Primary Immune Deficiency Treatment Consortium (PIDTC) report.

The Primary Immune Deficiency Treatment Consortium (PIDTC) is a network of 33 centers in North America that study the treatment of rare and severe primary immunodeficiency diseases. Current protocols address the natural history of patients treated for severe combined immunodeficiency (SCID), Wiskott-Aldrich syndrome, and chronic granulomatous disease through retrospective, prospective, and cross-sectional studies. The PIDTC additionally seeks to encourage training of junior investigators, establish partnerships with European and other International colleagues, work with patient advocacy groups to promote community awareness, and conduct pilot demonstration projects. Future goals include the conduct of prospective treatment studies to determine optimal therapies for primary immunodeficiency diseases. To date, the PIDTC has funded 2 pilot projects: newborn screening for SCID in Navajo Native Americans and B-cell reconstitution in patients with SCID after hematopoietic stem cell transplantation. Ten junior investigators have received grant awards. The PIDTC Annual Scientific Workshop has brought together consortium members, outside speakers, patient advocacy groups, and young investigators and trainees to report progress of the protocols and discuss common interests and goals, including new scientific developments and future directions of clinical research. Here we report the progress of the PIDTC to date, highlights of the first 2 PIDTC workshops, and consideration of future consortium objectives.

Effect of heat treatment on milk and egg proteins allergenicity.

BACKGROUND: Heating destroys many conformational epitopes and reduces allergenicity of some foods. IgE-epitope binding has been shown to be different among patients who outgrew their cow's milk or hen's egg allergy and those who did not. A significant proportion of milk- or egg-allergic children are tolerant to these foods in their baked forms. We sought to explore the effects of heating on milk and egg proteins and to evaluate for differences in immunolabeling among children with regard to reactivity to heated milk or egg. METHODS: Sera from participants in clinical dietary intervention trials were utilized. Milk and egg samples were variably heated and prepared (at times within a wheat matrix). Sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis (PAGE), protein transfer, and Western blot were completed. RESULTS: Sera from 20 milk-allergic and 24 egg-allergic children were utilized. Gel electrophoresis showed strongly staining casein bands that persisted for up to 60 min of heating. In contrast, ß-lactoglobulin and α-lactalbumin bands became progressively weaker with increasing heating times, with no detectable ß-lactoglobulin after 15-20 min of heating. The ovalbumin band became progressively weaker, whereas ovomucoid remained stable after 25 min of heating. Immunolabeling revealed that all heated milk-reactive children possessed IgE antibodies that bound the casein fraction regardless of heating time. Presence of wheat during heating resulted in decreased IgE antibody binding to milk and egg white proteins. CONCLUSION: Heating has a different effect on whey and caseins in cow's milk and ovalbumin and ovomucoid in hen's egg white. The effect of heat on protein allergenicity is affected by the temperature and duration, along with the presence of wheat.

Home care use of intravenous and subcutaneous immunoglobulin for primary immunodeficiency in the United States.

PURPOSE: Utilization reports on immunoglobulin (Ig) use for immunodeficiency in the United States (U.S.) have focused on prescribing practices in hospitals. There have been no large-scale reports on Ig use for immune deficiency in the home. We investigated the use of Ig in 3,187 subjects diagnosed with primary immunodeficiency. METHODS: Cross-sectional data on 4,580 subjects in the U.S. receiving Ig in 2011 was obtained from a major home care provider. Demographics, route, dose, and frequency of Ig use by subjects with ICD-9 coded primary immunodeficiencies were analyzed. RESULTS: Of 4,580 subjects, 3,187 had ICD-9 codes suggesting primary immunodeficiencies; 1,939 (60.8 %) were females and 1,248 (39.2 %) were males, with age ranging from 0 to 95 years. The predominant diagnoses were: common variable immunodeficiency (279.06; n=1,764; 55.3 %), hypogammaglobulinemia (279.00; n=635; 19.9 %), unspecified immunity deficiency (279.3; n=286; 9 %), other selective Ig deficiencies (279.03; n=171; 5.4 %), and agammaglobulinemia (279.04; n=127; 4 %). 54 % of subjects received Ig by the subcutaneous (SC) route, and 46 % by intravenous (IV) route, with more SC use by older subjects. The mean dose prescribed was 483 mg/kg/month, but less Ig was ordered for subjects on SCIg (409 mg/kg/month), as compared to subjects on IVIg (568 mg/kg/month). A highly significant inverse correlation between increasing age and dosage of Ig ordered was found (P= <.0001). CONCLUSION: Analysis of home care use of Ig in primary immune deficiency revealed that the SC route was prescribed more than the IV route, especially for older patients. By either method of administration, less immunoglobulin was prescribed for older subjects.

Anaphylaxis in a New York City pediatric emergency department: triggers, treatments, and outcomes.

BACKGROUND: Anaphylaxis incidence is increasing. OBJECTIVE: We sought to characterize anaphylaxis in children in an urban pediatric emergency department (PED). METHODS: We performed a review of PED records for anaphylactic reactions over 5 years. RESULTS: We identified 213 anaphylactic reactions in 192 children (97 male patients): 6 were infants, 20 had multiple reactions, and the median age was 8 years (age range, 4 months to 18 years). Sixty-two reactions were coded as anaphylaxis; 151 additional reactions met the second symposium anaphylaxis criteria. There was no increase in incidence over 5 years. The triggers included the following: foods, 71%; unknown, 15%; drugs, 9%; and "other," 5%. Food was more likely to be a trigger in multiple PED visits (P = .03). Epinephrine was administered in 169 (79%) reactions; in 58 (27%) reactions epinephrine was administered before arrival in the PED. Patients with Medicaid were less likely to receive epinephrine before arrival in the PED (P < .001). Twenty-eight (14.6%) patients were hospitalized, 9 in the intensive care unit. For 13 (6%) of the reactions, 2 doses of epinephrine were administered; 69% of the patients treated with 2 doses of epinephrine were hospitalized compared with 12% of the patients treated with a single dose (P < .001). Administration of both epinephrine doses before arrival to the PED was associated with a lower rate of hospitalization compared with epinephrine administration in the PED (P = .05). CONCLUSIONS: Food is the main anaphylaxis trigger in the urban PED, although the International Classification of Diseases-ninth revision code for anaphylaxis is underused. Treatment with 2 doses of epinephrine is associated with a higher risk of hospitalization; epinephrine treatment before arrival to the PED is associated with a decreased risk. Children with Medicaid are less likely to receive epinephrine before arrival in the PED.

IgE-mediated cow's milk allergy in children.

The age at which the majority of children outgrow cow's milk allergy now appears to be later than previously reported. Recent studies have attempted to elucidate factors that may help prevent cow's milk allergy, assess markers of persistence, and evaluate the usefulness of new diagnostic methods. Strict avoidance of cow's milk has been the mainstay of treatment. However, given the potential nutritional, social, and immunologic ramifications of cow's milk elimination from a child's diet, there has been a focus on reevaluating this therapeutic approach.

Extensively heated milk and egg as oral immunotherapy.

PURPOSE OF REVIEW: The introduction of extensively heated milk and egg protein into the diet has been explored in recent years. RECENT FINDINGS: Studies have suggested that a large subset of children who react to unheated milk or egg can tolerate extensively heated forms of these foods. Immunologic changes induced by a diet containing baked milk and egg are similar to changes that have been observed during oral immunotherapy trials. The baked milk and egg diet appears to accelerate the development of regular milk and egg tolerance when compared with strict avoidance. SUMMARY: An oral challenge to extensively heated milk and egg into milk and egg allergic children's diets should be considered when appropriate. Oral food challenges are the most reliable means of establishing a diagnosis and should be undertaken under physician supervision.

Radiofrequency catheter ablation of "typical" atrial flutter in a patient with Kartagener's syndrome.

Kartagener's syndrome and radiofrequency catheter ablation for the treatment of atrial flutter have been well described in separate reports. This case report includes both in describing a patient with Kartagener's syndrome who had medically refractory atrial flutter that was successfully treated with radiofrequency catheter ablation.