Drug allergy

Drug allergy is an increased specific immune reaction to drugs, accompanied by general or local clinical manifestations. Drug allergy is caused by the production of antibodies or the appearance of T-lymphocytes specific to the drug or its metabolites, and occurs even when the drug is prescribed in low doses. Only reactions mediated by immune mechanisms are considered allergic.

An allergy to a drug is always preceded by a period of sensitization, when primary contact between the body’s immune system and medications occurs. Several days usually pass between the first use of the drug and the appearance of a drug allergy. A drug allergic reaction develops only after repeated administration (contact) of drugs. It should be remembered that patients may not be aware that they have already taken any drug, for example, when eating meat containing penicillins.

There are two categories of patients with drug allergies. For some, it occurs as a complication in the treatment of a certain disease (mostly allergic in nature), significantly burdens its course, and sometimes even becomes a cause of disability and mortality. For others, drug allergies are an occupational disease - the main, and sometimes the only cause of temporary or permanent disability. As an occupational disease, drug allergy occurs in practically healthy individuals due to their prolonged contact with medications (doctors, nurses, pharmacists, workers in medical drug production plants).

Clinical manifestations

Four types of immunological mechanisms of tissue damage may be involved in the development of allergic reactions to drugs. Accordingly, these mechanisms of manifestation of drug allergies can be divided into the following types:

• immediate;
• cytotoxic - usually these are hematological reactions (hemolytic anemia, leukopenia, thrombocytopenia).
• immune complex type - a typical example is serum sickness syndrome.
• slow – caused by the cellular type of hypersensitivity.

Reactions of the first type are anaphylactic (reagin, IqE-dependent).

Allergic reactions caused by drugs are divided into three groups according to the speed of their development:

• reactions that occur immediately or within the first hour after the drug enters the body (anaphylactic shock, acute urticaria, Quincke's edema, bronchospasm, acute hemolytic anemia);
• subacute allergic reactions that develop during the first day after drug administration (agranulocytosis, thrombocytopenia, maculopapular exanthema, fever);
• reactions of a protracted type, which develop from several days to a week after administration of the drug (serum sickness, allergic vasculitis and purpura, arthralgia and polyarthritis, lymphadenopathy, damage to internal organs - allergic hepatitis, nephritis, etc.).

Skin rashes

Dermatitis is the most common clinical manifestation of drug allergies. They can occur as a result of external exposure to medications (contact drug dermatitis) or when drugs are administered orally or parenterally (toxidermia). They appear most often on the 8th day after starting the drug, are often accompanied by itching (sometimes it can be the only manifestation of an allergy) and disappear a few days after stopping treatment.

The most common causes of drug-induced allergic dermatitis are antibiotics (especially penicillin), sulfonamides, chlorpromazine, novocaine, quinoline derivatives, arsenic preparations, barbiturates, antipyrine, and mercury preparations. Contact allergic dermatitis can be caused by drugs such as psoriasin, antipsoriaticum, sulfur and tar ointments, some dyes (Ursol, azo dyes), etc. Drug dermatitis, especially toxidermia, in most cases - polymorphic rashes: erythematous, eczema-like, morbilliform, scarlatinoform, urticarial, hemorrhagic, exfoliative, erythrodermic, bullous, etc. In some cases, they resemble lichen rosea, lichen planus, erythema multiforme and other dermatoses. Sometimes toxicerma appears in the form of multiple scattered, sharply pigmented spots.

Allergic urticaria

Acute urticaria is characterized by a sudden onset, the appearance of severe itching, burning and rashes on any part of the skin, as well as on the mucous membranes of the lips, tongue, soft palate, and larynx. Blisters can be of various sizes and shapes; they may merge, accompanied by a disturbance in the general condition (nettle fever, arthralgia). Sometimes urticaria is accompanied by angioedema (Quincke's edema). Acute urticaria is often caused by drug (penicillin, streptomycin and other antibiotics) or food allergies, parenteral administration of drugs, serums, vaccines, and blood transfusions. In some patients, urticaria is only one of the symptoms of a serum-like reaction, combined with fever, headache, arthralgia, heart and kidney damage.

Quincke's edema

Quincke's edema (angioedema) is a clearly localized area of edema of the dermis and subcutaneous tissue, one of the forms of urticaria. As a rule, it is observed in places with loose tissue (lips, eyelids, scrotum) and on mucous membranes (tongue, palate, tonsils). Particularly dangerous is Quincke's edema, which develops in the larynx, which is observed in approximately 25% of cases. When swelling spreads to the larynx, hoarseness of the voice, a “barking” cough, loud, stridor breathing appear, cyanosis increases, and bronchospasm may occur. In the absence of timely assistance (including tracheotomy), the patient may die from asphyxia.

One of the first places in their ability to cause the development of angioedema is occupied by angiotensin-converting enzyme inhibitors (captopril, enalapril, ramipril, etc.). Therefore, the use of drugs of this group is contraindicated in patients with a history of angioedema of any nature.

An allergic reaction when using medicinal ointments and creams containing drugs may not be caused by the active substance itself, but by fillers, stabilizers, emulsifiers and aromatic substances. It is important to note that corticosteroids in the ointment do not prevent contact sensitization to its other components, although they may hide the presence of contact dermatitis. The risk of sensitization increases when an antibiotic ointment is combined with a corticosteroid.

Phenothiazines, sulfonamides, griseofulvin can cause photoallergic dermatitis in areas of the skin exposed to sunlight.

Allergic vasculitis

In mild cases, they manifest themselves as skin rashes (most often erythematous, maculopapular and in the form of purpura, occasionally the rashes have a urticarial character). With systemic vasculitis, fever, weakness, myalgia, swelling and pain in the joints, shortness of breath, and headache appear. Sometimes symptoms of kidney damage (hematuria, proteinuria) and intestines (abdominal pain, bloody stools) are observed. Compared to vasculitides of non-drug origin, eosinophilia is more often observed. Allergic vasculitis is caused by penicillins, sulfonamides, tetracyclines, alopurinol, diphenhydramine, butadione, indomethacin, iodides, isoniazid, meprobamate, diphenine, phenothiazines, propranolol, hypothiazide.

Allergic fever

It may be accompanied by serum sickness, vasculitis, etc., and in 3–5% of patients it is a single manifestation of drug allergy. An increase in temperature is usually observed on the 10th day of therapy. The drug origin of fever is indicated when the patient is in a relatively normal general condition, with evidence of a history of drug allergies, rashes and eosinophilia, and the use of a drug with allergenic properties (most often penicillins, cephalosporins, sometimes sulfonamides, barbiturates, quinine).

Damage to the digestive organs

It is observed in 20% of patients with drug allergies in the form of stomatitis, gingivitis, glossitis, gastritis, enteritis, colitis (allergic lesions of the food tract are often generalized).

Anaphylactic shock

It is a severe manifestation of an immediate allergic reaction. It is characterized by a rapidly increasing drop in vascular tone (decrease in blood pressure, collapse), an increase in vascular permeability with the release of the liquid part of the blood into the tissue (there is a decrease in the volume of circulating blood, thickening of the blood), the development of bronchospasm and spasm of the obese muscles of the internal organs. It develops 3–30 minutes after administration of the drug, and the route of administration does not matter. Anaphylactic shock can occur after taking drugs orally, in the form of inhalation, intradermal (in particular, during allergy tests), subcutaneous, intramuscular and intravenous administration. With parenteral and especially intravenous administration of the allergen, it develops more often and at an earlier time (sometimes “at the tip of the needle” - the rapid development of anaphylactic shock). After rectal, oral, external use of the drug, this condition is observed after 1–3 hours. The faster anaphylactic shock develops after contact with an allergen, the more severe its course and the more often death occurs. As a rule, the “culprits” for the development of this condition are penicillin (the incidence of anaphylactic shock is 1% with a fatal result in 0.002% of the patient) and local anesthetics, and occasionally streptomycin, tetracyclines, sulfonamides, pyrazolone drugs, B vitamins, and enzymes.

Depending on the severity of clinical manifestations, there are three degrees of anaphylactic shock: mild, moderate and severe.

In mild cases, a prodromal period is sometimes observed (5–10 minutes with parenteral administration, about 1 hour with oral administration): weakness, dizziness, headache, discomfort in the heart (a feeling of “compression” of the chest), heaviness in the head , tinnitus, numbness of the tongue, lips, feeling of lack of air, fear of death. Itching, urticarial rash, and sometimes skin hyperemia with a feeling of heat often appear. Quincke's edema may develop, and in some patients bronchospasm occurs. Cramping abdominal pain, vomiting, involuntary bowel movements and urination may occur. Patients lose consciousness. Blood pressure rapidly decreases (to 60/30 – 50/0 mm Hg), the pulse is threadlike, tachycardia up to 120–150 per minute, muffled heart sounds and dry wheezing in the lungs are observed.

In moderate cases, suffocation, often tonic and clonic convulsions, cold sticky sweat, pale skin, cyanosis of the lips, and dilated pupils are noted. Blood pressure is not determined. Due to the activation of the fibrinolytic system of the blood and the release of heparin by mast cells, nasal, gastrointestinal and uterine bleeding may develop.

In severe cases, the patient quickly loses consciousness (sometimes sudden death occurs), without having time to complain to others about changes in well-being. Severe pallor of the skin, cyanosis of the face, lips, acrocyanosis, and wetness of the skin are observed. The pupils are dilated, tonic and clonic convulsions, wheezing with prolonged exhalation develop. Heart sounds cannot be heard, blood pressure cannot be determined, and the pulse cannot be palpated. Despite the timely provision of medical care, patients often die.

Treatment of anaphylactic shock should begin immediately, since the result depends on timely, intensive, adequate therapy aimed at eliminating asphyxia, normalizing hemodynamics, eliminating spasm of smooth muscle organs, reducing vascular permeability, restoring the functions of vital organs, and preventing post-shock complications. It is important to follow a certain sequence of measures taken.

First published: Les Nouvelles Esthetiques Ukraine (6) 70 2011