How is frequent drug eruption?

Drug eruption, also known as drug dermatitis, is an inflammatory reaction of skin and mucosa caused by drugs entering the human body through various channels, and can also involve other systems of the body in severe cases. The most common way for drugs to enter the human body is oral administration, followed by injection, perfusion and external use. Non-therapeutic reactions caused by drugs are collectively called drug reactions or adverse reactions, and drug eruption is only one of them.

Cause of disease

1. Due to different individual factors, including genetic factors (allergic constitution), the defects of some enzymes and the influence of physical pathology or physiological conditions, the sensitivity of individuals to drug reactions varies greatly. The sensitivity of the same person to drugs may be different at different times.

2. Drug factors Most drugs can cause drug eruption in some individuals under certain conditions, but different kinds of drugs have different risks. The types of drugs that are easy to cause drug eruption in clinic are: ① Antibiotics: including semi-synthetic penicillins (such as ampicillin and amoxicillin), sulfonamides (such as compound sulfamethoxazole), tetracyclines and amide alcohols (such as chloramphenicol); (2) Antipyretic and analgesic drugs: such as aspirin, aminopyrine, paracetamol and phenylbutazone. These drugs are often made into compound preparations with other drugs, and their trade names are complex, so more attention should be paid to their use; ③ Sedative hypnotics and antiepileptic drugs: such as phenobarbital, phenytoin sodium, metoclopramide, carbamazepine, etc. Phenobarbital is the most common cause; ④ Antigout drugs: such as allopurinol; ⑤ Heterogeneous serum preparations and vaccines (such as tetanus antitoxin, rabies vaccine and snake venom immune serum). ); ⑥ Traditional Chinese Medicine: Some traditional Chinese medicines and preparations have also been reported to cause drug eruption.

Pathogenesis The pathogenesis of drug eruption can be divided into allergic reaction and non-allergic reaction.

1. Allergy Most drug eruptions belong to this reaction. Some drugs (such as serum, vaccine and biological products) have the function of complete antigen; But more drugs are small molecular compounds, which belong to haptens and need to be combined with large molecular weight carriers (such as protein, polysaccharides, peptides, etc.). ) becomes a complete antigen through valence bond and stimulates immune response. The substances that cause immune response can be drug prototypes, degradation products or metabolites, excipients and impurities in drugs. A few drugs (such as sulfonamides, quinolones, phenothiazines, tetracyclines and some contraceptives) can be transformed into antigenic substances under light induction, and the allergic drug eruption caused by them is called photoallergic drug eruption.

Allergic reactions related to drug eruption include type I allergic reactions (such as urticaria, angioedema and anaphylactic shock) and type II allergic reactions (such as hemolytic anemia, thrombocytopenic purpura and granulocytopenia). ), type III allergic reactions (such as vasculitis, serum sickness and serum sickness-like syndrome, etc. ) and type VI allergic reactions (such as eczema-like and measles-like drug eruption, exfoliative dermatitis, etc. ). The immune response to drug eruption is quite complicated. Drug eruption caused by some drugs (such as penicillin) can be mainly type I allergic reaction, type II or III allergic reaction, or two or more allergic reactions at the same time. The specific mechanism has not been fully clarified.

The characteristics of allergic drug eruption are as follows: ① It only occurs in a few people with allergic constitution, and most people do not respond; ② There is no correlation between the severity of illness and the pharmacological and toxicological effects and dosage of drugs; In a highly sensitive state, even a very small dose of drugs can cause a very serious drug eruption; ③ The onset has a certain incubation period. Generally speaking, it takes about 4-20 days for the first drug to appear clinically. If the sensitized person takes the drug again, it may appear clinically within a few minutes to 24 hours. ④ The clinical manifestations are complicated, and the lesions can be of various types, but for a certain patient, one type is often the main one; ⑤ There are cross allergy and polyvalent allergy. The former means that after being sensitized by a drug, the body may be allergic to drugs with similar chemical structure or the same chemical group. The latter means that when an individual is in a highly sensitive state, he may also be allergic to some drugs that are not allergic and have different chemical structures from sensitizing drugs; ⑥ The condition often improves after stopping using sensitizing drugs, and glucocorticoid therapy is often effective.

2. There are relatively few drugs that can cause non-allergic drug eruption. Its possible pathogenesis includes pharmacological effects (such as nicotinic acid can cause vasodilation and facial flushing, anticoagulant can cause purpura, aspirin can induce mast cells to degranulate and release histamine to cause urticaria, and non-steroidal anti-inflammatory drugs can cause drug eruption by inhibiting cyclooxygenase, etc. ), overreaction (for example, the therapeutic dose of methotrexate is very close to the toxic dose, which can often cause oral ulcers, hemorrhagic lesions and leukopenia. ) and accumulation (for example, long-term use of iodide and bromide)

Clinical manifestations The clinical manifestations of drug eruption are complicated. Different drugs can cause the same type of drug eruption, and the same drug can have different clinical types for different patients or the same patient at different times. The following are common types:

1. Fixed drug eruption is often caused by antipyretic and analgesic drugs, sulfonamides or barbiturates. Skin lesions are more common at the skin-mucosa junction of lips, mouth and glans, and can also occur on the back of hand, instep and trunk. Typical lesions are round or quasi-round, edematous dark purplish-red macula, with a diameter of 65,438+0 ~ 4 cm, often 65,438+0, occasionally several, with clear boundaries and redness around. In severe cases, blisters or bullae may appear on erythema, and mucosal folds are prone to erosion and exudation. Consciously mild itching. Generally no systemic symptoms, such as secondary infection can feel pain. Erythema can subside and leave gray-black pigmentation spots about 1 week after drug withdrawal. If the drug is used again, after a few minutes or hours, similar lesions will often appear in the same part and spread around. With the increase of recurrence times, the number of skin lesions can also increase.

2. Urticaria drug eruption is common, mostly caused by serum products, furazolidone and penicillin. The clinical manifestations are similar to those of acute urticaria, but they last for a long time and may be accompanied by serum sickness-like symptoms (such as fever, joint pain, lymphadenopathy and even proteinuria). If the allergenic drugs are excreted slowly or due to constant contact with trace allergens, it can be manifested as chronic urticaria.

3. Measles or scarlet fever drug eruption is mostly caused by penicillin (especially semi-synthetic penicillin), sulfonamides, antipyretic and analgesic drugs and barbiturates. The onset is sudden and may be accompanied by systemic symptoms such as fever, but it is lighter than measles and scarlet fever. Measles-type drug eruption is similar to measles, and the lesions are scattered or densely distributed. Red maculopapules or maculopapules the size of needles to rice grains are symmetrically distributed, which can spread all over the body, mostly on the trunk. In severe cases, it can be accompanied by small bleeding spots and obvious itching. Scarlet fever drug eruption started as a small erythema, which developed downward from the face, neck, upper limbs and trunk, spread all over the body and merged with each other within 2 ~ 3 days, accompanied by swelling of the face and limbs, similar to scarlet fever skin lesions, especially in the shriveled parts and flexion of limbs. The course of this type of disease is about 1 ~ 2 weeks, and the skin lesions may be accompanied by chaff desquamation after regression; If not treated in time, it will develop into a serious drug eruption.

4. Eczematous drug eruption patients first contact or topical penicillin, streptomycin, sulfonamides and quinine to cause contact dermatitis, thus increasing skin sensitivity, and then use the same or similar drugs. Skin lesions are erythema, papules, papules and blisters of different sizes, which are often combined into pieces and spread all over the body, and can be secondary to erosion, exudation and desquamation. Systemic symptoms are often mild. The course of disease is relatively long.

5. Purpura drug eruption can be caused by antibiotics, barbiturates and diuretics, and can be mediated by type II allergic reaction (causing thrombocytopenic purpura) or type III allergic reaction (causing vasculitis). Mild manifestations are red ecchymosis or ecchymosis on both legs, scattered or densely distributed, which can slightly bulge on the skin surface and will not fade after pressing, sometimes accompanied by small blisters or blood blisters in the air mass or center; Severe cases may involve all limbs and trunk, accompanied by joint swelling and pain, abdominal pain, hematuria, bloody stool and other manifestations.

6. Polymorphic rash is mostly caused by sulfonamides, antipyretic and analgesic drugs and barbiturates. The clinical manifestations are similar to erythema multiforme, which is symmetrically distributed in limbs and trunk. The lesions are round or oval edematous erythema and papules the size of peas to broad beans, with clear boundaries and purple-red center (iris phenomenon), and blisters often appear; Accompanied by itching, it will be painful when the oral cavity and external genital mucosa are involved. If the lesions spread all over the body and appear bullae, erosion and exudation on the basis of the original lesions, severe pain, high fever, elevated peripheral white blood cells, renal function damage and secondary infection will occur. The full name is severe erythema multiforme drug eruption, which belongs to one of the severe drug eruptions, and its condition is dangerous, which can lead to the death of patients.

7. Epidermolysis bullosa drug eruption is one of the severe drug eruptions, which is often caused by sulfonamides, antipyretic and analgesic drugs, antibiotics and barbiturates. Sudden onset, some patients initially showed erythema multiforme or fixed drug eruption, and the skin lesions quickly spread to the whole body with loose blisters or bullae of different sizes. Nissl's sign is positive, and a little external force can cause a large amount of exudation on the rotten surface, which can form a large area of epidermal necrosis and release, similar to shallow second-degree burns. Gentleness is obvious. Mucosa of oral cavity, eyes, respiratory tract and gastrointestinal tract can also be involved, with severe symptoms of systemic poisoning, accompanied by high fever, fatigue, nausea, vomiting, diarrhea and other systemic symptoms; Severe patients often die of secondary infection, liver and kidney failure, electrolyte disorder, visceral bleeding and so on.

8. Exfoliative dermatitis drug eruption is one of the severe drug eruptions, which is often caused by sulfonamides, barbiturates, antiepileptic drugs, antipyretic and analgesic drugs and antibiotics. It occurs after long-term medication, and the incubation period of the first onset is about 20 days. Some patients are caused by continued medication or improper treatment on the basis of measles-like, scarlet fever-like or eczema-like drug eruption. At first, the skin lesions were measles-like or scarlet fever-like, and gradually aggravated and merged into diffuse flushing and swelling all over the body, especially on the face, hands and feet, with herpes or blisters, accompanied by erosion and a small amount of exudation; After 2 ~ 3 weeks, the skin redness gradually subsided, and a large number of scales or deciduous desquamation appeared all over the body. Hands and feet fell off like gloves or socks, and hair and nails could fall off (renewable after recovery). Can involve oral mucosa and conjunctiva; Superficial lymph nodes in the whole body are often swollen, which may be accompanied by bronchopneumonia and drug-induced hepatitis. Peripheral white blood cells can be significantly increased or decreased, and even granulocyte deficiency occurs. This type of drug eruption has a long course of disease. If not treated in time, severe patients often die of systemic failure or secondary infection.

9. Acne drug eruption is mostly caused by long-term use of iodine, bromine, glucocorticoids and contraceptives. Skin lesions are acne-like lesions such as follicular papules and papules, which are more common in the face and chest and back. The course of the disease progresses slowly.

10. Photosensitive drug eruptions are mostly caused by the use of hibernating drugs, such as sulfonamides, tetracyclines, griseofulvin, psoralea corylifolia, quinolones, phenothiazine and birth control pills. Be exposed to sunlight or ultraviolet rays. It can be divided into two categories: ① drug eruption of phototoxic reaction: it mostly occurs 7 ~ 8 hours after exposure, and skin lesions similar to sunburn only appear in the exposed parts, which can happen to anyone; ② Photoallergic drug eruption: only a few people occur, with a certain incubation period, showing eczema-like lesions in exposed parts and involving non-exposed parts, with a long course of disease.

Clinically, severe erythema multiforme drug eruption, epidermolysis bullosa drug eruption and exfoliative dermatitis drug eruption with serious illness and high mortality are called severe drug eruption. In addition, drugs can also cause other forms of drug eruption, such as chloasma, skin pigmentation, systemic lupus erythematosus-like reaction, lichen planus-like, pemphigus-like lesions and so on.

Laboratory detection of allergic drugs can be divided into in vivo detection and in vitro detection, but there are still many shortcomings in sensitivity, specificity and safety of current detection methods.

1. In vivo test

(1) Skin test: The commonly used specific methods include laceration test, intradermal test, prick test, patch test, conjunctival test, tongue test and skin window test. Among them, intradermal test, prick test and patch test are commonly used, and the accuracy of intradermal test is high.

(2) Drug provocation test: after the drug eruption subsides for a period of time, the oral test dose (generally 1/8 ~ 1/4 or less of the therapeutic dose) is taken to detect suspected allergic drugs. This test is only applicable to mild drug eruption caused by oral drugs. When the disease itself requires the use of this drug (such as anti-tuberculosis drugs and antiepileptic drugs), it is forbidden to apply it to patients with acute allergic drug eruption and severe drug eruption.

2. In vitro test The safety of in vitro test is high, and basophil degranulation test, radioactive allergen adsorption test, lymphocyte transformation test and agar diffusion test can be selected, but the above test results are unstable.

The diagnosis and differential diagnosis of this disease should be based on the clear medication history, incubation period and typical clinical skin lesions of various drug eruptions, and other skin diseases and eruptive infectious diseases similar to skin lesions should be excluded. If patients take more than two kinds of drugs, it will be more difficult to accurately judge the sensitizing drugs. It should be comprehensively analyzed according to the patient's previous medication history, drug eruption history and the relationship between this drug and the disease.

Because of its complicated manifestations, the differential diagnosis of the disease is also very complicated. Measles-like or scarlet fever-like drug eruption should be differentiated from measles or scarlet fever; Epidermolysis bullosa drug eruption should be differentiated from golden grape scalded skin syndrome; When the fixed drug eruption in the genital area bursts, it should be differentiated from genital herpes and chancre.

Prevention of drug eruption is an iatrogenic disease, so prevention is particularly important. Attention must be paid to in the process of clinical medication:

(1) Before taking the medicine, you should carefully ask about the history of drug allergy to avoid using known allergic drugs or drugs with similar structures.

(2) When using drugs, such as penicillin, streptomycin, serum products, procaine, etc. , skin test should be carried out, and first-aid drugs should be prepared before the skin test in case of emergency. People who have a positive skin test should be banned from using this drug.

(3) Avoid drug abuse, adopt a safe route of administration, and try to choose drugs with low allergenicity for allergic people, especially known allergic drugs contained in compound preparations.

(4) Pay attention to the early symptoms of drug eruption, such as sudden itching, erythema and fever. , immediately stop using all suspicious drugs and closely observe them, and properly handle existing symptoms.

(5) Record the known sensitizing drugs on the first page of the patient's medical record or establish a drug taboo card for the patient, and inform the patient to keep it in mind and inform the doctor every time he visits a doctor.

All suspicious drugs should be stopped immediately after drug eruption is diagnosed, and then treatment should be carried out according to different types.

1. Mild drug eruption. After stopping using sensitizing drugs, the skin lesions quickly subsided. Antihistamines, vitamin c, etc. Can be given, if necessary, can be given a moderate dose of prednisone (30 ~ 60 mg/d). After the lesion subsides, it can be gradually relieved until the drug is stopped. If erythema and papules are the main symptoms, calamine lotion or glucocorticoid cream can be used externally, and 0. 1% Rafnuel, 3% boric acid solution or 0. 1% chlorhexidine solution can be used to wet compress erosion and exudation.

2. The principle of severe drug eruption is to rescue in time, reduce mortality, reduce complications and shorten the course of disease.

(1) Adequate use of glucocorticoids in early stage is the prerequisite for reducing mortality. Generally, hydrocortisone can be injected intravenously at 300 ~ 400 mg/d, or dexamethasone 10 ~ 20 mg/d can be injected intravenously twice, and the administration should be balanced as much as possible within 24 hours; If glucocorticoid is sufficient, the disease should be controlled within 3 ~ 5 days, and if it is not satisfactory, the dose should be increased (increasing the original dose by1/3 ~1/2); After the color of the focus fades, no new focus appears, and after the body temperature drops, it can be gradually reduced.

(2) Prevention and treatment of secondary infection is the key to reduce mortality. Disinfection and isolation should be emphasized, and antibiotics are not the only means to prevent infection routinely; If there is infection, we should pay attention to avoid allergic drugs (especially cross-allergy or polyvalent allergy) and antibiotics with less allergic reaction (such as erythromycin and lincomycin) when choosing antibiotics. ) can be selected in combination with the results of bacteriological examination. If the antibiotic treatment effect is not good, we should pay attention to the possibility of fungal infection, and add antifungal drugs as soon as possible once the diagnosis is made.

(3) Strengthening supportive therapy: it can create a stable individual environment and improve the quality of life of patients. Hypoalbuminemia and water-electrolyte disorder often occur due to high fever, difficulty in eating, wound exudation or skin peeling, which should be corrected in time. When necessary, fresh blood, plasma or albumin can be infused to maintain colloid osmotic pressure, which can effectively reduce exudation. If accompanied by liver damage, liver protection treatment should be strengthened.

(4) Strengthening nursing and external medication: it is an important guarantee for shortening the course of disease and successful treatment. Those with large skin lesions and serious erosion and exudation should pay attention to keep warm. Sterile sheets can be changed every day, and 3% boric acid solution or physiological saline can be used for local wet compress, and attention should be paid to preventing bedsores. People involved in mucous membrane should pay special attention to eye care and need regular washing to reduce infection and prevent bulbar conjunctival adhesion. Those who have difficulty in closing their eyes can be covered with oil gauze to prevent corneal damage caused by long-term exposure.