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Medications

Summary:

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.

Therapeutic approach:

1. Avoidance of external triggers
2. Stabilizing the secondary activated healthy mast cells with medication
3. To block the effect of individual free mediators by medication, inhibit their new synthesis or accelerate their degradation.
4. Treat remaining symptoms symptomatically.

Prognosis

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).

Medication

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
  • Ketotifen
  • ...
• 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.

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Incompatible medication

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.

Incompatible excipients

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.

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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.

Therapeutic approach

The therapy therefore consists in ...
(arranged according to priority)

1. ... minimizing mast cell activation by avoiding external triggers.
2. ... stabilizing the secondarily activated healthy mast cells with medication so that at least these do not release any mediators.
3. ... blocking the effect of individual free mediators with drugs, inhibiting their synthesis or accelerating their degradation.
4. ... chemotherapeutically reducing the number of cells in severe cases with an increased number of mast cells (cytoreductive therapy).
5. ... treating the remaining symptoms symptomatically (without resorting to incompatible products!).
6. ... diverting the attention away from the symptoms to other things through distracting activities.

Prognosis

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.

	SIGHI_Medication_Manual_PREVIEW.pdf (1 MB, version 2019-01-03)
	SIGHI_Medication_Manual.pdf (3 MB, version 2019-01-03)

Internal document, for members only. No retail sale.

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.
Examples:
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).

Breakdown accelerators

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...)

Incompatible medication

Histamine liberators

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].

DAO inhibitors

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.

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]

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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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