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In the United States, newborn screening (NBS) is currently recommended for identification of 31 debilitating and potentially fatal conditions. However, individual states determine which of the recommended conditions are screened. The addition of severe combined immunodeficiency (SCID) screening to the recommended NBS panel has been fully instituted by 18 states, with another 11 states piloting programs or planning to begin screening in 2014. Untreated, SCID is uniformly fatal by 2 years of age. Hematopoietic stem cell transplantation usually is curative, but the success rate depends on the age at which the procedure is performed. Short-term implementation costs may be a barrier to adding SCID to states' NBS panels. A retrospective economic analysis was performed to determine the cost-effectiveness of NBS for early (5 times higher ($350,252 vs $66,379), and operating room-anesthesia charges were approximately 4 times higher ($57,105 vs $15,885). The cost-effectiveness of early treatment for SCID provides a strong economic rationale for the addition of SCID screening to NBS programs of other states.

We present a 3-year-old Pakistani girl with autosomal recessive chronic granulomatous disease (CGD) due to a novel mutation of the CYBA gene, which affects the p22 phox protein, a history of CGD-related colitis, failure to thrive, and recurrent hypoalbuminemia presenting with a chronic acrodermatitis enteropathica like rash secondary to malnutrition and zinc deficiency. Although inflammatory bowel disease has been well described in CGD, zinc deficiency has not been previously reported. Screening for this micronutrient deficiency should be a consideration in the management of patients with CGD and other primary immunodeficiency diseases associated with colitis, given its critical role in immune function. CGD affects phagocytes, which leads to recurrent and/or persistent intracellular bacterial and fungal infections and granuloma formation. CGD-related colitis with subsequent malabsorption has been well documented. There are 4

A one-day intensive educational course on allergy and immunology theory and diagnostic procedure significantly increased the competency of allergy and immunology fellows-in-training.

The treatment of essential fatty acid deficiency (EFAD) in a 17-year-old male following allogeneic bone marrow transplantation is described. His transplant was complicated by gastrointestinal bleeding that precluded the use of enteral feedings. Due to a severe soy allergy, he could not tolerate any intravenous fat emulsions marketed in the US. After months of receiving fat-free parenteral nutrition and intermittent use of enteral feeds, he developed signs and symptoms consistent with EFAD, including a rash and an elevated plasma triene:tetraene ratio of 0.231 (0.013-0.05). After receiving FDA approval, a parenteral fish oil emulsion was administered to provide fat calories and sufficient alpha-linolenic and linoleic acid to correct his EFAD. Therapy was initiated at 0.2 g/kg/day and advanced to 0.67 g/kg/day, providing approximately 45 mg/kg/day of linoleic acid. After 10 days of therapy, his rash disappeared and his triene:tetraene ratio improved to 0.07. By day 17 the ratio normalized to 0.047. This suggests that using a fish oil emulsion with minimal linoleic acid may be safely used as the sole source of fat calories and may be an option to prevent or treat EFAD in subjects allergic to soy that require a parenteral source of fat.

Background The U.S.A. Accreditation Council for Graduate Medical Education (ACGME) requires that graduate medical education programs in A/I prepare specialists to provide expert medical care for patients with A/I disorders. The A/I intensive education course (boot camp) program was implemented at the University of South Florida (USF) to facilitate fellows' education of common clinical and diagnostic procedures conducted in the specialty. Educational methods included PowerPoint presentations and demonstration of clinical and diagnostic procedures by faculty and senior fellows and hands-on participation by the fellows-in-training. The topics covered included: anaphylaxis, spirometry, exhaled nitric oxide determination, routine and special skin testing, prescribing and administering immunotherapy, asthma education and inhaler technique, management of atopic dermatitis, food challenge, patch testing, antibiotic desensitization and challenge, principles of treatment with intravenous and subcutaneous gammaglobulin, and special immunology testing. Methods Six A/I fellows (four 1st and two 2nd year) participated in the boot camp on July 22, 2011. All completed a 49-item multiple-choice pre-test followed by the boot camp, after which same questions were administered as post-test. Scores were compared by paired t test. Results Six participants completed the study. The average number of correct answers increased from 26.3/49 to 39.0/49 with pre- and post-test mean scores of 53.8% and 79.6%, respectively (P = 0.009). There was a significant difference between 1st and 2nd year fellows in test results when comparing pre- and post-test scores (P ≤ 0.05). Conclusions An educational boot camp approach integrating theory and practice about A/I clinical and diagnostic procedures significantly increased the competency of A/I fellows at the beginning of their first and second year of training.

Background Mutations in signal transducer and activator of transcription (STAT) 1 cause a broad spectrum of disease, ranging from severe viral and bacterial infections (amorphic alleles) to mild disseminated mycobacterial disease (hypomorphic alleles) to chronic mucocutaneous candidiasis (CMC; hypermorphic alleles). The hypermorphic mutations are also associated with arterial aneurysms, autoimmunity, and squamous cell cancers. Objective We sought to investigate the role of STAT1 gain-of-function mutations in phenotypes other than CMC. Methods We initially screened patients with CMC and autoimmunity for STAT1 mutations. We functionally characterized mutations in vitro and studied immune profiles and regulatory T (Treg) cells. After our initial case identifications, we explored 2 large cohorts of patients with wild-type forkhead box protein 3 and an immune dysregulation–polyendocrinopathy–enteropathy–X-linked (IPEX)–like phenotype for STAT1 mutations. Results We identified 5 children with polyendocrinopathy, enteropathy, and dermatitis reminiscent of IPEX syndrome; all but 1 had a variety of mucosal and disseminated fungal infections. All patients lacked forkhead box protein 3 mutations but had uniallelic STAT1 mutations (c.629 G>T, p.R210I; c.1073 T>G, p.L358W, c.796G>A; p.V266I; c.1154C>T, T385M [2 patients]). STAT1 phosphorylation in response to IFN-γ, IL-6, and IL-21 was increased and prolonged. CD4 + IL-17–producing T-cell numbers were diminished. All patients had normal Treg cell percentages in the CD4 + T-cell compartment, and their function was intact in the 2 patients tested. Patients with cells available for study had normal levels of IL-2–induced STAT5 phosphorylation. Conclusions Gain-of-function mutations in STAT1 can cause an IPEX-like phenotype with normal frequency and function of Treg cells.

Rationale THI is a heterogeneous disorder with several associated comorbidities. The clinical and immunologic features of a cohort of children with THI were examined. Methods 24 patients diagnosed with hypogammaglobulinemia defined by any Ig isotype level Results The mean at diagnosis of hypogammaglobulinemia was 12 mos (male:female=1.2). 18 patients were followed to resolution with 12/18 normalizing by 24 mos and the remainder by 59 mos. The mean age at resolution was 27 mos. The average z-score for IgG level at presentation was −2.4 with a mean level of 254 mg/dl. 13/24 patients had IgA levels 95% for age and the mean percentage and absolute counts of CD19+ B cells was greater than that expected for age-matched controls (p=0.01). All but 2 patients had evidence of tetanus-specific antibody production at their initial evaluation. 20/24 patients carried at least one atopic diagnosis, and 5/24 had some form of developmental delay. 19/14 patients received prophylactic antibiotics and 5 patients received gammaglobulin therapy due to clinically inadequate response to antibiotics. Conclusions THI is a heterogeneous disorder often presenting and resolving well beyond infancy. A notable number of these patients have significant comorbidities. Observed elevation in B-cells may be suggestive of particular immunologic mechanisms resulting in hypogammaglobulinemia.

Rationale Adverse reactions to methotrexate are increasingly common and represent potential barriers to treatment options for oncologic diseases. There are no reports in the literature addressing intrathecal administration of methotrexate following adverse reactions to intravenous methotrexate. Methods A 6 year old, male patient developed hives and pruritus after intravenous infusion of 2 gm of methotrexate for Acute Lymphoblastic Leukemia as well as concomitant morphine infusion. Skin testing to methotrexate (skin prick 1 mg/ml, 10 mg/ml, intradermal 0.1 mg/ml, 1 mg/ml, 10 mg/ml) was negative. The patient required treatment with intrathecal methotrexate. Since the safety of intrathecal administration of methotrexate following desensitization is unknown, further assessment of the patient's sensitivity to methotrexate was determined by graded challenge (10% dose followed by 90% dose) in the Intensive Care Unit. Following two successful intravenous infusions, methotrexate was infused intrathecally, first with steroid pretreatment, then without steroid pretreatment. Results The patient tolerated the graded challenge to methotrexate and subsequent full dose infusions of methotrexate without complications, indicating no hypersensitivity to methotrexate. Methotrexate was subsequently administered intrathecally with steroid pretreatment followed by subsequent intrathecal infusions without steroid pretreatment. No adverse events occurred. Conclusions A combination of history, skin testing, and graded challenge may be utilized to elucidate the nature of adverse reactions to methotrexate. This information may help determinine the safety of future treatment options with methotrexate, including intrathecal administration.

Yoos HL, Kitzman H, McMullen A, et al. Ann Allergy Asthma Immunol. 2002;88:283–291 The purpose of this study was to evaluate the effects of 3 different regimens of symptom monitoring on asthma morbidity outcomes. One hundred sixty-eight children aged 6 to 19 years who had >3 asthma-related health care visits in the previous 12 months. The children were recruited from 11 different primary care sites and of diverse racial, geographic, and socioeconomic backgrounds. Patients were randomized into 1 of 3 treatment groups. Treatment groups were: group 1, …