Purpose of Review
This paper will review the pathophysiology, diagnosis, and treatment of exercise-induced anaphylaxis and food-dependent, exercise-induced anaphylaxis with an emphasis on novel ...studies published in the past several years.
Recent Findings
Exercise-induced anaphylaxis (EIAn) is a clinical syndrome characterized by anaphylaxis during or shortly after physical exertion. The syndrome is broadly grouped into two categories: exercise-induced anaphylaxis and food-dependent, exercise-induced anaphylaxis (FDEIAn). Recent literature indicates that FDEIAn is a primary IgE-mediated food allergy which is augmented by several cofactors. Cofactors such as exercise, NSAIDs, and alcohol increase intestinal permeability and allow increased antigen uptake, thereby causing symptoms. The pathophysiology of EIAn is still under investigation.
Summary
EIAn and FDEIAn are rare clinical syndromes characterized by symptoms during or shortly after exercise. Despite recent advances in the understanding of EIAn and FDEIAn, the pathophysiology of both conditions is not fully understood.
Autonomic symptom questionnaires are frequently used to assess dysautonomia. It is unknown whether subjective dysautonomia obtained from autonomic questionnaires correlates with objective ...dysautonomia measured by quantitative autonomic testing. The objective of our study was to determine correlations between subjective and objective measures of dysautonomia. This was a retrospective cross-sectional study conducted at Brigham and Women's Faulkner Hospital Autonomic Laboratory between 2017 and 2023 evaluating the patients who completed autonomic testing. Analyses included validated autonomic questionnaires Survey of Autonomic Symptoms (SAS), Composite Autonomic Symptom Score 31 (Compass-31) and standardized autonomic tests (Valsalva maneuver, deep breathing, sudomotor, and tilt test). The autonomic testing results were graded by a Quantitative scale for grading of cardiovascular reflexes, sudomotor tests and skin biopsies (QASAT), and Composite Autonomic Severity Score (CASS). Autonomic testing, QASAT, CASS, and SAS were obtained in 2627 patients, and Compass-31 in 564 patients. The correlation was strong between subjective instruments (SAS vs. Compass-31, r = 0.74, p < 0.001) and between objective instruments (QASAT vs. CASS, r = 0.81, p < 0.001). There were no correlations between SAS and QASAT nor between Compass-31 and CASS. There continued to be no correlations between subjective and objective instruments for selected diagnoses (post-acute sequelae of COVID-19, n = 61; postural tachycardia syndrome, 211; peripheral autonomic neuropathy, 463; myalgic encephalomyelitis/chronic fatigue syndrome, 95; preload failure, 120; post-treatment Lyme disease syndrome, 163; hypermobile Ehlers-Danlos syndrome, 213; neurogenic orthostatic hypotension, 86; diabetes type II, 71, mast cell activation syndrome, 172; hereditary alpha tryptasemia, 45). The lack of correlation between subjective and objective instruments highlights the limitations of the commonly used questionnaires with some patients overestimating and some underestimating true autonomic deficit. The diagnosis-independent subjective-objective mismatch further signifies the unmet need for reliable screening surveys. Patients who overestimate the symptom burden may represent a population with idiosyncratic autonomic-like symptomatology, which needs further study. At this time, the use of autonomic questionnaires as a replacement of autonomic testing cannot be recommended.
Idiopathic anaphylaxis is a condition caused by paroxysmal episodes of sudden-onset multiorgan involvement variably including laryngeal edema, urticaria, bronchoconstriction, dyspnea, hypoxia, ...abdominal pain, nausea, vomiting, diarrhea, and hypotension. Rarely, the episodes can lead to cardiovascular collapse and death in the absence of a clear trigger, especially in the presence of other cardiovascular comorbidities. Elevated mast cell mediators such as tryptase and histamine have been reported during episodes, and mast cells are considered the primary cells responsible for driving anaphylaxis in humans. Basophils also secrete histamine and LTC4 when activated and theoretically can contribute to symptoms. As our understanding of mast cell disorders continue to grow, the classification for these disorders evolves. The purpose of this article was 2-fold: to review the epidemiology, clinical manifestations, and diagnosis of idiopathic anaphylaxis and to discuss the classification of idiopathic anaphylaxis within the broader context of mast cell activation disorders.
Mast cells (MCs) play a pathobiologic role in type 2 (T2) allergic inflammatory diseases of the airway, including asthma and chronic rhinosinusitis with nasal polyposis (CRSwNP). Distinct MC subsets ...infiltrate the airway mucosa in T2 disease, including subepithelial MCs expressing the proteases tryptase and chymase (MC
) and epithelial MCs expressing tryptase without chymase (MC
). However, mechanisms underlying MC expansion and the transcriptional programs underlying their heterogeneity are poorly understood. Here, we use flow cytometry and single-cell RNA-sequencing (scRNA-seq) to conduct a comprehensive analysis of human MC hyperplasia in CRSwNP, a T2 cytokine-mediated inflammatory disease. We link discrete cell surface phenotypes to the distinct transcriptomes of CRSwNP MC
and MC
, which represent polarized ends of a transcriptional gradient of nasal polyp MCs. We find a subepithelial population of CD38
CD117
MCs that is markedly expanded during T2 inflammation. These CD38
CD117
MCs exhibit an intermediate phenotype relative to the expanded MC
and MC
subsets. CD38
CD117
MCs are distinct from circulating MC progenitors and are enriched for proliferation, which is markedly increased in CRSwNP patients with aspirin-exacerbated respiratory disease, a severe disease subset characterized by increased MC burden and elevated MC activation. We observe that MCs expressing a polyp MC
-like effector program are also found within the lung during fibrotic diseases and asthma, and further identify marked differences between MC
in nasal polyps and skin. These results indicate that MCs display distinct inflammation-associated effector programs and suggest that in situ MC proliferation is a major component of MC hyperplasia in human T2 inflammation.
Mastocytosis is a myeloproliferative neoplasm characterized by abnormal proliferation and activation of clonal mast cells typically bearing the KITD816V mutation. Symptoms manifest due to the release ...of bioactive mediators and the tissue infiltration by neoplastic mast cells. Mast cell activation symptoms include flushing, pruritus, urticaria, abdominal cramping, diarrhea, wheezing, neuropsychiatric symptoms, and anaphylaxis. Up to 50% of patients with mastocytosis report a history of provoked and unprovoked anaphylaxis, with Hymenoptera venom and drugs the most common culprits. NSAIDs, antibiotics, vaccines, perioperative medications, and radiocontrast media are often empirically avoided without evidence of reactions, depriving patients of needed medications and placing them at risk for unfavorable outcomes. The purpose of this review is to highlight the most common agents responsible for adverse drug reactions in patients with mastocytosis, with a review of current epidemiology, diagnosis, and management of drug hypersensitivity and Hymenoptera venom allergy.
Patients with systemic mastocytosis often have symptoms of mast cell activation, which is associated with elevated levels of urinary mast cell mediator metabolites. Patients with hereditary ...α-tryptasemia (HαT) may present with symptoms of mast cell activation. Whether levels of mast cell mediators are elevated in this patient population is not known.
The purpose of this study was to determine whether patients with HαT and symptoms of mast cell activation have elevated levels of urinary mediators and compare the levels with those in patients with systemic mastocytosis.
We retrospectively analyzed mast cell mediators in 63 patients with a confirmed diagnosis of HαT, 20 patients with a confirmed diagnosis of indolent systemic mastocytosis (ISM), and 23 healthy controls. All patients were referred to the Brigham and Women’s Hospital Mastocytosis Center or the Mayo Clinic for evaluation of mast cell activation disorders.
Our population was predominantly female (85.7%) with an average age of 53.8 years. The average baseline serum tryptase level was significantly higher in patients with ISM than in those with HαT (65.9 vs 19.3 ng/mL P < .01). When compared with patients with HαT, those with ISM had statistically significant increases in their levels of urinary N-methylhistamine (P < .01) and 2,3-dinor-11β-prostaglandin F2α (P < .05).
Patients with symptomatic HαT do not have elevations of mast cell urinary metabolites, suggesting that granule- and membrane-derived mediators may not drive symptoms in HαT.
Mast cell disorders including hereditary alpha tryptasemia (HαT) and idiopathic mast cell activation syndrome (MCAS) can be associated with neurologic symptoms such as orthostatic intolerance, pain, ...and cognitive impairment. The origin of these symptoms is not well understood.
To characterize neurologic findings in patients with HαT and MCAS through objective measurements.
Patients with a confirmed diagnosis of HαT or MCAS with neurologic symptoms were referred for standardized autonomic testing encompassing Valsalva maneuver, deep breathing, sudomotor and tilt tests with cerebral blood flow velocity (CBFv) determination, and skin biopsies for small fiber neuropathy (SFN).
There were 15 patients with HαT (age 44.4 ± 15.9 years), 16 with MCAS (34.4 ± 15.5), and 14 matched controls who were evaluated. Baseline serum tryptase level was increased in patients with HαT when compared with patients with MCAS (14.3 ± 2.5 ng/mL vs 3.8 ± 1.8; P <.001) and neurologic symptoms were similar between the 2 groups. When compared with controls, orthostatic CBFv was reduced in HαT (-24.2 ± 14.3%; P <.001) and MCAS (-20.8 ± 5.5%; P <.001). Reduced nerve fibers consistent with SFN were found in 80% of patients with HαT and 81% of those with MCAS. Mild-to-moderate dysautonomia was detected in all patients with HαT and MCAS when results of sympathetic, parasympathetic, and sudomotor tests were combined.
We provide evidence of reduced orthostatic CBFv and SFN associated with mild-to-moderate autonomic dysfunction in patients with HαT and MCAS. Our findings suggest that comprehensive autonomic testing may be helpful to explain neurologic symptoms and guide treatment in patients with HαT and MCAS.
A multi-core FPGA-based 2D-clustering implementation for real-time image processing is presented in this paper. The clustering algorithm is using a moving window technique to reduce the time and data ...required for the cluster identification process. The implementation is fully generic, with an adjustable detection window size. A fundamental characteristic of the implementation is that multiple clustering cores can be instantiated. Each core can work on a different identification window that processes data of independent "images" in parallel, thus, increasing performance by exploiting more FPGA resources. The algorithm and implementation are developed for the Fast TracKer processor for the trigger upgrade of the ATLAS experiment but their generic design makes them easily adjustable to other demanding image processing applications that require real-time pixel clustering.
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