Pathogenesis (development of disease)
The term pseudoallergy is used to describe intolerance symptoms that are similar to those of allergy. However, unlike allergy, the cause is nonimmunologic, meaning that there is no hypersensitivity reaction of the immune system to the foreign substance. Pseudoallergic reactions are based on a disposition of the affected person, i.e. on an innate or acquired malfunction of the defense mechanisms or the target cells or target organs. Environmental factors in particular (possibly also viral infections) are essential for the exposure of the genetic effect.The allergy-like symptoms are triggered because increased mediators, such as histamines, are released from the mast cells, or because histamine cannot be broken down due to an enzyme deficiency (diamine oxidase, DAO) (histamine intolerance). In pseudoallergy, mast cell activation is triggered nonspecifically, i.e., without the involvement of surface-bound antibodies. In this case, the symptoms resemble an allergy of the immediate type.The group of pseudoallergies includes intolerances to biogenic amines and food additives as well as pharmacological intolerances (drugs).
Etiology (causes)
Biographic causes
- Genetic burden – see below Pathogenesis.
Behavioral causes
- Nutrition
- Foods high in vaso- or psychoactive biogenic amines (naturally occurring flavor and taste compounds found in foods, such as tyramine, serotonin, histamine, synephrine, feruloylputrescine, putrescine, cadaverine, spermidine, spermine)
- Foods that lead to increased histamine release such as strawberries, chocolate, citrus fruits, tomatoes.
- Food additives or naturally occurring food ingredients in food, such as:
- Antioxidants (e.g. butylated hydroxyanisole (BHA)/E320, butylated hydroxytoluene (BHT)/E321, gallates/E310 – E312).
- Flavorings
- Colorants or azo dyes (e.g. amaranth/E123, quinoline yellow/E104, cochineal red, erythrosine/E 127, yellow orange S/E127, indigotine (indigcarmine)/E132, curcumin/E100, patent blue/E131, tartrazine/E102, etc.; see under food additives/dyes).
- Gelling agents (e.g. mannitol/E421, sorbitol/E420/).
- Flavor enhancers (glutamic acid and its salts (glutamates)/E620-625).
- Preservatives (benzoates – p-hydroxybenzoic acid: benzoic acid and its salts/E210; metasulfites, nitrites and nitrates/E49 – E252, PHB esters/E214 – E219, propionic acid, sulfur dioxide and sulfites/E 221 – E227, sorbic acid and its salts/E200).
- Acidity regulators (e.g. tartrate/E337).
- Stabilizers or gelling agents (eg sorbitol/E420/, mannitol/E421).
- Salicylates (salicylic acid)
- Pesticide residues
Medication groups*
- Anesthetics (intravenous)
- Analgesics
- Acetylsalicylic acid (ASA)
- Β-lactam antibiotics
- Non-acid analgesics (ketoprofen, metamizole, paracetamol).
- Non-steroidal anti-inflammatory drugs (diclofenac, flurbiprofen, ibuprofen, meclofenamic acid, mefenamic acid, naproxen).
- Antiadiposita (orlistat).
- Antibiotics
- Aminoglycosides (gentamycin (gentamicin), gentamycin-AT, streptomycin, tobramycin).
- Cephalosporins (cefoxitin, ceftazidime, ceftriaxone, cefuroxime).
- Quinolones/fluoroquinolones/gyrase inhibitors (ciprofloxacin, moxifloxacin, nalidixic acid, norfloxacin, lomefloxacin, levofloxacin, ofloxacin).
- Dapsone
- Glycopeptide antibiotics (teicoplanin, vancomycin).
- Antiepileptic drugs (carbamazepine, gabapentin, pregabalin).
- Antiglutamatergic drugs (memantine).
- Anticonvulsants (carbamazepine, oxcarbamazepine).
- Antimalarials (atovaquone, quinine, hydroquinine, pyrimethazine).
- Antiparkinsonian drug (amantadine).
- Antituberculostat drug (rifampicin)
- Beta blockers
- Dipeptidyl peptidase 4 inhibitors (DPP-4 inhibitors; gliptins) – saxagliptin.
- Hemorrhoidal agents (Policresulen).
- Hormones
- Antiandrogens (cyproterone acetate)
- Prostaglandin derivatives (local) – bimatoprost, latanoprost, travoprost, unoprostone.
- 5-α-reductase inhibitors (dutasteride, finasteride).
- Immunosuppressants (azathioprine
- Colloidal plasma substitutes
- Local anesthetics
- Muscle relaxants/antispasmodics (tolperisone)
- X-ray contrast media
- Sedatives (clomethiazole)
- Sympathomimetics
Drugs that are inhibitors of DAO (diamine oxidase):
- Antibiotics
- Aminoglycosides (framycetin, neomycin, paromomycin).
- Clavulanic acid
- Isoniazid
- Antiarrhythmics
- Calcium antagonists (verapamil)
- Antidepressants
- Tricyclic antidepressants (amitriptyline).
- Antiemetics (metoclopramide).
- Antimalarials (chloroquine)
- Antiprotozoal agents (pentamidine)
- Antipsychotics (neuroleptics) – promethazine
- Bronchospasmolytics (aminophylline).
- Expectorants (ambroxol, N-acetylcysteine).
- Neuroleptics (promethazine)
- Parasympatholytics (pirenzepine).
- Plasma expander (gelatin)
- Vasodilators (dihydralazine)
Non-steroidal analgesics or anti-inflammatory drugs listed below may additionally lead to histamine release in individuals with allergic disposition, so there may be an increased histamine effect:
- Acetylsalicylic acid
- Diclofenac
- Indometacin
- Flurbiprofen
- Ketoprofen
- Meclofenamic acid
- Mefenamic acid
- Naproxen
Cave!Alcohol decreases the enzyme activity of DAO (diamine oxidase) and increases the absorption of histamine! This simultaneously leads to a non-IgE-mediated release of histamine from mast cells and basophilic granulocytes. * Patients with pseudoallergies often also react to dyes in foods and medications: Azo dye tartrazine (E 102) and yellow borange S (E 110) is often added to various drugs, including anti-allergy drugsOther dyes in drugs with allergy risk are: Quinoline Yellow (E 104), True Yellow (E 105) and Ponceau 4R (E 124)! Under “Food additives” you will find a database with all substance groups: Food additives with allergic and/or pseudoallergic potential are marked there accordingly.
