Laurianne G. Wild

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 immunopathogenesis 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.

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.

Immunotherapy for food allergies. Past, present, future.

ConclusionThe future certainly holds promise for the treatment of food allergies. Generally, future treatments can be divided into immunological manipulation of the food-allergic subject (mucosal vaccines, new immunotherapies, cytokine level alterations) or manipulation of the food through genetic engineering to diminish or abolish its allergenic activity.

Immunotherapy for food allergy

Food allergy is an important cause of life-threatening hypersensitivity reactions. Avoidance of allergenic foods is the only method of prevention that currently is available for sensitized patients. This method of prevention is difficult and often impossible. With better characterization of allergens and better understanding of the immunologic mechanism, investigators have developed several therapeutic modalities that potentially are applicable to the treatment and prevention of food allergy. Therapeutic options currently under investigation include peptide immunotherapy, DNA immunization, immunization with immunostimulatory sequences, anti-IgE therapy, and genetic modification of foods. These exciting developments hold promise for the safe and effective treatment and prevention of food allergy in the next several years.

IMMUNOTHERAPY FOR FOOD HYPERSENSITIVITY

Foods are an important cause of severe acute hypersensitivity reactions including fatal anaphylaxis. Food allergy has been estimated to be the most frequent cause of anaphylaxis treated in emergency rooms. 69 Severe reactions to foods can occur at all ages, from infants receiving cows milk or casein or whey hydrolysate formulas 21 , 57 to children, adolescents, and adults. 56 , 70 Although some reactions caused by formula proteins in infants may decrease in intensity with age, 7 the risk for severe reactions to other foods persists for long periods of time, even in absence of exposure. 8 The current management of patients with severe acute food reactions is based on avoidance of specific foods and on the availability of emergency medications to immediately treat an acute reaction. These severe reactions have been associated with fish, shellfish, nuts and seeds, legumes, celery, and to a lesser extent with grains, milk, and eggs. 7 , 8 , 70 It is clear from looking at this list that even the most careful patients may not be safe from an accidental or inadvertent exposure. In most instances, individuals experiencing a food-induced anaphylactic reaction have inadvertently ingested the food that caused the allergic reaction. 56 The unpredictability of accidental exposures and the long periods of time during which patients at risk may not come in contact with the offending foods makes it difficult to have acute treatment medications available at all times, which is necessary for the prevention of fatal food reactions. 56 , 70 The vast majority of the acute, severe reactions to food appear to be IgE-mediated, although non–IgE-mediated reactions can also account for some severe food reactions. 28 The presence of IgE antibodies as the likely cause for severe acute food reactions suggests the possibility of changing this allergic reactivity to a less noxious or even protective form of immune response through immunotherapy or by altering the ability of major food allergens to interact with IgE antibodies through molecular biology methods. Strategies for developing any potentially successful food allergy immunotherapy for patients with life-long sensitivities must satisfy several requirements. First, these methods must be safe and provide an optimal risk-to-benefit ratio for the patient. Procedures must be cost effective and relatively easy to perform so that patients can be treated on a routine basis. In the ensuing discussion, we explore the mucosal immune response as it relates to food allergy, potential treatments of food-allergic individuals through alteration of the host immune responses, use of mucosal vaccines, and traditional and novel approaches to immunotherapy. Finally, genetic engineering and its use to alter allergenic protein molecules to reduce or abolish their allergenicity is discussed.

A critical role for IL-18 in transformation and maturation of naive eosinophils to pathogenic eosinophils

The current studies demonstrate a critical role of IL-18 in transforming IL-5 generated naïve eosinophils into the distinct inflammatory CD101+CD274+ expressing mature and activated tissue eosinophils that promote disease pathogenesis.

357 SKIN TEST REACTIVITY OF SHRIMP-ALLERGIC SUBJECTS TO INHALANT AND OTHER FOOD ALLERGENS

Rationale Shrimp is a major seafood consumed in the U.S. and also an important seafood allergen. The major shrimp allergen is the muscle protein tropomyosin, which is present in other inhaled and ingested allergens. Thus, it was of interest to determine potential sensitivity of shrimp-allergic subjects to these other allergens. Methods Shrimp-allergic subjects were recruited by advertisement. 58 subjects (25 male, 33 female) ages 18-63, with definitive histories of shrimp allergy, as determined by questionnaire, were selected. Subjects were skin prick tested (ST) with aeroallergen and shellfish food extracts from Hollister-Stier; positive ST was determined by wheal with flare. IgE antibody responses to shrimp were measured by CAP-RAST. Results 37/58 (64%) subjects were ST positive to at least 1 of the 2 shrimp extracts tested, 41 (71%) were positive to either crab, lobster, crawfish, or oyster, 51 (88%) to either cockroach or dust mite, 19 (33%) to tree pollens, and 14 (24%) to grass pollens. Of the 37 subjects ST positive for shrimp, 35 (96%) were positive to crab, lobster, or crawfish. 36 (97%) reacted to either cockroach or dust mite. Of the 58 original subjects, 28 (48%) had undetectable IgE to shrimp (class 0) on CAP-RAST analysis. Of the 37 shrimp ST positive subjects, only 10 (27%) had no detectable IgE to shrimp. Conclusions Shrimp-allergic subjects showed significant reactivity to other shellfish, the greatest was to lobster (89%), the least to oysters (43%). Significant reactivity was observed to cockroach and dust mite extracts which is probably due in part to cross reactivity of invertebrate tropomyosin allergens. Better understanding of food and aeroallergen cross-reactivity should help improve diagnosis and therapy of food allergy.