IKBKG (NEMO) 5' Untranslated Splice Mutations Lead to Severe, Chronic Disseminated Mycobacterial Infections.

Four patients with adult-onset, disseminated mycobacterial infection had 5' UTR mutations in IKBKG without clear physical stigmata of NEMO deficiency. These mutations caused decreased levels of NEMO protein and Toll-like receptor driven cytokine production. Three patients died from disseminated disease. These mutations may be missed by whole exome sequencing.

Hypersensitivity pneumonitis in children: clinical features, diagnosis, and treatment.

Hypersensitivity pneumonitis (HP), or extrinsic allergic alveolitis, is a form of immune-mediated inflammatory lung disease involving the distal portions of the lungs associated with intense or repeated exposure to a variety of finely dispersed environmental antigens. Although once believed to be a disease of adults because of its frequent association with the occupational setting, HP exists in the pediatric population and often goes unrecognized. Childhood HP is often associated with exposure to antigens in the home environment as well as with certain hobbies. Patients present in any one of the three disease stages: acute, subacute, and chronic, all with unique clinical presentations. Histopathologic findings depend on the disease stage at the time of evaluation. The immuno-pathogenesis is complex, but immune-complex (type III hypersensitivity) and cell-mediated (type IV hypersensitivity) immune responses appear to be the primary immune mechanisms involved in the pathogenesis of HP. Diagnosis can be very challenging. Although no single diagnostic or clinical laboratory test is available to diagnose HP, the most significant diagnostic tool is a detailed environmental exposure history. Avoidance of the inciting antigen is the most important form of treatment. Acute HP is responsive to antigen removal alone. However, a short course of prednisone for 2-3 weeks can be useful in patients with severe attacks. Subacute and chronic HP may require higher doses of corticosteroids for a longer duration (i.e. months); however, the long-term efficacy of using corticosteroids is still not well defined. As with most hypersensitivity diseases, early diagnosis provides the best prognosis.

Fish and shellfish allergy.

Fish and shellfish are important in the American diet and economy. Nearly $27 billion are spent each year in the United States on seafood products. Fish and shellfish are also important causes of food hypersensitivity. In fact, shellfish constitute the number one cause of food allergy in the American adult. During the past decade, much has been learned about allergens in fish and shellfish. The major allergens responsible for cross-reactivity among distinct species of fish and amphibians are parvalbumins. The major shellfish allergen has been identified as tropomyosin. Many new and important potential cross-reacting allergens have been identified within the fish family and between shellfish, arachnids, and insects. Extensive research is currently underway for the development of safer and more effective methods for the diagnosis and management of fish and shellfish hypersensitivity.

Occupational asthma caused by high-molecular-weight substances.

More than 250 agents that are encountered in the workplace have been shown to induce asthma in susceptible individuals. It is estimated that 2% to 15% of cases of asthma may be occupational. High-molecular-weight substances, such as plant and animal proteins, enzymes, and large carbohydrate molecules, can induce IgE-mediated occupational asthma. The incidence of disease varies among industries and is dependent on the physiochemical properties of the agent, the level and duration of exposure, industrial hygiene, engineering practices, and host factors. Risk factors, common high-molecular-weight workplace antigens, diagnosis, treatment, and prognosis are discussed.

Hereditary angioedema: a rare but potentially lethal disease.

Hereditary angioedema, although uncommon, should be considered in the differential diagnosis of all patients with facial edema. In this article, we present a case of hereditary angioedema and discuss the presentation, diagnosis, and management of the disease.