Systemic allergic reactions (SARs), including anaphylaxis, are caused by insect venom, foods, medications, allergen immunotherapy, radiocontrast media, and other agents. This chapter defines anaphylaxis along a spectrum of SARs and examines the historical context for terminology used to describe SARs. Allergen immunotherapy causes anaphylaxis in some subjects, a topic of interest to clinicians who prescribe such therapies. Mechanisms of anaphylaxis are outlined including mediators, effector cells, and effects on the cardiovascular system. Manifestations and differential diagnosis of anaphylaxis are discussed. Early recognition and treatment of SARs is emphasized, to prevent progression to a level of severity termed anaphylaxis. Variations on the theme including exercise-induced anaphylaxis, cholinergic urticaria, idiopathic anaphylaxis, and anaphylaxis attributed to endogenous progesterone are explored. Prevention and management of anaphylaxis are addressed.

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.

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.

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.

First recognized in the early 20th century, growth hormone deficiency (GHD) has been treated with growth hormone (GH) replacement since 1958. Initial replacement was with cadarevic GH. In 1985, GH therapy with recombinant human GH (rhGH) replaced cadaveric GH, which increased not only safety, but also efficacy (because of increased supply). Improvements in GH dosing and frequency of injection has resulted in adult heights now usually in the normal range. GHD is diagnosed from the clinical picture, along with measurement of serum insulin-like growth factor 1 (IGF-I), IGF binding protein-3, and GH response to provocative stimuli. Several long-acting GH preparations are now under development. There has been a great deal of data from databases that confirms safety of GH administration while patients are taking GH. A recent report of increased mortality risk in adults who were treated with GH as children has not been confirmed by a second similar retrospective evaluation. Additional long-term follow-up studies of adults who took GH as children are needed.

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.

Anaphylaxis is an acute, potentially life-threatening multisystem syndrome resulting from the sudden release of mast cell- and basophil-derived mediators into the systemic circulation. Foods, medications, and insect stings cause most anaphylaxis for which a cause can be identified, but virtually any agent capable of directly or indirectly activating mast cells or basophils can cause it. This syndrome can consist of some or all the following signs and symptoms: diffuse pruritus, erythema, urticaria, and/or angioedema; bronchospasm; laryngeal edema; hypotension; and/or cardiac arrhythmias. Some of the other symptoms that can occur include nausea, vomiting, diarrhea, lightheadedness, headache, feeling of impending doom, and unconsciousness. Regardless of the presenting signs or symptoms, which usually present within 5-30 min following the administration of the offending agent, this reaction can progress to respiratory compromise and cardiovascular collapse resulting in human fatalities. Usually, the more rapid the onset of clinical manifestations, the more likely the anaphylaxis will be life threatening. Immediate and appropriate therapy, especially with epinephrine, is mandatory to reverse the reactions. While most reactions are uniphasic, some can be biphasic or protracted. This chapter discusses the immunopathologic mechanisms and effects 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.

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 β-cell function, although a larger clinical trial would be required to confirm this.

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.

These parameters were developed by the Joint Task Force on Practice Parameters, representing the American Academy of Allergy, Asthma and Immunology; the American College of Allergy, Asthma and Immunology; and the Joint Council of Allergy, Asthma and Immunology.The American Academy of Allergy, Asthma and Immunology (AAAAI) and the American College of Allergy, Asthma and Immunology (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.

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.

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.

Growth hormone (GH) acts directly at the growth plate and through the production of insulin-like growth factor (IGF)-I. At least 50% of the hormone circulates bound to GH binding protein, and its secretion is controlled by growth hormone-releasing hormone and somatostatin. Once GH binds to two GH receptors, the janus activated kinase/signal transducers and activators of transcription (JAK/STAT) protein pathway is activated, resulting in the production of IGF-I. Serum IGF-I is produced predominantly in the liver and circulates in a 140 kDa complex, along with its binding protein, IGF binding protein 3, and acid-labile protein. Recombinant human (rh) IGF-I (mecasermin) is approved by the US FDA and the European Medicines Agency for the treatment of patients with severe primary IGF deficiency or for patients with GH1 gene deletion who have developed neutralizing antibodies to GH. It has been shown to increase growth velocity in children with either condition. In the past, there have been adverse events, particularly hypoglycemia, reported with the administration of mecasermin. However, a recent report of long-term therapy with mescasermin in children with severe IGF-I deficiency has concluded that although adverse events are common, they are rarely severe enough to interrupt or modify treatment. The serum half-life of mecasermin is shorter in patients with GH insensitivity syndrome and low serum levels of its binding protein, the insulin-like growth factor binding protein (IGFBP)-3 and acid-labile subunit, compared with the serum half-life in normal volunteers or in patients with an IGF1 gene deletion who have normal levels of IGFBP-3. Mecasermin rinfabate, a complex of rhIGF-I and rhIGFBP-3, appears to prolong the serum half-life and might counteract acute adverse events, particularly hypoglycemia, associated with the administration of mescasermin. Mecasermin rinfabate, however, is no longer available in the USA or Europe for treating conditions involving short stature, because of a legal requirement. Mecasermin has been shown to be effective in increasing height velocity and adult height in patients with severe GH resistance and in IGF1 gene deletion. There has been some interest in using mecasermin to treat patients with partial GH resistance or idiopathic short stature. At the present time, the data are insufficient to make this recommendation.

Anaphylaxis is a life-threatening syndrome resulting from the sudden release of mast cell- and basophil-derived mediators into the circulation. Foods and medications cause most anaphylaxis for which a cause can be identified, but virtually any agent capable of directly or indirectly activating mast cells or basophils can cause this syndrome. This review discusses the pathophysiologic mechanisms of anaphylaxis.

For adults, proven benefits of recombinant human growth hormone (GH) replacement therapy have been demonstrated in those with GH deficiency (GHD) (1 [EL 2], 2 [EL 2], 3 [EL 1], 4 [EL 2]). This has resulted in its expanding use in clinical endocrine practice. GH has also been misused in recent years in certain factions of the sporting world because of its increased availability (5 [EL 3], 6 [EL 3]) and has been touted in the media as a formula for the "fountain of youth" for the elderly population (7 [EL 4], 8 [EL 4]).

Background/Aims: Determine (1) frequency of attention-deficit hyperactivity disorder (ADHD) treatment and (2) growth responses in growth hormone (GH)-treated children who are receiving ADHD medication versus GH alone. Methods: Prepubertal children with idiopathic short stature (ISS) or GH deficiency (IGHD) enrolled in Genentech’s National Cooperative Growth Study. ADHD treatment was determined by documentation of psycho-stimulant medication use at enrollment. Results: ADHD medication use increased from 0.8% (7/850) in 1985 to 5.8% (752/12,113) in 2005. First-year GH treatment response for ADHD + IGHD versus IGHD: 8.5 ± 2.0 vs. 9.4 ± 2.6 cm/year, but when adjusted for age, sex, and enrollment body mass index, the difference is clinically insignificant (–0.4 cm/year). First-year growth was similar in all ISS: 8.1 ± 1.9 versus 8.6 ± 2.1 cm/year (ADHD + ISS vs. ISS, an adjusted –0.2-cm/year difference). Conclusion: Increasing numbers of GH-treated children are taking ADHD medications and their growth responses during the first year of GH therapy are similar to those not taking ADHD medications.

The American Association of Clinical Endocrinologists Medical Guidelines for Growth Hormone use in Growth Hormone Deficient Adults and Transition Patients – 2009 Update are systematically developed statements to assist health care providers in medical decision making for specific clinical conditions. Most of the content herein is based on literature reviews. In areas of uncertainty, professional judgment was applied. These guidelines are a working document that reflects the state of the field at the time of publication. Because rapid changes in this area are expected, periodic revisions are inevitable. We encourage medical professionals to use this information in conjunction with their best clinical judgment. The presented recommendations may not be appropriate in all situations. Any decision by practitioners to apply these guidelines must be made in light of local resources and individual circumstances.