Mast Cell Activation Disorders Research Articles

Sildenafil-inducing allergic angina in elderly with intertwining sinus arrhythmia, wavy triple sign, wavy double sign (Yasser’s signs), and mild covid-infection; interpretation and management

Rationale: Sildenafil is a phosphodiesterase-5 inhibitor (PDE5-I) drug used to treat erectile dysfunction (ED) and pulmonary arterial hypertension. Allergic angina and infarction are broad-spectrum mast cell activation disorders accompanied by acute coronary syndromes (ACS) and are known as Kounis-Zafras (KZ) syndrome. Sinus arrhythmia is a variation of normal sinus rhythm (NSR) that is associated with an irregular rate in which the change in the R-R interval is greater than 0.12 seconds. Wavy triple and Wavy double ECG signs (Yasser’s sign) are new specific diagnostic and therapeutic signs seen in the cases of hypocalcemia. Mild COVID-19 infection means you have symptoms like cough, sore throat, and fatigue, but no dyspnea. Patient concerns: An elderly married male farmer patient was admitted to the intensive care unit with angina, hypotension, generalized hives, Wavy triple, and Wavy double ECG signs after ingestion of sildenafil tablet with mild COVID-19 infection in a previous chronic obstructive pulmonary disease (COPD). Diagnosis: Sildenafil-inducing Kounis syndrome in the elderly with intertwining sinus arrhythmia, Wavy triple sign, Wavy double sign (Yasser’s signs), and mild COVID-19 infection. Interventions: Electrocardiography, oxygenation, IV fluids, and echocardiography. Outcomes: A dramatic clinical and electrocardiographic improvement had happened. Lessons: Sildenafil-inducing Allergic angina and anaphylaxis may be innovative cardiovascular findings. Mild COVID-19 infection, sometimes, can be insignificant. An associated sinus arrhythmia may be a good cardiovascular sign. The dramatic improvement in both clinical and electrocardiographic ST-segment depressions and elevations supports the efficacy of both anti-ischemic and anti-allergic measures.

Mast cells: The unregulated master immune response conductor

Mast cells (MC) are found perivascularly in all tissues and may function as the sentinel immune cells sensing danger and then acting as the master conductor to orchestrate responses aimed at restoring homeostasis. Yet, MC are best known for their critical role in allergic, but also inflammatory and other neuroimmune conditions. MC are stimulated by allergens, but also by many other environmental, neuroimmune, pathogenic and stress triggers. Stimulation of MC is called “activation” and is associated with the release of numerous neurohormonal, proinflammatory, tissue remodeling and vasoactive mediators via different secretory mechanisms, some of which do not involve the release of histamine and tryptase. However, mast cell activation and the subsequent responses may become excessive either because of persistent stimulation or dysregulation. Clinical and experimental evidence indicates that MC may be regulated by innate molecules, some derived from MC, themselves. However, discovery of such innate, natural, inhibitors has not been a priority even though they would substantially change the treatment of mast cell activation disorders (MCADs) since drugs that are available or under development focus on inducing MC apoptosis. Development of effective inhibitors of MC activation would require access to MC from healthy and MCAD subjects, preferably identical twins, that would allow differential investigation of the respective transcriptome.

How to handle off-label prescriptions of rupatadine, a second-generation antihistamine and PAF antagonist: a review.

The off-label use of second-generation antihistamines, used outside of the formal indications authorized by regulatory authorities, in different age groups, doses or in special populations, is very common for many allergic, autoimmune and dermatological diseases. The off-label use of rupatadine (a second-generation antihistamine with PAF antagonist activity) in these conditions is reviewed here, including in combination with immunotherapy in the treatment of food allergy or allergic rhinitis, at high doses in chronic urticaria, and with prescriptions of less common but challenging conditions such as skin pruritus or mast cell activation disorders like mastocytosis. Rupatadine use is reviewed herein to confirm if its off-label management is supported by well-designed clinical trials or by published real-world cases. This review will contribute to increasing compliance and achieving better results in clinical practice. Off-label use of rupatadine should be left to the discretion of the prescribing healthcare professional after careful clinical evaluation.

Oral tofacitinib in refractory chronic spontaneous urticaria

Chronic spontaneous urticaria (CSU) is a skin condition marked by the emergence of wheals on their own that persist for six weeks or more. CSU is quite common, affecting up to 1% of the population, and has a serious detrimental effect on a patient's health and quality of life. Antihistamines (AH) are currently the backbone of treatment for chronic urticaria (CU), however up to 40% of patients do not respond to even large (four-fold) daily dosages of AH. Tofacitinib is a small-molecule that inhibits intracellular signalling of several important cytokines involved in the inflammatory cascade and blocks JAK1/3. While there are reports of tofacitinib's positive effects in patients with mast cell activation disorder, there are none in those with urticaria. The aim of our study is to assess the efficacy of oral tofacitinib in refractory chronic spontaneous urticaria. 5 cases of refractory CSU between the age group of 20 to 40 years were included in our study and they were followed up for 6 months. The patients were started on oral tofacitinib 5mg twice a day. On every weekly follow-up, we used clinical assessment, urticaria activity score and urticaria control test to evaluate the treatment response The usage of oral tofacitinib significantly improves the clinical picture in refractory CSU. Although more research is required to determine Tofacitinib's effectiveness in CSU, our study raises the possibility that it could represent a novel therapeutic option for individuals with refractory CSU.

A Puzzling Mast Cell Trilogy: Anaphylaxis, MCAS, and Mastocytosis.

Our knowledge of biology and mast cell (MC) function, as well as disorders associated with the pathologic activation of MCs, has evolved over the last few decades. Anaphylaxis, mast cell activation syndrome (MCAS), and mastocytosis are interrelated yet distinct conditions within the spectrum of mast cell activation disorders. Nevertheless, all three conditions can co-exist in one and the same patient, as pathologic MC activation is the key finding in all three. When mediator release is excessive and involves multiple systems, anaphylaxis and MCAS may occur. Furthermore, mastocytosis is a clonal disorder of MCs and often presents with anaphylaxis and MCAS. Nevertheless, in some cases, even the proliferative and accumulative features of MCs in mastocytosis can account for symptoms and disease progression. In each case, diagnosis can be only made when the diagnostic consensus criteria are fulfilled. The current article aims to provide a concise clinical update and pinpoint the main difficulties in diagnosing these puzzling disorders of MCs in medical practice.

Editorial introductions.

Editorial introductions.

Acute abdomen due to anaphylactic intestinal edema associated with systematic mastocytosis: a case report

BackgroundAmong various anaphylactic conditions resulting in acute abdomen, mast cell activation disorders, although rare, are included in the differential diagnosis.Case presentationThis report describes a 63-year-old Caucasian man who was brought to the emergency room with sudden onset abdominal pain, vomiting, and diarrhea, with breathing difficulty, and with facial swelling after quarrelling with an acquaintance. Computed tomography showed edematous and swollen intestines, consistent with splenomegaly. Physical findings included maculopapular cutaneous mastocytosis. He also had a long history of repeated episodes of anaphylaxis requiring occasional epinephrine auto-injector administration; however, the precise cause of anaphylaxis was previously undetermined. Blood tests showed high serum concentrations of soluble IL-2R and tryptase, suggesting mast cell-related disease. Subsequent biopsies of his bone marrow and cutaneous rash confirmed the diagnosis of systemic mastocytosis (SM).ConclusionSM was diagnosed in a patient with acute abdomen who visited the emergency room.

Kounis Syndrome: A Novel Review

Kounis syndrome is characterised by a group of symptoms that manifests as unstable vasospastic or non-vasospastic angina secondary to a hypersensitivity reaction. It was first described by Kounis and Zavras in 1991 as the concurrence of an allergic response with an anaphylactic or anaphylactoid reaction and coronary artery spasm or even myocardial infarction. Since then, this condition has evolved to include a number of mast cell activation disorders associated with acute coronary syndrome. There are many triggering factors, including reactions to multiple medications, exposure to radiological contrast media, poison ivy, bee stings, shellfish, and coronary stents. In addition to coronary arterial involvement, Kounis syndrome comprises other arterial systems with similar physiologies, such as mesenteric and cerebral circulation resulting in ischemia / infraction of the vital organs. The Incidence of this condition is difficult to establish owing to the number of potential instigating factors and its relatively infrequent documentation in the literature. Anaphylaxis rarely manifests as a vasospastic acute coronary syndrome with or without the presence of underlying coronary artery disease. The variability in the underlying pathogenesis produces a wide clinical spectrum of this syndrome. Kounis syndrome is not just a single organ but also a complex multisystem and multiorgan arterial clinical conditions, it affects the coronary, mesenteric, and cerebral arteries and is accompanied by allergy hypersensitivity anaphylaxis involving Skin , respiratory system and vascular system in the context of anaesthesia, surgery, radiology ,oncology or even dental and psychiatric medicine , further it has significantly influences both morbidity and mortality. Kounis syndrome is caused by inflammatory mediators released during allergic insults, post inflammatory cell activation and interactions via multi directional stimuli. A platelet subset of 20% with high and low affinity IgE surface receptors is also involved in this process.

Mast Cell Diseases in Practice and Research: Issues and Perspectives Raised by Patients and Their Recommendations to the Scientific Community and Beyond

Since 2010, patients and physicians have collaborated to understand unmet needs of patients with mast cell diseases, incorporating mastocytosis and mast cell activation disorders, which include mast cell activation syndromes. This Open Innovation in Science project aims to expand understanding of the needs of patients affected by mast cell diseases, and encourage global communication among patient advocacy groups, physicians, researchers, industry, and government. A major aim is to support the scientific community's efforts to improve diagnosis, management, therapy, and patients' quality of life by addressing unmet needs. In collaboration with mast cell disease specialists, 13 patient advocacy groups from 12 countries and regions developed lists of top patient needs. A core team of leaders from patient advocacy groups collected and analyzed the data and proposed possible actions to address patient needs. Findings identified similarities and differences among participating countries in unmet needs between patients with mastocytosis and those with mast cell activation syndromes. Issues emphasized struggles relating to the nature and rarity of mast cell diseases, their impact on quality of life, the diagnostic process, access to appropriate care, more effective treatment, and the need for research. Solutions vary across countries because situations differ, in particular regarding the existence of and access to centers of excellence and reference centers. Multifaceted mast cell activation syndrome barriers necessitate innovative approaches to improve access to appropriate care. The outcomes of this project should greatly support scientists and clinicians in their efforts to improve diagnosis, management, and treatment of patients with mastocytosis and mast cell activation disorders.

Global Classification of Mast Cell Activation Disorders: An ICD-10-CM–Adjusted Proposal of the ECNM-AIM Consortium

Mast cell activation (MCA) is common and occurs in a number of pathologic conditions, including IgE-dependent and independent allergic reactions, atopic disorders, autoimmune processes, and mastocytosis. In a subset of patients, no underlying disease and no known trigger of MCA are found. When the symptoms are severe, systemic, and recurrent, and accompanied by a diagnostic increase in the serum tryptase level or other mast cell mediators, an MCA syndrome (MCAS) may be diagnosed. In these patients, the symptoms typically respond to drugs suppressing MCA, mediator production in mast cells, or mediator effects. In each case, diagnostic consensus criteria must be fulfilled to diagnose MCAS. In other patients, MCA may be local, less severe, or less acute, or may be suspected but not confirmed, so that the diagnostic criteria of MCAS are not fulfilled. In these patients, it may be difficult to prove MCA, for example, by measuring multiple mast cell mediators or basophil activation, the latter as a surrogate of IgE-dependent hypersensitivity. However, validated diagnostic criteria for implicating suspected MCA behind such conditions are lacking, even if some of these conditions have recently been assigned to an International Classification of Diseases-10-Clinical Modification code (ICD-10-CM). In this article, we discuss diagnostic features and criteria and propose a ICD-10-CM-adjusted classification for disorders associated with MCA, herein referred to as MCA disorders (MCADs), with special emphasis on the delineation between confirmed MCAS, MCAD not fulfilling MCAS criteria, and suspected MCAD that is not present. In addition, we discuss the discrimination between overt MCAD and predisposing conditions, such as atopic states, mastocytosis, and hereditary alpha tryptasemia.

Differential mast cell mediators in systemic mastocytosis and hereditary α-tryptasemia

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.

Association of mast-cell-related conditions with hypermobile syndromes: a review of the literature.

Ehlers–Danlos syndrome (EDS) is a group of related connective tissue disorders consisting of 13 subtypes, each with its own unique phenotypic and genetic variation. The overlap of symptoms and multitude of EDS variations makes it difficult for patients to achieve a diagnosis early in the course of their disease. The most common form, hypermobile type EDS (hEDS) and its variant, hypermobile spectrum disorder (HSD), are correlated with rheumatologic and inflammatory conditions. Evidence is still needed to determine the pathophysiology of hEDS; however, the association among these conditions and their prevalence in hEDS/HSD may be explained through consideration of persistent chronic inflammation contributing to a disruption of the connective tissue. Aberrant mast cell activation has been shown to play a role in disruption of connective tissue integrity through activity of its mediators including histamine and tryptase which affects multiple organ systems resulting in mast cell activation disorders (MCAD). The overlap of findings associated with MCAD and the immune-mediated and rheumatologic conditions in patients with hEDS/HSD may provide an explanation for the relationship among these conditions and the presence of chronic inflammatory processes in these patients. It is clear that a multidisciplinary approach is required for the treatment of patients with EDS. However, it is also important for clinicians to consider the summarized symptoms and MCAD-associated characteristics in patients with multiple complaints as possible manifestations of connective tissue disorders, in order to potentially aid in establishing an early diagnosis of EDS.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12026-022-09280-1.

Drug-induced mast cell eradication: A novel approach to treat mast cell activation disorders?

Mast cell (MC) activation is a key event in allergic reactions, other inflammatory states, and MC activation syndromes. MC-stabilizing agents, mediator-targeting drugs, and drugs interfering with mediator effects are often prescribed for these patients. However, the clinical efficacy of these drugs varies depending on the numbers of involved MCs and the underlying pathology. One straightforward approach would be to eradicate the primary target cell. To date however, no MC-eradicating treatment approach has been developed for patients with MC activation disorders. Nevertheless, recent data suggest that long-term treatment with agents effectively inhibiting KIT function results in the virtual eradication of tissue MCs and a sustained decrease in serum tryptase levels. In many of these patients, MC depletion is associated with a substantial improvement in mediator-induced symptoms. In patients with an underlying KIT D816V-positive mastocytosis, such MC eradication requires an effective inhibitor of KIT D816V, such as avapritinib. However, the use of KIT inhibitors must be balanced against their potential side effects. Here we discuss MC-eradicating strategies in various disease models, the feasibility of this approach, available clinical data, and future prospects for the use of KIT-targeting drugs in MC activation disorders.

Life-threatening Malnutrition in very severe Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

Patients with very severe Myalgic Encephalomyelitis/ Chronic Fatigue Syndrome (ME/CFS) can experience difficulty maintaining their nutrition and hydration. In the most severe cases it is not uncommon. The commonest reason is simple debility. Dysphagia, severe gastrointestinal problems in tolerating food, possibly indicative of Mast Cell Activation Disorder, and conditions such as gastroparesis may also be contributing factors. These patients require enteral or parental nutrition. In our experience there is often a delay in implementing Clinically Assisted Nutrition and Hydration (CANH), until the malnutrition becomes life-threatening.

Effective Anti–SARS-CoV-2 Immune Response in Patients With Clonal Mast Cell Disorders

BackgroundMast cells are key players in innate immunity and the TH2 adaptive immune response. The latter counterbalances the TH1 response, which is critical for antiviral immunity. Clonal mast cell activation disorders (cMCADs, such as mastocytosis and clonal mast cell activation syndrome) are characterized by abnormal mast cell accumulation and/or activation. No data on the antiviral immune response in patients with MCADs have been published.ObjectiveTo study a comprehensive range of outcomes in patients with cMCAD with PCR- or serologically confirmed coronavirus disease 2019 and to characterize the specific anti–severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immune response in this setting.MethodsClinical follow-up and outcome data were collected prospectively over a 12-month period by members of the French Centre de Référence des Mastocytoses rare disease network. Anti–SARS-CoV-2–specific T-cell activity was measured with an ELISA, and humoral responses were evaluated by assaying circulating levels of specific IgG, IgA, and neutralizing antibodies.ResultsOverall, 32 patients with cMCAD were evaluated. None required noninvasive or mechanical ventilation. Two patients were admitted to hospital for oxygen and steroid therapy. The SARS-CoV-2–specific immune response was characterized in 21 of the 32 patients. Most had high counts of circulating SARS-CoV-2–specific, IFN-γ–producing T cells and high titers of neutralizing antispike IgGs. The patients frequently showed spontaneous T-cell IFN-γ production in the absence of stimulation; this production was correlated with basal circulating tryptase levels (a marker of the mast cell burden).ConclusionsPatients with cMCADs might not be at risk of severe coronavirus disease 2019, perhaps due to their spontaneous production of IFN-γ.

Adult-onset mast cell activation syndrome following scombroid poisoning: a case report and review of the literature

BackgroundMast cells are closely associated with epithelium, serving as sentinels responsible for the recognition of tissue injury and coordination of the initial inflammatory response. Upon detection of the injured cell content, mast cells then tailor the release of preformed and newly produced chemical mediators to the detected challenge, via an array of pathogen receptors. In addition to immunoglobulin E receptor-triggered mast cell activation, commonly referred to as allergic or atopic disorders, non-immunoglobulin E receptor mediated mast cell activation follows engagement of toll-like receptors, immunoglobulin G receptors, and complement receptors. Upon containment of the extrinsic challenge, acute inflammation is downregulated, and repair of the injured tissue ensues. The mast cell compartments must return to a baseline steady state to remain tolerant towards self-antigens and harmless entities, including environmental conditions, to prevent unnecessary immune activation and chronic hypersensitivity disorders. Over the past 50 years, an increasing number of patients are experiencing episodes of aberrant mast cell activation, not associated with allergen-specific mast cell disease or systemic mastocytosis. This led to proposed diagnostic criteria of mast cell activation syndrome. Mast cell activation syndrome is a heterogeneous disorder, defined by a combination of (1) recurrent symptoms typical of mast cell activation, (2) an increase of validated mast cell derived mediators, and (3) response to treatment with mast cell stabilizing or mast cell mediator-targeted therapies. Onset of mast cell activation syndrome ostensibly reflects the loss of tolerance in the mast cell compartment to nonthreatening entities and nonhazardous environmental conditions. The etiology of chronic mast cell dysregulation and associated intolerance to self-antigens or harmless entities is not well understood, but a growing number of studies point to exposure of the epithelial borders, which leads to inappropriate or excessive mast cell activation or impaired resolution of acute inflammation following neutralization of the identified pathogen.Case presentationHere we present a case of adult onset mast cell activation syndrome following scombroid poisoning. Scombroid toxicity is usually a self-limited illness, but there are individuals who have been shown to have severe symptoms or persistent illness following histamine fish poisoning. We describe a 74-year-old Caucasian woman, with a history of drug-induced urticaria, who developed a constellation of hypersensitivity illnesses consistent with the diagnosis of mast cell activation syndrome after ingestion of tainted fish.ConclusionMast cell activation disease causes problems of increased complexity in children and adults. The increased prevalence and severity of mast cell activation disease has been attributed to dramatic changes in our lifestyles and modern living environments. These changes likely impact the integrity of the epithelial barriers, leading to loss of tolerance in the mast cell compartment. Here, we present a case of a nonatopic, 74-year-old female who developed mast cell activation disease after exposure to a potent environmental toxin. Mast cell activation disease commonly involves several organ systems, with patients often referred to a succession of different specialists. This results in delayed diagnosis and suboptimal care. Instead, early recognition of mast cell activation disease would lead to better outcomes. We review the literature, describing the diagnostic criteria for mast cell activation disorders that can improve recognition of this multiorgan system syndrome. Further research is needed into the interaction of epithelial barrier disruption and the dysregulation of the immune system.

Kounis Syndrome: Dexketoprofen-Associated ST-Elevation Myocardial Infarction.

Allergic angina and allergic myocardial infarction are common diseases associated with acute coronary syndromes and encompass a wide spectrum of mast cell activation disorders termed “Kounis Syndrome”. We present here a patient with Kounis syndrome presenting with sudden cardiac arrest after intravenous infusion of dexketoprofen in the emergency room.LEARNING POINTSThere are 3 types of Kounis syndrome, of which Type I, allergic coronary vasospasm, is the most common.The most common presentation of Kounis syndrome is ST-elevation myocardial infarction.Although not all cases of Kounis syndrome are reported, they are common in clinical practice and many more causal factors are predicted to play a role in the future.

Mastocytosis and Mast Cell Activation Disorders: Clearing the Air

Mast cells are derived from hematopoietic stem cell precursors and are essential to the genesis and manifestations of the allergic response. Activation of these cells by allergens leads to degranulation and elaboration of inflammatory mediators, responsible for regulating the acute dramatic inflammatory response seen. Mast cells have also been incriminated in such diverse disorders as malignancy, arthritis, coronary artery disease, and osteoporosis. There has been a recent explosion in our understanding of the mast cell and the associated clinical conditions that affect this cell type. Some mast cell disorders are associated with specific genetic mutations (such as the D816V gain-of-function mutation) with resultant clonal disease. Such disorders include cutaneous mastocytosis, systemic mastocytosis (SM), its variants (indolent/ISM, smoldering/SSM, aggressive systemic mastocytosis/ASM) and clonal (or monoclonal) mast cell activation disorders or syndromes (CMCAS/MMAS). Besides clonal mast cell activations disorders/CMCAS (also referred to as monoclonal mast cell activation syndromes/MMAS), mast cell activation can also occur secondary to allergic, inflammatory, or paraneoplastic disease. Some disorders are idiopathic as their molecular pathogenesis and evolution are unclear. A genetic disorder, referred to as hereditary alpha-tryptasemia (HαT) has also been described recently. This condition has been shown to be associated with increased severity of allergic and anaphylactic reactions and may interact variably with primary and secondary mast cell disease, resulting in complex combined disorders. The role of this review is to clarify the classification of mast cell disorders, point to molecular aspects of mast cell signaling, elucidate underlying genetic defects, and provide approaches to targeted therapies that may benefit such patients.

Editorial introductions.

Editorial introductions.

Mast Cell Activation Disorder and Postural Orthostatic Tachycardia Syndrome: A Clinical Association.

BackgroundRecently there has been increased interest in a possible association between mast cell activation (MCA) disorder and postural orthostatic tachycardia syndrome (POTS). This study examined the frequency with which symptoms and laboratory findings suggesting MCA disorder occurred in patients diagnosed with POTS.Methods and ResultsData were obtained from patients in whom symptoms and orthostatic testing were consistent with a POTS diagnosis. Individuals with <4 months symptom duration, evident ongoing inflammatory disease, suspected volume depletion, or declined consent were excluded. All patients had typical POTS symptoms; some, however, had additional nonorthostatic complaints not usually associated with POTS. The latter patients underwent additional testing for known MCA biochemical mediators including prostaglandins, histamine, methylhistamine, and plasma tryptase. The study comprised 69 patients who met POTS diagnostic criteria. In 44 patients (44/69, 64%) additional nonorthostatic symptoms included migraine, allergic complaints, skin rash, or gastrointestinal symptoms. Of these 44 patients, 29 (66%) exhibited at least 1 laboratory abnormality suggesting MCA disorder, and 11/29 patients had 2 or more such abnormalities. Elevated prostaglandins (n=16) or plasma histamine markers (n=23) were the most frequent findings. Thus, 42% (29/69) of patients initially diagnosed with POTS exhibited both additional symptoms and at least 1 elevated biochemical marker suggesting MCA disorder.ConclusionsLaboratory findings suggesting MCA disorder were relatively common in patients diagnosed with POTS and who present with additional nonorthostatic gastrointestinal, cutaneous, and allergic symptoms. While solitary abnormal laboratory findings are not definitive, they favor MCA disorder being considered in such cases.