In-utero exposure to immunosuppressive medications resulting in abnormal newborn screening for severe combined immunodeficiency: a case series on natural history and management.

Exposure to immunosuppressive medication in utero is an important cause of secondary T cell lymphopenia in infancy, which can be detected via T cell receptor excision circle (TREC) quantification on severe combined immunodeficiency (SCID) newborn screening (NBS). At present, there is a paucity of literature surrounding management of these infants. A protocol including recommendations for vaccinations and follow-up is needed to augment care. Patients referred to immunology for abnormal TREC results on NBS were identified as having in utero exposure to immunosuppressive medications and were followed until lymphopenia improved. The natural history of these patients' lymphopenia was used to develop general management guidelines. Four infants with low TRECs secondary to in utero immunosuppressive exposure were evaluated. Medication exposures included azathioprine, infliximab, hydroxychloroquine, and fingolimod. All infants were born full term. TRECs ranged from 101-206 (normal value in IL ≥ 250 at time of testing, B-actin control). T cell lymphopenia (CD3 < 1500) was present in 50% of cases. Undetectably low effector CD4 naïve T cell population was present in 100% of cases. Mitogen proliferation was uniformly normal. Severity of TREC abnormality did not correlate with presence of T cell lymphopenia. Immune abnormalities normalized in 75% patients by age 4 months. All age-appropriate vaccinations, including live vaccines, were administered to all patients by age 4 months. It is critical to assess for in utero immunosuppressive exposure in infants with abnormal TREC results on NBS. In the infants evaluated, secondary T cell lymphopenia associated with maternal immunosuppressive use resolved or significantly improved by age 4 months. Once abnormal TREC count is deemed to be secondary to in utero immunosuppression and there are no other contraindications, infants may safely receive live vaccination, are able to drink breast milk, and do not require prophylactic anti-microbials.

Stinging insect allergy and venom immunotherapy.

The Hymenoptera order is divided into three families: Apidae, Vespidae, and Formicidae. Apidae include the honeybee, bumblebee, and sweat bee, which are all docile and tend to sting mostly on provocation. The Africanized killer bee, a product of interbreeding between the domestic and African honeybee, is very aggressive and is mostly found in Mexico, Central America, Arizona, and California. The yellow jacket, yellow hornet, white (bald) faced hornet, and paper wasp all belong to the Vespidae family. The Formicidae family includes the harvester ant and the fire ant. When a "bee" sting results in a large local reaction, defined as >10 cm induration and lasting > 24 hours, the likelihood of anaphylaxis from a future sting is approximately 5%. For comparison, when there is a history of anaphylaxis from a previous Hymenoptera sting and the patient has positive skin test results to venom, at least 60% of adults and 20-32% of children will develop anaphylaxis with a future sting. Both patient groups should be instructed about avoidance measures and about carrying and knowing when to self-inject epinephrine, but immunotherapy with Hymenoptera venom is indicated for those patients with a history of anaphylaxis from the index sting and not for patients who have experienced a large local reaction. Immunotherapy is highly effective in that, by 4 years of injections, the incidence of subsequent sting-induced reactions is 3%. This incidence may increase modestly after discontinuation of injections but has not been reported to be > 10% in follow up.

Food allergy: Diagnosis and treatment.

Immunoglobulin E-mediated food reactions usually develop within minutes of food ingestion. Although most reactions are not life-threatening, fatalities do occur. Risk factors for fatal food-induced anaphylaxis include the presence of asthma (a risk factor for anaphylaxis in general), failure to use epinephrine autoinjectors promptly, a history of severe reactions, known food allergy, denial of symptoms, and adolescent and young adult age. The most commonly implicated foods are cow's milk, egg, peanut, soy, tree nuts, fish, shellfish, and wheat. Peanut, tree nuts, and seafood are the most common food allergens in adults, whereas cow's milk, peanut, egg, soy, and wheat are more common in children. The major food allergens are glycoproteins, which are generally water soluble and stable to the effects of heat, proteases, and acids. Recent studies showed that natural tolerance can be acquired at a later age than previously thought, even during adolescence. Allergies to peanut, tree nuts, and seafood are frequently life-long. Patients and their caregivers should be taught when and how to administer injectable epinephrine. In terms of primary prevention, there is evidence that early introduction, followed by ongoing regular consumption of peanut has a protective effect on the development of peanut allergy.

In vitro testing for allergic and immunologic diseases.

In vitro tests are used to assist in the diagnosis of both allergic and immunologic diseases. Unfortunately, there is no single test that is pathognomonic for most allergic diseases. The most commonly ordered in vitro test by allergists is allergen specific IgE (sIgE), which is used to help diagnose IgE mediated hypersensitivity to foods, aeroallergens and venoms. Multiple assays exist, although none of these assays have been adopted as the industry standard. Epicutaneous skin test is also a fundamental test in the diagnosis of IgE mediated hypersensitivity. In addition, total IgE, basophil activation test (BAT), and serum tryptase may also be useful in elucidating allergic diseases. Immunologists rely on laboratory testing to diagnose primary immunodeficiency diseases. These tests include serum quantitative immunoglobulins, lymphocyte immunophenotyping by flow cytometry and immune cell functional testing. Furthermore, genetic testing is invaluable in the diagnosis of many primary Immunodeficiencies.