Anaphylaxis: Advances in the Past 10 Years.

In the past 10 years, anaphylaxis has grown into its own special area of study within Allergy-Immunology, both at the bench and at the bedside. This review focuses on some of the most clinically relevant advances over the past decade. These include simplified and more inclusive diagnostic criteria for adults and children, uniform definition of biphasic anaphylaxis, and improved systems for objective severity grading.

The Utility of Measuring Urinary Metabolites of Mast Cell Mediators in Systemic Mastocytosis and Mast Cell Activation Syndrome.

Mast cells (MCs) leave evidence of their presence and activation. Aside from increased numbers of MCs in tissues, this evidence includes detecting elevated serum levels of tryptase and discovering increased excretion of urinary metabolites of prostaglandin (PG) D, leukotriene (LT) C, and/or histamine. The importance of measuring these nontryptase mediator metabolites has largely gone unnoticed.

AAAAI Mast Cell Disorders Committee Work Group Report: Mast cell activation syndrome (MCAS) diagnosis and management.

Our current recommendations for diagnosing and treating primary mast cell (MC) activation syndrome make use of the latest studies and consensus guidelines for clinically recognizing systemic anaphylaxis in real time, regardless of whether allergen-triggered or other pathways are involved; our current understanding of the biomarkers secreted by activated MCs that best discriminate this disorder from other conditions; and the therapeutic drugs that might selectively affect those mediators or MCs themselves. Finding familial or somatic mutations of genes that cause MCs to be hyperactivatable would extend our diagnostic tools and potentially indicate new therapeutic interventions, targeting either the mutated gene product or the associated molecular pathway. In conclusion, we trust that the clinical, laboratory, and therapeutic criteria for primary MC activation syndromes described herein will provide clinicians with practical criteria of sufficient sensitivity and specificity to diagnose most cases without overdiagnosing the disorder in patients who likely have other conditions.

Mast Cell Activation Syndrome: Tools for Diagnosis and Differential Diagnosis.

The current consensus diagnostic criteria for mast cell activation syndrome(s) (MCAS[s]) were first established in 2012 and updated in 2019. This diagnosis has been attached to multiple medical conditions not intended as part of the diagnosis. In this article, the diagnostic criteria are reviewed and other diseases in the differential diagnosis outlined.

Hypereosinophilic syndrome: endomyocardial biopsy versus echocardiography to diagnose cardiac involvement.

Objective: To compare echocardiograms and endomyocardial biopsies to diagnose cardiac involvement in hypereosinophilic syndrome.

Methods: We examined the agreement between echocardiography and endomyocardial biopsies to detect cardiac involvement in hypereosinophilic syndrome by reviewing cases identified as hypereosinophilia or hypereosinophilic syndrome in Mayo Clinic databases from January 1978 through June 2009. Single-organ cases of eosinophilia such as eosinophilic fasciitis and eosinophilic gastroenteritis were excluded.

Tolerance and Efficacy with Simultaneous Use of Two Monoclonal Antibodies for a Patient with Hypereosinophilic Syndrome and Ulcerative Colitis.

The development and utilization of monoclonal antibodies (mAbs) have been of great interest in all fields of medicine. A substantial increase in the production and development of mAbs has occurred because these biologic agents are proving to be effective and less toxic given their targeted mechanism of action. However, data are limited on coadministration of two or more mAbs.

Hematologic Malignancies Identified in Patients with Hypereosinophilia and Hypereosinophilic Syndromes.

Background: Certain hematologic malignancies are associated with hypereosinophilia or tissue eosinophilia. It is unclear if patients with hypereosinophilia are more likely to develop one of these malignancies.

Objective: This study sought to quantify the specific hematologic malignancies that developed in patients with preexisting hypereosinophilia.

Mast cell activation syndrome: improved identification by combined determinations of serum tryptase and 24-hour urine 11β-prostaglandin2α.

Background: Mast cell activation syndrome (MCAS) describes patients with episodes of mast cell mediator release, with negative bone marrow biopsy results, and the failure to meet the criteria for systemic mastocytosis.

Objective: Identify elevation of mast cell mediators of patients with MCAS.

Methods: We performed a retrospective study of 25 patients with MCAS who were evaluated at Mayo Clinic from 2006 to 2012.

Mast cell sarcoma: clinical management.

Mast cell sarcoma is a disorder that results in abnormal mast cells as identified by morphology, special stains, and in some publications, c-kit mutation analysis. It affects animal species such as canines more commonly than humans. In humans it is a very rare condition, with variable clinical presentation.

Presentation of untreated systemic mastocytosis as recurrent, pulseless-electrical-activity cardiac arrests resistant to cardiac pacemaker.

Recurrent, pulseless-electrical-activity (PEA) cardiac arrests were the novel presentation of untreated systemic mastocytosis in an 85-year-old woman who lacked cutaneous findings of mastocytosis. Despite prior implantation of a dual-chamber cardiac pacemaker 3 weeks previously for similar spells, she experienced a PEA arrest accompanied by flushing, increased urinary N-methylhistamine excretion and serum tryptase values on the day of presentation to our clinic. Bone marrow biopsy findings conducted to rule out breast cancer metastases showed 30% mast cell infiltration, aberrant expression of CD25 and a positive c-kit Asp816Val mutation.

Systemic mastocytosis in the elderly.

"Later onset" of systemic mastocytosis (SM) has been associated with a poorer prognosis. We examined clinical and laboratory findings, associated disorders, and survival in an older mastocytosis population. After receiving Mayo Clinic Institutional Review Board approval, we identified 42 patients aged 70 years and older at the time of diagnosis of SM.

The Melkersson-Rosenthal syndrome: a retrospective study of biopsied cases.

Melkersson-Rosenthal syndrome (MRS) is a rare neuromucocutaneous syndrome marked by the triad of recurrent nonpitting orofacial edema, fissured dorsal tongue (lingua plicata), and lower motoneuron facial paralysis. Large case series including treatment are limited. A retrospective records review was performed for the diagnoses Melkersson-Rosenthal syndrome, granulomatous cheilitis, and orofacial granulomatosis, confirmed by noncaseating granulomas on biopsy, at the Mayo Clinic in Rochester, Minnesota (1979-2009).

Eosinophilic esophagitis: allergic contribution, testing, and management.

Both basic science and clinical data indicate a strong role for allergy as a cause of eosinophilic esophagitis. As a result, one of the desired goals of therapy is identification and elimination of food antigens that trigger the allergic inflammatory pathway. Traditional methods for identification of causative food antigens include induction of symptoms with exposure to the antigen, demonstration of serum IgE antibodies against antigens and induction of immediate (IgE) or delayed (Th2) reactions against dermal instillation of antigens.

Increased numbers of eosinophils, rather than only etiology, predict histologic changes in patients with esophageal eosinophilia.

Background & Aims: It can be a challenge to differentiate individuals with eosinophilic esophagitis (EoE) from those with gastroesophageal reflux disease (GERD). We investigated differences in histologic and eosinophil patterns and numbers of mast cells between patients with these disorders.

Methods: We performed histologic analyses and immunohistochemical assays for eosinophil-derived neurotoxin (EDN), major basic protein (MBP), and tryptase, using biopsy samples from 10 patients with GERD (positive results from a pH study and response to proton pump inhibitors), Barrett's esophagus, or EoE (negative results from a pH study and positive response to budesonide).

Use of pegylated interferon in hypereosinophilic syndrome.

Scant information exists about pegylated interferons (PEG-IFNs) use for treating hypereosinophilic syndrome (HES). We describe 6 patients with HES-1 patient with a newly identified chromosomal abnormality-who received PEG-IFNs. PEG-IFN alpha-2b replaced interferon (IFN) alpha-2b for 4 patients and was initial treatment of 2 patients.

Prevention of mast cell activation disorder-associated clinical sequelae of excessive prostaglandin D(2) production.

Background: Patients with systemic mastocytosis have increased numbers of mast cells in the bone marrow and other organs, such as the liver, spleen, gastrointestinal tract and skin. Symptoms result from the local and remote effects of mediator release from mast cells and from the local effects of increased mast cell numbers in various organs. Patients with mast cell activation experience many of the same clinical symptoms as do patients with systemic mastocytosis from chronic or spontaneous release of mast cell mediators.

Eosinophilic esophagitis: is it all allergies?

Eosinophilic esophagitis (EE) is an increasingly recognized disorder in the adult population, most often manifested by symptoms of dysphagia and food impaction. Mechanisms involving eotaxin-3, interleukin 5, and signal transducer and activator of transcription 6 have been studied and may represent future therapeutic targets. Patients commonly have a personal and family history of atopy, and both food allergies and aeroallergens have also been investigated as triggers of EE.