A. Skin manifestations of drug allergy
1, common adverse drug reactions
Adverse drug reactions are very complex and are broadly divided into: drug overdose, drug intolerance, drug side effects, secondary effects and allergic reactions. Drug injection, internal, inhalation and other routes into the body caused by skin, mucous membrane reactions called drug rash. Drug rash is the most common type of drug allergic reactions, accounting for 25%-30% of all kinds of adverse drug reactions. Zhang Yanfeng, Department of Dermatology, Chengde Central Hospital
2, the factors that trigger drug rash
Common types of drugs that cause drug rash.
(1) antipyretic and analgesic drugs, with pyrazolones and salicylate preparations being common.
(2) Sulfonamides, with long-acting sulfa being the most common.
(3) Sleeping and sedative drugs, with more barbiturates.
(4) antibiotics, of which penicillin is more common.
Other drugs such as serums, antiepileptics, furans, phenothiazines, etc. are not uncommon in causing drug rashes, and drug rashes caused by herbal medicines are gradually increasing.
It is worth noting that many drugs, especially the compounded formulations of anti-cold drugs, often contain some component of the above categories of drugs, which are not noticed and cause serious allergic reactions.
Factors influencing drug allergic reactions: the more opportunities for drug intake, the greater the possibility of drug allergy, and the severity of drug rash is not clearly related to the dose of drugs ingested at one time. With the exception of irritant dermatitis, drug allergy is not related to the mode of administration. By nature, drugs with benzene and pyrimidine nuclei are highly allergenic. Drug dosage forms can influence the occurrence of drug allergy, for example, the non-crystalline form of insulin is more prone to allergy than the quickly absorbed form.
Genetic and environmental factors of drug allergic reactions: genetic factors have some significance in the occurrence of drug rash.
About 37.5% of domestic reports of drug rash have a history of allergic diseases (such as asthma, urticaria, allergic rhinitis, etc.), and 18.18% have a family history. The incidence of penicillin anaphylaxis is 2-3 times higher in those with a family history of anaphylaxis than in those without a family history. Environmental factors can directly affect the body’s response to therapeutic drugs. Allergy to antibiotics mostly occurs in the application of antibiotics for the treatment of certain diseases, but rarely occurs in healthy people who apply antibiotics to prevent certain diseases.
Cross-sensitivity and multiple sensitization: Cross-sensitivity refers to an allergic reaction caused by a compound that later causes the same allergic reaction due to another compound that is structurally similar to the initial allergen, such as penicillin and cephalosporins. Multiple allergy refers to the fact that some patients are allergic to multiple drugs that have no similarity in chemical structure.
II. Types of drug rash and severe drug rash
Drugs tend to appear after sensitization 7-10 days after starting treatment, but can also appear rapidly within hours or 1-2 days if similar drugs have been used previously.
Common types of drug rashes include: urticarial, angioedema, scarlet fever-like, measles-like eruption, fixed drug rash, and erythema multiforme.
In addition, there are several severe drug rashes, which are very rare but can be life-threatening, and their incidence can account for up to 1 in 1,000 hospitalized patients. The main types include the following: toxic epidermolysis bullosa (TEN), severe erythema multiforme, exfoliative dermatitis (erythrodermic type), and drug hypersensitivity syndrome.
The common sensitizing drugs for severe drug rash are NSAIDs, antiepileptics (e.g., carbamazepine, phenobarbital, phenytoin sodium, etc.), antibiotics, and allopurinol. The incubation period varies from a few hours to 6 weeks. It is worth noting that some drugs (e.g., allopurinol and carbamazepine) have a long sensitization period, up to 3-6 weeks, and are easily overlooked when looking for triggers, and timely discontinuation is not achieved. This is why it is critical to carefully follow up on the patient’s medication use in the last 1-2 months. The main clinical manifestations of severe drug rash are: rapid progression of the disease, erythema all over the body, surface blistering and epidermal loosening, the skin can be rubbed with slight force, with a rotten peach skin-like, scalded, burn-like appearance. There are large areas of necrosis and exfoliation of the oral and vulvar mucosa. It may also show flushing and swelling of the skin all over the body, oozing, crusting, large area of flaking, and odor. Systemic toxicity symptoms are severe, accompanied by high fever, enlarged lymph nodes, abnormal blood indicators, splenomegaly, myalgia, arthralgia and visceral lesions. If resuscitation is not timely, death can be caused by infection, toxemia, liver failure, kidney failure, etc.
Prevention and treatment of severe drug rash
For the prevention and treatment of severe drug rash, first of all, the use of drugs should be strictly controlled, according to the indications, as far as possible to reduce the variety of drugs, to eliminate the abuse of drugs. The first thing you should do is to take a careful medical history before using drugs, and try not to use similar drugs for those with a history of drug sensitivity. Pay attention to the preliminary manifestations of drug rash, such as fever, itching, mild erythema on the face or body, chest tightness and general discomfort, etc., so that early detection and timely discontinuation of drugs can avoid serious reactions. Treatment begins with discontinuation of the suspected drug and enhanced hydration to promote drug excretion. High-dose corticosteroids are generally applied early, combined with IVIG therapy. Due to the patient’s large epidermal peeling and exudation, coupled with high-dose hormone therapy, it is easy to cause skin, mucous membrane, lung infection and even sepsis. Strict disinfection and isolation measures should be taken to minimize the chance of infection. In foreign countries, patients with severe drug rash are usually admitted to a burn ward to provide a sterile environment and comprehensive care. Attention is paid to rehydration, maintenance of electrolyte balance, and prevention of hormone-related side effects. Patients are often unable to eat due to mucosal damage and require prompt nutritional supplementation.
The mortality rate of severe drug rash is high and is inconsistently reported across countries and regions, ranging from 5%-75% depending on the type of severe drug rash. The marked differences in mortality are inextricably linked to the prompt and appropriate treatment, supportive therapy, management of comorbidities, comprehensive care and the patient’s previous underlying disease.