I have had 3 severe anaphylactic reactions in my medical history and one doctor afraid to administer any pain reliever besides aspirin. It didn't really mean anything to me at the time, because I have never been in need of pain management other than the multiple sugeries connected with my middle ear.
Those 3 reactions were to coedine, hydrocodone, and Inderal. Coedine and hydrocodone resulted in whole body erythema and circulatory collapse in which I was hopsitialized. Inderal, I was already admitted, and given this prior to surgery for a migraine. I went down in the pre-surgical unit with massive mast cell degranulation, severe itching, and loss of consciousness. Never seen a presurgical unit move so fast or a physician show up so fast. Those reactions took months to recover from.
Laurie
Hi, Laurie.
I'm sorry to hear about your problems with histamine and anaphylactic reactions. I would like to help you, but I am a researcher, not a licensed physician, and cannot give medical advice. As you have described, anaphylactic reactions are quite serious, and I do not feel qualified or authorized to give advice about them.
I suggest that you work with a physician, and ask the physician about substances that can lower histamine production, such as quercetin, or antihistamines that can block histamine receptors. I would also suggest that you ask your physican to test you for copper deficiency.
It's true that one of the main pathways for breaking down histamine involves methyation. However, that's the intracellular reaction. The extracellular one uses an enzyme called diamine oxidase. The skin-type reactions result from a deficiency in the activity of this enzyme. It requires copper as a cofactor, and some people have inherited polymorphisms in it, which can lower its activity.
Maybe the abstracts below will be of help to you.
Best regards,
Rich
Am J Clin Nutr. 2007 May;85(5):1185-96.
Histamine and histamine intolerance.
Maintz L, Novak N.
Department of Dermatology, University of Bonn, Bonn, Germany.
Abstract
Histamine intolerance results from a disequilibrium of accumulated histamine and the capacity for histamine degradation. Histamine is a biogenic amine that occurs to various degrees in many foods. In healthy persons, dietary histamine can be rapidly detoxified by amine oxidases, whereas persons with low amine oxidase activity are at risk of histamine toxicity. Diamine oxidase (DAO) is the main enzyme for the metabolism of ingested histamine. It has been proposed that DAO, when functioning as a secretory protein, may be responsible for scavenging extracellular histamine after mediator release. Conversely, histamine N-methyltransferase, the other important enzyme inactivating histamine, is a cytosolic protein that can convert histamine only in the intracellular space of cells. An impaired histamine degradation based on reduced DAO activity and the resulting histamine excess may cause numerous symptoms mimicking an allergic reaction. The ingestion of histamine-rich food or of alcohol or drugs that release histamine or block DAO may provoke diarrhea, headache, rhinoconjunctival symptoms, asthma, hypotension, arrhythmia, urticaria, pruritus, flushing, and other conditions in patients with histamine intolerance. Symptoms can be reduced by a histamine-free diet or be eliminated by antihistamines. However, because of the multifaceted nature of the symptoms, the existence of histamine intolerance has been underestimated, and further studies based on double-blind, placebo-controlled provocations are needed. In patients in whom the abovementioned symptoms are triggered by the corresponding substances and who have a negative diagnosis of allergy or internal disorders, histamine intolerance should be considered as an underlying pathomechanism.
PMID: 17490952
Pharmacogenomics. 2009 May;10(5):867-83.
Histamine pharmacogenomics.
Garca-Martn E, Ayuso P, Martnez C, Blanca M, Agndez JA.
University of Extremadura, Badajoz, Spain.
elenag@unex.es
Abstract
Genetic polymorphisms for histamine-metabolizing enzymes are responsible for interindividual variation in histamine metabolism and are associated with diverse diseases. Initial reports on polymorphisms of histamine-related genes including those coding for the enzymes histidine decarboxylase (HDC), diamine oxidase (ABP1) and histamine N-methyltransferase (HNMT), as well as histamine receptor genes, often have pointed to polymorphisms that occur with extremely low frequencies or that could not be verified by later studies. In contrast, common and functionally significant polymorphisms recently described have been omitted in many association studies. In this review we analyze allele frequencies, functional and clinical impact and interethnic variability on histamine-related polymorphisms. The most relevant nonsynonymous polymorphisms for the HDC gene are rs17740607 Met31Thr, rs16963486 Leu553Phe and rs2073440 Asp644Glu. For ABP1 the most relevant polymorphisms are rs10156191 Thr16Met, rs1049742 Ser332Phe, and particularly because of its functional effect, rs1049793 His645Asp. In addition the ABP1 polymorphisms rs45558339 Ile479Met and rs35070995 His659Asn are relevant to Asian and African subjects, respectively. For HNMT the only nonsynonymous polymorphism present with a relevant frequency is rs1801105 Thr105Ile. For HRH1 the polymorphism rs7651620 Glu270Gly is relevant to African subjects only. The HRH2 rs2067474 polymorphism, located in an enhancer element of the gene promoter, is common in all populations. No common nonsynonymous SNPs were observed in the HRH3 gene and two SNPs were observed with a significant frequency in the HRH4 gene: rs11665084 Ala138Val and rs11662595 His206Arg. This review summarizes relevant polymorphisms, discusses controversial findings on association of histamine-related polymorphisms and allergies and other diseases, and identifies topics requiring further investigation.
PMID: 19450133
APMIS Suppl. 1999;96:1-46.
Mammalian Cu-containing amine oxidases (CAOs): new methods of analysis, structural relationships, and possible functions.
Houen G.
Statens Serum Institut.
Abstract
This thesis describes new and original experimental results on Cu-dependent amine oxidases (CAOs), which show that these enzymes can be conveniently and specifically detected in situ using a peroxidase-coupled activity staining method with 4-Cl-1-naphtole as hydrogen donor substrate. Even more sensitive in situ detection can be achieved using a chemiluminescence-based coupled peroxidase assay which was applied to show that human placenta CAO activity is confined to maternal vessels. A general purification scheme for CAOs is described, and applied to purification of different CAOs. Peptide maps and immunological crossreactivity studies with monoclonal antibodies raised against the purified enzymes showed that they were closely related. Amino acid sequence data for the bovine serum CAO showed that they form a separate group (E.C. 1.4.3.6) with no homology to other enzymes. A cDNA sequence was obtained on the basis of the amino acid sequence data, and this was found to encode a bovine lung CAO, related to bovine serum CAO. The genes for bovine lung and bovine serum CAO are characterized, and Southern blotting analysis of bovine chromosomal DNA shows the existence of a least one more bovine CAO. The purification of human neutrophil CAO is attempted, but it is described how lactoferrin, a protein with many properties in common with CAOs, and with a low degree of sequence identity can account for many observations on human neutrophil CAO. The products of bovine serum CAO oxidation of polyamines are characterised, and 3-aminopropanal is found to be the principal aminoaldehyde produced. Finally, a polyamine-stimulated binding of human placenta CAO to single-stranded DNA is described, and it is reported that the DNA-bound CAO is enzymically active and that the oxidation of DNA-bound polyamines leads to degradation of DNA. In addition to the experimental results, the properties of polyamines and Cu-dependent amine oxidases are reviewed. The polyamines spermidine and spermine interact specifically with nucleic acids and several other molecules. They are synthesised from putrescine, which is a key regulatory molecule formed from ornithine by ornithine decarboxylase, a highly inducible and regulated enzyme. The polyamines can be converted to putrescine by CAOs or spermidine/spermine acetyltransferase and polyamine oxidase. Putrescine is degraded by CAOs, which are also involved in degradation of histamine, a mediator of inflammatory processes. CAOs catalyse the general reaction: R1CH2NHR2 + O2 + H2O-->R1CHO + R2NH2 + H2O2 and in addition to the catabolism of putrescine and histamine CAOs are involved in regulation of growth and apoptosis by to the generation of aminoaldehydes and hydrogen peroxide which have growth inhibitory properties. Several homologous CAOs have been purified and characterized and they form a family with two subgroups. They are homodimers with a relative molecular weight of 180,000 and contain Cu2+ and a modified tyrosine, topaquinone, in the active site. CAOs are present in most tissues with highest amounts in intestine, kidneys, liver and placenta, but the cellular distributions and functions of CAOs are still poorly described, partly due to the use of many different assays and partly due to a broad substrate specificity of the enzymes. However, polyamines and CAOs seem to form a universal system contributing to regulation of growth, differentiation, and apoptosis.
PMID: 10668504
