Comparative responses of tracheal spirals and parenchymal strips to histamine and carbachol in vitro. Ahmed T. Characterization of H1- and H2-receptor function in pulmonary and systemic circulations of sheep. Nadel J. Control of mucus secretion and ion transport in airways.
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Koarai A. Disruption of L-histidine decarboxylase reduces airway eosinophilia but not hyperresponsiveness. Identification of a histamine H4 receptor on human eosinophils—Role in eosinophil chemotaxis. Signal Transduct. Makabe-Kobayashi Y. The control effect of histamine on body temperature and respiratory function in IgE-dependent systemic anaphylaxis. Enhanced goblet cell hyperplasia in HDC knockout mice with allergic airway inflammation. Nakanishi A. Role of gob-5 in mucus overproduction and airway hyperresponsiveness in asthma.
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Japanese Society of Allergology Japanese guidelines for adult asthma Busse W. Omalizumab, anti-IgE recombinant humanized monoclonal antibody, for the treatment of severe allergic asthma. Analysis of the comorbidity of bronchial asthma and allergic rhinitis by questionnaire in 10, patients. Buckland K. Histamine induces cytoskeletal changes in human eosinophils via the H 4 receptor.
Neumann D. Does the histamine H4 receptor have a pro- or anti-inflammatory role in murine bronchial asthma? Hofstra C. Histamine H4 receptor mediates chemotaxis and calcium mobilization of mast cells. Dunford P. Cowden J. Histamine H4 receptor antagonism diminishes existing airway inflammation and dysfunction via modulation of Th2 cytokines. Thurmond R. Clinical and preclinical characterization of the histamine H 4 receptor antagonist JNJ Aspirin can relieve flushing but may make other symptoms worse.
Children are not given aspirin because Reye syndrome Reye Syndrome Reye syndrome is a very rare but life-threatening disorder that causes inflammation and swelling of the brain and impairment and loss of function of the liver.
The cause of Reye syndrome is Corticosteroids Corticosteroids: Uses and Side Effects Rheumatoid arthritis is an inflammatory arthritis in which joints, usually including those of the hands and feet, are inflamed, resulting in swelling, pain, and often destruction of joints When taken by mouth for more than 3 to 4 weeks, they can have many, sometimes serious side effects. If leukemia develops, chemotherapy drugs such as daunomycin, etoposide , and mercaptopurine may help.
People with systemic mastocytosis should always carry a self-injecting syringe of epinephrine for prompt emergency treatment of anaphylactic or anaphylactoid reactions.
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This site complies with the HONcode standard for trustworthy health information: verify here. Common Health Topics. Commonly searched drugs. Types of mastocytosis. Allergic Reactions and Other Hypersensitivity Disorders. Test your knowledge. A physical allergy is an allergic reaction triggered by a physical stimulus, such as pressure on the skin or minor injury. For some people, symptoms occur only in response to a physical trigger.
For other people, the physical trigger worsens responses caused by other allergens. Which of the following is NOT an example of a physical trigger? More Content. Mastocytosis By Peter J. Click here for the Professional Version. Symptoms suggest the diagnosis, and a biopsy of the skin or bone marrow can confirm it. Images of Urticaria Pigmentosa. This photo shows small reddish brown bumps covering the body of an infant with mastocytosis.
This photo shows reddish-brown spots on the back of a school-aged child with mastocytosis. A single mastocytoma may not cause symptoms. Changes in temperature. A doctor's evaluation. Drugs to relieve symptoms.
Generic Name Select Brand Names mercaptopurine. Was This Page Helpful? In addition to histamine-rich food, many foods such as citrus foods are considered to have the capacity to release histamine directly from tissue mast cells, even if they themselves contain only small amounts of histamine Table 4. In vitro studies of persons with a history of pseudoallergic reactions to food have shown a fragility of duodenal mast cells with massive degranulation in the presence of histamine-releasing substances that is significantly greater than that shown by control subjects However, clinical studies using oral challenge tests to support the hypothesis for the histamine-releasing capacity of foods are required Foods with suggested histamine-releasing capacities 1.
Data were taken from reference Alcohol, especially red wine, is rich in histamine and is a potent inhibitor of DAO 9 , The relation between the ingestion of wine, an increase in plasma histamine, and the occurrence of sneezing, flushing, headache, asthma attacks, and other anaphylactoid reactions and a reduction of symptoms by antihistamines has been shown in various studies 7 , 8 , 14 , 65 , 87 , In DBPC wine tests with healthy persons 91 and in patients with chronic urticaria and wine intolerance 92 , the histamine content did not influence wine tolerance.
In the latter group, an increase in plasma histamine could be shown, paradoxically, after ingestion of the histamine-poor wine. In these patients, the ethanol metabolite acetaldehyde has been discussed as a histamine-releasing substance Sulfiting agents are widely used as antioxidants and preservatives in foods, beverages, and pharmaceuticals.
Adverse reactions with a presumed relation to sulfites include anaphylactic shock, bronchospasm, urticaria, angioedema, nausea, abdominal pain, diarrhea, stroke, and death Asthmatic reactions have been attributed to reflex activation of the parasympathetic system by the irritating effect of sulfites, possibly enhanced by a deficiency of sulfite oxidase.
Besides this pseudoallergic mechanism, in at least some cases of sulfite hypersensitity, an immunoglobulin E IgE —mediated immediate-type allergic reaction must be considered Sulfites may be contained in wine, but they are also contained in foods that are poor in histamine, such as fruit juice, frozen vegetables, and lettuce.
Thus, in patients reporting intolerance to wine, a careful history of reactions to other foods rich in histamine or sulfites should be taken. In patients who are suspected of having sulfite intolerance, skin testing and a DBPC challenge with capsules containing increasing doses of bisulfite or placebo should be performed. In contrast to an IgE—mediated food allergy, in which the ingestion of even a small amount of the allergen elicits symptoms, in histamine intolerance, the cumulative amount of histamine is crucial.
Besides variations in the amount of histamine in food according to storage and maturation, the quantity consumed, the presence of other biogenic amines, and the additional intake of alcohol or DAO-blocking drugs are pivotal factors in the tolerance of the ingested food. This threshold may be too high, considering the occurrence of histamine-mediated symptoms after oral ingestion of 75 mg histamine in 5 of 10 females without a history of histamine intolerance However, most of the positive studies for intolerant reactions to sulfite, histamine, and other biogenic amines do not fulfill the current scientific criteria for providing substantiated evidence of the clinical effect of these foods.
Nevertheless, patients who have a conclusive history of adverse reactions to food, alcohol, drugs containing histamine, other biogenic amines, and sulfite but without proof of IgE exist.
In such patients, a DBPC provocation of the suspected causal agents under close supervision by experienced specialists should be performed after exclusion of other causal diseases and informed consent of the patients—if the provocation is not unreasonably hazardous, considering the grade of the anaphylactoid reaction.
Because of the great effort, time, and costs or because of patients' fear of a repeated reaction, DBPC provocations often are not performed in clinical practice, even when they are indicated. The effect of drugs as specific DAO inhibitors and their capacity to induce histamine intolerance have been shown in various studies with human placental DAO and in animal experiments 10 , 40 , 97 , A clinically relevant activity via histamine release or inhibition of DAO has been observed for various drugs 10 , 40 , 97 , 98 Table 5.
Therefore, the intake of drugs, especially long-term medication, should be considered in interpretation of histamine intolerance symptoms and DAO concentrations.
Reduced DAO activity—or, rather, reduced DAO release—after the application of heparin could be shown to be a marker of tissue damage in patients with chronic renal failure 99 , , viral hepatitis , or gut failure and of endotoxemia in patients with liver cirrhosis Reduced DAO activity has also been shown in patients with chronic urticaria as a typical histamine-mediated disease 60 combined with a reduced tolerance for infused histamine 16 and an improvement of urticaria by maintaining a histamine-free diet Higher basal plasma histamine concentrations , and increased spontaneous histamine release toward different stimuli — and after food challenges have been shown in patients with severe atopic eczema AE than in control subjects.
Thus, these patients have a significantly greater occurrence of chronic headache, dysmenorrhea, flushing, gastrointestinal symptoms, and intolerance to alcohol and food than do control subjects. Reduction of both the symptoms of histamine intolerance and the severity score of atopic dermatitis SCORAD has been shown in a subgroup of patients with AE and low DAO serum activity who were following a histamine-free diet for 2 wk A feedback inhibition of DAO through its degradation product imidazole acetic acid , or substrate inhibition , caused by the elevated histamine concentrations in AE may be a pathomechanism of a reduced histamine degradation capacity in a subgroup of patients with AE.
In the female genital tract, histamine is mainly produced by mast cells, endothelial cells, and epithelial cells in the uterus and ovaries. Histamine-intolerant women often suffer from headache that is dependent on their menstrual cycle and from dysmenorrhea. Besides the conctractile action of histamine, these symptoms may be explained by the interplay of histamine and hormones. Histamine has been shown to stimulate, in a dose-dependent manner, the synthesis of estradiol via H1R; meanwhile, only a moderate effect on progesterone synthesis was observed Thus, histamine may augment dysmenorrhea by increasing estrogen concentrations.
And, in reverse, estrogen can influence histamine action. A significant increase in weal and flare size in response to histamine has been observed to correspond to ovulation and peak estrogen concentrations In pregnancy, DAO is produced at very high concentrations by the placenta , , and its concentration may become times that when the woman is not pregnant This increased DAO production in pregnant women may be the reason why, in women with food intolerance, remissions frequently occur during pregnancy Because of the multifaceted symptoms in multiple organs, a detailed history of the basal histamine-mediated symptoms, any triggering of symptoms after the intake of histamine-rich food or drugs interfering with the histamine metabolism, and concomitant gastrointestinal diseases or allergies is indispensable for diagnosis of histamine intolerance Figure 3.
Clinically, histamine-induced symptoms cannot always be assigned to the underlying pathomechanism. A massive intake of histamine from decomposed fish may result in the same symptoms as are seen in a person with an IgE-mediated fish allergy.
Histamine actions may be possible causes of endogenous cell activation, increased exogenous uptake, decreased histamine degradation, or a combination of these mechanisms. An occult systemic mastocytosis should be excluded by measurement of the serum tryptase. The diagnosis of allergy using using the skin-prick test for food allergens or determination of specific IgE should be carried out to exclude food allergy.
The diagnosis of allergy usually proves to be negative because histamine intolerance is a pseudoallergy. Keeping of a diet diary has proven useful in tracking significant improvement of symptoms with a histamine-free diet and relapses in histamine intolerance after dietary errors. Diagnostic pathway for histamine intolerance. Several radioextraction assays REA have been developed for the determination of the enzymatic activity of DAO by using [3H]- or [ 14 C]-labeled putrescinedihydrochloride as a substrate , Determination of the HNMT activity is based on transmethylation of histamine by S -adenosyl- l [methyl- 14 C] methionine Furthermore, the total histamine degradation capacity can be measured Plasma activity of DAO, which generally is relatively low, may be increased by the liberation of tissue-bound DAO through an injection of heparin — , which was the main method used before the development of more sensitive assays.
Serum DAO concentrations showed no significant daily variations and no significant sex differences Conversely, in some patients with a clear clinical picture of histamine intolerance, normal DAO activities have been observed, so that an additional determination of histamine concentrations and interpretation of laboratory data in view of the clinic seem advisable.
Histamine can be measured in plasma or in urine, as can its degradation product N -methylhistamine 53 , Deficiency of the DAO cofactors vitamin B-6, copper, and vitamin C, which are thought to supplement histamine degradation , has been discussed as being controversial Elevated histamine concentrations, reduced DAO activities, or both are classically found in histamine intolerance. A DBPC histamine provocation after a 4-wk histamine-free diet is considered the gold standard in diagnosis.
Because the amount of histamine in natural food varies pronouncedly according to storage and maturation, the provocation can be performed with alternate administration of capsules containing increasing doses of histamine-di-hydrochloride 0. Blood pressure and heart rate should be continuously controlled, and positive reactions eg, hypotonia, tachycardia, urticaria, or other symptoms of an anaphylactoid reaction should be immediately treated by a physician.
Afterward, symptoms should be evaluated by using a standardized symptom-scoring system. Therapy is based on the consequent conduction of a histamine-free diet. Alcohol and long-ripened or fermented and therefore histamine-rich food, such as aged cheese, cured meat, and yeast products; histamine-rich food, such as spinach or tomatoes; or histamine liberators, such as citrus fruit, should be avoided 65 , ; the histamine-free diet can be complemented with adjuvant administration of H1 and H2 antagonists.
Most antihistamines have no influence on DAO activity, although inhibition of DAO by cimetidine and dihydralazine and increased activity by diphenhydramine have been observed In patients consuming a strictly histamine-free diet, no additional benefit due to an intake of antihistamines could be observed An increase in DAO activity with the histamine-free diet was shown in migraine patients In addition, histamine degradation can be supported by the administration of vitamin C and vitamin B-6, which leads to an increase in DAO activity 14 , Positive effects have been reported for mast cell stabilizers and pancreatic enzymes , especially with respect to gastrointestinal symptoms.
Because of the frequent intolerant reactions toward drugs that interfere with the histamine metabolism, their intake should be avoided. Recently, capsules containing DAO isolated from pig kidneys have been generated to supplement the lack of endogenous human DAO in patients with histamine intolerance.
These capsules contain only stabilizers—ie, cellulose, sucrose, solanum tuberosum, polyacrylic acid, cellulose gum, triethyl citrate, and potato starch. Patients who are suspected of having histamine intolerance should be given a certificate noting that condition and stating that the administration of contrast and other drugs that release histamine should be avoided.
If the administration of theses drugs is unavoidable , prior medication with antihistamines is recommended. In patients with typical symptoms of histamine intolerance that are triggered by histamine-rich food and alcohol, with intolerance of drugs that liberate histamine or block DAO, and with a negative diagnosis of allergy or internal disorders, histamine intolerance should be considered.
A histamine-free diet, if necessary, supported by antihistamines or the substitution of DAO, leads to an improvement of symptoms. However, further studies investigating histamine intolerance due to DBPC provocations are indispensable.
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