Anne B. Yates

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.

Management of Patients with a History of Allergy to Beta-Lactam Antibiotics

Patients with a history of penicillin allergy pose a treatment dilemma. Unnecessary avoidance of this relatively nontoxic class of drugs exposes the patient to potentially more toxic drugs, increases health care costs, and contributes to the development of antibiotic resistance. Yet for those who truly have allergy or other serious adverse reactions to beta-lactams, the use of alternate drugs is a must. This article reviews current management strategies to determine which patients are good candidates for reintroduction of beta-lactams and which patients should continue avoidance.

Approach to Patients With Suspected Hypersensitivity to Local Anesthetics

Adverse reactions to local anesthetics are relatively common, but true IgE-mediated hypersensitivity is extremely rare. Fortunately, the vast majority of adverse reactions occur via nonimmunologic means, but considerable confusion still exists among providers. We conducted a review of the literature to determine if earlier estimates of IgE-mediated allergy are consistent with current reports and whether current management strategies are consistent with these findings. We identified several confounding variables involved in the evaluation, including the roles of preservatives/additives, epinephrine, latex, and inadequate testing procedures. These problems may cause significant diagnostic challenges for clinicians. It is in fact much more likely that there is an alternate diagnosis, and in many cases clinicians can begin the evaluation in the office. When local anesthetic allergy is still suspected, the patient should be referred to an allergist for testing to determine if the suspected culprit drug can be safely used, or, if necessary, identify a suitable alternative.

Allergic reactions to Triatoma bites

BACKGROUND Triatoma bugs are best known in the medical community as vectors of trypanosomiasis (Chagas disease). However, bites of Triatoma bugs are a cause of local cutaneous reactions and anaphylaxis, mainly in the western and southwestern United States. The reactions typically occur at night during sleep, and the bite may not be recognized. There is continuing public interest in medical complications of bites of these bugs, although the scope of the problem remains undefined. OBJECTIVE To review the relevant medical literature, identify present knowledge, and determine future research goals for allergy to Triatoma. DATA SOURCES Computerized databases were used to search the medical literature for articles in the English language on Triatoma bites, allergy and entomology, and Chagas disease. STUDY SELECTION Almost all identified articles on Triatoma allergy were used. Only selected articles on Triatoma bites and entomology were pertinent to the objectives. Articles on Chagas disease were limited to cases in the United States. RESULTS Bites of Triatoma bugs have been known to cause anaphylaxis for more than a century. These insects inhabit a large area of the United States, but to date most reports of allergic reactions to their bites have originated in the West and Southwest. The reactions typically occur at night during sleep following a bite on uncovered skin and may be unrecognized. Procalin has been identified as the major salivary allergen of Triatoma protracta and was recently cloned and expressed through recombinant technique. Allergenic reactivity has been demonstrated to salivary gland extracts of 2 species. The extracts of these 2 species have not shown immunologic cross-reactivity. Immunotherapy using a salivary gland extract appeared to be beneficial in a small number of patients; however, no commercial testing or treatment allergen is available. CONCLUSIONS Triatoma bites appear to be an important cause of anaphylaxis, especially in the western and southwestern United States. Because exposure to these insects often occurs during sleep, the incidence of allergic reactions to them is unclear. An epidemiologic study should be performed to determine the incidence, prevalence, and range of allergic responses to the bites of these insects. The lack of commercial antigen limits diagnostic and treatment capabilities. The development of an allergen under the Orphan Drug Act should be encouraged.

DELAYED HYPERSENSITIVITY SKIN TESTING

Many substances, both natural and manufactured, cause inflammation when introduced into living tissue. Some compounds cause a local inflammatory reaction in all exposed individuals and often are called toxic or irritant reactions. Skin testing with other compounds causes an inflammatory response in a limited number of subjects. Those reactions that occur on the basis of specific immune responses are termed hypersensitivity reactions, and the responding individuals are said to be hypersensitive to that antigen. Intradermal skin testing may induce four or more types of cutaneous hypersensitivity reactions in humans 35 : (1) an immediate wheal and flare reaction related to the presence of antigen-specific immunoglobulin E (IgE) in the skin; (2) an IgE-mediated late-phase reaction that follows the wheal and flare, begins several hours after injection, and peaks at 12 to 24 hours; (3) a local vasculitic reaction peaking at 12 to 24 hours that results from the interaction of complement-fixing antibody and antigen at the injection site (Arthus reaction); and (4) a lymphocyte and macrophage-dependent delayed hypersensitivity reaction (DHR). Erythema and induration at the injection site peaks at 48 hours after the injection. The latter reaction is the subject of this article.

Cardiodepressant and neurologic actions of Solenopsis invicta (imported fire ant) venom alkaloids

BACKGROUND We hypothesized that the alkaloid compounds that are the majority components of fire ant (Solenopsis invicta) venom are capable of producing cardiovascular and central nervous system toxic effects in mammals. OBJECTIVE To evaluate toxic effects of synthetic S. invicta alkaloids in rodent models. METHODS Cardiovascular effects of intravenous injection of the racemic (+/-)-cis- and trans-isomers of 2-methyl-6-nundecylpiperidine (isosolenopsin A and solenopsin A, respectively) were evaluated in anesthetized, gallamine-paralyzed rats who had received artificial ventilation and in isolated, perfused rat hearts. RESULTS (+/-)-Solenopsin A dose dependently (3-30 mg/kg [10 to 104 micromol/kg]) depressed cardiovascular function. Maximal percent changes following injection of 30 mg/kg were -42.96% +/- 5.8% for blood pressure, -29.13% +/- 3.6% for heart rate, and -43.5% +/- 9.2% for left ventricular contractility (dP/dt). (+/-)-Isosolenopsin A (3-15 mg/kg [10 to 52 micromol/kg]) produced responses similar to those seen with the corresponding doses of solenopsin A. In conscious, spontaneously breathing rats, solenopsin A (30 mg/kg intravenously) caused seizures, respiratory arrest, and death. Infusion of working, isolated, perfused hearts with solenopsin A reduced contractile function (dP/dt) at 10 microM and caused cardiac arrest at 100 microM. CONCLUSIONS Two alkaloid components of imported fire ant venom possess robust cardiorespiratory depressant activity and elicit seizures in the rat. Such effects identify these alkaloids as toxic compounds in biological systems and may explain the cardiorespiratory failure noted in some individuals who experience massive fire ant stings.

Candida endocarditis in a child with hyperimmunoglobulinemia E syndrome

Hyperimmunoglobulin E syndrome (HIE) is a disorder characterized by extremely elevated serum levels of IgE and recurrent infections. Patients are particularly predisposed to have staphylococcal abscesses, usually involving skin, lungs, and joints; but they are also at risk for infections with other bacteria and fungi. We report the case of a 46-month-old boy with HIE who had Candida endocarditis and sepsis with a large fungal mass extending through the tricuspid valve and into the surrounding heart tissue, requiring surgical excision and replacement with a prosthetic valve. He had an indwelling central line for previous antibiotic therapy and had oral thrush for a month before presentation, which had been treated with oral nystatin. He was first seen with very dark urine, a new murmur, petechial rash, in shock, and disseminated intravascular coagulation. The white blood cell count was 38,700 with 70% segmented neutrophils, 9% banded neutrophils, 15% lymphocytes, 4% monocytes, and 2% eosinophils. Hemoglobin was 7.1, and platelet count was 14,000. Prothrombin time was 15.5, and partial thromboplastin time was 31; fibrinogen level was 110 mg/ml, and fibrin degradation products were greater than 40 mg/ml. Serum IgE was 38,664 and 44,510 on repeat measurement. He has had recurrent staphylococcal pneumonias with pneumatoceles, twice requiring segmental lung resection. Blood and tricuspid valve cultures grew Candida albicans. He was treated with amphotericin and flucytosine, and later switched to fluconazole, with good response to therapy. A literature search revealed no other reported case of Candida endocarditis in patients with HIE. Fungai endocarditis is a rare complication, which may occur in patients with HIE and indwelling central catheters.

Allergic and nonallergic drug reactions.

Allergic drug reactions may be difficult to distinguish from nonallergic reactions. In this article, we review a pragmatic approach to the management of adverse drug reactions on the basis of knowledge of the classification and patterns of these reactions. Algorithms for management of patients with a previous adverse drug reaction who require treatment for the same indication, and the approach to a patient who experiences a drug reaction while on multiple drugs, are presented.

ALLERGY TO INSECT STINGS : A NEED FOR IMPROVED PREVENTIVE MANAGEMENT

Allergy to insect venom is a major health problem for a significant number of people. Immunotherapy can reduce the risk of subsequent reaction from about 60% to less than 5%. Standard preventive care should include (1) advice concerning avoidance of insects, (2) prescription of an epinephrine kit or syringe for self-administration (unless medically contraindicated), and (3) referral for evaluation. Results of several studies from various regions of the country raise concern about the preventive care and advice given these patients and suggest a need for continuing medical education to improve preventive management of allergy to insect stings.

Pathologic Findings in Hymenoptera Sting Fatalities

The medically important Hymenoptera includes bees, hornets, yellow jackets, paper wasps, and stinging ants. The stings from these insects can cause fatal reactions in some individuals. There are two main mechanisms by which fatality occurs: Type 1 hypersensitivity reactions and envenomation from massive stinging leading to systemic toxicity. Much of the information available detailing Hymenoptera sting fatalities are from published case reports. These reports show death from multi-organ failure due to systemic anaphylactic reactions as well as systemic toxic reactions. The pathologic findings will be discussed further in this chapter.