Introduction

Introduction to drug allergy

Drug overdose refers to the reaction of the sensitive drug into the human body through various ways, causing the reaction of organs and tissues, also known as drug reaction (drugreaction). Among the side effects of the drug, about 1/3 to 1/4 of the skin is involved, so a skin drug reaction (cutaneousdrugraciotns) has been proposed. In all skin and mucosal drug reactions, drug rash or drug dermatitis (dermatitis medicinosa) is more prominent.

basic knowledge

The proportion of illness: 1%

Susceptible people: no special people

Mode of infection: non-infectious

Complications: anaphylactic shock asthma abdominal pain nausea and vomiting jaundice hematuria renal failure

Pathogen

Drug allergy cause

Allergic reaction (35%):

Most drug eruptions are related to this, and the main basis is:

1 almost all of the doses allowed by pharmacology.

2 has a certain incubation period.

3 patients are only allergic to certain drugs or certain types of drugs and are highly specific.

4 If a drug has been sensitized, if the same drug is used again, even a small amount often causes the drug rash to recur.

5 Cross-allergy may occur with drugs that are similar in structure to sensitizing drugs.

6 With a sensitizing drug for a skin test, a positive result can be obtained.

7 A small amount of drug-induced rash caused by type I reaction can be desensitized for a short time.

8 anti-allergic drugs, especially corticosteroid treatments are commonly effective.

Non-allergic reactions and others (15%):

1, toxic effects: mostly due to excessive dosage, such as central nervous system depression caused by high dose of barbiturate sleeping drugs. Myelosuppression or liver damage caused by nitrogen mustard, Bai Xuening, etc. The poisoning reaction caused by the absorption of pesticides 1059 and 1605.

2, pharmacological effects: such as anti-histamine drugs caused by lethargy. The euphoria caused by corticosteroids. Facial flushing caused by niacin.

3, the role of light: after taking chlorpromazine, sulfa drugs, and then exposed to sunlight, can cause dermatitis mainly in the exposed parts, according to its mechanism can have two kinds of photoallergic and phototoxic reactions.

4, the disturbance of the enzyme system: such as Dalun Ding can cause oral ulcers by interfering with the absorption and metabolism of folate. 13-cis vitamin A acid can alter the metabolism of yellow blood caused by lipid metabolism. Isoniazid can affect the metabolism of vitamin B6 and cause polyneuritis.

5. Sedimentation: reactions caused by deposition of drugs or their products in special tissues, such as barium, mercury, silver, lead and other heavy metal salts deposited on the gums, arsenic deposits on the skin (pigmentation, keratinization), and a flat Caused by yellowing of the skin.

6, special local stimulating effect: such as aspirin can directly corrode the gastric mucosa, causing stomach bleeding, gastric ulcer. Sulfonamide crystal blocks renal tubules, renal pelvis and tube, causing dysuria, hematuria, oliguria and even urinary closure.

7. Flora imbalance: The normal flora in the human body can be suitable for each other in the process of co-evolution for many years. Some flora can inhibit the overgrowth of other flora, and some flora can still synthesize vitamin B and vitamin K for The health needs of the body, in short, the microbes and microorganisms, the microbes and the body have reached a contradiction, but if long-term or large-scale application of antibiotics, corticosteroids or immunosuppressants, can disturb these balances, such as the application of broad-spectrum antibiotics Can cause infection of conditional pathogens.

8, teratogenic, carcinogenic effects: some drugs may have teratogenic and carcinogenic effects after long-term application, such as thalidomide and trestin.

Influencing factors (5%):

In addition to the above-mentioned drugs as direct pathogenic factors and their possible pathogenic mechanisms, the following factors tend to play a role in the occurrence and development of drug reactions.

1, medication situation

(1) Abuse: Most of them are due to the lack of strictness in the principles of physician medication, and some are due to the drug reaction caused by the patient's ignorant use of self-contained drugs or self-purchased drugs.

(2) Misuse: The doctor prescribes the wrong prescription, or the pharmacy sends the wrong medicine, or the patient mistakes the medicine. Of course, these are accidental events.

(3) Suicide by taking drugs: This is a rare phenomenon.

(4) Dosage: If the dosage is too large, it may cause serious or even death. However, sometimes the normal dose may also have a drug reaction, which is related to the different absorption, metabolism and excretion rate of different drugs, especially in elderly patients.

(5) medication course. In acute cases, the time of administration is generally not long. Even if the drug used is more toxic, the harm may be less. However, in chronic diseases, especially in patients with cancer, the anticancer drugs used have a longer course of treatment, and the accumulation of drugs often occurs. Toxic production, of course, there are also some drugs such as sleeping pills, sedatives, etc., in the long-term repeated application of the right and wrong, can cause drug addiction.

(6) Too many types of drugs: For those with allergies, the more commonly used drugs, the more chances of reaction, which may be due to cross-reaction or synergy between drugs.

(7) Medication route: It is generally believed that the drug is more likely to cause a reaction than the oral administration by injection. The surrogate rate of the externally used antigenic ointment such as sulfonamide or tetracycline ointment is much higher than that of the oral administration, and the external application of boric acid solution is wet. Cases of excessive intake of infants have long been reported, and drugs taken by pregnant or lactating women can cause reactions in the fetus or infant.

(8) Cross-allergy: Many drugs that have something in common in structure, such as sulfa drugs containing a common "aniline" core, general-purpose ruthenium, and salicylic acid, can cause the same reaction, called cross-allergy, which The reaction can take place within about 10 hours of the first administration without the need for an incubation period of 4 to 5 days or more.

(9) Reuse of sensitizing drugs: If the patient has become allergic to a certain drug and then repeat the application, a more serious reaction may occur. The reuse of the sensitizing drug is usually due to:

1 The doctor's negligence did not understand the patient's past drug reaction history.

2 The patient did not take the initiative to tell the doctor about his history of drug allergy.

3 used a drug that can cause cross-allergy.

4 Individual patients with drug rash in high-sensitivity state are prone to allergic reactions to drugs that are not sensitive.

(10) Syringe is dirty: Unclean syringes, needles, syringes, vials, and skin tubes may cause adverse reactions due to the introduction of certain pyrogens into the body.

2, the body situation

(1) Gender: Drug response can be surnamed for both men and women, but males are slightly more than females (3:2). Due to gender differences, estrogen, griseofulvin can cause gynecomastia in males, and males can cause males in female patients. Chemical.

(2) Age: Children are more resistant to general drugs than adults, and children are more resistant to allergic reactions to drugs.

(3) Idiosyncrasy: an abnormal reaction to a drug that is not caused by an immune mechanism, and the cause is unknown.

(4) Genetic factors: Patients with a genetic allergic (atopy) constitution have a potential risk of serious reactions to penicillins.

(5) Allergic or allergic constitution: Most drug reactions occur in patients with certain allergic constitution, and the pathogenesis of allergies has been discussed above.

Prevention

Drug allergy prevention

Because the incidence of drug reactions is high, the harm is great, and serious people can cause death. Therefore, it is important to pay attention to prevention. For example, doctors do not administer drugs casually, patients do not abuse drugs, and drug reactions can be greatly reduced.

1. Before using the drug, first make a clear diagnosis. Do not use a variety of drugs to besiege before the disease is clear, thinking that there is always a drug that will have an effect, which is likely to cause unnecessary drug reactions.

2, the composition of the drug, performance, indications, contraindications, side effects, incompatibility, etc. should be fully familiar with, do not abuse, misuse, use drugs.

3, before the medication should be asked in detail whether the patient has a history of drug allergy, especially for those with allergic constitution can not be ignored, those who have had drug allergic reactions, should pay attention to cross-sensitive or multi-source sputum sensitive reactions.

4, medication should be planned, the dose should not be too large, the type should not be too much, the time should not be too long, and regular observation, especially the application of certain toxic drugs, such as immunosuppressants, anti-cancer drugs, etc., should be closely observed , often check blood and so on.

5, some organs have dysfunction, often can not tolerate certain drugs, such as patients with kidney disease need to use heavy metal drugs with caution.

6, during the medication should pay attention to some warning symptoms or intolerance, such as skin itching, erythema or fever, should be considered to stop the drug immediately.

7. Anyone who has developed an allergic drug reaction should be given a drug contraindication card, indicating the name of the sensitizing drug and the type of response for reference during the referral.

8. The state medical management department must strengthen the administration of pharmaceuticals. Before the products are placed on the market, they must undergo strict inspections to control the quality of good drugs.

Complication

Drug allergy complications Complications anaphylactic shock asthma abdominal pain nausea and vomiting jaundice hematuria renal failure

1, severe drug allergic reactions can cause systemic damage, such as anaphylactic shock, blood cell reduction, hemolytic anemia, neutropenia.

2, respiratory symptoms such as rhinitis, asthma, alveolitis, pulmonary fibrosis.

3, digestive system symptoms such as nausea, vomiting, abdominal pain, diarrhea and so on.

5, liver damage such as jaundice, biliary stasis, liver necrosis and so on.

6, kidney damage such as hematuria, protein years, renal failure and so on.

7, nervous system damage such as headache, epilepsy, encephalitis and so on.

Symptom

Symptoms of drug allergy Common symptoms Iodine allergy rash pruritus rash rash rash hypoxic ischemic nerve damage pigmented exfoliative dermatitis chills high fever

Because the drug response can affect a variety of systems and organs, a wide range, from the whole body to the local, this section only discusses some typical drug eruptions and a few special types of drug reactions.

(1) Allergic drug eruption This is the most common and most common type of drug eruption. According to its incubation period, development, rash performance and outcome, it can be divided into at least 10 subtypes, such as fixed erythema. Scarlet fever erythema, measles-like erythema, urticaria-like, polymorphous erythema, nodular erythema, rose prion-like, purpura-shaped and bullous epidermal necrolysis, they have the following commonalities:

1 has a certain incubation period, usually 4 to 20 days, an average of 7 to 8 days, if it has been sensitized, again with the same drug, often in 24 hours, an average of 7 to 8 hours can occur, the shortest is only a few minutes, The late is also no more than 72 hours.

2 Most of the onset is sudden, and there may be prodromal symptoms such as chills, discomfort, and fever.

3 The development of rash, in addition to fixed erythema, is generally distributed and symmetric distribution.

4 often accompanied by different systemic reactions, light can be not obvious, heavy can headache, chills, high fever and so on.

5 The course of disease has a certain self-limiting nature, the lighter is about a week, and the heavy one is no more than one month.

6 In addition to the prognosis of blister epidermal necrolysis, the residual is good, and several representative subtypes are introduced below.

1, fixed erythema (fixed rash) is the most common type of drug rash, according to statistics accounted for 22% to 44% of drug rash, 318 cases of 909 cases of undergraduate drug rash, accounting for 34.98%, common pathogenic drugs Sulfonamides (long-acting sulfonamides), antipyretic analgesics, tetracyclines and sedative edema patches, round or oval, with clear edges, one or several blisters or bullae on severe spots, erythema The number varies from one to several, and the distribution is asymmetrical. It can occur in any part. It often occurs at the junction of the skin and mucous membranes such as the lips and the external genitalia. It is often caused by abrasion, such as recurrence, usually still in the same place. The left pigment spots are completely or partially overlapped, and often enlarge and increase compared with the previous one. The lesions may be accompanied by itching. The skin lesions have different degrees of fever. The erythema often leaves the bright purple pigment spots. It has not been retired for many years and has diagnostic value. A few edematous erythema without purple color will fade quickly and leave no trace. Individual cases may be accompanied by polymorphous erythema, urticaria or measles-like erythema.

2, scarlet fever like erythema rash occurs suddenly, often accompanied by chills, fever (38 ° C or more), headache, general malaise, etc., the rash begins to be large, small erythema, from the face and neck, trunk, upper limbs and lower extremity development, 24 hours It is distributed throughout the body, symmetrically distributed, edematous, bright red, and the color can be faded. After the rash is enlarged and enlarged, it can be integrated with the whole skin, which is similar to scarlet fever. However, the patient is generally in good condition, and other manifestations without scarlet fever develop the rash. After the climax, the redness and swelling disappeared, followed by large pieces of desquamation. After the body temperature, the scales became thinner and thinner, less like sputum, and the skin returned to normal. The whole course was no more than one month. Generally, there was no visceral damage. If the rash is like measles, It is called a rose rash. I analogy.

3, severe polymorphic erythema (Stevens-Johnso syndrome) This is a serious bullous polymorphic erythema, in addition to skin damage, eyes, mouth, external genital and other serious mucosal damage, there are obvious paralysis, exudation, often accompanied Chronic, high fever, but also complicated by bronchitis, pneumonia, pleural effusion and kidney damage, eye damage can lead to blindness, children with this type of drug eruption are more common, but it must be pointed out that this syndrome is sometimes not caused by drugs.

4, bullous epidermal necrolysis loose drug eruption This is the first type of drug eruption we saw in China in 1958, clinically rare, but quite serious, acute onset, rash in 2 to 3 days throughout the body, early It is a bright red or purple-red spot. Sometimes it is multi-shaped erythema-like when it starts. It will enlarge and expand later, and it will be merged into a brown-red large piece. In severe cases, the mucous membrane will be involved at the same time. It can be said that the body is not finished, and there are loose bullae on the large piece, forming many parallel 3~ 10cm long wrinkles can be pushed from one place to another, the skin is extremely thin, slightly rubbed and broken, showing obvious acantholytic phenomenon, the whole body is often accompanied by high heat of about 40 °C, and the heavy ones can be simultaneously or sequentially Involved in the stomach, intestines, liver, kidney, heart, brain and other organs, I have seen a case of death due to this disease, the mucosa on the wall of the nasal feeding tube is densely covered, the course of disease has a certain self-limiting, rash often 2 to 4 weeks After the beginning of the regression, such as serious complications or serious involvement of some important organs, or due to improper treatment can die in about 2 weeks.

The total number of white blood cells is more than 10 × 109 / L (10000 / mm3), neutrophils are about 80%, the absolute count of eosinophils is 0 or very low, pathological anatomy of severe death cases:

1 The epidermis is significantly atrophied, and only one to two layers of acanthosis cells disappear or disappear, intercellular and intracellular edema, dermal congestion and edema, infiltration of small round cells in the surrounding tube, broken collagen fibers, and oral mucosal lesions similar to skin;

2 lymph node enlargement, medulla hyperplasia, endothelial mucosal hyperplasia, cortical follicle atrophy;

3 liver section yellow-red phase, visible blood stasis, and liver cells become more and more, microscopic examination showed that the upper part of the upper step of the foot is severely blood stasis, residual liver cell lipid changes, dissociation. The liver parenchyma and the portal are not clearly defined, and some liver cell boundaries are ambiguous, and some necrosis dissolves and is absorbed;

4 The kidney section is swollen, the capsule is everted, the microscopic examination shows vascular congestion, the curved tube is swollen, there are lymphocytes in the cortical interstitium, and the focal infiltration of mononuclear cells is formed;

5 The gray matter cells of the gray matter are all degenerated. The occipital nerve cells are water-like degeneration, swelling, and there are satellite cell phenomena, and the basal ganglia and microglia are hyperplasia.

6 Myocardium has interstitial edema and diffuse mild incomplete cell infiltration.

The bullous epidermis of the bad-skinned drug eruption is similar to the toxic epidermal necrolysis reported by Lyell (1956). The latter lesion is like a scald, not necessarily bullous. Local pain is obvious, no obvious visceral damage, and often recurrence, but some people think that the two may be the same disease.

(2) Other types of drug eruptions and drug reactions The etiology is not completely clear, and there are many types. The following are the following:

1. Systemic exfoliative dermatitis is one of the more serious types of drug eruption. Its severity is second only to bullous epidermal necrolysis and drug eruption. In the absence of corticosteroids, the mortality rate is high. The drug eruption has a large dose or a long course of treatment, so it may be combined with a certain toxic reaction based on the allergic reaction.

The disease is characterized by a long incubation period, often in the 20 to 20 days. The course of disease is long, usually at least one month, and the whole course of disease development can be divided into four stages:

1 prodromal period, manifested as a transient rash, such as symmetrical erythema confined to the chest, abdomen or thigh, consciously itching, or with fever, this is a warning symptom, if you stop at this time may avoid the disease;

2 rash period, can slowly gradually develop from the face down, or start an acute attack, the road with a rash or spread quickly or slowly to the whole body, when the rash episode is at a climax, the whole body skin is red and swollen, facial edema is significant, often There are discharge scars, accompanied by chills and fever, some patients may have liver, kidney, heart and other visceral damage, the total number of peripheral white blood cells increased, generally 15 × 109 ~ 20 × 109 / L (15000 ~ 20000 / mm3) between;

3 exfoliation period, this is the characteristic manifestation of this disease, the redness and swelling of the rash begins to subside, and then the scales are scaly to large-sized desquamation, the scales can be covered with sheets in the morning, and the hands are worn like broken gloves, such as wearing socks and repeatedly falling off , which lasts for a period of one to several months, and the hair and nails often fall off at the same time;

4 In the recovery period, the scaly desquamation or sputum, and then gradually disappeared, the skin returned to normal, after the application of corticosteroids, the course of disease can be significantly shortened, and the prognosis is greatly improved.

2, short-term tincture dermatitis type This is a light toxic dermatitis seen in the short-term treatment of schistosomiasis in Japan in the 1950s by intravenous injection of alcoholic acid and potassium sulphate. Its characteristics are:

1 The prevalence rate is high, generally between 30% and 40%, and some can be as high as 60% to 70%.

2 The incubation period is short, and both occur within 2 to 3 days after the start of treatment.

3 rash after the amount of tincture reached 0.3g.

4 more common in summer.

5 rashes are symmetrically distributed on the face, neck, back of the hand and fingers, occasionally in the chest and abdomen, resembling a scorpion, dense and not fused, mild inflammatory reaction, consciously itchy or burning sensation, individual fever and other systemic symptoms.

6 The course of disease is self-limiting. Even if the drug is not stopped, the rash will mostly disappear within 3 to 5 days, accompanied by sputum-like desquamation.

7 recurrence of occasional recurrence, no complications and sequelae, histochemical examination found that the rash and normal skin sputum content is not very different (about 2.5g / dl), histopathology like contact dermatitis, no specificity.

3, papillary proliferative type due to long-term use of left iodine, bromine agents, etc., the incubation period is often about one month, we have seen 2 cases, scattered on the basis of the whole body erythema-like drug rash, not very regular, significantly higher The leather surface, about 3 ~ 4cm, the diameter of the papillary proliferative granuloma, the touch is quite solid, mainly occurs in the trunk, gradually subsided after symptomatic treatment, the whole process is about 3 weeks.

4, lupus-like reaction since the early 1960s found that hydralazine can cause lupus-like reactions, so far known to have more than 50 drugs such as penicillin, procainamide, isoniazid, p-aminosalicylic acid, Bao Taisong, methylthiouracil, reserpine, metronidazole and oral contraceptives can cause such reactions. The main clinical manifestations are polyarticular pain, myalgia, polyserositis, pulmonary symptoms, fever. , liver and spleen and lymph nodes, limbs cyanosis and rash, etc., the difference between this disease and true lupus erythematosus is caused by fever, tubular urine, hematuria and azoazine, after the symptoms disappear, the laboratory is positive. It lasts for months or years.

5, fungal disease response due to a large number of antibiotics, corticosteroids and immunosuppressive applications, often cause environmental imbalance in the body and flora imbalance, the emergence of fungal case reactions, manifested as Candida albicans, Aspergillus or dermatophytes infection, before Both may have gastrointestinal, lung or other visceral infections, which may involve multiple organs at the same time. It is not uncommon to find serious systemic fungal infections in the autopsy of immunosuppressants before birth. It is worth noting that some of them suffer from dermatophytes. Patients, due to the application of the above drugs, the range of rickets lesions has become more extensive, and is not easy to treat, even if cured, it is easy to relapse, causing difficulties in the prevention and treatment of rickets.

6, corticosteroid-type reaction If the dose of hormone application is large, the time is long, often can cause a variety of adverse reactions, and even lead to death, it causes the main side effects are:

1 secondary bacterial or fungal infection: the most common.

2 gastrointestinal tract: "steroid ulcers", even with blood, perforation.

3 central nervous system: euphoria, irritability, dizziness, headache, insomnia, etc.

4 cardiovascular system: palpitations, elevated blood pressure, thrombosis, heart rhythm and so on.

5 endocrine system: Kexing-like syndrome, osteoporosis, diabetes, cortical dysfunction and inhibition of growth and development of children.

6 skin: acne, hairy, telangiectasia, ecchymosis, skin atrophy, etc.

7 eyes: blurred vision, increased intraocular pressure, cataracts and glaucoma.

Examine

Drug allergy check

In laboratory tests, skin scratches, intradermal tests often detect patients' sensitivity to penicillin or iodide, have certain value in preventing anaphylactic shock, but have little significance in preventing drug eruption. Lymphocyte transformation test and radioallergosorbernt test (RAST) have been used for the detection of allergens, but only for some drugs are reliable, can be used under conditions, have certain reference value.

Diagnosis

Drug allergy diagnosis

1. In view of the wide range of drug reactions, complex performance, and more specificity, it is sometimes difficult to determine the diagnosis. For the diagnosis of drug eruption, the clinical history is still the main basis, combined with rash performance and laboratory tests, and other The possibility of disease is analyzed and judged comprehensively.

2, laboratory examination, skin scratches, intradermal test often to detect the patient's sensitivity to penicillin or iodide, has a certain value to prevent anaphylactic shock, but the significance of prevention of drug eruption is small, in vitro The test has been used for the detection of allergens by lymphocyte transformation test and radioallergosorbernt test (RAST), but it is only reliable for some drugs, and can be used under certain conditions, and has certain reference value.

3, mainly the differential diagnosis of allergies between various drugs: In view of the wide range of drug reactions, complex performance, and more specific, it is sometimes difficult to determine the diagnosis, for the diagnosis of drug eruption, the current clinical history is the main basis, and then Combined with rash performance and laboratory tests, and the possibility of other diseases, comprehensive analysis and judgment.