The diagnosis and management of anaphylaxis practice parameter: 2010 update.

These parameters were developed by the Joint Task Force on Practice Parameters, representing the American Academy of Allergy, Asthma & Immunology (AAAAI); the American College of Allergy, Asthma & Immunology (ACAAI); and the Joint Council of Allergy, Asthma and Immunology. The AAAAI and the ACAAI have jointly accepted responsibility for establishing "The Diagnosis and Management of Anaphylaxis Practice Parameter: 2010 Update." This is a complete and comprehensive document at the current time. The medical environment is a changing environment, and not all recommendations will be appropriate for all patients. Because this document incorporated the efforts of many participants, no single individual, including those who served on the Joint Task Force, is authorized to provide an official AAAAI or ACAAI interpretation of these practice parameters. Any request for information about or an interpretation of these practice parameters by the AAAAI or ACAAI should be directed to the Executive Offices of the AAAAI, the ACAAI, or the Joint Council of Allergy, Asthma and Immunology. These parameters are not designed for use by pharmaceutical companies in drug promotion.

Anaphylaxis: office management and prevention.

Anaphylaxis, an acute and potentially lethal multisystem allergic reaction, is almost unavoidable in medical practice. Health care professionals must be able to recognize the signs of anaphylaxis, treat an episode promptly and appropriately, and be able to provide preventive recommendations. Epinephrine, which should be administered immediately, is the drug of choice for acute anaphylaxis.

Twenty years of recombinant human growth hormone in children: relevance to pediatric care providers.

Recombinant human growth hormone has revolutionized the management of children and adolescents with growth hormone deficiency and other growth disorders, but clinical and ethical controversies remain regarding diagnostic approach, optimal recombinant human growth hormone dose and duration, and expected outcomes. Management of pubertal and transitioning patients with growth hormone deficiency has also commanded increased attention. Recent clinical studies that demonstrate the positive health benefits of recombinant human growth hormone in children with cystic fibrosis, inflammatory bowel disease, and juvenile rheumatoid arthritis have not yet clarified issues about patient selection and appropriate long-term use. An understanding of current recombinant human growth hormone indications and controversies can facilitate patient evaluation and expedite referral for potential treatment. This review summarizes current indications for recombinant human growth hormone use, discusses clinical challenges, and provides recommendations for pediatricians caring for children who may be appropriate candidates for recombinant human growth hormone therapy.

Navigating the updated anaphylaxis parameters.

: Anaphylaxis, an acute and potentially lethal multi-system clinical syndrome resulting from the sudden, systemic degranulation of mast cells and basophils, occurs in a variety of clinical scenarios and is almost unavoidable inmedical practice. Healthcare professionalsmust be able to recognize its features, treat an episode promptly and appropriately, and be able to provide recommendations to prevent future episodes. Epinephrine, administered immediately, is the drug of choice for acute anaphylaxis. The discussion provides an overview of one set of evidence-based and consensus parameters for the diagnosis and management of anaphylaxis.

Efficacy and safety results of long-term growth hormone treatment of idiopathic short stature.

CONTEXT: Small clinical trials of GH treatment of idiopathic short stature (ISS) show variable efficacy. OBJECTIVE: The study was an analysis of a large GH registry for efficacy and safety of GH treatment of ISS. There was also a comparison with a specific clinical trial. DESIGN: Up to 7 yr of GH treatment of ISS was evaluated for efficacy and safety in the National Cooperative Growth Study (NCGS). SETTING: The NCGS study was conducted at Genentech, Inc. and included 47,226 patients. PATIENTS: The ISS group included maximum stimulated GH 10 ng/ml or more and/or a report of ISS by investigator (n = 8018; all included for safety). Cohort 1 (n = 2520) was similar to the clinical trial, cohort 2 (n = 283) included subjects younger than 5 yr of age, and cohort 3 (n = 940) was pubertal at GH start. INTERVENTION: GH, approximately 0.30 mg/kg.wk, was given. MAIN OUTCOME MEASURES: These included growth velocities and height sd (HtSDS). RESULTS: Mean first-year growth velocities in cohorts 1, 2, and 3 increased 4.6, 3.9, and 4.4 cm/yr over pretreatment, respectively. Measures included: baseline mean HtSDS, -2.9, -3.2, and -2.8; mean HtSDS at 1 yr, -2.4, -2.3, and -2.3, respectively. Mean HtSDS after 7 yr in cohorts 1 (n = 303) and 2 (n = 85) and 5 yr in cohort 3 (n = 58) were: -1.2, -1.0, and -1.5, respectively. Cohort 3 shorter treatment time was due to advanced baseline age (mean 13.8 yr) and puberty. Mean HtSDS gain in cohort 1 was comparable with the clinical trial. No new safety signals specific to the NCGS ISS population were observed. CONCLUSION: ISS patients in the GH registry demonstrate a significant increase in HtSDS with the safety profile similar to GH-deficient patients. RESULTS were similar to the clinical trial.

SomatoKine: is there a use in treating growth disorders?

Growth hormone (GH) has been used to treat GH deficiency since the late 1950s, and recombinant GH has been available since 1985. GH is also approved to treat non-GH-deficient short stature, such as that seen in Turner syndrome, chronic renal insufficiency, Prader-Willi syndrome, children who are small for gestational age, and idiopathic short stature. There has been interest in using recombinant insulin-like growth factor I (IGF-I) to treat short stature, either alone or in combination with its binding protein, IGF binding protein (IGFBP)-3 (SomatoKine). IGF-I increases growth velocity in children with IGF deficiency, either as a result of growth hormone insensitivity syndrome (GHIS) or IGF-I gene deletion. However, there have been adverse events, particularly hypoglycemia, reported with administration of unbound IGF-I. In addition, the serum half-life of unbound IGF-I is shorter when administered to patients with GHIS, who have low serum concentrations of its primary binding protein IGFBP-3 than when administered to healthy individuals or to patients with an IGF-I gene deletion (who have normal levels of IGFBP-3). SomatoKine was developed to prolong the half-life and to counteract acute adverse events (particularly hypoglycemia) associated with IGF-I administration. SomatoKine appears to have a longer half-life in patients with GHIS than unbound IGF-I and fewer adverse events (including hypoglycemia) have been reported when administered to patients with diabetes.

Growth hormone treatment of idiopathic short stature: history and demographic data from the NCGS.

Idiopathic short stature (ISS) is a term used to describe children without an identifiable cause for growth failure; these children comprise the largest group of candidates for growth hormone (GH) therapy. Over the past four decades, clinical trials have examined the efficacy and safety of GH treatment in the ISS population; for many of these trials, interpretation of results has been limited by variability in the criteria for ISS, small numbers of subjects, and a short term of study. Recent trials involving larger GH doses for longer periods suggest greater height improvements, but extrapolation to the larger ISS population is still debated. The National Cooperative Growth Study (NCGS) provides an opportunity to evaluate the treatment trends over time. In 1994, there were 20,279 patients enrolled in the NCGS, and 25% were identified as ISS. The most recent analysis was in 2003, and at that time 47,226 patients were enrolled; but only 17% were identified as ISS. This most recent analysis of patients enrolled in the NCGS provides a framework for examining the impact of this new indication for GH on clinical practice patterns.

Bisphosphonate treatment of pediatric bone disease.

The science of measuring bone mineral density has developed rapidly and, with it, an improved understanding of the efficacy and safety of various therapeutic interventions in adults. In contrast, the meaning and precision of such measurements in children are equivocal, and the concept of treatment for low bone density in the young patient is still largely undecided. In this report we review the present state of knowledge regarding the use of bisphosphonates during childhood to ameliorate the skeletal abnormalities associated with osteogenesis imperfecta, idiopathic juvenile osteoporosis, fibrous dysplasia of bone and cerebral palsy. Because of the paucity of long-term studies among children regarding the safety and efficacy of these drugs, it is difficult to formulate strong evidence-based recommendations for their use, except perhaps in children with osteogenesis imperfecta.

Pediatric allergic rhinitis.

Allergic rhinitis is a common pediatric problem with significant comorbidities and potential complications. This article is an overview of the epidemiology, pathophysiology, and current therapeutic strategies. Allergic rhinitis management in a specific child is age dependent and influenced by the severity and frequency of the symptoms and the presence of any concurrent conditions. Current strategies permit symptomatic control and improved quality of life for most patients.

Recognition, treatment, and prevention of anaphylaxis.

Anaphylaxis is an acute and potentially lethal multisystem allergic reaction that occurs in a variety of clinical scenarios and is almost unavoidable. Immunologic reactions to medications, foods, and insect stings cause most episodes, but virtually any substance capable of inducing systemic degranulation of mast cells and basophils can produce anaphylaxis. All health care professionals must be able to recognize anaphylaxis promptly, be prepared to treat it appropriately, and be able to provide preventive recommendations. Similarly, at-risk individuals must be prepared to self-treat anaphylaxis promptly if prevention fails.

Fire ant attacks on patients in nursing homes: an increasing problem.

We review the medical reports of fire ant attacks on residents of nursing homes in the context of the medical entomology of these insects, and present recommendations to prevent and manage future attacks. Two reports were recent cases, while a computer-assisted search yielded four other similar cases of attacks by foraging fire ants in the last 10 years. One patient experienced an anaphylactic reaction and 4 patients died within 1 week of the attack. Ants were usually noted in health care facilities days before the attacks. The presence of fire ants around immobile, often cognitively impaired, patients seems to be the primary risk factor for massive fire ant attacks. Health care providers and administrators in fire ant endemic areas must be aware that the presence of fire ants in hospitals and nursing homes represents a hazard. Fire ant infestation can lead to sting attacks on patients, causing respiratory tract obstruction, worsening of pre-existing medical conditions, or frank anaphylaxis. All the attacks reported here have resulted in legal action involving physicians and health care facilities.

Near adult heights after growth hormone treatment in patients with idiopathic short stature or idiopathic growth hormone deficiency.

OBJECTIVE: Determination of near adult height (NAH) after recombinant human growth hormone (rhGH) therapy in patients with idiopathic short stature (ISS, maximum stimulated growth hormone [MSGH] > 10 ng/ml) or idiopathic growth hormone deficiency (IGHD, MSGH < or = 10 ng/ml) enrolled in the National Cooperative Growth Study Substudy 2. METHODS: Female NAH was defined as height at age 18 or age 14 plus Tanner stage 4; male NAH was defined as height at age 20 or age 16 plus Tanner stage 4 or 5. RESULTS: Both groups had similar enrollment heights: IGHD -2.7 +/- 0.7 versus ISS -2.8 +/- 0.6 (mean height standard deviation score [SDS] +/- SD). After rhGH treatment, there were no significant differences in NAH between the IGHD and ISS groups (-1.4 +/- 1.0 versus -1.6 +/- 1.0). Enrollment height SDS and MSGH value were significant predictors of delta height for the children with IGHD but not for the children with ISS (R2 = 0.45 IGHD versus R2 = 0.22 ISS). CONCLUSION: We conclude that MSGH values should not be used as the primary criterion for rhGH therapy.

Use of magnetic resonance imaging in short stature: data from National Cooperative Growth Study (NCGS) Substudy 8.

The primary use of magnetic resonance imaging (MRI) in the evaluation of children with short stature (SS) is to discover lesions in the central nervous system (CNS), particularly tumors that may require intervention. MRI has a secondary role in identifying structural abnormalities responsible for growth hormone deficiency (GHD). We examined data from the National Cooperative Growth Study (NCGS) Substudy 8 to determine how American physicians are using MRI in evaluating children with SS. Of the 21,738 short children enrolled in NCGS, 5% underwent MRI during their follow-up. Children who had GH stimulation testing were more likely to have had an MRI than those in whom no GH stimulation test was performed (19% vs 2%, p <0.0001). Moreover, children diagnosed with severe GHD (maximum GH <5 ng/ml) were more likely to have an abnormal finding on MRI. Of these patients, 27% demonstrated an abnormality as compared to 12% and 12.5% in patients with partial GHD and normal GH stimulation test results (>10 ng/ml), respectively. Abnormalities unrelated to the hypothalamus or pituitary represented 30% of these findings, while disorders in pituitary anatomy, including pituitary hypoplasia, pituitary stalk interruption, and ectopic posterior pituitary, represented an additional 30% of abnormal MRI examinations. CNS tumors comprised 23% of abnormal findings in these patients. We conclude that MRI provides significant value in the evaluation of children with SS, by identifying CNS tumors associated with growth failure as well as anatomical abnormalities of the pituitary. These findings are useful in confirming the diagnosis of GHD in children and identifying potential candidates for continued GH replacement in adulthood.

Pharmacotherapy in refractory anaphylaxis: when intramuscular epinephrine fails.

PURPOSE OF REVIEW: This review aims to provide an evidence-based overview of several pharmacotherapeutic options available for refractory anaphylaxis when intramuscular epinephrine, the drug of choice, fails to provide resolution of signs and symptoms. RECENT FINDINGS: The evidence base for the therapy of anaphylaxis is comparatively weak and is largely based on consensus expert recommendations and case reports. There is an increasing recognition that this is problematic. The level of evidence for epinephrine use in anaphylaxis is higher than for other agents. Recent systematic reviews have confirmed the lack of high-grade evidence to support use of antihistamines and corticosteroids in anaphylaxis, both of which statistically continue to be used more frequently than epinephrine. Newer pharmacotherapeutic agents have been proffered, but none has been evaluated with scientific rigor. SUMMARY: Some anaphylactic reactions are so severe that treatment is unsuccessful despite rapid recognition and treatment. Improving the evidence base for the various treatment modalities may further help minimize fatalities once anaphylaxis is recognized. Consensus expert recommendations and case reports suggest a number of pharmacotherapeutic agents that are worthy of high-quality scrutiny through randomized controlled studies in which both treatment and placebo arms receive intramuscular epinephrine injections.

Growth and growth hormone treatment in children with chronic diseases.

Growth hormone has been available for treatment of various conditions for over 50 years. There have been a number of chronic disease states in which it has been used, such as chronic kidney disease, which became a US Food and Drug Administration (FDA)-approved indication in 1993. For other chronic disease states there have been clinical studies supporting its use, but they have not yet been approved as a indications by the FDA. Examples of such diseases are cystic fibrosis, chronic arthritis, short bowel syndrome, burn trauma, and hypophosphatemic rickets.

Pathophysiology of anaphylaxis.

PURPOSE OF REVIEW: This review aims to provide an overview of the evolving understanding of the pathophysiology of anaphylaxis. RECENT FINDINGS: Immunopathologic mechanisms of anaphylaxis have traditionally focused on the IgE-dependent and IgE-independent release of mediators from mast cells and basophils. There are accumulating data supporting the significance of alternative pathways of anaphylaxis. Increasing attention has also focused on the internal compensatory mechanisms activated in response to anaphylaxis. SUMMARY: Recent advances will enhance understanding of the pathophysiology of anaphylaxis and might have future implications for diagnosis and management.

Emerging options in growth hormone therapy: an update.

Growth hormone (GH) was first used to treat a patient in 1958. For the next 25 years it was available only from cadaver sources, which was of concern because of safety considerations and short supply. In 1985, GH produced by recombinant DNA techniques became available, expanding its possible uses. Since that time there have been three indications approved by the US Food and Drug Administration (FDA) for GH-deficiency states and nine indications approved for non-GH-deficiency states. In 2003 the FDA approved GH for use in idiopathic short stature (ISS), which may indirectly cover other diagnoses that have short stature as a feature. However, coverage for GH therapy is usually more reliably obtainable for a specific indication, rather than the ISS indication. Possible future uses for GH therapy could include the treatment of syndromes such as Russell-Silver syndrome or chondrodystrophy. Other non-short-stature indications could include wound healing and burns. Other uses that have been poorly studied include aging and physical performance, in spite of the interest already shown by elite athletes in using GH. The safety profile of GH developed over the past 25 years has shown it to be a very safe hormone with few adverse events associated with it. The challenge for the future is to follow these patients into adulthood to determine whether GH therapy poses any long-term risks.

Insulin pump therapy started at the time of diagnosis: effects on glycemic control and pancreatic ß-cell function in type 1 diabetes.

BACKGROUND: In the interest of preserving residual insulin secretory capacity present at the time of diagnosis with type 1 diabetes (T1D), we compared the efficacy of starting insulin pump therapy at diagnosis with standard multiple daily insulin injections (MDIs). METHODS: We conducted a prospective, randomized, pilot trial comparing MDI therapy with continuous subcutaneous insulin therapy (pump therapy) in 24 patients, 8-18 years old, with newly diagnosed T1D. Subjects were evaluated at enrollment and 1, 3, 6, 9, and 12 months after initial diagnosis of T1D. Preservation of insulin secretion, measured by mixed-meal-stimulated C-peptide secretion, was compared after 6 and 12 months of treatment. Between-group differences in glycosylated hemoglobin (HbA1c), continuous glucose sensor data, insulin utilization, anthropometric measures, and patient satisfaction with therapy were also compared at multiple time points. RESULTS: Initiation of pump therapy within 1 month of diagnosis resulted in consistently higher mixed-meal tolerance test-stimulated C-peptide values at all time points, although these differences were not statistically significant. Nonetheless, improved glycemic control was observed in insulin pump-treated subjects (more time spent with normoglycemia, better mean HbA1c), and pump-treated subjects reported comparatively greater satisfaction with route of treatment administration. CONCLUSIONS: Initiation of insulin pump therapy at diagnosis improved glycemic control, was well tolerated, and contributed to improved patient satisfaction with treatment. This study also suggests that earlier use of pump therapy might help to preserve residual ß-cell function, although a larger clinical trial would be required to confirm this.

Managing idiopathic short stature: role of somatropin (rDNA origin) for injection.

Idiopathic short stature (ISS) is a term that describes short stature in children who do not have growth hormone (GH) deficiency and in whom the etiology of the short stature is not identified. Between 1985 and 2000, more than 40 studies were published regarding GH therapy for ISS. Only 12 of these had data to adult height, of which only 4 were controlled studies. A subsequent placebo-controlled study that followed subjects to adult height indicated that there was a gain of 3.7-7.5 cm in height with GH treatment. In 2003, the US Federal Drug Administration (FDA) approved GH for treatment of short stature. Even before FDA approval, patients with ISS made up about 20% of patients in GH databases, which is largely unchanged since FDA approval. There remains some controversy as to whether GH should be used to treat ISS. This controversy centers on the fact that there has been no definitive demonstration that short stature results in a disadvantage or problems with psychological adjustment, and thus, no demonstration that GH therapy results in improvement in quality of life.

The evaluation and followup of children referred to pediatric endocrinologists for short stature.

Objective. To characterize the pediatric endocrinologists' evaluation and followup of short-statured patients. Study Design. Observational study of 21,548 short-statured children (April 1996 to December 1999). Baseline demographics, laboratory testing, height standard deviation score (SDS), target height, and height relative to target height were analyzed at initial and return visits with the specialist. Patients were scheduled for at least one return visit and no recombinant human growth hormone therapy was administered. Results. Mean patient age was 8.6 years with a mean height SDS of -2.1. Patients were predominantly male (69%), prepubertal (73%), and white (76%). Few screening tests were obtained during initial evaluation. Nearly 40% of children did not return for their second scheduled visit. The follow-up rate was unrelated to demographics or degree of short stature. Conclusions. Low return rates limit specialists' ability to monitor growth or obtain laboratory testing over time. Further studies are needed to determine which tests should be obtained at the initial clinic visit as well as the basis for the low return rate in this group of children.