Immunology and Allergy Clinics of North America

No abstract text is available yet for this article.

No abstract text is available yet for this article.

Mast cell granules are packed with proteases, which are released with other mediators by degranulating stimuli. Several of these proteases are targets of potentially therapeutic inhibitors based on hypothesized contributions to diseases, notably asthma and ulcerative colitis for β-tryptases, heart and kidney scarring for chymases, and airway infection for dipeptidyl peptidase-I. Small-molecule and antibody-based β-tryptase inhibitors showing preclinical promise were tested in early-phase human trials with some evidence of benefit...

This article reviews the effects of gender on anaphylaxis in general and focuses on mastocytosis-specific issues. Incidence of anaphylaxis is increased in female compared with male patients during the pubertal years through the fifth decade of life, in which these disparities decrease. Estrogen is thought to increase the severity of anaphylaxis through increased endothelial nitric oxide synthase release. Despite this, all-cause fatal anaphylaxis does not appear to show a gender predilection. Systemic mastocytosis incidence is higher in women; however, mortality is increased in men owing to increased molecular and cytogenetic abnormalities...

Mastocytosis is a heterogeneous disease with a wide spectrum of signs, symptoms, and concomitant disorders, such as skin lesions, anaphylaxis, osteoporosis, gastrointestinal involvement, and organomegaly. Disease specificity for frequently reported symptoms, such as fatigue, headache, anxiety, and brain fog, is poorly defined and need to be addressed in further studies. Patients with CM and non-AdvSM are mostly affected by mast cell mediator-related symptoms, whereas in AdvSM symptoms also result from organ damage, which makes their assessment challenging...

Systemic mastocytosis is associated with KIT D816V mutation in more than 90% of cases. Patients with non-advanced forms of mastocytosis (indolent systemic mastocytosis, bone marrow mastocytosis, and smoldering systenic mastocytosis) have a low rate of progession to advanced variants and generally have a comparable life expectancy to age-matched general population. Symptomatology in non-advanced mastocytosis is variable and is related to mast cell mediator release. While some patients require no or minimal symptomatic therapy with antimediator drugs, other may suffer from refractory symptoms impacting the quality of life despite being on multiple anti-mediator drugs...

Advanced systemic mastocytosis (AdvSM) is a heterogeneous group of disorders characterized by neoplastic mast cell-related organ damage and frequently associated with a myeloid neoplasm. The 3 clinical entities that comprise AdvSM are aggressive SM (ASM), SM-associated hematologic neoplasm, and mast cell leukemia. A gain-of-function KIT D816 V mutation is the primary oncogenic driver found in about 90% of all patients with AdvSM. Midostaurin, an oral multikinase inhibitor with activity against KIT D816V, and avapritinib, an oral selective KIT D816V inhibitor are approved for AdvSM...

Gastrointestinal symptoms are prevalent in patients with systemic mastocytosis and contribute to morbidity. In indolent disease, the symptoms, which include heartburn, abdominal pain, and diarrhea, are largely due to release of mast cell mediators but may be due to other factors. A thorough evaluation that incorporates abdominal imaging and endoscopy with intestinal biopsy assists with diagnosis and management. Patients with advanced mastocytosis experience signs and symptoms of gastrointestinal dysfunction owing to the massive infiltration of clonal mast cells in the tissues...

Patients with mastocytosis have an increased risk for mast cell activation events including anaphylaxis when exposed to certain drugs and Hymenoptera venom. Hypotension and cardiovascular collapse without skin or other systemic manifestations can occur after Hymenoptera stings, during the perioperative period, and after exposure to nonsteroidal ntiinflammatory drugs, opioids, and other mast cell activating medications, including vancomycin and quinolones. This chapter reviews the epidemiology, mechanisms, diagnosis, management, and treatment options for Hymenoptera venom and drug-induced reactions in patients with mastocytosis...

Mastocytosis is characterized by expansion and activation of clonally aberrant mast cells (MCs) in one or more organ systems. Inappropriate MC activation is a key finding in both allergy and mastocytosis; therefore, symptoms in both conditions show some degree of overlap. When mediator release is excessive and involves multiple systems, anaphylaxis may occur. In mastocytosis, the prevalence of atopy is similar to those of the general population, whereas the incidence of anaphylaxis is significantly higher. The purpose of this review is to discuss features of allergy and anaphylaxis as well as the principles of managing MC mediator release symptoms in mastocytosis...

To a large extent, the clinical picture of pediatric mastocytosis depends on the age at which it is diagnosed. A neonate with diffuse cutaneous mastocytosis may frequently present in a severe state requiring treatment. Toddlers may require long-term anti-mediator therapy, and this may lead to concerns such as organizing preschool education due to the need for epinephrine injections. A teenager may have to face cutaneous disease persistence or a diagnosis of systemic mastocytosis. Further studies are needed to refine the available treatment options and prognosis for different age groups...

A KIT activating mutation (usually KIT D816V) is detected in neoplastic cells in greater than 90% of indolent patients with systemic mastocytosis (SM). In more advanced variants of SM, additional genetic defects can be found in several myeloid malignancy-related genes, which can be detected by applying next-generation sequencing. Currently, the techniques recommended to detect the KIT D816V mutation and quantify the mutational burden in peripheral blood, bone marrow, or other organs/tissues are allele specific-quantitative PCR or droplet digital PCR...

Experts of the European Competence Network on Mastocytosis (ECNM) and the American Initiative on Mast Cell Disorders have discussed and updated diagnostic criteria and the classification of mastocytosis, based on new insights in the field and data collected in recent years, mostly within ECNM registry projects in which studies on several thousand cases have been performed. Based on this proposal, the World Health Organization has updated its classification of mastocytosis. This article discusses the revised classification of mastocytosis in light of a rapidly moving field and the advent of new diagnostic parameters, new prognostication tools, and new therapies...

No abstract text is available yet for this article.

Systemic lupus erythematosus and rheumatoid arthritis are just 2 of several autoimmune connective tissue diseases that are primarily chronic in nature but can present to the emergency department by virtue of an acute exacerbation of disease. Beyond an acute exacerbation of disease, their predilection for invading multiple organ systems lends itself to the potential for patients presenting to the emergency department with either a single or isolated symptom or a myriad of signs and/or symptoms indicative of a degree of disease complexity and severity that warrant timely recognition and resuscitation...

The spondyloarthritides are a diverse group of distinct yet interrelated disease processes with overlapping clinical features. They are ankylosing spondylitis, reactive arthritis, inflammatory bowel disease-associated arthritis, and psoriatic arthritis. Genetically, these disease processes have been linked by the presence of HLA-B27. They manifest with axial and peripheral symptoms, such as inflammatory back pain, enthesitis, oligoarthritis, and dactylitis. The onset of symptoms can begin before the age of 45; however, because of the wide range of signs and symptoms, diagnosis can be delayed, leading to unchecked inflammation, structural damage, and later, restriction in physical mobility...

Sarcoidosis has a multitude of manifestations and affects the human body widely. Pulmonary complaints are most common; however, cardiac, optic, and neurologic manifestations carry high mortality and morbidity. Acute presentations in the emergency room can cause life-altering effects if not appropriately diagnosed and treated. Generally, less severe cases of sarcoidosis have a favorable prognosis and can be treated with steroid therapy. Resistant and more severe cases of the disease carry high mortality and morbidity...

Immunotherapy is a treatment modality that has a broad and rapidly growing range of applications to treat both chronic and acute diseases, including rheumatoid arthritis, Crohn disease, cancer, and COVID-19. Emergency physicians must be aware of the breadth of applications and be able to consider the effects of immunotherapies when patients on these treatments present to the hospital. This article provides a review of the mechanisms of action, indications for use, and potential complications of immunotherapy treatments that are relevant in the emergency care setting...

Scombroid poisoning, systemic mastocytosis, and hereditary alpha tryptasemia all present with episodes that resemble allergic reactions. Knowledge regarding systemic mastocytosis and hereditary alpha tryptasemia is quickly evolving. Epidemiology, pathophysiology, and strategies to identify and diagnose are discussed. Evidence-based management in the emergency setting and beyond is also explored and summarized. Key differences are described between these events and allergic reactions.

Hereditary angioedema (HAE) is a rare autosomal dominant genetic disorder that usual results from a decreased level of functional C1-INH and clinically manifests with intermittent attacks of swelling of the subcutaneous tissue or submucosal layers of the respiratory or gastrointestinal tracts. Laboratory studies and radiographic imaging have limited roles in evaluation of patients with acute attacks of HAE except when the diagnosis is uncertain and other processes must be ruled out. Treatment begins with assessment of the airway to determine the need for immediate intervention...