- General information on the treatment
- Medication for mast cell activation diseases
- Mast cell stabilizers
- Mediator inhibitors (receptor antagonists, synthesis inhibitors, etc.)
- Immunosuppressants, cytostatic drugs, cytoreductive therapies
- Incompatible medication
General information on health topics
Please note our information on health topics! Consult a specialist (doctor, pharmacist) and read the package inserts carefully. The information provided here is not intended to replace a visit to the doctor, but to support and supplement the doctor-patient relationship.
In most cases medication is useful or even necessary to support the therapy. Much more important than medication, however, is the permanent avoidance of known mast cell activating triggers to the extent required, in particular the change in diet.
Pathologically altered mast cells cause spontaneous symptoms not only through an activating gene mutation. The activation of mast cells is also further enhanced by external stimuli. Only the activation by external stimuli can be influenced.
- Avoidance of external triggers
- Stabilizing the secondary activated healthy mast cells with medication
- To block the effect of individual free mediators by medication, inhibit their new synthesis or accelerate their degradation.
- Treat remaining symptoms symptomatically.
Mast cell diseases are not yet curable. With correct treatment, however, the symptoms are usually controllable and often even largely preventable.
Without drug treatment, the course of the disease is stable at best, but often very slow over the years, and sometimes rapidly increasing. Spontaneous improvements are not to be expected. Medication is therefore necessary if the avoidance of the triggers is not sufficient to achieve freedom from symptoms.
In principle, the prognosis is positive in the sense that it is a stable disease in the vast majority of cases, which does not directly cause an increased mortality rate (albeit with exceptions).
The therapy normally requires the combination of several active substances with complementary action. The selection of active substances and their dosage must be adapted to the individual case and reviewed regularly. Due to the lack of measurable indicators, the dosage is determined on the basis of the patient's experience.
Avoiding the triggers is not always feasible. In addition to a basic medication, the patient therefore also needs access to additional medication as required.
Various drug categories are available for the medical treatment of mast cell activation diseases:
- Mast cell stabilizers
- cromoglicic acid, sodium cromoglicate
- Mediator inhibitors
- Antihistamines (histamine receptor antagonists)
- Prostaglandin synthesis inhibitors
- Degradation accelerators
- Ascorbic acid (vitamin C)
- Diamine oxidase (DAO), only effective against exogenous amines in the intestine
For aggressive forms, the doctor still has a number of stronger drugs at his disposal.
The SIGHI Medication Manual lists numerous active ingredients and preparations and explains their mode of action:
On more than 120 pages, the various possibilities of medication are presented in detail and clearly structured. Members can download the brochure online as a PDF file. This treatment manual is constantly being expanded and adapted to our growing state of knowledge.
Many drugs are incompatible with MCAD. These include many commonly used products, as well as products that are often prescribed for the symptomatic treatment of symptoms of unknown origin (which includes also undiagnosed cases of MCAD). Both active ingredients and excipients (additives) can cause unspecific intolerance reactions (pseudoallergic reactions, "drug allergy").
Incompatible active ingredients
Numerous active drug ingredients are liberators of mast cell mediators, also called histamine liberators. This means that - as an unwanted side effect - they are triggering the dose-dependent unspecific release of endogenous histamine, inflammation mediators and other messengers. Other active substances can block enzymes, which are necessary for the degradation of released mediators. The most prominent example would be histamine degradation via diamine oxidase (DAO), which can be blocked by inhibitors.
Incompatible active substances are probably found in all categories of active substances, especially in the following ones: Antibiotics, painkillers, local anaesthetics, anaesthetics, sedatives, mucolytics, muscle relaxants, as well as all X-ray contrast media.
Well-known examples: Acetylcysteine, acetylsalicylic acid, alprenolol, barbiturates, cimetidine, codeine, clavulanic acid, diazepam, diclofenac, metamizole, metoclopramide, nitroglycerin, opiates, polyvinylpyrrolidone (E1201), prilocaine, rifampicine, tacrin, thiopental.
List of intolerable drug substances
A more detailed list of intolerable active substances (not exhaustive) can be found below.
An enormous number of excipients can also trigger intolerance reactions: fillers, tableting agents, dyes, coating agents, preservatives, solvents, flavourings, sweeteners, surfactants, etc.). The excipients are usually incompletely declared. Which are incompatible, is not yet conclusively known.
List of incompatible excipients
As a minimum precaution, the tolerance of any declared excipient or additive should be looked up in our food list.
Keywords: recommended, antihistamine, drug, medication, medicine, medications, medicament, remedy, pharmaceutical, physic, medicinal, treatment, manual, guide, medical, cure, pill, capsule, preparation, prescription, administered, chemist, doctor, remedies, therapy, healing, active substances, active ingredients, additives, intolerated, incompatible, symptoms, adverse reactions, intolerance, incompatibility, allergy, mastocytosis, mast cell, MCAD, MCAS, behind-the-counter, over-the-counter, elixir.
General information on the treatment
Origin and triggering of symptoms, aetiopathogenesis
The symptoms are caused by...:
- ... pathologically altered mast cells, which become permanently activated or hypersensitive through gene mutation or presumably also through epigenetic changes. As a consequence, they release mast cell mediators in excess. (The activity of such altered mast cells cannot be influenced externally.)
- ... healthy mast cells, which are secondarily activated by the mediators released in excess by the altered mast cells. (The activity of such secondarily activated mast cells can be influenced by medication.)
- ... other cell types of the immune system, which are activated and/or chemotactically mobilized by the released mediators.
- ... ordinary cells in organs and tissues, which are influenced by mediators or displaced by mast cell proliferation.
The symptoms in pathologically altered mast cells are triggered...:
- ... spontaneously through an activating gene mutation or epigenetic changes
- ... triggered by external stimuli
Only the activation by external stimuli can be influenced.
The therapy therefore consists in ...
(arranged according to priority)
- ... minimizing mast cell activation by avoiding external triggers.
- ... stabilizing the secondarily activated healthy mast cells with medication so that at least these do not release any mediators.
- ... blocking the effect of individual free mediators with drugs, inhibiting their synthesis or accelerating their degradation.
- ... chemotherapeutically reducing the number of cells in severe cases with an increased number of mast cells (cytoreductive therapy).
- ... treating the remaining symptoms symptomatically (without resorting to incompatible products!).
- ... diverting the attention away from the symptoms to other things through distracting activities.
A causal cure of mast cell diseases is not possible according to the current state of scientific research. Genetic mutations are not reversible and cannot be recognized by the body as a degeneration to be eliminated. Epigenetic alerations may also be inherited over several generations. With correct treatment, however, the symptoms are controllable and often even completely avoidable.
Without drug treatment, the course of the disease is stable at best, but often very slowly increasing over the years, and in very rare cases rapidly increasing. Spontaneous improvements are not to be expected. Medication is therefore necessary if the avoidance of the triggers is not sufficient to get rid of all symptoms.
In principle, the prognosis is favourable in the sense that it is a stable disease in the vast majority of cases, which does not directly cause an increased mortality rate. However, the following reservations apply:
- With MCAD, the risk of secondarily acquired diseases is increased. These associated diseases can lead to a higher mortality rate and usually to a significant reduction in the quality of life.
- A small proportion of those affected are susceptible to anaphylactic reactions, which can lead to dangerous circulatory shocks and, in the worst case, death. These "accidents" can occur spontaneously (without recognisable known triggers) as well as through mast cell activating stimuli.
- The disease can cause concentration disorders, fatigue, inertia, coordination disorders, depressive moods or generally severe physical distress. This could increase the risk of accidents and suicides.
Medication for mast cell activation diseases
Various active ingredients with different principles of action are available. Normally a complex medication is necessary, with the application of several complementary active substances in combination. Due to the very different clinical pictures and degrees of severity, the choice of the active ingredients and the dosage must be adapted to the individual case and regularly checked and adjusted.
There are no measurable indicators for determining the dosage. Laboratory values such as serum tryptase do not provide any meaningful indication of the level of suffering. Depending on the severity of the condition, the patient starts with the normal daily dose and after a while the patient's experience will show if the dose should be raised or lowered.
Avoiding the triggers does not always work equally well or is sometimes not possible at all (e.g. allergies to house dust mite excrements, pollen or fungal spores). Therefore, in addition to a basic medication, the patient should also have access to supplementarymedication, which he can take as required.
It is not indifferent which of the available active substances will be selected. In order to use and combine them effectively, it is important to understand their different mechanisms of action. The SIGHI Medication Manual lists numerous active ingredients and preparations and explains their mode of action:
The SIGHI Medication Manual: pharmaceutical treatment of MCAD / Histaminosis.
The SIGHI Medication Manual describes in detail and well-structured on more than 120 pages the different possibilities of medical treatment for systemic mast cell activation diseases, histamine intolerance or histaminosis and shows the advantages of numerous active substances as well as their disadvantages. In addition to pharmaceuticals, medical devices, foods for special medical purposes and dietary supplements are also explained. The Medication Manual explains the therapy concept and provides numerous suggestions for basic therapy and symptomatic additional treatment of the chronic phase as well as for the treatment of acute phases. It also presents treatment in special situations such as anaphylaxis / anaphylactic shock, infectious diseases, vaccinations, pollen allergies, pregnancy and breastfeeding, as well as premedication and other precautions regarding anesthesia, surgery and dental treatment. There is also a list of incompatible active substances and instructions on how to assess the tolerance of pharmaceutical products. This is complemented by many other tips and tricks.
(1 MB, version 2019-01-03)
(3 MB, version 2019-01-03)
Here we can only briefly explain individual active ingredients:
Mast cell stabilizers
Mast cell stabilizers are a group of drugs with antiallergic effects. They stabilize the cell membrane of mast cells. This reduces their willingness to release histamine and other (inflammatory) mediators. Stabilizing mechanisms are theoretically conceivable: Modification of the properties of the lipid bilayer that makes up the cell membrane, inhibition of activating mast cell receptors by means of receptor antagonists, stimulation of attenuating mast cell receptors by means of receptor agonists, interruption of the signal transmission chain that initiates mediator synthesis and release after stimulation of the receptors, influencing of the genes that control receptor density.
Currently, two substances from the chemical group of cromogens are available as drugs: Cromoglicic acid (also called sodium cromoglycate or cromolyn sodium) and nedocromil sodium. Oral preparations prevent the release of mediators locally in the intestine. In the form of eye drops and nasal sprays, the active ingredients are mainly used against pollen allergies and also have only a local effect.
Mediator inhibitors (receptor antagonists, synthesis inhibitors, etc.)
If the degranulation of mast cells or the release of mediators cannot be prevented sufficiently, the mediator inhibitors are used in a second stage. They can be used to specifically block the effects of individual mediators or prevent their formation. Antihistamines are certainly the most important, but also the inhibition of prostaglandin synthesis and possibly the blocking of other mediators are often necessary:
Antihistamines (=histamine receptor antagonists)
Histamine is a messenger substance that unfolds its effect by docking to different histamine receptors, similar to a key that fits into certain locks and can thus set a certain mechanism in motion. So far, four different histamine receptors are known, which are referred to as H1 to H4. Antihistamines (= histamine receptor antagonists, histamine receptor blockers) act against histamine-related symptoms by blocking specific histamine receptors. They figuratively block certain "keyholes" so that the "key" no longer fits there. Antihistamines therefore do not act directly against histamine and cannot directly lower the histamine level in the body. They can only temporarily block certain effects of histamine.
Most important are the H1 antihistamines, which normally suppress most symptoms. In addition, the administration of an H2 antihistamine can be useful in cases of excessive gastric acid production (heartburn, acid upset). H3 and H4 blockers are currently of little therapeutic importance.
The older antihistamines (so-called first-generation active substances) have the ability to cross the blood-brain barrier. In the brain they can have a sedative effect on the central nervous system (CNS), i.e. they can make you tired. During the day, this can be an unwanted side effect. Taken before going to bed, this class of antihistamines can also be used as a welcome sedative.
Newly developed antihistamines (so-called second-generation active substances) were designed in such a way that they cannot penetrate the blood-brain barrier or only slightly. Since they cannot reach the central nervous system, they hardly cause fatigue.
In the SIGHI Medication Manual you will find an overview of the approved active ingredients with a tabular comparison of their properties, advantages and disadvantages as well as tips and tricks.
Antihistamines as breakdown inhibitors
Certain antihistamines appear to inhibit histamine-degrading enzymes or other amine oxidases as an unwanted side effect. The application of such active substances has the consequence that on the one hand specifically one of the histamine receptors is blocked and thereby a part of the histamine effects becomes weaker, but on the other hand the histamine level rises due to the inhibition of a degrading enzyme, which intensifies other histamine effects. However, the active substances affected are not necessarily incompatible. Normally the positive effect predominates. Nevertheless, one should first try better alternatives.
Diphenhydramine (e.g. in benoctene, nardyl) blocks the histamine binding site of the HNMT, so that no histamine can reach the active centre of this enzyme [Horton et al. 2005].
Hydroxyzin (e.g. in Atarax) inhibits the monoamine oxidase B (MAO-B) and the semicarbazid-sensitive amine oxidase (SSAO) in plasma, to a lesser extent also the membrane-bound form of SSAO as well as the MAO-A. This impairs the degradation of certain biogenic amines. [O'Sullivan et al. 2006]
Prostaglandin synthesis inhibitors
Prostaglandins (a large group of tissue hormones), along with histamine, are among the most important mast cell mediators that trigger symptoms and are released from mast cells by liberators. The body forms prostaglandins with the help of cyclooxygenases (enzymes). There are two subtypes of cyclooxygenase: cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2). An important difference is that the cyclooxygenase-2 gene is mainly activated by inflammatory processes and other conditions. Prostaglandin synthesis inhibitors relieve pain and inflammation by inhibiting the enzymes COX-1 and/or COX-2, thus reducing the formation of prostaglandins. Because prostaglandins are not only harmful but also have important functions, there may be fewer side effects if a selective COX-2 inhibitor is chosen, which inhibits COX-2 more than COX-1. The possible adverse effects of COX-1 inhibition include gastric mucosal bleeding and possible kidney damage due to reduced renal blood flow.
The SIGHI Medication Manual presents suitable active substances and filters out those without intolerable excipients from the large variety of available preparations (related to CH approvals).
Diamine oxidase (DAO), DAOSIN®, DAOZym®
Usage and mode of action
(To be continued...)
Vitamin C (ascorbic acid)
(To be continued...)
Other supplemente (vitamins, minerals)
(To be continued...)
Immunosuppressants, cytostatic drugs, cytoreductive therapies
(To be continued...)
Numerous pharmaceutical active substances are histamine liberators, i.e. they unspecifically release the body's own histamine as an undesirable side effect. These intolerances usually manifest themselves through skin rashes or other symptoms typical of allergies. When intolerance reactions occur after taking medication, many doctors therefore first think of a type I allergy. If in such cases IgE antibodies against the drug cannot be detected, the histamine-liberating effect of the active substance should be considered as the most probable cause of the observed drug intolerance (pseudoallergy).
Many allergy sufferers also have MCAD and vice versa. Therefore, it should not be forgotten that an allergy to a drug substance can also be accompanied by MCAD, especially if the reaction is severe [Jarisch 2004, p.123].
There are also drugs that inhibit the activity of diamine oxidase (DAO). Such undesirable side-effects are difficult to recognise as drug intolerance, because the symptoms do not appear after taking the drug, but only later when histamine is added to the body. In people who are histamine-intolerant, medication may not work as expected or may even aggravate the symptoms they are used to treat. DAO blockers (DAO inhibitors) are particularly tricky because the delayed onset of allergy-like symptoms is not so easily associated with the medication administered [Jarisch 2004, p.123].
List of incompatible active substances for mast cell activation disease (MCAD) or histamine intolerance (HIT)
The following table lists the incompatible active substances, as well as active substances for which it was only shown that they inhibit one of the degrading enzymes, without having been investigated whether they are therefore incompatible. Not all substances listed here are therefore incompatible in every case, but could nevertheless be worth a try if it is not possible to switch to a better alternative. The list is not exhaustive and has not been checked by us for accuracy. A printable version in A4 format can be found in the SIGHI Medication Manual.
|Active substance||Examples of products ®||Categories||Histamine effects||References|
|Acemetacin||Antirheumatic||DAO inhibitor||[Sattler 1985, Fritzsche 2009]|
|Acetylcysteine||Fluimucil, Helvetussin, Muco-Mepha, NeoCitran, Solmucol||Mucolytic, antidote||DAO inhibitor||[Jarisch 2004, Maintz et al. 2006]|
|Acetylsalicylic acid, ASS||Aspirin||Analgesic||Histamine liberator||[Jarisch 2004, Maintz et al. 2006]|
|Acriflavin||Antiseptic||DAO inhibitor||[Fritzsche 2009]|
|Alcuronium||Muscle relaxant||DAO inhibitor||[Sattler 1985, Maintz et al. 2006, Forth 2008]|
|Alprenolol||Beta blocker||DAO inhibitor||[Maintz et al. 2006]|
|Ambroxol||Ambrovene, Ambroxol, Broxol, Mucosolvan, Mucospas||Expectorant||DAO inhibitor||[Jarisch 2004, Maintz et al. 2006]|
|Amiloride||Diuretic||?||[Maintz et al. 2006]|
|Aminocycline||DAO inhibitor||[Sattler 1985]|
|Aminophyllin||Euphyllin, Mundiphyllin, Myocardon||Antiasthmatic||DAO inhibitor||[Sattler 1985, Jarisch 2004, Maintz et al. 2006]|
|Amiphenazole||DAO inhibitor||[Sattler 1985]|
|Amitriptyline||Saroten, Tryptizol, Limbritol||Tricyclic antidepressant||DAO inhibitor||[Jarisch 2004, Maintz et al. 2006]|
|Amodiaquins||Antimalarials||HNMT-Blocker||[Horton et al. 2005, Aschenbach 2002]|
|Amphetamine||Histamine liberator||[Uni Bochum]|
|Amphotericin B||Antibiotic||Histamine liberator||[Livingstone 2013, Büttiker]|
|Atracurium||Muscle relaxant||Histamine liberator||[Sido et al. 2014, Dewachter et al. 2014]|
|Barbiturates||Hypnotics, sedatives, anaesthetics||Histamine liberator||[Steneberg 2007]|
|Bile acids, bile salts||Histamine liberator||[Büttiker]|
|Bupropion||NDRI||Histamine liberator||[Afrin et al. 2015]|
|Carbamazepine||Anticonvulsant||Histamine liberator||[Afrin et al. 2015]|
|Carbocromene||DAO inhibitor||[Sattler 1985]|
|Cefotiam||Antibiotic||DAO inhibitor||[Maintz et al. 2006]|
|Cefuroxime||Antibiotic||Histamine liberator||[Sido et al. 2014, Maintz et al. 2006]|
|Chloroquine||Chlorochin, Nivaquine, Resochin||Antimalarials, antirheumatic||DAO inhibitor, HNMT-Blocker||[Sattler 1985, Jarisch 2004, Donatelli et al. 1994, Maintz et al. 2006]|
|Cimetidine||H2 antihistamine||DAO inhibitor||[Prof. Ralf Bauer Uni Bonn; found in: Jarisch 2004 S.12, Maintz et al. 2006, Fritzsche 2009]|
|Ciprofloxacin||Antibiotic||Histamine liberator||[Livingstone 2013, SIGHI: 1 Fallbericht]|
|Clavulanic acid||Augmentin||Antibiotic||DAO inhibitor||[Sattler 1985, Jarisch 2004, Maintz et al. 2006]|
|Codeine||Opiate, analgesic, cough medicine||Histamine liberator||[Afrin et al. 2015, , Steneberg 2007]|
|Colistin mesilate||DAO inhibitor||[Sattler 1985]|
|Curare||Arrow poison alkaloids, anaesthetic||[Büttiker]|
|Cyclophosphamide||Cytostatic||?||[Maintz et al. 2006]|
|D-Cycloserine||Seromycin||Antibiotic||DAO inhibitor (Vitamin B6-Antagonist)||[Sattler 1985, Steneberg 2007]|
|Dextranes||Sephadex||Blood plasma substitute, antithrombotic||Histamine liberator||[Giertz und Hahn 1966, Büttiker]|
|Diazepam||Valium||Tranquilizer||DAO inhibitor||[Fritzsche 2009]|
|Diclofenac||Voltaren||Antirheumatic||Histamine liberator||[Jarisch 2004]|
|Dihydralazine||Nepresol||Antihypertensive, vasodilator||DAO inhibitor||[Wantke et al. 1989, Sattler 1985, Maintz et al. 2006, Fritzsche 2009]|
|Diphenhydramine||Nardyl, Benocten||Sedative, antihistamine||HNMT-Blocker||[Horton et al. 2005, Farag et al. 2008]|
|Dipyrone: see Metamizol|
|Dobutamine||Antihypotonic||?||[Maintz et al. 2006]|
|Fenpiverinium||DAO inhibitor||[Sattler 1985]|
|Flurbiprofen||Histamine liberator||[Jarisch 2004]|
|Framycetin||Antibiotic||DAO inhibitor||[Sattler 1985, Fritzsche 2009]|
|Furosemide||Lasix||Diuretic||DAO inhibitor||[Fritzsche 2009]|
|Gadolinium chelates||X-ray contrast media||Histamine liberator||[Sido et al. 2014]|
|Gelatine||Plasma substitute||Histamine liberator||[Sido et al. 2014]|
|Glyceroltrinitrate, glyceryltrinitrate, nitroglycerin, Propantrioltrinitrat||Vasodilator||Histamine liberator||[Pedersen et al. 2015]|
|Haloperidol||Haldol||Neuroleptic||DAO inhibitor||[Fritzsche 2009]|
|Heroin||Histamine liberator||[Nesterenko 2010]|
|Hydralazine||Histamine liberator||[Uni Bochum]|
|Hydroxyethyl starch||Plasma substitute||Histamine liberator||[Sido et al. 2014]|
|Indomethacin||Histamine liberator||[Jarisch 2004]|
|Isoniazide||Rimifon, Rifater||Tuberculostatic||DAO inhibitor (Vitamin B6-Antagonist)||[Jarisch 2004, Maintz et al. 2006]|
|Ketoprofen||Histamine liberator||[Jarisch 2004]|
|Latex gloves||Histamine liberator||[Sido et al. 2014]|
|Levofloxacin||Antibiotic||Histamine liberator||[Sido et al. 2014]|
|Meclofenamic acid||Histamine liberator||[Jarisch 2004]|
|Mefenamic acid||[Jarisch 2004]|
|Meperidine: see pethidine||Opioid|
|Metamizole, dipyrones||Novalgin, Minalgin||Analgesic, antipyretic||DAO inhibitor||[Jarisch 2004, Maintz et al. 2006]|
|Methohexital||Injection narcotic||Histamine liberator||[Sido et al. 2014]|
|Metoclopramide||Migpriv, Paspertin, Primperan||Antiemetic, gastroenterologic, dopamine antagonist||DAO inhibitor||[Sattler 1985, Jarisch 2004, Maintz et al. 2006]|
|Metoprine||HNMT-Blocker||[Horton et al. 2005, Jochem]|
|Mivacurium||Muscle relaxant||Histamine liberator||[Sido et al. 2014, Dewachter et al. 2014]|
|Morphine||Analgesic, opioid||Histamine liberator||[Afrin et al. 2015, Maintz et al. 2006, Steneberg 2007, Forth 2008]|
|Naproxen||Histamine liberator||[Jarisch 2004]|
|Nefopam||Analgesic||Histamine liberator||[Dewachter et al. 2014]|
|Neomycin||Antibiotic||DAO inhibitor||[Mathelier-Fusade 2006]|
|Nitroglycerin, glycerol trinitrate, glyceryl trinitrate, propane triol trinitrate||Vasodilator||Histamine liberator||[Pedersen et al. 2015]|
|Nonsteroidal anti-inflammatory drugs (NSAID)||Analgesic||Histamine liberator||[Sido et al. 2014]|
|Novamine sulfone||(=Metamizol) Novalgin, Minalgin||Analgesic, antipyretic||DAO inhibitor||[Jarisch 2004]|
|NSAP, NSAR, NSAID||Verträglichkeit individuell!||NSAR, NSAID||(Histamine liberator)||[Afrin et al. 2015]|
|Opiates, Opioids||(Heroin, Morphium)||Aalgesic||Histamine liberator||[Sido et al. 2014, Wirz and Molderings 2017]|
|Orciprenaline||DAO inhibitor||[Sattler 1985]|
|Pancuronium||Muscle relaxant||DAO inhibitor||[Sattler 1985, Maintz et al. 2006, Fritzsche 2009]|
|Pentamidine||Antibiotic||DAO inhibitor||[Sattler 1985, Maintz et al. 2006]|
|Pethidine, Meperidine||Analgesic, opioid||Histamine liberator||[Sido et al. 2014, Wirz and Molderings 2017, Afrin et al. 2015, Maintz et al. 2006, Forth 2008]|
|Phenobarbital||Injection narcotic||Histamine liberator||[Sido et al. 2014]|
|Pirenzepine||DAO inhibitor||[Sattler 1985]|
|Polymyxin B||Antibiotic||Histamine liberator||[Büttiker]|
|Polyvinylpyrrolidone (E1201)||Povidone, PVP, Periston||Blood plasma substitute, antithrombotic, excipient in tablets and capsules||Histamine liberator||[Giertz und Hahn 1966, Novartis 2008]|
|Prilocaine||Local anaesthetic||DAO inhibitor||[Maintz et al. 2006, Nesterenko 2010]|
|Procaine||Local anaesthetic||Histamine liberator||[Sido et al. 2014]|
|Promethazine||Atosil, Closin, Proneurin, Prothazin||Sedative, antihistamine, antipsychotic||DAO inhibitor||[Irion 2009]|
|Propafenone||Rytmonorm||Antiarrhythmic||DAO inhibitor||[Jarisch 2004, Maintz et al. 2006]|
|Propanidide||Anaesthetic||DAO inhibitor||[Nesterenko 2010]|
|Protamine||Heparin antagonization||Histamine liberator||[Sido et al. 2014; Horrow 1985]|
|Quinidine||Cardiac||DAO inhibitor||[Fritzsche 2009]|
|Rifampicin||Antibiotic||Histamine liberator||[Livingstone 2013]|
|Rifaximin||Antibiotic||Histamine liberator||[1 Einzelfallbericht SIGHI]|
|SSRIs, selective serotonin reuptake inhibitors||Antidepressant||Unverträglich||[Afrin et al. 2015]|
|Suxamethonium||Muscle relaxant||Histamine liberator||[Forth 2008Sido et al. 2014]|
|Tacrin||Acetylcholinesterase inhibitor, Alzheimer's drug||HNMT-Blocker||[Cumming and Vincent 1992, Taraschenko et al. 2005]|
|Teicoplanin||Antibiotic||Histamine liberator||[Livingstone 2013]|
|Tetracaine||Local anaesthetic||Histamine liberator||[Sido et al. 2014]|
|Tetroxoprim||DAO inhibitor||[Sattler 1985]|
|Thiamine (vitamin B1)||(In parenteral administration. Compatible with food.)||Histaminliberator, DAO inhibitor||[Büttiker, Sattler 1985]|
|Thiopental||Sedative||Histaminliberator / DAO inhibitor ?||[Sido et al. 2014, Maintz et al. 2006]|
|Tolazoline||Histamine liberator||[Uni Bochum]|
|Topiramate||Migraine, anti-epileptic||Histamine liberator||[Afrin et al. 2015]|
|tricyclic antidepressants||Unverträglich||[Afrin et al. 2015]|
|Tubocurarins, D-Tubocurarin||Muscle relaxant||Histamine liberator||[Sattler 1985, Maintz et al. 2006, Forth 2008, Steneberg 2007]|
|Tyramine||Histamine liberator||[Uni Bochum]|
|Vancomycine||Antibiotic||Histamine liberator||[Sido et al. 2014, Livingstone 2013]|
|Verapamil||Flamon, Isoptin, Tarka||Coronaryvasodilatant, antihypertensive, antiarrhythmic, calcium antagonist||DAO inhibitor||[Jarisch 2004, Maintz et al. 2006]|
|X-ray contrast media||All of them!||X-ray contrast media||Histamine liberator||[Jarisch 2004]|
|ß-Adrenoceptor blockers||Histamine liberator||[Sido et al. 2014]|
Note that all X-ray contrast media, both ionic and anionic, are very strong liberators and very poorly tolerated by MCAD sufferers and histamine intolerants. Therefore, patients should receive at least an H1 antihistamine prior to examinations with X-ray contrast media. [Jarisch 2005].
Incompatible excipients in medicines
In addition to one or more active ingredients, medicines also contain several excipients (fillers, tableting agents, dyes, coating agents, preservatives, solvents, flavourings, sweeteners, surfactants, etc.). As a rule, these additives are not or only incompletely declared on the package insert. In addition, very little is known about which of the many possible excipients may be incompatible. Here are a few well-known examples:
Pills are usually coloured. However, many artificial dyes are strong histamine liberators. Whenever possible, uncoloured pills/tablets/capsules should be preferred to coloured ones.
Intravenously administered drugs often contain surfactants (emulsifiers, wetting agents or detergents) to dissolve water-insoluble active substances or ingredients. Besides the active ingredients of drugs, these excipients can inhibit the DAO as well. In a study investigating whether water-insoluble active drug ingredients inhibit DAO, 7 out of 42 surfactants tested proved to be DAO inhibitors. The authors conclude that some of the observed drug intolerances may be due to the presence of incompatible detergents as a formulation aid. [Sattler et al. 1987]
If you should find out that other preparations, active substances or excipients not mentioned on our pages probably cause intolerance reactions in connection with a mast cell activation disease or histaminosis, please let us know!
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|A||Back to the previous position|
|Afrin et al. 2015||Afrin LB, Pöhlau D, Raithel M, Haenisch B, Dumoulin FL, Homann J, Mauer UM, Harzer S, Molderings GJ.: "Mast Cell Activation Disease: An Underappreciated Cause of Neurologic and Psychiatric Symptoms and Diseases." Brain Behav Immun. 2015 Jul 7. pii: S0889-1591(15)00236-6. doi: 10.1016/j.bbi.2015.07.002.|
("We describe MCAD's pathogenesis, presentation (focusing on [central and/or peripheral neurologic and/or psychiatric symptoms] (NPS)), and therapy, especially vis-à-vis neuropsychotropes. Since MCAD patients often present NPS, neurologists and psychiatrists have the opportunity, in recognizing the diagnostic possibility of MCAD, to short-circuit the often decades-long delay in establishing the correct diagnosis required to identify optimal therapy.")
|Agner 1991||Agner T.: "Susceptibility of atopic dermatitis patients to irritant dermatitis caused by sodium lauryl sulphate." Acta Derm Venereol. 1991;71(4):296-300.|
("The skin response to sodium lauryl sulphate was found to be statistically significantly increased in atopic patients compared with controls [...]")
|Aschenbach et al. 2002||Aschenbach JR, Ahrens F, Garz B, Gäbel G.: "Paracellular tightness and catabolism restrict histamine permeation in the proximal colon of pigs". Pflugers Arch. 2002 Oct;445(1):115-22. Epub 2002 Jul 16. https://www.ncbi.nlm.nih.gov/pubmed/12397395|
|B||Back to the previous position|
|Bielenberg 2005||Bielenberg, Jens: "Korrelate einer schadstoffinduzierten Veränderung des Histaminstoffwechsels? Die Allergie-Hypothese". Österreichische Apotheker-Zeitung ÖAZ Aktuell (Ausgabe 15/2005), Hauptartikel 15/2005. Anschrift des Autors: Apotheker Jens Bielenberg, Raphael-Apotheke, D-25364 Westerhorn, Bahnhofstr. 53|
(Sehr interessanter Artikel über mögliche Ursachen von Allergien, Störfaktoren im Histaminstoffwechsel, Abbaumechanismen von Histamin, Ascorbate (Vitamin C), Umweltschadstoffe, Schilddrüsenerkrankungen, mit Kommentar von Prof. Jarisch)
|Büttiker||Dr. med. U. Büttiker, Konsiliararzt Universitätsklinik Bern: "Histaminliberatoren", http://www.hautarzt-bubenberg.ch/sites/hautarzt-bubenberg.ch/files/pdf/Histaminliberatoren.pdf, abgerufen am 16.07.2011.|
|C||Back to the previous position|
|Cumming and Vincent 1992||Cumming P, Vincent SR.: "Inhibition of histamine-N-methyltransferase (HNMT) by fragments of 9-amino-1,2,3,4-tetrahydroacridine (tacrine) and by beta-carbolines." Biochem Pharmacol. 1992 Sep 1;44(5):989-92.|
("Histamine-N-methyltransferase (HNMT), the major enzyme for the metabolism of histamine in rat brain, is potently inhibited by 9-amino-1,2,3,4-tetrahydroacridine (tacrine).")
|D||Back to the previous position|
|Dewachter et al. 2014||Dewachter P, Castells MC, Hepner DL, Mouton-Faivre C: "Perioperative management of patients with mastocytosis". Anesthesiology. 2014 Mar;120(3):753-9. doi: 10.1097/ALN.0000000000000031. https://www.ncbi.nlm.nih.gov/pubmed/24135579|
|Donatelli et al. 1994||Donatelli, P., Marchi, G., Giuliani, L., Gustafsson, L.L., Pacifici, G.M.: "Stereoselective inhibition by chloroquine of histamine N-methyltransferase in the human liver and brain.", Eur. J. Clin. Pharmacol. (1994). www.wikigenes.org/e/ref/e/7875186.html|
|F||Back to the previous position|
|Farag et al. 2008||Farag NA, Mohamed SR, Soliman GA.: "Design, synthesis, and docking studies of novel benzopyrone derivatives as H(1)-antihistaminic agents." Bioorg Med Chem. 2008 Oct 1;16(19):9009-17. doi: 10.1016/j.bmc.2008.08.039. Epub 2008 Aug 26.|
("histamine N-methyltranseferase (HNMT) active site in complex with its bound inhibitor (diphenhydramine)")
|Forth 2008||Forth, Wolfgang; Hofmann, Franz; Förstermann, Ulrich: "Allgemeine und spezielle Pharmakologie und Toxikologie", 9. Auflage, Elsevier,Urban&Fischer Verlag, 2008.|
|Fritzsche 2009||Fritzsche, Doris: "GU Kompass Nahrungsmittel Intoleranzen, Laktose, Fruktose, Histamin", Gräfe und Unzer Verlag, 1. Auflage 2009. ISBN 978-3-8338-1368-9.|
|G||Back to the previous position|
|Giertz und Hahn 1966||H. Giertz und F: Hahn: "Makromolekulare Histaminliberatoren", In: Mauricio Rocha e Silva (Hrsg.): Histamine and Anti-Histaminics Part 1. Handbuch der experimentellen Pharmakologie Band XVIII/1. Berlin, Springer-Verlag 1966, hier Seite 481–568|
|Gilfillan and Beaven 2011||Gilfillan AM, Beaven MA.: "Regulation of mast cell responses in health and disease." Crit Rev Immunol. 2011;31(6):475-529.|
(Das Antibiotikum Novalgin ist ein Histaminliberator.)
|H||Back to the previous position|
|Horrow 1985||Horrow JC: "Protamine: a review of its toxicity". Anesth Analg. 1985 Mar;64(3):348-61.|
(Protamin kann massive Mastzellmediatorfreisetzungen auslösen. Die Gabe von Protamin sollte deshalb auf Fälle beschränkt werden, in denen die Blutgerinnungsstörung eindeutig die Folge einer Hyperheparinämie ist.)
|Horton et al. 2005||Horton JR, Sawada K, Nishibori M, Cheng X.: "Structural basis for inhibition of histamine N-methyltransferase by diverse drugs". J Mol Biol. 2005 Oct 21;353(2):334-44.|
(Medikamentenwirkstoffe als HNMT-Blocker: Folgende Stoffe, von denen bekannt ist, dass sie starke HNMT-Inhibitoren sind, wurden darauf hin untersucht, auf welche Weise sie den Histaminabbau blockieren: Diphenhydramine (ein H1-Antihistaminikum!), Amodiaquine, Metoprine, Tacrine. Alle blockieren die Histamin-Bindungsstelle des Enzyms, so dass kein Histamin mehr zum aktiven Zentrum der HNMT gelangen kann.)
|I||Back to the previous position|
|Irion 2009||Dr. Roland Irion: Internetseite "Biogene Amine. Auslöser von pseudoallergischen Reaktionen".|
http://www.alles-zur-allergologie.de/Allergologie/Artikel/3526/Allergen,Allergie/Biogene%20Amine/, abgerufen am 30.04.2013.
|J||Back to the previous position|
|Jarisch 2004||Jarisch, Reinhart: "Histamin-Intoleranz, Histamin und Seekrankheit", Thieme Verlag, 2004, ISBN 3-13-105382-8.|
|Jarisch 2005||Jarisch, Reinhart: "Histamin-Intoleranz: Ein oft übersehenes Problem". Arzt & Praxis VerlagsGmbH, Wien, Sonderdruck Oktober 2005, Heft Nr. 908, S. 380-382, 59. Jahrgang.|
http://www.reizmageninfo.de/ArztPraxis_2005_Jarisch.pdf, abgerufen am 08.11.2009 (inzwischen nicht mehr abrufbar).
|Jochem 2004||Jochem J.: "Cardiac and regional haemodynamic effects of histamine N-methyltransferase inhibitor metoprine in haemorrhage-shocked rats." Inflamm Res. 2004 Jul;53(7):316-23. Epub 2004 Jun 25.|
Metoprin = HNMT-Hemmer
|K||Back to the previous position|
|Komericki et al. 2010||Peter Komericki, Georg Klein, Norbert Reider, Thomas Hawranek, Tanja Strimitzer, Roland Lang,Bettina Kranzelbinder, Werner Aberer: "Histamine intolerance: lack of reproducibility of single symptoms by oral provocation with histamine: A randomised, double-blind, placebo-controlled cross-over study", Wien Klin Wochenschr (2010). DOI 10.1007/s00508-010-1506-y.|
http://pubget.com/paper/21165702, abgerufen am 11.12.2011.
Erfolgreicher Wirksamkeitsnachweis von Diaminoxidasepräparaten (DAOSIN). Zudem wurde gezeigt, dass das Auftreten einzelner Symptome nicht reproduzierbar ist. Es ist sinnlos, eine Korrelation zwischen der Histaminbelastung und einem bestimmten Symptom zu suchen. Man sollte in Studien immer die gesamte Palette der histaminvermittelten Symptomatik als Ganzes erfassen.
|L||Back to the previous position|
|Livingstone 2013||Dr. med. Elisabeth Livingstone, PD Dr. med. Uwe Hillen, PD Dr. med. Andreas Körber: "Unerwünschte Arzneimittelreaktionen" PowerPoint Präsentation Universitätsklinikum Essen.|
www.uk-essen.de/fileadmin/user_upload/hautklinik/fuer_studenten/arzneireaktionen_livingstone_23_05_2013.pdf (nicht mehr abrufbar)
|M||Back to the previous position|
|Maintz and Novak 2007|| Maintz L, Novak N.: "Histamine and histamine intolerance.", Am J Clin Nutr. 2007 May;85(5):1185-96. Department of Dermatology, University of Bonn, Bonn, Germany.|
|Maintz et al. 2006||Maintz, Laura; Bieber, Thomas; Novak, Natalija: "Die verschiedenen Gesichter der Histaminintoleranz: Konsequenzen für die Praxis (Histamine Intolerance in Clinical Practice)", Deutsches Ärzteblatt 2006; 103(51-52).|
http://www.aerzteblatt.de/archiv/53958, abgerufen am 25.08.2009.
|Mathelier-Fusade 2006||Mathelier-Fusade P.: "Drug-induced urticarias" Clin Rev Allergy Immunol. 2006 Feb;30(1):19-23.|
Gelesen in Gilfillan and Beaven 2011.
(Das Antibiotikum Novalgin ist ein DAO-Inhibitor.)
|Medivere GmbH||ganzimmun.ch: "Ernährungsempfehlungen bei Histamin-Intoleranz", Medivere GmbH.|
http://www.histaminose.de/07_pdf/histamin.pdf, abgerufen am 06.12.2009 (inzwischen nicht mehr abrufbar).
www.ganzimmun.ch/seiten/download_file.php?download_id=1855, abgerufen am 1.9.2014.
|N||Back to the previous position|
|Nassif et al. 1994||Nassif A, Chan SC, Storrs FJ, Hanifin JM.: "Abnormal skin irritancy in atopic dermatitis and in atopy without dermatitis.". Arch Dermatol. 1994 Nov;130(11):1402-7.|
("Past observations have shown increased irritancy in patients with "conditioned hyperirritability" due to active dermatitis, including atopic dermatitis (AD). In less active atopic conditions, irritancy levels are less certain. We have utilized 48-hour Finn Chamber testing with graded dilutions of sodium lauryl sulfate to detect irritancy thresholds in well-defined groups of patients [...]. Significantly greater frequency of response to sodium lauryl sulfate in both AD groups and also in patients with allergic rhinitis with no dermatitis was seen. Effective concentrations of sodium lauryl sulfate causing irritation in 50% or more of subjects (ED50) ranged from 0.0625% to 0.31% in all atopic groups, percentages that were significantly lower than the normal ED50 of 0.60%.")
|Nesterenko 2010||Nesterenko, Sigi: "Histaminintoleranz - die unentdeckte Krankheit", Rainer Bloch Verlag, 2010, ISBN-10: 3981095189, ISBN-13: 978-3981095180.|
|Novartis 2008||Novartis: "FACHINFORMATION Program® 40, Suspension zur Injektion für Katzen", Juli 2008.|
http://www.ah.novartis.de/platform/content/element/1612/ProgramInj40-Katze.pdf, abgerufen am 12.2.2013.
("Nicht bei Hunden anwenden. Der Hilfsstoff Polyvinylpyrrolidon (Povidon) ist für Hunde eine starke Histamin freisetzende Substanz. Beim Hund können deshalb, im Gegensatz zuKatzen, schwere Reaktionen auftreten.") Anm. d. Red.: Hunde erkranken besonders häufig an Mastozytomen oder Mastzellsarkomen. Ein Indiz, dass Mastozytosepatienten auf Povidon vielleicht ähnlich empfindlich reagieren könnten wie Hunde?
|O||Back to the previous position|
|O'Sullivan et al. 2006||O'Sullivan J, O'Sullivan MI, Tipton KE, Davey G.: "Inhibition of amine oxidases by the histamine-1 receptor antagonist hydroxyzine". J Neural Transm Suppl. 2006;(71):105-12.|
(Hydroxyzine (ein H1-Antihistaminikum!) blockiert die DAO.)
|P||Back to the previous position|
|Pedersen et al. 2015||Pedersen SH, Ramachandran R, Amrutkar DV, Petersen S, Olesen J, Jansen-Olesen: "Mechanisms of glyceryl trinitrate provoked mast cell degranulation." Cephalalgia. 2015 Feb 27. pii: 0333102415574846.|
(Intravenös verabreichtes Glyceroltrinitrat (Nitroglyzerin) führt einige Stunden nach der Injektion zu starker Mastzelldegranulation. Mechanismus noch unbekannt.)
|S||Back to the previous position|
|Sattler et al. 1987||Sattler J, Hesterberg R, Schmidt U, Crombach M, Lorenz W.: "Inhibition of intestinal diamine oxidase by detergents: a problem for drug formulations with water insoluble agents applied by the intravenous route?" Agents Actions. 1987 Apr;20(3-4):270-3.|
(Intravenös verabreichte Medikamente enthalten oft Detergentien/Tenside als Hilfsstoffe. Mehrere dieser Detergentien erwiesen sich als DAO-Hemmer und könnten für Unverträglichkeitsreaktionen auf Medikamente verantwortlich sein.)
|Sattler et al. 1985||Sattler J, Hesterberg R, Lorenz W, Schmidt U, Crombach M, Stahlknecht CD.: "Inhibition of human and canine diamine oxidase by drugs used in an intensive care unit: relevance for clinical side effects?" Agents Actions. 1985 Apr;16(3-4):91-4.|
(Liste unverträglicher Medikamente (DAO-Hemmer))
|Sido et al. 2014||Sido B, Dumoulin FL, Homann J, Hertfelder HJ, Bollmann M, Molderings GJ: "Chirurgische Eingriffe an Patienten mit Mastzellüberaktivitätserkrankung. Operationsrelevante Aspekte am Beispiel einer Cholezystektomie" - [Surgical interventions in patients with mast cell activation disease. Aspects relevant for surgery using the example of a cholecystectomy] Chirurg. 2014 Apr;85(4):327-33. doi: 10.1007/s00104-013-2642-5.|
(Beispiel Medikation und operative Prämedikation bei MCAD)
|Steneberg 2007||Steneberg, Andreas: "Biogene Amine – Ernährung bei Histamin-Intoleranz", Umwelt & Gesundheit 2/2007.|
http://www.iug-umwelt-gesundheit.de/pdf/072_47_56_SP_HIT_neu.pdf, abgerufen am 06.11.2009.
|T||Back to the previous position|
|Taraschenko et al. 2005||Taraschenko OD, Barnes WG, Herrick-Davis K, Yokoyama Y, Boyd DL, Hough LB.: "Actions of tacrine and galanthamine on histamine-N-methyltransferase." Methods Find Exp Clin Pharmacol. 2005 Apr;27(3):161-5.|
("Tacrine (0.01-10 microM) inhibited both human and rat HNMT activity in a concentration-dependent manner, but was less potent on both human embryonic kidney and recombinant human brain HNMT than on rat kidney HNMT [...]. Tacrine, but not galanthamine, may achieve brain levels sufficient to influence histamine metabolism in some patients treated for Alzheimer's disease.")
|Thomsen et al. 2002||Thomsen JS, Sonne M, Benfeldt E, Jensen SB, Serup J, Menné T.: "Experimental itch in sodium lauryl sulphate-inflamed and normal skin in humans: a randomized, double-blind, placebo-controlled study of histamine and other inducers of itch." Br J Dermatol. 2002 May;146(5):792-800.|
("[...] 1% sodium lauryl sulphate (SLS) used as a standard contact irritant to induce inflammation.")
|U||Back to the previous position|
|Uni Bochum||Klinik für Dermatologie, Venerologie und Allergologie, Ruhr-Universität Bochum – St. Josef-Hospital: "Patienteninformation Mastozytose", undatiert.|
http://www.derma.de/bochum/tl_files/dermatologie/dermatologie-pdf/Informationsblaetter/Merkblaetter_Mastozytose.pdf, abgerufen am 23.12.2014.
|W||Back to the previous position|
|Wantke et al. 1998||Wantke F, Proud D, Siekierski E, Kagey-Sobotka A.: "Daily variations of serum diamine oxidase and the influence of H1 and H2 blockers: a critical approach to routine diamine oxidase assessment." Inflamm Res. 1998 Oct;47(10):396-400.|
("[...] Serum diamine oxidase levels showed no significant daily variations [...] and no significant sex differences [...]. Antihistamines had no influence on diamine oxidase activity except for cimetidine, which caused 25% inhibition at the highest dose tested ( p < 0.0002) (positive control: aminoguanidine 85% inhibition (p< 0.0001), dihydralazine 68% inhibition (p<0.0001)) and diphenhydramine, which caused 19% increase (p<0.0001) of enzyme activity.")
|Wantke, Götz and Jarisch 1993||Wantke F, Götz M, Jarisch R.: "Histamine-free diet: treatment of choice for histamine-induced food intolerance and supporting treatment for chronic headaches." Clin Exp Allergy. 1993 Dec;23(12):982-5.|
("[...] a histamine-free diet was implemented to reduce histamine intake. Forty-five patients with a history of suffering from intolerance to food or wine (n = 17) and chronic headache (n = 28) were put on the diet over months to years. Fish, cheese, hard cured sausages, pickled cabbage and alcoholic beverages had to be avoided. [...] After 4 weeks on the diet 33/45 patients improved considerably (P < 0.01), eight of them had total remission. In 12/45 patients, however, no changes in symptoms were observed. Symptoms of food or wine intolerance significantly decreased (P < 0.02; treatment of choice), headaches decreased in frequency (P < 0.001), duration and intensity. After eating histamine-rich food symptoms were reproducible and could be eliminated by anti-histamines in most patients. These data indicate the role of histamine in food and wine intolerance and that histamine-rich food causes a worsening of symptoms in patients suffering from chronic headaches.")
|Wirz and Molderings 2017||Wirz S, Molderings GJ: "A Practical Guide for Treatment of Pain in Patients with Systemic Mast Cell Activation Disease" Pain Physician. 2017 Sep;20(6):E849-E861.|
(Schmerzbehandlung bei MCAD-Patienten) Frei zugänglicher Volltext.
|Y||Back to the previous position|
|Yokoyama 2007||Yokoyama A, Mori S, Takahashi HK, Kanke T, Wake H, Nishibori M: "Effect of amodiaquine, a histamine N-methyltransferase inhibitor, on, Propionibacterium acnes and lipopolysaccharide-induced hepatitis in mice", Eur J Pharmacol. 2007 Mar 8;558(1-3):179-84. Epub 2006 Nov 22.|
http://www.ncbi.nlm.nih.gov/pubmed/17222819, visited 13.06.2010.