Robert W. Sugerman

Newborn Screening for Severe Combined Immunodeficiency in 11 Screening Programs in the United States

IMPORTANCE Newborn screening for severe combined immunodeficiency (SCID) using assays to detect T-cell receptor excision circles (TRECs) began in Wisconsin in 2008, and SCID was added to the national recommended uniform panel for newborn screened disorders in 2010. Currently 23 states, the District of Columbia, and the Navajo Nation conduct population-wide newborn screening for SCID. The incidence of SCID is estimated at 1 in 100,000 births. OBJECTIVES To present data from a spectrum of SCID newborn screening programs, establish population-based incidence for SCID and other conditions with T-cell lymphopenia, and document early institution of effective treatments. DESIGN Epidemiological and retrospective observational study. SETTING Representatives in states conducting SCID newborn screening were invited to submit their SCID screening algorithms, test performance data, and deidentified clinical and laboratory information regarding infants screened and cases with nonnormal results. Infants born from the start of each participating program from January 2008 through the most recent evaluable date prior to July 2013 were included. Representatives from 10 states plus the Navajo Area Indian Health Service contributed data from 3,030,083 newborns screened with a TREC test. MAIN OUTCOMES AND MEASURES Infants with SCID and other diagnoses of T-cell lymphopenia were classified. Incidence and, where possible, etiologies were determined. Interventions and survival were tracked. RESULTS Screening detected 52 cases of typical SCID, leaky SCID, and Omenn syndrome, affecting 1 in 58,000 infants (95% CI, 1/46,000-1/80,000). Survival of SCID-affected infants through their diagnosis and immune reconstitution was 87% (45/52), 92% (45/49) for infants who received transplantation, enzyme replacement, and/or gene therapy. Additional interventions for SCID and non-SCID T-cell lymphopenia included immunoglobulin infusions, preventive antibiotics, and avoidance of live vaccines. Variations in definitions and follow-up practices influenced the rates of detection of non-SCID T-cell lymphopenia. CONCLUSIONS AND RELEVANCE Newborn screening in 11 programs in the United States identified SCID in 1 in 58,000 infants, with high survival. The usefulness of detection of non-SCID T-cell lymphopenias by the same screening remains to be determined.

Oral Immunotherapy for Peanut Allergy: Multipractice Experience With Epinephrine-treated Reactions

BACKGROUND Peanut allergy creates the risk of life-threatening anaphylaxis that can disrupt psychosocial development and family life. The avoidance management strategy often fails to prevent anaphylaxis and may contribute to social dysfunction. Peanut oral immunotherapy may address these problems, but there are safety concerns regarding implementation in clinical practice. OBJECTIVE The purpose of this report is to communicate observations about the frequency of epinephrine-treated reactions during peanut oral immunotherapy in 5 different allergy/immunology practices. METHODS Retrospective chart review of peanut oral immunotherapy performed in 5 clinical allergy practices. RESULTS A total of 352 treated patients received 240,351 doses of peanut, peanut butter, or peanut flour, and experienced 95 reactions that were treated with epinephrine. Only 3 patients received 2 doses of epinephrine, and no patient required more intensive treatment. A total of 298 patients achieved the target maintenance dose for a success rate of 85%. CONCLUSION Peanut oral immunotherapy carries a risk of systemic reactions. In the context of oral immunotherapy, those reactions were recognized and treated promptly. Peanut oral immunotherapy may be a suitable therapy for patients managed by qualified allergists/immunologists.

Tolerance to Allergenic Foods Following Food Oral Immunotherapy (FOIT)

Rationale: FOIT treatment desensitizes most food allergic individuals, but the achievement of immunologic tolerance is uncertain. We report on 21 selected patients who underwent food challenges (FC) after FOIT was withheld for at least 30 days. Methods: Retrospective record review of FOIT patients approved by the North Texas IRB. After 453-1752 days of maintenance dosing selected patients stopped ingesting the allergenic food for 1 month and then were subjected to an open, graded FC. Results: 19/21 patients passed the FC (FCP) (5/5 egg, 6/7 milk, 7/8 peanut, 1/1 cashew). 15/19 FCP and 0/2 who failed the FC (FCF) had a history of anaphylaxis to the allergenic food prior to starting FOIT. Median IgE (kU/L) before beginning FOIT for FCP were egg 5.04 (0.37-49.97), milk 5.23 (1.52-10.93), peanut 10.39 (2.44-61.33), cashew 4.53; and for FCF: milk 54.24, peanut >100. Median IgE values before FC for FCP were egg 0.35 (0.1-15.9), milk 0.17 (0.08-0.3), peanut 0.96 (0.08-7.38), and cashew 1.14; and milk 1.16, peanut 11.5 for FCF. There were 0.26 epinephrine treated reactions per patient (ETRpp) during FOIT escalation and 0.05 ETRpp during maintenance for FCP. There were 2 ETRs in escalation and none in maintenance for the 2 FCF patients. Conclusions: 90% of selected FOIT patients achieved tolerance to their allergenic food. These data suggest that patients with high pre-OIT IgE values, high pre-FC values, and more ETRs during escalation are less likely to pass FC. More FOIT patients will need to undergo FC before meaningful conclusions may be drawn concerning tolerance. Abstract