Faculty Bibliography

OBJECTIVE:To characterize the immunodeficiency in ataxia-telangiectasia (A-T) and to determine whether the immunodeficiency is progressive and associated with increased susceptibility to infections. STUDY DESIGN/METHODS:Records of 100 consecutive patients with A-T from the Johns Hopkins Ataxia-Telangiectasia Clinical Center (ATCC) were reviewed. RESULTS:Immunoglobulin (Ig) deficiencies are common, affecting IgG4 in 65% of patients, IgA in 63%, IgG2 in 48%, IgE in 23%, and IgG in 18%. Lymphopenia affected 71% of patients, with reduced B-lymphocyte number in 75%, CD4 T lymphocytes in 69%, and CD8 T lymphocytes in 51%. There was no trend for increased frequency or severity of immune abnormalities with age. Recurrent upper and lower respiratory tract infections were frequent: otitis media in 46% of patients, sinusitis in 27%, bronchitis in 19%, and pneumonia in 15%. Sepsis occurred in 5 patients, in 2 patients concurrent with cancer chemotherapy. Warts affected 17% of patients, herpes simplex 8%, molluscum contagiosum 5%, candidal esophagitis 3%, and herpes zoster 2%. Uncomplicated varicella infection occurred in 44% of patients; 2 patients had more than one clinical episode. No patient had Pneumocystis jerovici pneumonia or a complication of live viral vaccine. CONCLUSIONS:In spite of the high prevalence of laboratory immunologic abnormalities, systemic bacterial, severe viral, and opportunistic infections are uncommon in A-T. Cross-sectional analysis suggests that the immune defect is rarely progressive.

Novel approaches to the treatment and prevention of IgE-mediated food allergy include anti-IgE, food allergy vaccines, herbal preparations, and probiotics. They bring real hope to the patients for whom no specific therapy is available. These immunomodulatory therapies have to be evaluated carefully for potential side effects, such as overstimulation of T helper cell type 1 immune antibodies. Animal models of food allergy are invaluable in testing new therapies for food allergy.

BACKGROUND:Infantile food protein-induced enterocolitis syndrome (FPIES) is a severe, cell-mediated gastrointestinal food hypersensitivity typically provoked by cow's milk or soy. Solid foods are rarely considered a cause. OBJECTIVE:To describe the clinical characteristics and natural history of FPIES provoked by solid foods. METHODS:Patients with FPIES induced by solid foods were identified and their clinical course compared with a control group with FPIES caused by cow's milk and/or soy evaluated over the same time period. RESULTS:Fourteen infants with FPIES caused by grains (rice, oat, and barley), vegetables (sweet potato, squash, string beans, peas), or poultry (chicken and turkey) were identified. Symptoms were typical of classical FPIES with delayed (median: 2 hours) onset of vomiting, diarrhea, and lethargy/dehydration. Eleven infants (78%) reacted to >1 food protein, including 7 (50%) that reacted to >1 grain. Nine (64%) of all patients with solid food-FPIES also had cow's milk and/or soy-FPIES. Initial presentation was severe in 79% of the patients, prompting sepsis evaluations (57%) and hospitalization (64%) for dehydration or shock. The diagnosis of FPIES was delayed, after a median of 2 reactions (range: 2-5). Thirty patients with typical cow's milk- and/or soy-FPIES were identified for comparison. Overall, 48% of the 44 infants with FPIES were reactive to >1 food protein, and the risk for multiple food hypersensitivity approached 80% in the infants with solid food or soy-induced FPIES. None of the patients developed FPIES to maternally ingested foods while breastfeeding unless the causal food was fed directly to the infant. CONCLUSIONS:Cereals, vegetables, and poultry meats, typically regarded as of low allergenic potential, must be considered in the evaluation of FPIES, particularly in infants previously diagnosed with FPIES to cow's milk or soy, and as an initial cause in patients who have been exclusively breastfed. Infants with FPIES are at risk for multiple dietary protein hypersensitivities during an apparent period of immunologic susceptibility. Pediatricians should consider FPIES in the differential diagnosis of shock and sepsis.

Food allergy affects approximately 2% of the general US population, and its prevalence seems to be increasing. Despite the potential for a fatal outcome, no definitive therapies are available for food allergy. This article reviews novel approaches for the diagnosis and treatment of food allergy. Improved diagnostic methods include more precise in vitro and in vivo tests for immunoglobulin E-mediated food allergies, in vitro assays for predicting development of oral tolerance, and novel noninvasive tests for cell-mediated food allergies such as patch testing, cytokine assays, and detection of eosinophil activation markers. Several promising novel immunomodulatory approaches to food allergy are discussed, including monoclonal anti-immunoglobulin E; probiotics; traditional Chinese medicine; and immunotherapy with modified food proteins, peptides, bacterial adjuvants, and immunostimulatory sequences.

BACKGROUND:Montelukast is a leukotriene antagonist approved for the treatment of childhood asthma in children age 2 years and older. There are limited studies on its effects on allergic asthma in children. OBJECTIVE:We sought to evaluate montelukast's effects on upper and lower airway responses to intense cat allergen exposure. METHODS:In a double-blind, placebo-controlled, cross-over trial 18 subjects aged 6 to 14 years with cat-induced asthma were randomly assigned to receive 1 week each of either montelukast or placebo, followed by a 1-hour cat challenge in an environmental exposure unit. Upper and lower respiratory tract symptoms were rated, and spirometry and acoustic rhinometry were performed. Challenges were stopped early if the subject became too uncomfortable or had a greater than 50% decrease in FEV1. RESULTS:Overall changes in FEV1 were significantly different with montelukast treatment and remained significant after adjusting for allergen level (P =.02; adjusted P =.01). Lower respiratory tract symptom scores were significantly reduced with montelukast versus placebo (P =.007) but lost significance after adjusting for allergen level (P =.16). Challenge length was significantly longer with montelukast versus placebo (P <.001) and remained significant after adjusting for allergen level (P =.019). Montelukast did not significantly affect upper respiratory responses, as measured by means of symptom scores (P =.43) and changes in acoustic rhinometry (P =.078). CONCLUSIONS:Montelukast was significantly more effective than placebo in attenuating lower respiratory responses and extending challenge length when cat-sensitive children with mild persistent asthma were exposed to high levels of cat allergen.

Autoimmune diseases are rare in patients with severe combined immunodeficiency (SCID). The authors describe an 11-month-old infant girl with SCID with fatal warm autoimmune hemolytic anemia (AIHA) resulting from IgM autoagglutinins. Serologic evaluation revealed IgM autoantibodies that caused in vitro hemagglutination at 37 degrees C. The patient had clinical evidence of ongoing hemolysis and agglutination despite aggressive treatment. She had three strokes and died 6 weeks after unsuccessful bone marrow transplantation. Autoimmune disease is an unexpected complication of SCID. The presence of warm reactive IgM autoagglutinins in AIHA confers a dismal prognosis.