Mast Cell Activation Syndrome.

Mast cell activation syndrome (MCAS) involves the skin, gastrointestinal, cardiovascular, respiratory, and neurologic systems, classified as primary, secondary, and idiopathic. Earlier criteria for MCAS diagnosis included episodic symptoms with mast cell mediators affecting two or more organ systems with urticaria, angioedema, flushing, nausea, vomiting, diarrhea, abdominal cramping, hypotensive syncope, tachycardia, wheezing, conjunctival injection, pruritus, nasal stuffiness, decrease in frequency, severity, or resolution of symptoms with anti-mediator therapy including H1/H2 receptor antagonists, anti-leukotrienes, or mast cell stabilizers. Laboratory data includes an increased validated urinary or serum markers of MCAS, documentation of an increase of the marker above the patient's baseline value during symptomatic periods on more than two occasions, or baseline serum tryptase levels that are persistently above 15 ng/mL. Laboratory data also includes an increase of the tryptase level above baseline value on one occasion. Other assays are 24-h urine histamine metabolites, PGD2 or its metabolite, and 11-ß-prostaglandin F2 alpha. A recent global classification is a response of clinical symptoms, a substantial transient increase in serum total tryptase or increase in other mast cell-derived mediators, histamine or PGD2 or urinary metabolites, and agents that attenuate production or mast cell mediator activities. "Spectrum of MCAS disorders" has been proposed, highlighting symptoms' diagnostic tests and treatments.

Antibiotic resistance.

Antimicrobial resistance in bacterial pathogens is a challenge that is associated with high morbidity and mortality. Multidrug resistance patterns in Gram-positive and -negative bacteria are difficult to treat and may even be untreatable with conventional antibiotics. There is currently a shortage of effective therapies, lack of successful prevention measures, and only a few new antibiotics, which require development of novel treatment options and alternative antimicrobial therapies. Biofilms are involved in multidrug resistance and can present challenges for infection control. Virulence, Staphylococcus aureus, Clostridium difficile infection, vancomycin-resistant enterococci, and control in the Emergency Department are also discussed.

A link: Allergic rhinitis, Asthma & Systemic Lupus Erythematosus.

This review has discussed a link between allergic rhinitis, asthma and systemic lupus erythematosus (SLE) and a case report in this area. A clear link with symptoms of allergic rhinitis, asthma and SLE exists. Several articles found on pubmed in the literature are listed on allergic rhinitis and allergy, Th1-immune responses, mast cells in autoimmunity, total immunoglobulin E levels in lupus, atopic diseases and SLE are reviewed. In addition, risks and correlations, genetic predisposition, environmental factors, immune regulation, elevated serum IgE levels, regulatory B cells for both allergic and autoimmune diseases are mentioned, Asthma and the vascular endothelial cell growth factor, asthma and autoimmune diseases, allergy and autoimmunity, neutrophils, innate and adaptive immunity in the development of SLE, the (Tim) gene family, complement activation in SLE and immunomodulation, hypersensitivity reactions in autoimmunity are discussed.

Systemic lupus erythematosus and atherosclerosis: Review of the literature.

The purpose of this manuscript is to extensively review the literature related to systemic lupus erythematosus and atherosclerosis. The conclusion of this review has covered accelerated atherosclerosis in systemic lupus erythematosus, the role of complement, interferon in premature atherosclerosis, inflammatory mediators such as cytokines, leukocytes, innate and adaptive immunity, hydrolytic enzymes, reactive oxygen species, vascular endothelial growth factor, toll receptors in lupus nephritis, several specific anti-inflammatory pharmacological therapies, and potential prevention strategies for atherothrombotic events, interferons and the inflammasome. It is important for allergist-immunologists, rheumatologists both in academic institutions and in practice to understand this important disorder.

Review: Immunology of sinusitis, trauma, asthma, and sepsis.

BACKGROUND: This review article is important for allergists/immunologists and otolaryngologists. It discussed chronic rhinosinusitis, epidemiology, pathogenesis, innate adaptive immunology, nuclear factor-kappa B related to inflammation, sepsis, complement, reactive oxygen species, asthma, sinusitis, elderly pathogenesis, oxidative stress, depression, seasonal variation, vitamin D, genetic susceptibility and sepsis, hereditary angioedema related to trauma and stress. OBJECTIVE: The objective of this review is to link chronic rhinosinusitis, epidemiology, innate and adaptive immunology, NF-kappa B related to inflammation, sepsis, complement, reactive oxygen species, asthma and sinusitis. METHODS: A literature search was conducted from several articles, prospective studies, recent reviews and earlier reports. A synergistic relationship develops between activation of the innate immune system and the loss of organ barrier functions. Many complex factors, such as genetics, physical agents, mediators in the development of organ failure both in asthma, sinusitis, stress, depression and trauma, leading to posttraumatic organ failure. Asthma and sepsis, a common condition encountered in hospital environments remains an important cause of death at intensive care units where allergists/immunologists and otolaryngologists are frequently consulted. The patient's immune surveillance could fail to eliminate the pathogen, allowing it to spread and there is a proinflammatory mediator release with inappropriate activation. CONCLUSION: This review discussed chronic rhinosinusitis, sinusitis related to trauma, the innate and adaptive immunology, NF-kappa B related to inflammation, sepsis, complement, inflammation, reactive oxygen species, asthma pathogenesis, and asthma in the elderly, oxidative stress, depression, seasonal variation and vitamin D, cytokines, genetic susceptibility related to sepsis, hereditary angioedema related to trauma and stress.

Asthma, stress, and depression in women.

The occurrence of depression with asthma is very common, especially in women, and can influence behavioral factors, such as treatment compliance, self-assessment, and management of environmental triggers, that can collectively result in poor asthma management and control. This review describes the association and major clinical implications of stress, anxiety, and depression, and the associated hormonal changes frequently seen in women with poorly controlled asthma. Several validated instruments have recently been developed for screening patients for depression that can now be used and benefit patients with asthma by earlier detection of these confounding risk factors. The review also highlights the need for further delineation and characterization of specific underlying pathophysiologic and immunologic mechanisms responsible for depression in women.

Efficacy of novel monoclonal antibody belimumab in the treatment of lupus nephritis.

Recently introduced into the market, belimumab (Benlysta) is a monoclonal antibody that has potential clinically efficacious applications for the treatment of lupus nephritis. Lupus nephritis is a major complication of systemic lupus erythematosus (SLE) that can lead to significant illness or even death without proper intervention and treatment. With vast implications through a novel mechanism, belimumab offers a new standard of treatment for physicians in the complications associated with SLE, specifically lupus nephritis. By targeting B cell signaling and maturation, belimumab is able to mitigate the underlying pathological complications surrounding SLE. Phase 3 clinical trials with belimumab have depicted clinically efficacious applications, suggesting belimumab as a revolutionary breakthrough in the treatment armamentarium for practicing clinicians. This article explains the precise mechanism of action of belimumab on the soluble protein BlyS that plays a major role in the pathogenesis of lupus nephritis. In addition, the extensive pharmacokinetics and clinical implications are exemplified in this review with belimumab's comparison with standard therapeutic guidelines for the treatment of lupus nephritis.

Good's syndrome, CVID, and selective antibody deficiency in patients with chronic rhinosinusitis.

Good's syndrome and common variable immune deficiency (CVID) are associated with chronic rhinosinusitis. Good's syndrome is characterized by hypogammaglobulinemia, B-cell depletion, variable defects in cellular immunity and thymoma. Immunodeficiency and recurrent infections can initially present after thymectomy. The pathogenesis can involve cytokines from bone marrow along with genetic defects. Intravenous gamma globulin (IVIG) restores defective signaling and can reestablish immune homeostasis. IVIG at regular intervals is the most effective way to improve the clinical symptoms and reduce patient mortality. Increased awareness of the clinical and immunological profile of this syndrome may increase its early recognition. CVID patients have hypogammaglobulinemia, respond to IVIG and have a dysregulated antimicrobial peptide response to pathogenic bacteria in the upper respiratory tract. This article reviewed selected literature on Good's syndrome, described an unusual case of Good's syndrome, CVID including SAD related to chronic rhinosinusitis.

Asthma linked with rhinosinusitis: An extensive review.

Current literature related to asthma diagnosis, epidemiology, pathogenesis, and treatment linked with rhinosinusitis is important. Asthma is very heterogeneous; new theories and treatments are emerging. It is a growing epidemic among children and adults in the United States and the severity of asthma is caused by many factors such as lack of education, poor early recognition, decreased symptom awareness, improper medications, and phenotypic changes. Genetic variation, innate immune genes, those involved in tissue remodeling and arachidonic acid metabolism, and inflammatory mediators might contribute to the pathogenesis of chronic rhinosinusitis (CRS) linked with asthma. This extensive review addresses concepts of the burden of asthma and sinusitis, altered innate immunity, adaptive immunity, asthma remodeling, the airway epithelium, the role of airway smooth muscle cells, united allergic airway, genetics, an integral part in asthma, and CRS. In addition, the role of vitamin D in both asthma and CRS in the elderly and pediatric population, various treatment options, and exhaled nitric oxide are briefly addressed.

New insights into an autoimmune mechanism, pharmacological treatment and relationship between multiple sclerosis and inflammatory bowel disease.

Inflammatory bowel disease (IBD) and multiple sclerosis (MS) are autoimmune diseases with a close relationship to their disease pattern and immunologic cascade with considerable morbidity and mortality. This article provides insight of why tumor necrosis factor blockers couldn't work in multiple sclerosis and why interferon-beta doesn't work in inflammatory bowel disease. In this article, we provide a detailed review of the linkage and potential interchangeable medication between IBD and MS in addition to Natalizumab, Trichuris suis egg therapy and vitamin D. Different treatment strategies may have potential in treating both diseases in the future.

Lupus nephritis: review of the literature.

Physicians in practice should be knowledgeable regarding several aspects of autoimmune disorders, especially systemic lupus erythematosus (SLE) and lupus nephritis. These disorders can present to the clinician's clinic and private office regardless of their specialty. This review will discuss various aspects of SLE, its mechanisms of disease, role of accelerated atherosclerosis, proinflammatory cytokines, and therapeutic approaches. The role of vascular endothelial growth factor in which and plasma levels have been associated with disease activity, classification of severity, and diagnosis of lupus nephritis is addressed. Current treatment options, prognosis, and future therapeutic approaches and common side effects are also discussed.

Asthma in the geriatric population.

Asthma is associated with significant morbidity and mortality in the geriatric population. Despite the rising incidence of asthma in people >65 years of age, the diagnosis is frequently missed in this population. Factors that contribute to this include respiratory changes caused by aging, immunosenescence, lack of symptoms, polypharmacy, clinician unawareness, and lack of evidence-based guidelines for diagnosis and management that target this population. This literature review addresses the current state of research in this area. Age-related changes influence the pathophysiology and role of allergy in elderly asthmatic patients. Specific obstacles encountered in caring for these patients are discussed. Asthma in the elderly and younger population are compared. We conclude with a broad set of goals to guide future management driven by a multidiscipline approach.

Alzheimer's disease and immunotherapy.

Alzheimer's disease (AD) is a growing health care epidemic. It is the most common cause of dementia and its incidence is rising. Age, which influences the oxidative and inflammatory states of the brain, is the most important risk factor. Currently there is no disease modifying treatments available for this irreversible, progressive debilitating disease. Immunotherapy represents an emerging, potentially disease modifying strategy aimed at reducing the pathological lesions of AD and facilitating cognitive improvement. Many clinical trials are currently underway. This literature review highlights current knowledge regarding the physiology of aging and how it relates to the pathogenesis of AD. In addition, immunotherapy is discussed in the context of its mechanism, current studies and future goals.

NF-κB and systemic lupus erythematosus: examining the link.

Physicians should be knowledgeable regarding several aspects of autoimmune disorders, especially systemic lupus erythematosus (SLE), with which patients can present in their office with urticaria or vasculitis and which may masquerade as another condition. This paper reviews the link between NF-κB and SLE, including B-cell development, signaling and cytokines which play a crucial role in the pathogenesis of SLE and T-cell development, a key player in T-cell activation. The roles of dendritic cells, which can promote tolerance or immunity to antigens, of polymorphisms and of NF-κB, which are linked with SLE, are also discussed. The role of Toll-like receptors which are important in the pathogenesis of SLE and lupus nephritis is also discussed.

Bacterial biofilms and chronic rhinosinusitis.

Chronic rhinosinusitis (CRS) is a highly prevalent disease in the adult and pediatric population. It causes significant burden and the management is considered one of the most costly public health conditions. Comorbidities include asthma, aspirin sensitivity, and nasal polyposis. Staphylococcus aureus biofilms and exotoxins that act as superantigens have been implicated to play an important pathological role in the incidence, maintenance, and ongoing burden of CRS. A better understanding of the interplay between bacterial factors, host factors, and the environment will facilitate better management of this disease. This literature review focuses on these factors and highlights current research in this field.

Mechanisms of disease for the clinician: systemic lupus erythematosus.

OBJECTIVE: To review the complex interactions and processes in systemic lupus erythematosus (SLE). DATA SOURCES: Brief review of the important literature in peer-reviewed journals. STUDY SELECTION: Studies on the clinical and immunologic features, pathogenesis, epidemiology, laboratory evaluation, and treatment of SLE are included in this review. RESULTS: SLE may include a variety of disease entities, such as isolated cutaneous lupus, undifferentiated connective tissue disease, mixed connective tissue disease, and drug-induced lupus. There are many ongoing clinical trials in SLE patients of therapeutics with different mechanisms of cellular action, such as classic immunosuppression, cell depletion, antigen-specific immunomodulation, and targeting of antigen-nonspecific, immune-activating molecules. New immune cell-targeted therapies are now available that are specifically designed to block cellular pathways involved in disease pathogenesis. CONCLUSION: The practicing physician should understand the immunology, pathogenesis, laboratory evaluation, and updated treatment options when diagnosing SLE in their clinic or daily practice.

The T-cell immunoglobulin and mucin domain (Tim) gene family in asthma, allergy, and autoimmunity.

The T-cell immunoglobulin and mucin domain (Tim) gene family is a relatively newly discovered group of molecules with a conserved structure and important immunologic functions. Tim molecules express on many types of immune cells including T cells, B cells, dendritic cells, macrophages, and mast cells that have been shown to be involved in asthma, allergic rhinitis, food allergy, and autoimmunity. Tim-1-Tim-4 interaction promotes Th2 cytokine responses, and blocking this interaction can decrease airway inflammation in asthma and in allergic rhinitis. Tim-3 stimulates mast cells to produce Th2 cytokines, and anti-Tim-3 is able to dampen asthmatic inflammation. The Tim-3 ligand was shown to be greatly enhanced on intestinal epithelial cells in patients with food allergy and Tim-4 may play a role in maintaining oral tolerance and prevention of food allergy. Tim-3 deregulation plays a role in the pathogenesis of multiple sclerosis. Increased Tim-1 expression has been shown in mononuclear cells from systemic lupus erythematosus patients and Tim-3 may be involved in a protective role in rheumatoid arthritis.

Immune response to nanomaterials: implications for medicine and literature review.

Nanomaterials, substances below 100 nm, are increasingly used in medical diagnosis and treatment every day. The use of such materials has helped deliver drugs across the blood-brain barrier, alleviate allergy symptoms, specifically target cancer or HIV cells, and more. However, the tunable characteristics of such materials have not been perfected. The different materials, sizes, shapes, and structures have different responses on the body. This paper will investigate the successful treatments made with nanoparticles and some general health effects. A review of the literature revealed an inflammatory response and an increased production of reactive oxidative species (ROS) to be common immune responses to nanomaterial use. The mechanisms by which the inflammatory response and ROS production occur will also be discussed.

Role of nuclear factor-ĸB in breast and colorectal cancer.

The purpose of this review article is to highlight articles and new research regarding the link between NF-ĸB and several cancers. This review presents the most up-to-date NF-ĸB research and how it links this important transcription factor with hematology and oncology. It was written by conducting a thorough search of Pubmed as well as several journals such as Cancer, Nature, Science, Cell and those of one of the authors. The articles relating to the link between NF-ĸB and cancer were used to write this review. The results of this study clarified that there is a critical link between NF-ĸB and cancer. NF-ĸB has often been implicated in a variety of different diseases and it plays a variety of roles in cell survival, differentiation, and proliferation of cells. In cancer, NF-ĸB plays a pivotal role by facilitating oncogenesis as well as metastasis. A thorough understanding of NF-ĸB and its role in cancer can lead to future studies and drug development which could provide a novel option in the treatment of this disease.