Type-1 hypersensitivity reaction represents an acute IgE-mediated reaction that can cause life-threatening conditions, such as anaphylactic shock, angioedema, and airway obstruction. Other reactions that can mimic type-1 hypersensitivity reactions include IgE-independent mast cell degranulation, bradykinin-mediated reactions, leukotrienes-mediated reactions, and pseudo-allergies. We use the term pseudo-allergy in this article for histamine-mediated reactions that are mast cell-independent. We did not discuss pseudo-allergic reactions that are not acute or life-threatening, such as celiac disease, Heiner\'s syndrome, eosinophilic esophagitis, and food protein-induced enterocolitis in our article because the emergency department is not the primary location to diagnose or treat these reactions. Herein, we present some allergic-like reactions that can be life-threatening, such as scombroid food poisoning (SFP), bradykinin-induced angioedema, IgE-independent angioedema, opioid-induced angioedema, and non-steroidal anti-inflammatory drug (NSAID)-induced hypersensitivity and angioedema. These reactions may have different treatments based on their mechanism of reaction. Histamine-mediated reactions, such as SFP, histamine-mediated angioedema, and mast cell degranulation induced by NSAIDs, and opioids can be treated with antihistamines, epinephrine, and corticosteroids. Bradykinin-induced angioedema, including hereditary angioedema and acquired angioedema, can be treated with fresh frozen plasma. Hereditary angioedema can be treated with many FDA-approved targeted medications, such as plasma-derived C1-INH, plasma kallikrein inhibitor (Ecallantide), and selective bradykinin-2 receptor antagonist (Icatibant). However, these targeted agents are not well-studied enough to be used for acquired angioedema. It is crucial for emergency medicine physicians to be familiar with and predict these reactions to prevent misdiagnosis, be prepared to treat these life-threatening conditions appropriately without delay and eliminate patients\' exposure to any unnecessary investigations or treatments.

Within the gastrointestinal tract, histamine is present at relatively high concentrations, especially during inflammatory processes. Histamine is a biogenic amine with numerous effects on many cell types, mediated by the activation of its four different histamine receptors (H1-H4Rs). It is produced and released by immune cells as mast cells and basophils. Some cells such as dendritic cells or T cells can express histidine decarboxylase, an enzyme for histamine synthesis after stimulation. The same can be done by the human gut microbiota. The production of histamine by bacteria in the human gut influence the immune response, although the major source of histamine is food. The large spectrum of histamine effects on a number of cellular processes results in various gastrointestinal disorders including food allergy, histamine intolerance, irritable bowel syndrome, and inflammatory bowel disease, among others. In this review, the protective or pathogenic effects of histamine on various gut disorders are discussed.

Histamine (HIST) and other biogenic amines found in fish and fishery products accumulated by the action of bacterial amino acid decarboxylase cannot be decomposed and eliminated by heating or other chemical methods. A simple method for HIST elimination is proposed by a coupling reaction of the fungal amine oxidase (FAO) and bacterial aldehyde oxidase (ALOX) of acetic acid bacteria. As a model reaction, FAO oxidized benzylamine to benzaldehyde, which in turn was oxidized spontaneously to benzoic acid with ALOX. Likely, in HIST elimination, FAO coupled well with ALOX to produce imidazole 4-acetic acid from HIST with an apparent yield of 100%. Imidazole 4-acetaldehyde was not detected in the reaction mixture. In the absence of ALOX, the coupling reaction was incomplete given a number of unidentified substances in the reaction mixture. The proposed coupling enzymatic method may be highly effective to eliminate toxic amines from fish and fishery products.

BACKGROUND: Mast 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.
METHODS: Here 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.
CONCLUSIONS: Mast 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.

Histamine intoxications result when histamine-metabolizing enzymes are compromised or overwhelmed by dietary histamine in the human body. This can occur either due to metabolic enzyme deficiencies, such as in histamine intolerance to wines, aged cheese and other foods or from high concentrations of histamine following ingestion of decomposed fish. The presence of histamine in decomposed fish and fish products results from bacterial decarboxylation of free L-histidine following product mishandling. Consequently, histamine intoxications from mishandled fish, commonly referred to as scombrotoxin fish poisoning (SFP) or scombroid poisoning, require high levels of free L-histidine only found in certain species of pelagic fish. Differential diagnosis is required of clinicians since dietary histamine intoxications produce the same symptoms typical of release of endogenous histamine due to IgE -mediated seafood allergies or anisakiasis. Although high levels of dietary histamine are responsible for SFP, histamine has important physiological functions and tends to exert toxic effects only at doses beyond the physiological range. Endogenous histamine is essential to local immune responses, regulation of gastric acid secretion in the gut, and neurotransmission in the central nervous system. Scombrotoxins, postulated to explain histamine\'s augmented toxicity in scombrotoxic fish, are a milieu of histamine and other bioactives. Since time-and-temperature abuse is required to produce high levels of histamine in fish, management consists of ensuring proper handling by identifying hazards and critical control points (HACCP) and maintaining a \"cold chain\" from catch to consumption. Reference methods for detecting histamine have received increased attention and the European Commission has validated a popular precolumn dansylation-based HPLC method through inter-laboratory collaboration and studied method equivalence with the AOAC fluorescence method 977.13 recognized by Codex Alimentarius. Much progress has been made during the last decade in the development and validation of rapid screening methods for detecting histamine in food and especially in fish products. These include many innovative sensors and several validated commercial test kits, many of them based on a recombinant form of the enzyme histamine dehydrogenase (HD).

UNASSIGNED: In scombroid poisoning, a seafood-associated disease, consumption of fish that contains high levels of histamine results in allergy-like symptoms that range from mild to occasionally severe. To date, there is no published information on scombroid poisoning from Selar crumenophthalmus on the Caribbean island of Grenada, West Indies. S. crumenophthalmus is of particular interest because it is a common and heavily consumed fish that has been implicated in scombroid poisoning in Hawaii. Preliminary data on S. crumenophthalmus in Grenada have demonstrated the presence of Photobacterium damselae, a bacterium associated with scombroid poisoning. The present study further tested S. crumenophthalmus purchased in Grenada for factors that would indicate the potential for scombroid poisoning, including increased histamine levels in fish muscle and DNA evidence of bacteria associated with scombroid poisoning. Histamine levels between 7,160 and 66,688 ppm were found after temperature abuse at 37°C for 19 h; this far exceeds the acceptable limit for the United States (50 ppm) and the European Union (100 to 200 ppm). Even after 4 h of incubation at ambient temperature (28.9°C) during a time-point study, histamine levels exceeded U.S. acceptable limits (>50 ppm), and five samples used for temperature-abuse studies had elevated histamine levels (ranging from 141 to 2,510 ppm) at 0 h. PCR and sequence analysis of bacteria in temperature-abused fish identified P. damselae and Morganella morganii, which are histamine-producing bacteria known to be implicated in scombroid poisoning. These results suggest the potential for scombroid poisoning in Grenada and the need for promoting awareness about this disease.
CONCLUSIONS:

In European countries, vitamin A toxicity is most often the result of an excessive intake of vitamin supplements and rarely the consequence of the ingestion of a large carnivorous fish liver. We report 3 cases of vitamin A poisoning after fish liver ingestion in mainland and overseas France. The patients were a 12-y-old girl, a 36-y-old pregnant woman, and a 62-y-old man. They experienced headache, nausea, emesis, and desquamation. Laboratory examination showed a high serum retinol level in the girl. The woman\'s pregnancy progressed to a miscarriage. This case series shows that this kind of poisoning is not restricted to the polar regions. In patients presenting with flushing combined with signs of intracranial hypertension, accurate questioning of the patient\'s diet is crucial to avoid misdiagnosis and unnecessary examinations. Pregnant women or women of child-bearing age should be informed of the risk to pregnancy in the case of excessive fish liver ingestion.

Monitoring of biogenic amines in food is important for quality control, in terms of freshness evaluation and even more for food safety. A novel and cost-effective method was developed and validated for the determination of the main biogenic amines: histamine, putrescine, cadaverine, spermidine and spermine in fish tissues. The method includes extraction of amines with perchloric acid, pre-column derivatization with Pyrene Sulfonyl Chloride (PSCl), extraction of derivatives with toluene, back-dissolution in ACN after evaporation and determination by reversed phase high performance liquid chromatography with UV and intramolecular excimer fluorescence detection. The structure of the pyrene-derivatives was confirmed by liquid chromatography-mass spectrometry with electrospray ionization. The standard addition technique was applied for the quantitation due to significant matrix effect, while the use of 1,7-diaminoheptane as internal standard offered an additional confirmation tool for the identification of the analytes. Method repeatability expressed as %RSD ranged between 7.4-14% for the different amines and recovery ranged from 67% for histamine up to 114% for spermine. The limits of detection ranged between 0.1-1.4 mg kg-1 and the limits of quantification between 0.3-4.2 mg kg-1. The method was applied to canned fish samples and the concentrations of the individual biogenic amines were below the detection limit up to 40.1 mg kg-1, while their sum was within the range 4.1-49.6 mg kg-1.

The Food Safety Act of the Philippines strengthens the welfare of consumer\'s health by protecting the public from foodborne illnesses such as scombroid fish poisoning due to unusually high levels of histamine. The present study investigated the formation of histamine substance in driedsalted fish products that were sold in different local supermarkets of Samar. A total of fifty samples of dried-salted fish samples were used to analyze the histamine substance. Results of the analysis revealed that 81.3% are detected beyond the regulatory limits of 200.0mg/kg by the Bureau of Food and Drugs-Philippine National Standard. Based on the Box-whisper plot, the species with the highest concentration of histamine are Bolinao (Stolephorus sp.), Hasa-hasa (Rastrelliger sp.), Lambiao (Selar boops), and Tamban (Sardinella sp). In the non-linear regression model, a low r2 found out that histamine concentration in the products generally increased through time as sold in the local supermarkets.

BACKGROUND: Scombroid poisoning is a poorly known type of food poisoning due to the presence of histamine in spoiled fish of the Scombridae family. We report 3 cases of scombroid poisoning seen at the Fréjus-Saint-Raphaël hospital in the Var region.
METHODS: Within around thirty minutes of eating a meal containing tuna, three patients presented varied symptoms: malaise, itchy rash, headache, and for two of them, nausea. The diagnosis of scombroid poisoning was based on the circumstances in which the clinical signs appeared and on the signs themselves. The patients were given antihistamines and one injection of intravenous corticosteroids, and symptoms regressed rapidly within a few hours.
CONCLUSIONS: The symptoms of scombroid poisoning appear within a few minutes after eating fish of the Scombridae family and related species. The first symptoms are cutaneous, with flush, pruritus, and erythema of the face and trunk having an urticarial appearance, together with faintness. Gastrointestinal symptoms include nausea, vomiting, abdominal cramps and occasionally diarrhea. Symptoms subside within a few hours. Histamine is present in the flesh of these fish due to decarboxylation of histidine through the action of Gram-negative bacteria whose development is enhanced by heat and sun. Scombroid poisoning is one of the most common types of poisoning caused by eating fish but it is underdiagnosed by dermatologists. The diagnosis is made by measuring histamine levels in the incriminated fish or in the patient\'s plasma.