune changes occur both in the sublingual mucosa and in the periphery of a patient following SLIT. SLIT also promotes the synthesis of allergen-specific IgG and IgA antibodies that block allergen-IgE complex formation and binding to inflammatory cells, thus encouraging an anti-inflammatory environment. Several of these revealing findings have also paved the way for the identification of biomarkers of the clinical efficacy of SLIT. This review presents the emerging elucidation of the immune mechanisms mediated by SLIT.

Efficacy and Safety of Long-Term Antibiotics (Macrolides) for the Treatment of Chronic Rhinosinusitis

Abstract: Long-term treatment of airway inflammation/infection with macrolide antibiotics has now been in use for almost 30 years. Whereas the beneficial clinical effect in cystic fibrosis and COPD have been backed up by randomized controlled trials, the evidence from the upper airways is not as strong. We have identified 22 open studies in chronic rhinosinusitis, with and without polyps, but only 2 randomized controlled trials. Of the controlled trials, the one including CRS patients just without polyps, showed a significant effect in sino-nasal outcome test, saccharine transit time, nasal endoscopy, and IL-8 levels in lavage fluid after 12 weeks of roxithromycin, whereas, in the other RCT with a mixed study group of CRS patients with and without polyps, 12 weeks of azithromycin showed no effect compared to placebo. Concerns regarding the risk of macrolides to induce arrhythmia have been raised. Recent FDA guidelines changes has recommended caution in patients with risk factors such as long QT syndrome, bradycardia, hypokalemia, or hypomagnesemia. Ototoxicity is another concern. Long-term macrolide antibiotics in the treatment of CRS patients is still a viable option in a select group of patients.

Systemic contact dermatitis to foods: nickel, BOP, and more.

Abstract: Systemic contact dermatitis (SCD), a cutaneous reaction that is a direct manifestation of systemic exposure to a known allergen in a sensitized individual, has been increasingly recognized as a cause of persistent cutaneous contact dermatitis that is refractory to conventional therapies. While SCD in response to drugs has been described well in the literature, SCD to allergens in common foodstuffs is a less well-articulated phenomenon. Several foods that are universally consumed throughout the world contain potent allergens including nickel, balsam of Peru, trace metals, urushiol, and sesquiterpene lactones as well as a host of others that may cause a distinctive clinical picture. In this review article, the authors review the typical presentation and prevalence of SCD to foods, pathophysiology, the most common offensive ingestible food allergens, several appropriate diets, and effectiveness of dietary avoidance for situations in which SCD is suspected.

MicroRNA in chronic rhinosinusitis and allergic rhinitis.

Abstract: Inflammatory upper airway diseases, particularly chronic rhinosinusitis (CRS) and allergic rhinitis (AR), have a high worldwide prevalence. CRS and AR involve sustained and exaggerated inflammation that is associated with marked changes in gene and protein expression under tight regulation. A novel group of gene expression regulators is a class of short single-stranded RNA molecules termed microRNAs (miRNAs). miRNAs can cause gene silencing through degradation of target mRNAs or inhibition of translation. Dysregulated expression of miRNAs has been shown in various human diseases, such as cancer, inflammatory skin and bowel diseases, rheumatoid arthritis, and asthma. Although studies of miRNAs in inflammatory upper airway diseases are relatively new and few, emerging evidence implicates an involvement of miRNAs in shaping the inflammation pattern in upper airways. The purpose of this review is to provide an overview on our current understanding of miRNA expression and function in CRS and AR, and to underscore the potential for clinical usage of miRNAs in CRS and AR.