Idiosyncrasy is a genetically determined pathological hyperreaction to specific substances, which develops already at the first contact with the stimulus. The disease occurs as a result of fermentopathies and is mainly associated with taking medications. Pathology does not have a clear clinical picture, since the symptoms are largely determined by the type of congenital gene mutation and the composition of the medication taken. Diagnosis of idiosyncrasy involves a detailed immunological and genetic examination. Treatment requires the exclusion of contact with the provoking antigen, the use of detoxification methods and desensitizing medications.
T78.4 Allergy, unspecified
The frequency of idiosyncratic reactions ranges from 1:30,000 to 1:50,000. The risk group includes patients who receive pharmacotherapy for a long time, as well as suffer from congenital fermentopathies or other gene mutations. Idiosyncrasy must be distinguished from allergy: the disorder occurs at the first meeting of a macroorganism with a trigger, whereas in allergic conditions, the organism is first sensitized, and clinical symptoms develop only at the second and subsequent contacts.
Causes of idiosyncrasy
As a rule, pathology is associated with the use of medicines. The reaction belongs to type B of adverse side effects (NPE) of medications, it does not depend on the dose taken and may occur after the first use of the drug. The disease most often develops when taking sulfonamides, psychotropic and narcotic drugs, some antibiotics and NSAIDs. Idiosyncrasy is rarely formed under the influence of food and household antigens.
The main risk factor is the presence of genetic syndromes that cause congenital fermentopathies or immune disorders. Persons with glucose-6-phosphate dehydrogenase deficiency, hepatic porphyria, hereditary hyperbilirubinemia (Gilbert, Kriegler-Nayyar, Rotor syndromes) are most susceptible to the disease. Idiosyncrasy occurs in phenylketonuria, Huntington’s chorea, hemophilia. The risk group includes people who are prescribed long-term pharmacotherapy protocols with the use of several medications.
Most cases of pathology are caused by fermentopathies associated with polyallelism of the corresponding genes. As a result, the body cannot ensure the normal metabolism of incoming foreign substances (drugs), so they become toxins and antigens. Pathological reactions manifest themselves in the form of an increase in the effect of the drug, an increase in its toxicity or an exacerbation of the underlying disease.
Basically, idiosyncrasy is observed with low activity of a certain enzyme, which is due to both insufficient synthesis of it and the production of an altered molecule with reduced catalytic properties or unstable structure. In rare cases, fermentopathies are diagnosed with mutations of regulatory genes that control inhibitors and activators of a particular enzyme, but do not have a direct effect on its synthesis.
Symptoms of idiosyncrasy
Idiosyncratic pathologies are characterized by polymorphism of clinical manifestations. The symptoms are determined by the type of antigen, the type of fermentopathy, the general conditions of the body, the presence of provoking factors. The disease often proceeds according to the type of a classic allergic reaction: with swelling and rash on the skin, respiratory symptoms (runny nose, nasal congestion), gastrointestinal disorders (nausea, diarrhea). Headaches and fever are less likely to bother.
With genetic mutations and taking certain medications, pathognomonic signs of idiosyncrasy appear. For example, after taking sulfonamides and antimalarial drugs, patients with a lack of G-6-FDG experience hemolytic anemia, and the use of barbiturates against the background of hepatic porphyria causes a sharp deterioration of the condition. With primary gout, exacerbations are provoked by loop and thiazide diuretics.
Idiosyncrasy refers to life-threatening adverse reactions to medications. In 33% of patients undergoing inpatient treatment, it occurs in severe form, and mortality rates, according to various data, range from 3.3% to 8.5%. Typical causes of death: acute liver failure, acute bone marrow aplasia, malignant hyperthermia, endotoxicosis.
The initial examination of the patient is carried out by an allergist-immunologist, whose task is to exclude the anaphylactic component of the disease. The doctor collects anamnesis of life, finds out the presence of allergic and genetic abnormalities in relatives. The absence of signs of allergodermatosis or respiratory allergoses in the patient and the appearance of symptoms at the time of the first intake of the drug indicates in favor of idiosyncrasy. Of the diagnostic methods , the following are assigned:
Blood tests. In the hemogram, there may be a decrease in the level of hemoglobin and erythrocytes (with idiosyncratic anemia) and deviations caused by the underlying disease. The level of eosinophils remains normal. In the immunogram, the doctor determines an adequate level of class E antibodies, the absence of specific immunoglobulins.
Genetic consultation. Since idiosyncrasy is caused by congenital metabolic disorders, it is necessary to be examined by a geneticist to identify burdened heredity. The diagnosis is confirmed by molecular genetic examination, studying the levels of metabolites in blood and urine by gas or liquid chromatography.
Treatment of idiosyncrasy
The main condition is the immediate cessation of contact with the medication that caused the symptoms. Taking into account the risk of endotoxicosis and drug damage to internal organs, infusions of crystalloid solutions, including sodium thiosulfate, which perform the function of detoxification, are necessary. Desensitizing agents (antihistamines, mast cell stabilizers, antileukotriene medications) are indicated for the relief of hyperreactivity of the body.
The frequent development of medicinal hepatopathies with idiosyncrasy requires the appointment of N-acetylcysteine and L-carnitine as non-specific antidotes. In severe systemic reactions, glucocorticoids are used. Ursodeoxycholic acid preparations, essential phospholipids and ademethionine-based hepatoprotectors are recommended to protect hepatocytes from destruction. Massive hyperbilirubinemia is corrected by plasmapheresis.
Prognosis and prevention
The probability of full recovery is determined by the severity of idiosyncrasy, the initial state of health, the presence of genetic diseases. With moderate pseudoallergic signs without multiple organ disorders, it is possible to quickly stop the condition. With a sharp deterioration in well-being and exacerbation of congenital pathology, the prognosis is doubtful, since lesions of internal organs sometimes end in death.
The prevention of idiosyncrasy is based on a rational approach to prescribing drug therapy in patients with congenital fermentopathies. The selection of treatment is carried out by a specialized specialist together with a geneticist and a clinical pharmacologist, while avoiding polypragmasia and the use of deliberately toxic drugs. Patients need to explain the importance of monitoring well-being during therapy and the need to seek help with atypical symptoms.