Autoimmune endocrine diseases are serious disorders that utilize immense health care resources and cause tremendous disability. They include type 1 diabetes mellitus, thyroiditis, Graves disease, Addison disease, and polyglandular syndromes. Analysis of the basis of autoimmune diseases has been aided by the application of new knowledge in immunologic physiology. Recent investigations using these techniques have revealed complicated disorders that have varied pathogenesis and complex genetic predispositions. While the mainstay of treatment for these diverse diseases remains the replacement of hormones produced by the damaged endocrine organ, investigations into the pathogenesis of these disorders provide hope for the development of specific therapeutic measures to block their pathologic basis.

Immunologic lung disorders are accompanied by an array of laboratory abnormalities, some of which contribute to disease pathogenesis. Allergic bronchopulmonary aspergillosis, which complicates asthma and cystic fibrosis, causes mucous plugging of airways, eosinophilic pneumonia, and bronchiolitis obliterans. Aspergillus fumigatus, growing saprophytically in bronchial mucus, is responsible for most cases, and prednisone, not antifungal agents, is the drug of choice because it controls the immunologic responses of the lung. In cystic fibrosis, epithelial surface fluid from the lung does not kill Pseudomonas aeruginosa, in part because antibodies to P aeruginosa are plentiful but ineffective in opsonizing bacteria. Neutrophil-derived elastase cleaves immunoglobulins and digests the C3b receptor on neutrophils, which limits phagocytosis of pathogens. In helminth infections and infestations, pulmonary and peripheral blood eosinophilia can be accompanied by increases in total and antiparasite IgE concentrations and generate T(H)2 CD4+ T-lymphocyte responses. Understanding the immunologic abnormalities of lung disorders may lead to more effective therapies.

The skin represents a unique immunologic organ poised to protect the host from invading organisms and environmental antigens. The skin is also an important target for a variety of allergic and autoimmune responses. Mast cells are key to the pathogenesis of urticaria, angioedema, and mastocytosis. Atopic dermatitis is the consequence of an immunoregulatory abnormality resulting in a skin-directed T helper type 2 response. Allergic contact dermatitis is an example of classic delayed type hypersensitivity. Circulating autoantibodies against the epidermis are a key mechanism by which bullous skin diseases occur.

Allergic sensitization to workplace allergens can result in occupational asthma (OA), rhinitis, and dermatoses. Occupational asthma, accounting for 2% to 15% of all new cases of asthma, is caused by more than 240 reactive chemicals or natural proteins. Diisocyanates, used in urethane production and spray painting, are the leading causes of OA. Occupational asthma must be objectively confirmed by demonstrating significant decreases in lung function associated with exposure to a causative agent. An early diagnosis of OA followed by elimination of exposure to a causative agent may be curative and prevent progression to chronic asthma. In the last decade, protein allergens in natural rubber latex gloves have emerged as the leading cause of work-related cutaneous and respiratory allergic disorders in health care workers. In the workplace, occupational allergic contact dermatitis is almost always caused by chemicals, including nickel, chromates, and epoxy resins, whereas contact urticarial reactions are most often due to protein allergens. The primary treatment of occupational allergic disorders is strict avoidance of exposure to the inciting agent.

Drug allergies are adverse reactions resulting from immunologic responses to drugs or their metabolites. These reactions result in predictable patterns of organ-specific or systemic hypersensitivity that usually recur on subsequent exposure to the same drug. Although diagnostic testing for drug allergy is available for only a few drugs, protocols have been developed to assist in management of allergic reactions to many drugs and biologic agents. Other protocols assist in the management of patients who develop drug reactions while undergoing multiple drug therapy or those with a history of adverse drug reactions who again require treatment for the same condition.

The evaluation of adverse reactions to foods involving abnormal immune responses to food allergens remains an important part of the practice of allergy and immunology. Approximately 5% of children younger than 3 years and 1.5% of the general population experience food allergic disorders, indicating that about 4 million Americans suffer from food allergies. The evaluation of adverse reactions to foods depends on a careful clinical history, diagnostic studies including appropriate skin testing or in vitro testing with food extracts, and/or endoscopy and biopsy. The mainstay of therapy remains avoidance of incriminated foods and education to deal with inadvertent exposures. Experience over the past decade suggests that the ready availability and early introduction of highly allergenic foods (eg, peanuts and nuts) into the diet will only increase the number of individuals suffering from hypersensitivity reactions to foods. Research has focused on the identification and characterization of allergenic proteins and the development of new therapeutic strategies, eg, plasmid DNA vaccines, to treat these disorders.

Allergen immunotherapy has been shown to be efficacious in numerous studies for the clinical indications of allergic asthma and rhinitis, as well as hymenoptera venom hypersensitivity. How allergen immunotherapy improves clinical symptoms is still not entirely clear. Decreases in specific IgE follow a complex cascade of effects: a shifting of the cytokine milieu from T(H)2 to T(H)1 predominance, with resultant decrease in interleukin 4, decreased recruitment and activation of eosinophils, and decreased proliferation of mast cells. Allergen exposure has a lessened ability to stimulate an inflammatory cell response, with decreased target organ hyperreactivity. Since allergen immunotherapy is not without risk, the decision needs to be made whether injection therapy is safe and provides benefit not achievable by medical management. The continued clarification of optimal allergen concentrations through careful studies of standardized extracts will allow better control of adverse events by limiting unnecessarily potent mixtures.

Physicians, patients, employers, managed care organizations, insurance companies, and government all want to know how different approaches to management of asthma are improving care. To this end, the field of outcomes analysis in asthma is playing a major role. Clinical, physiologic, humanistic, and economic outcomes are being assessed using different types of general and asthma-specific instruments. Historically, clinical and physiologic outcomes have been of most concern to clinicians. However, humanistic outcomes, such as health-related quality of life and patient satisfaction, shift the focus to the patient. Economic outcomes, especially cost-effectiveness, evaluate how to achieve the best outcomes at the lowest cost. These outcomes have been used to evaluate asthma intervention programs. Several large asthma outcomes research projects, which should define the future of outcomes analysis in asthma, are under way.

For unknown reasons, the morbidity and mortality from asthma are increasing in many parts of the world, making it a global health concern. The heterogeneous nature of the clinical manifestations and therapeutic responses of asthma in both adult and pediatric patients indicate that it may be more of a syndrome rather than a specific disease entity. Numerous factors, including viral infections, allergen and irritant exposure, and exercise, among others, complicate both the short- and long-term management of asthma. Therapeutic intervention has focused on the appreciation that airway obstruction in asthma consists of bronchial smooth muscle spasm and variable degrees of airway inflammation characterized by edema, mucous secretion, and the influx of a variety of inflammatory cells. Choosing appropriate medications depends on the disease severity (intermittent, mild persistent, moderate persistent, severe persistent), patterns of disease activity (exacerbations related to viruses, allergens, exercise, etc), and the age at onset (infancy, childhood, adulthood).

Despite the prevalence and long history of nasal polyps, many questions still exist with respect to incidence and pathogenesis. Although allergy has been commonly thought to be a major cause, much compelling evidence argues against this. Medical therapy consists of a short course of systemic steroids followed by intranasal steroids. Sinusitis is the most commonly reported chronic disease in the United States. Decrease in ostial size, retention of secretions, and decrease in mucociliary action all contribute to the pathogenesis of sinusitis. The clinical presentation of chronic sinusitis is generally subtle and the clinical index of suspicion must be high. Limited coronal computed tomography is regarded as the most definitive and cost-effective imaging technique for the diagnosis of sinusitis. Appropriate antibiotics must be administered for a sufficient period. In medically resistant sinusitis, functional endoscopic sinus surgery has emerged as the procedure of choice.

Allergic rhinitis affects about 20% of the US population. The diagnosis is based on patterns of symptoms, physical examination, and assessment of IgE antibodies by skin or in vitro testing. The most common offending allergens are pollens of grasses, trees, and weeds; fungi; animal allergens; and dust mites. In an individual with nasal allergy, exposure leads to rapid release of mast cell-derived mediators. This immediate response is followed by a cell-dominated response, including eosinophils and lymphocytes. Cytokines from T(H)2 lymphocytes, such as interleukin 4 and interleukin 5, orchestrate allergic inflammation. Resulting tissue changes produce symptoms of the disease and augment responses on subsequent exposure to allergens and irritants. Strategies for avoiding offending agents are important in management. In intermittent disease, antihistamines and/or decongestants are first prescribed. More continuous symptoms may mandate intranasal steroids. Immunotherapy is often helpful for patients who respond poorly to pharmacotherapy and avoidance.

Primary immunodeficiencies are rare, but important for 3 reasons. First, a high index of suspicion and prompt diagnosis can lead to lifesaving treatment or significant improvement in quality of life. Second, appreciation of the genetic nature of a host defense defect makes possible family counseling and carrier and prenatal diagnosis. Finally, the large and growing list of human genetic defects in immune pathways provides an important tool for understanding human immunoregulation. Many inherited immunodeficiency diseases have had their genetic cause proven with the discovery of their disease genes within the past 5 years. These diseases provide a framework into which additional diseases and disease gene discoveries can be added as the rapid progress in molecular immunology and genetics continues.

Assays performed in the diagnostic immunology laboratory support the diagnosis and management of a wide spectrum of clinical conditions. This chapter reviews immunologic principles as they apply to diagnostic laboratory assays. Most of the determinations are based on well-established principles of antigen-antibody reactions. Some of the specific areas discussed include flow cytometric analyses, critical in the care of patients with hematologic malignancies, with the acquired immunodeficiency syndrome, or undergoing transplantation, and protein electrophoretic assays to identify the presence of monoclonal gammopathies. We also discuss the use of molecular techniques in the diagnosis of hematologic malignancies and primary immunodeficiencies, characterization of the major histocompatibility complex, and enumeration of viral burden.

Mast cells, basophils, and eosinophils have long been regarded as important effector cells in allergic disorders. Indeed, it is thought that the cells' cytoplasmic granule-associated or lipid mediators contribute to many of the signs and symptoms that are characteristic of these diseases. Mast cells, basophils, and eosinophils also probably contribute to protective host responses, especially to parasites. In addition, recent evidence shows that mast cells, basophils, and eosinophils can secrete a wide spectrum of cytokines and, in some cases, express functions that may permit them to regulate the development or perpetuation of allergic responses. Thus, mast cells, basophils, and eosinophils may express immunoregulatory activities, as well as serve as effector cells.

Intact immunity is fundamental for survival. The human immune system has evolved with the sophisticated biologic capacity to distinguish self from nonself and for memory through the process of clonal expansion. The ability to distinguish even subtle differences from self, and among myriad antigens, is possible by the rearrangement of genes that encode immunoglobulins and T-cell receptors, as well as by the requirement for T cells to recognize antigens in the context of presentation by HLA molecules encoded within the major histocompatibility complex. Modulation of immune function initiated by antigenic stimulation and cell-cell interactions is facilitated by a plethora of soluble mediators such as cytokines. This overview of the biology of the immune system provides a framework for understanding physiologic immune responses and how lacunar defects within the immune system explain the pathogenesis of immunologic disorders. Through such understanding, potential targets can be identified for therapeutic modulation of the immune system.

Some human cases of the transmissible neurodegenerative disorder Creutzfeldt-Jakob disease recently seen in Great Britain are thought to have resulted from eating beef infected with the agent of bovine spongiform encephalopathy. Reasons for and against this presumption are explained, and the question of a similar situation occurring in countries other than Britain-in particular, the United States-is discussed in terms of the existence of scrapie (in sheep) or unrecognized bovine spongiform encephalopathy (in cattle), the practice of recycling nonedible sheep and cattle tissue for animal nutrition, and precautionary measures already taken or under consideration by government agencies

A consensus conference on the diagnosis and treatment of Alzheimer disease (AD) and related disorders was organized by the American Association for Geriatric Psychiatry, the Alzheimer's Association, and the American Geriatrics Society on January 4 and 5, 1997. The target audience was primary care physicians, and the following questions were addressed: (1) How prevalent is AD and what are its risk factors? What is its impact on society? (2) What are the different forms of dementia and how can they be recognized? (3) What constitutes safe and effective treatment for AD? What are the indications and contraindications for specific treatments? (4) What management strategies are available to the primary care practitioner? (5) What are the available medical specialty and community resources? (6) What are the important policy issues and how can policymakers improve access to care for dementia patients? (7) What are the most promising questions for future research?

To review the scientific literature on the alterations in the senses of taste and smell in the elderly, including causes, diagnosis, prognosis, and treatment.

To examine more closely the association between apolipoprotein E (APOE) genotype and Alzheimer disease (AD) by age and sex in populations of various ethnic and racial denominations.

To reexamine the conclusions of the 1991 National Institutes of Health Consensus Panel on Diagnosis and Treatment of Depression in Late Life in light of current scientific evidence.