| disease | Drug Allergy |
| alias | Drug-induced Dermatitis, Drug Rash, Skin Drug Reaction |
After drugs enter the human body through various pathways, they cause reactions in organs and tissues, which are referred to as drug reactions. Among the side effects of drugs, approximately one-third to one-fourth affect the skin, leading some to propose the term cutaneous drug reactions. Among all cutaneous and mucosal drug reactions, drug rash (drug eruption) or dermatitis medicamentosa is particularly prominent. Therefore, this article focuses on describing drug rash.
bubble_chart Epidemiology
Since the founding of the People's Republic of China, the rapid development of the medical and health sector has led to a continuous increase in new drug varieties, providing more opportunities for patients to use medications. Consequently, drug reactions have also shown a significant upward trend. According to a 10-year post-founding statistical analysis by our university's dermatology department, the incidence of drug rash alone rose from 0.1% of initial dermatology consultations in 1949 to 1.2% in 1958—a 12-fold increase. Statistics from several major hospitals in Shanghai revealed that drug rash cases increased from 0.5% of 200,000 initial dermatology consultations between 1949 and 1954 to 1.2% of 280,000 consultations between 1955 and 1958, aligning closely with the earlier data. More recently, our university's dermatology department analyzed 380,000 initial consultations from 1982 to 1986, finding that the proportion of drug rash cases had further risen to 2.37%. From 1983 to 1991, among 2,418 inpatients in the dermatology department of Huashan Hospital affiliated with our university, 208 cases (8.6%) were drug-related. Previously, drug reactions were more common in urban areas, but in recent years, with the widespread availability of medical care, they have become increasingly prevalent in rural regions as well. Due to the extensive use of Chinese herbal medicine, drug reactions caused by Chinese medicinals have also risen. In reality, nearly everyone will encounter one or another medication in their lifetime, meaning almost all individuals are potentially susceptible to drug reactions under certain circumstances. With the continuous expansion of drug varieties, the types and manifestations of drug reactions have correspondingly evolved. Since most medications are prescribed by doctors, drug reactions are primarily iatrogenic diseases. While drug reactions cannot be entirely avoided, they can certainly be significantly reduced if physicians exercise caution when prescribing.
bubble_chart EtiologyUndoubtedly, the direct cause of drug reactions is, of course, the drugs themselves. According to statistical data from the 1960s, the main drugs causing drug rashes can be categorized into the following four groups: sulfonamides (accounting for 21.6%), antipyretics and analgesics (14.3%), antibiotics (12.3%), and sedatives and hypnotics (11%). Together, these accounted for nearly 60% of the causative agents. An analysis of 104 cases of severe drug rashes hospitalized between 1983 and 1992 revealed that the top four categories of causative drugs were: antibiotics, anti-gout medications (26 cases each, accounting for 25% respectively), antipyretics and analgesics (20 cases, 19.2%), and sulfonamides (12 cases, 11.5%). Compared to earlier data, there have been significant changes in the ranking and types of causative drugs. For instance, the proportion of sulfonamide-induced cases has notably decreased, with only compound sulfamethoxazole (SMZ) being reported. Anti-gout medications, particularly allopurinol, have risen to the top. Among antibiotics, cephalosporins have become predominant. In recent years, other frequently reported causative agents include furazolidone, thiazide drugs, nonsteroidal anti-inflammatory agents, isoniazid, para-aminosalicylic acid, chlorpromazine, carbamazepine, immunosuppressants, anticancer drugs, serum biological products, and Chinese herbal medicines—especially certain Chinese patent drug formulations.
The mechanism of drug reactions is quite complex, involving allergic reactions, non-allergic reactions, or other special mechanisms.
(1) Allergic Reactions Most drug rashes are related to this. The main evidence includes: ① They almost always occur at pharmacologically permissible doses; ② There is a certain latent period; ③ Patients are only allergic to a specific drug or class of drugs, showing high specificity; ④ For individuals already sensitized to a drug, re-exposure to the same drug, even in trace amounts, often leads to recurrence of the drug rash; ⑤ Cross-allergy may occur with drugs structurally similar to the sensitizing drug; ⑥ Skin tests with the sensitizing drug can yield positive results; ⑦ Short-term desensitization is possible for drug rashes primarily caused by Type I reactions; ⑧ Anti-allergic drugs, particularly corticosteroids, often show significant therapeutic effects.
Allergic drug reactions can manifest as any type from Type I to Type IV, and sometimes a single patient may exhibit two or more types simultaneously.
(2) Non-Allergic Reactions and Others
1. Toxic Effects Often caused by excessive doses, such as central nervous system depression from high doses of barbiturates; bone marrow suppression or liver damage from nitrogen mustard or aminopterin; or toxic reactions from pesticide absorption (e.g., 1059, 1605).
2. Pharmacological Effects Examples include drowsiness caused by antihistamines, euphoria from corticosteroids, and facial flushing from niacin.
3. Photosensitivity Reactions Taking chlorpromazine or sulfonamides followed by sun exposure can cause dermatitis, primarily in exposed areas. These reactions can be further classified as photoallergic or phototoxic.
4. Disruption of Enzyme Systems For example, phenytoin can interfere with folate absorption and metabolism, leading to oral ulcers; 13-cis retinoic acid can alter lipid metabolism, causing xanthomas; and isoniazid can affect vitamin B6
5. Deposition Effects Reactions caused by the deposition of drugs or their byproducts in specific tissues, such as heavy metal salts (bismuth, mercury, silver, lead) depositing in the gums, arsenic compounds in the skin (hyperpigmentation, keratosis), or yellowing of the skin from atabrine.
6. Special Local Irritation For example, aspirin can directly corrode the gastric mucosa, causing gastric bleeding and ulcers; sulfonamide crystals can block renal tubules, renal pelvis, and ureters, leading to dysuria, hematuria, oliguria, or even anuria.
7. Dysbiosis The normal flora in the human body has evolved over time to coexist harmoniously, with some populations inhibiting the overgrowth of others. Certain flora can also synthesize B vitamins and vitamin K, meeting the body's health needs. In short, a balanced unity exists between microorganisms and the host. However, prolonged or excessive use of antibiotics, corticosteroids, or immunosuppressants can disrupt this balance, such as broad-spectrum antibiotics leading to opportunistic infections.
8. Teratogenic and Carcinogenic Effects Some drugs may have teratogenic or carcinogenic effects with long-term use, such as thalidomide and tretinoin. {|114|}
(3) Influencing Factors In addition to the drug itself and its potential disease-causing mechanisms as direct pathogenic factors, the following aspects often play a certain role in the occurrence and development of drug reactions.
1. Medication Conditions
(1) Abuse: Mostly due to physicians not adhering strictly to medication principles and prescribing drugs arbitrarily. Another part is caused by patients self-administering or purchasing drugs with incomplete knowledge, leading to drug reactions.
(2) Misuse: Doctors prescribing incorrectly, pharmacies dispensing the wrong medication, or patients taking the wrong drugs, all of which are of course accidental occurrences.
(3) Suicide by medication: This is an extremely rare phenomenon.
(4) Drug dosage: Excessive drug dosage can cause severe reactions or even death. However, sometimes normal doses can also trigger drug reactions, which is related to individual differences in drug absorption, metabolism, and excretion rates, especially in elderly patients who require close attention.
(5) Treatment duration: For acute sexually transmitted diseases, the duration of medication is generally short, and even if the drugs used are highly toxic, the harm may be minimal. But for chronic sexually transmitted diseases, especially in cancer patients, the prolonged use of anticancer drugs often leads to cumulative effects and toxicity. Of course, some drugs like sedatives and hypnotics can cause addiction with long-term repeated use.
(6) Excessive types of medication: For individuals with allergic constitutions, the more types of drugs used, the higher the chance of reactions. This may be due to cross-reactions or synergistic effects between drugs.
(7) Route of administration: Generally, drugs administered via injection are more likely to cause reactions than oral administration. Topical application of highly antigenic medicinal pastes, such as sulfonamide or tetracycline ointments, has a much higher reaction rate upon absorption compared to oral administration. Cases of infant deaths due to excessive absorption of boric acid solution used in wet compresses have been reported. Drugs taken by pregnant or breastfeeding women can enter the fetus or infant and cause reactions.
(8) Cross-allergy: Many drugs with similar structures, such as sulfonamides, procaine, and para-aminosalicylic acid, which share a common "aniline" core, can cause identical reactions, known as cross-allergy. Such reactions can occur within about 10 hours of the first dose, without requiring a 4–5 day incubation period.
(9) Reuse of sensitizing drugs: If a patient has previously had an allergic reaction to a certain drug, reusing it can lead to more severe reactions. Reuse of sensitizing drugs usually occurs due to: ① Physician oversight, failing to review the patient’s drug reaction history; ② The patient not proactively informing the doctor of their drug allergy history; ③ Use of drugs that can cause cross-allergy; ④ Some patients in a highly sensitive state, such as those with drug rash, may easily develop allergic reactions to drugs they were not previously sensitive to.
(10) Unclean syringes: Contaminated syringes, needles, vials, tubing, etc., can introduce pyrogens into the body, causing adverse reactions.
2. Physical Conditions
(1) Gender: Drug reactions can occur in both males and females, but males are slightly more affected (3:2). Due to gender differences, estrogen and griseofulvin can cause gynecomastia in males, while androgens can lead to masculinization in female patients.
(2) Age: Children, aside from being more sensitive to anesthetics than adults, generally have greater tolerance to most drugs. Allergic reactions to drugs are also less common in children.
(3) Idiosyncrasy: An abnormal reaction to a drug not mediated by immune mechanisms. The cause is unknown.
(4) Genetic factors: Patients with an atopic constitution have a potential risk of severe reactions to penicillin-class drugs.
(5) Allergic or atopic constitution: Most drug reactions occur in patients with a certain allergic constitution. The pathological mechanism of such allergic reactions has been discussed earlier.
bubble_chart Pathological Changes
The histopathological changes caused by drug reactions are mostly similar to those not induced by drugs, lacking specificity and diagnostic value, hence they are omitted here.
bubble_chart Clinical Manifestations
Since drug reactions can involve various systems and organs, their manifestations are broad-ranging, encompassing both systemic and local effects. This section will only discuss some typical drug rashes and a few special types of drug reactions.
**(1) Allergic Drug Rash** This is the most common and diverse type of drug rash. Based on factors such as the latent period, progression, rash presentation, and outcome, it can be classified into more than 10 subtypes, including fixed erythema, scarlatiniform erythema, measles-like erythema, urticaria-like, erythema multiforme-like, erythema nodosum-like, pityriasis rosea-like, purpuric, and bullous epidermal necrolysis. These subtypes share the following common features: ① A certain latent period, typically 4–20 days (average 7–8 days). If sensitized, re-exposure to the same drug often triggers symptoms within 24 hours (average 7–8 hours), with the shortest being minutes and the longest not exceeding 72 hours. ② Sudden onset, sometimes preceded by prodromal symptoms such as fear of cold, malaise, or fever. ③ Except for fixed erythema, the rash is generally widespread and symmetrically distributed. ④ Often accompanied by systemic reactions of varying severity, ranging from mild (barely noticeable) to severe (headache, shivering, high fever, etc.). ⑤ The course is self-limiting, with mild cases resolving within a week and severe cases not exceeding a month. ⑥ Prognosis is generally good, except for bullous epidermal necrolysis, which is severe. Below are descriptions of several representative subtypes.
**1. Fixed Erythema (Fixed Drug Eruption)** This is the most common type of drug rash, accounting for 22–44% of cases. In our department’s 909 cases of drug rash, 318 (34.98%) were of this type. Common causative drugs include sulfonamides (especially long-acting sulfonamides), antipyretics and analgesics, tetracyclines, and sedatives. The rash presents as edematous patches, round or oval, with well-defined borders. In severe cases, one or several blisters or bullae may appear on the erythema. The number of erythematous patches varies, and their distribution is asymmetric. They can occur anywhere but are often found at mucocutaneous junctions such as the lips and external genitalia, where friction may cause erosion. Recurrences typically appear in the same location, overlapping completely or partially with previous pigmented patches, often expanding or increasing in number. Localized lesions may be accompanied by cutaneous pruritus, while widespread lesions may involve varying degrees of fever. After resolution, the erythema often leaves behind a bright purplish-brown pigmentation that persists for years, serving as a diagnostic clue. A few non-purplish edematous erythemas resolve quickly without leaving marks. Some cases may present with erythema multiforme-like, urticaria-like, or measles-like rashes.
**2. Scarlatiniform Erythema** The rash appears suddenly, often accompanied by shivering, fever (above 38°C), headache, and general malaise. It begins as large or small erythematous patches, spreading from the face, neck, and torso to the limbs, covering the entire body within 24 hours. The distribution is symmetrical, with edematous, bright red lesions that blanch on pressure. As the rash progresses, the patches enlarge and merge, potentially involving the entire skin, resembling scarlet fever. However, the patient’s general condition remains good, lacking other features of scarlet fever. After peaking, the erythema and swelling gradually subside, followed by large-scale desquamation. The scales become thinner and finer over time, resembling bran-like flakes, and the skin returns to normal within a month, usually without visceral damage. If the rash resembles measles, it is termed a pityriasis rosea-like drug rash, and so on.
**3. Severe Erythema Multiforme (Stevens-Johnson Syndrome)** This is a severe bullous form of erythema multiforme, involving not only the skin but also severe mucosal lesions in the eyes, mouth, and external genitalia, with significant erosion and exudation. It is often accompanied by shivering and high fever and may complicate with bronchitis, pneumonia, pleural effusion, or kidney damage. Ocular involvement can lead to blindness. This type of drug rash is more common in children. However, it must be noted that this syndrome is not always drug-induced.
4. Bullous Epidermal Necrolysis-Type Drug Rash This is a type of drug rash first observed domestically in 1958, which is relatively rare in clinical practice but quite severe. The onset is acute, with the rash spreading across the entire body within 2–3 days. Initially, the lesions appear as bright red or purplish-red patches. Sometimes, the onset resembles erythema multiforme, which later proliferates and expands, merging into large brownish-red patches. In severe cases, the mucous membranes are also affected, leaving no part of the skin intact. Large, flaccid bullae develop on these patches, forming numerous parallel folds 3–10 cm in length that can be pushed from one area to another. The epidermis is extremely thin and fragile, breaking with minimal friction, demonstrating pronounced acantholysis. Systemic symptoms often include high fever around 40°C. In critical cases, the gastrointestinal tract, liver, kidneys, heart, brain, and other organs may be affected simultaneously or sequentially. One fatal case was observed where the nasogastric tube was densely covered with shed mucous membranes. The course of the disease is somewhat self-limiting, with the rash typically beginning to subside after 2–4 weeks. However, severe complications, critical organ involvement, or improper management may lead to death within approximately 2 weeks.
The total white blood cell count is mostly above 10×109/L (10,000/mm3), with neutrophils accounting for about 80%, and the absolute eosinophil count being 0 or very low. Pathological autopsy findings in fatal severe cases reveal: ① Significant epidermal atrophy, with the stratum spinosum reduced to only 1–2 layers or even completely disappeared, intercellular and intracellular edema, dermal congestion and edema, perivascular small round cell infiltration, and fragmented collagen fibers. Oral mucosal lesions resemble those of the skin. ② Lymphadenopathy, medullary hyperplasia, endothelial mucosal hyperplasia and swelling, and cortical follicular atrophy. ③ The liver surface shows alternating yellow and red patches with visible static blood and hepatocyte degeneration. Microscopic examination reveals severe static blood in the central lobules of the liver, lipid degeneration and dissociation of residual hepatocytes; the boundary between liver parenchyma and portal areas is indistinct, with some hepatocyte borders blurred and others necrotic, lysed, and absorbed. ④ The kidney surface appears swollen with everted membranes. Microscopy shows vascular congestion, tubular turbidity and swelling, and focal infiltrates composed mainly of lymphocytes and monocytes in the cortical interstitium. ⑤ Neurons in the gray matter exhibit various degenerative changes, with those in the occipital lobe showing hydropic degeneration and swelling, occasionally accompanied by satellite cell phenomena. Basal ganglia and microglial cells display focal hyperplasia. ⑥ The myocardium exhibits interstitial edema and diffuse grade I non-round cell infiltration.
Bullous epidermal necrolysis-type drug rash shares many similarities with toxic epidermal necrolysis (TEN) reported by Lyell (1956). The latter presents with burn-like skin lesions, not necessarily with bullae, marked local pain, no significant visceral damage, and frequent recurrences. However, some consider the two to possibly be the same disease.
(2) Other types of drug rash and drug reactions—The etiology remains incompletely understood. There are many types; the main ones are described below:
1. Generalized exfoliative dermatitis type—This is one of the more severe forms of drug rash, second only to bullous epidermal necrolysis-type drug rash in severity. In the era before corticosteroids, its mortality rate was very high. Since this type of drug rash is often caused by larger doses or prolonged courses of medication, it may involve both allergic and toxic reactions.
This type of drug rash is uncommon. According to incomplete statistics from our department, it accounted for 2.53% of 909 drug rash cases from 1949–1958, 7.9% of 418 hospitalized drug rash cases from 1959–1975, and 23 cases (22%) among 104 severe drug rash cases treated from 1983–1992. Due to its severity, delayed treatment can lead to death.
The characteristic features of this condition are a long incubation period, often exceeding 20 to 20 days, and a prolonged course, generally lasting at least one month or more. The entire disease progression can be divided into four stages: ① The prodromal stage, manifested by transient skin eruptions such as symmetrical erythema confined to the chest, abdomen, or thighs, accompanied by cutaneous pruritus, or fever. These are warning symptoms; discontinuing medication at this stage may prevent the onset of the disease. ② The eruptive stage, which may develop gradually from the face downward or begin with an acute onset, followed by rashes spreading to the entire body at varying speeds. At the peak of the rash outbreak, the skin becomes intensely red and swollen, with significant facial edema, often oozing and crusting, accompanied by fear of cold and fever. Some patients may develop damage to internal organs such as the liver, kidneys, or heart. The total white blood cell count in peripheral blood is usually elevated, typically ranging between 15×109 and 20×109/L (15,000 to 20,000/mm3). ③ The desquamative stage, which is a hallmark of this condition. The redness and swelling of the rash begin to subside, followed by fish-scale-like to large-sheet desquamation. Scales may cover the bedsheets in the morning, with hands resembling torn gloves and feet like worn socks, shedding repeatedly for one to several months. Hair and nails often fall out simultaneously. ④ The stage of convalescence, where fish-scale-like desquamation turns bran-like and gradually disappears, restoring the skin to normal. Since the application of corticosteroids, the disease course has been significantly shortened, and the prognosis has greatly improved.
2. Short-course Antimony Dermatitis Type This is a mild toxic dermatitis observed in China during the 1950s when potassium antimony tartrate was used for short-course intravenous treatment of schistosomiasis japonica. Its characteristics include: ① High incidence rate, generally above 30–40%, sometimes as high as 60–70%; ② Short incubation period, with symptoms appearing within 2–3 days of starting treatment; ③ Rash occurs after the antimony dose reaches 0.3g; ④ More common in summer; ⑤ Symmetrical distribution of rash on the face, neck, back of hands, and extensor surfaces of fingers, occasionally on the chest and abdomen, resembling prickly heat—dense but non-confluent, with mild inflammatory reaction, slight itching or burning sensation, and occasional systemic symptoms like fever; ⑥ Self-limiting course, with most rashes resolving spontaneously within 3–5 days even without discontinuation of medication, followed by bran-like desquamation; ⑦ Rare recurrence upon retreatment. No complications or sequelae have been observed. Histochemical examination reveals no significant difference in antimony content between rash and normal skin (both approximately 2.5μg/dl). Histopathology resembles contact dermatitis, with no specificity.
3. Papillomatous Hyperplasia Type Often caused by prolonged use of iodides, bromides, etc. The incubation period is usually around one month. We observed two cases where mushroom-like papillomatous granulomas, 3–4 cm in diameter, irregularly distributed, significantly elevated, and firm to the touch, developed on a background of generalized erythematous drug rash, primarily on the trunk. These lesions gradually resolved with symptomatic treatment over approximately three weeks.
4. Lupus Erythematosus-like Reaction Since the initial discovery in the 1960s that hydralazine could induce lupus erythematosus-like reactions, over 50 drugs—including penicillin, procainamide, isoniazid, para-aminosalicylic acid, phenylbutazone, methylthiouracil, reserpine, metronidazole, and oral contraceptives—have been found to cause such reactions. Clinically, they primarily manifest as polyarthralgia, myalgia, polyserositis, pulmonary symptoms, fever, hepatosplenomegaly, lymphadenopathy, acrocyanosis, and rash. Unlike true lupus erythematosus, this condition lacks fever, cast urine, hematuria, and azotemia. After symptoms resolve, laboratory abnormalities may persist for months or even years.
5. Mycotic Reaction The extensive use of antibiotics, corticosteroids, and immunosuppressants often disrupts internal balance and microbial flora, leading to mycotic reactions. These manifest as infections by Candida albicans, Aspergillus, or dermatophytes. The former two may involve the gastrointestinal tract, lungs, or other internal organs, sometimes affecting multiple systems. Autopsies of patients treated with immunosuppressants frequently reveal severe systemic fungal infections. Notably, some dermatophyte infections become more extensive and refractory due to these medications, complicating prevention and treatment efforts, with high recurrence rates even after cure.
6. Corticosteroid-type Reaction High-dose or prolonged corticosteroid use can cause various adverse reactions, even death. Major side effects include: ① Secondary bacterial or fungal infections (most common); ② Gastrointestinal: "steroid ulcer," possibly complicated by bleeding or perforation; ③ Central nervous system: euphoria, irritability, dizziness, headache, insomnia; ④ Cardiovascular system: palpitations, hypertension, thrombosis, arrhythmias; ⑤ Endocrine system: Cushingoid syndrome, osteoporosis, diabetes, adrenal suppression, and growth retardation in children; ⑥ Skin: acne, hirsutism, telangiectasia, ecchymoses, atrophy; ⑦ Eyes: blurred vision, increased intraocular pressure, cataracts, and glaucoma.
In recent years, with the emergence of a large number of new drugs, the concept of "new drug rash" was proposed in the 1980s, furthering people's understanding of drug reactions. Almost all new drugs can cause various adverse drug reactions. β-lactam antibiotics are diverse, and various cephalosporins and penicillins can induce macula and papule or maculopapular rashes. Cytotoxic drugs may lead to alopecia areata, urticaria, toxic green tangerine peel necrosis, photosensitive dermatitis, and stomatitis. There are also many types of new anti-wind-dampness drugs, which can cause photosensitive dermatitis, urticaria, purpura, macula and papule, and stomatitis. Rifampin, D-penicillamine, and captopril may induce macula and papule, urticaria, and erythematous pemphigus (foliaceus type). Long-term use of β-blockers such as alprenolol, oxprenolol, and propranolol can result in psoriasis-like rashes, with some patients developing palmar metatarsus hyperkeratosis. They may also cause eczema, lichenoid eruptions, and other types of hypertrichosis, reverse male-pattern alopecia areata, and even trigger Stevens-Johnson syndrome.
Given the wide range of drug reactions, their complex manifestations, and their often specific nature, establishing a diagnosis can sometimes be challenging. For the diagnosis of drug rash, the primary basis remains the clinical history, combined with the presentation of the rash and laboratory tests, while excluding the possibility of other diseases, to conduct a comprehensive analysis and judgment.
In terms of laboratory tests, skin scratch and intradermal tests are often used to detect a patient's sensitivity to penicillin or iodides, which have some value in preventing anaphylactic shock reactions but are of limited significance in preventing the occurrence of drug rash. In vitro tests such as the lymphocyte transformation test and the radioallergosorbent test (RAST) have been used for the detection of allergens, but they are reliable only for certain drugs and can be adopted under appropriate conditions, providing some reference value.
bubble_chart Treatment Measures
(1) Removal of Disease Cause Discontinuing all suspected causative drugs is the first essential step. It is crucial to avoid delaying the discontinuation of medication when early signs of drug reactions have already appeared.
(2) Supportive Therapy Provide the patient with favorable conditions and avoid adverse factors to facilitate a smooth recovery through the self-limiting course of the disease. Measures include bed rest, a nutritious diet, maintaining a suitable temperature environment, and preventing secondary infections.
(3) Enhanced Excretion Use laxatives or diuretics as appropriate to promote the elimination of drugs from the body.
(4) Drug Therapy Different measures should be taken depending on the severity of the condition.
1. Mild Cases ① Oral administration of 1–2 types of antihistamines; ② Intravenous injection of 1g vitamin C once daily; ③ Intravenous injection of 10ml 10% calcium gluconate or 10% sodium thiosulfate once or twice daily; ④ Topical application of calamine lotion containing camphor or menthol, shaken lotion, or powder multiple times a day to relieve itching, dissipate heat, and reduce inflammation. Recovery typically occurs within about one week.
2. Moderately Severe Cases Refers to cases with widespread rash accompanied by fever. ① Bed rest; ② Application of the aforementioned topical medications; ③ Oral prednisone 20–30mg daily, divided into 3–4 doses. Complete recovery usually occurs within about two weeks.
3. Severe Cases Includes severe erythema multiforme, bullous epidermal necrolysis, and generalized exfoliative dermatitis-type drug rash. Immediate measures should be taken as follows:
⑴ Corticosteroids: Hydrocortisone 300–500mg, vitamin C 3g, and 10% potassium chloride 20–30ml added to 1000–2000ml of 5–10% glucose solution for slow intravenous drip once daily. Continuous 24-hour infusion is recommended. Once body temperature normalizes, the rash mostly subsides, and blood tests return to normal, the corticosteroid dosage can be gradually reduced and switched to an equivalent oral dose of prednisone or dexamethasone. If the rash resolves and overall condition improves further, the oral corticosteroid dosage should be tapered stepwise. The principle is to reduce the daily dose by 1/6–1/10 each time, with each reduction followed by 3–5 days of observation to monitor for rebound effects. Common issues in managing severe drug rash often stem from inappropriate corticosteroid dosage or tapering, such as an initial dose that is too small or subsequent reductions that are too rapid.
⑵ Antihistamines: Two types should be administered orally simultaneously.
⑶ Fresh Blood or Plasma Transfusion: 200–400ml per session, 2–3 times weekly, typically 4–5 sessions in total.
⑷ Antibiotics: Appropriate antibiotics should be selected to prevent infection, but caution is necessary. Patients with severe drug rash are often highly sensitized, making them prone to cross-reactivity or polyvalent sensitization—developing allergies to drugs structurally unrelated to the original causative agent, potentially triggering new drug rashes.
⑸ Local Treatment: For severe drug rash, local treatment and care of skin and mucous membrane lesions are critical and often determine the success of therapy. In the early acute phase, skin lesions can be managed with large amounts of powder or calamine lotion to protect the skin and reduce inflammation and swelling. For exudative lesions, wet compresses with saline or 3% boric acid solution should be applied, changed 4–6 times daily. Once dry, switch to 0.5% neomycin or 3% ichthammol paste, applied once or twice daily.
The conjunctiva and cornea are often affected and require prompt treatment. Rinse with saline or 3% boric acid solution to remove secretions, followed by triamcinolone acetonide or hydrocortisone eye drops every 3–4 hours. Apply boric acid or hydrocortisone eye ointment nightly to prevent corneal detachment (leading to blindness) and conjunctival adhesions. Oral and lip mucosal lesions may interfere with eating. Rinse with compound borax solution several times daily, and apply mucosal ulcer ointment or topical powders like Zhuhuang San or Xilei San. Nasogastric feeding may be necessary for patients unable to eat.
⑹ Concurrent damage to the heart, lungs, liver, kidneys, brain, or hematopoietic dysfunction requires timely and appropriate management.
(7) Closely monitor the balance of water and electrolytes; and administer drugs such as adenosine triphosphate, coenzyme A, inosine, and vitamin B6 as appropriate.
Due to the high incidence and significant harm of drug reactions, which can even be fatal in severe cases, prevention is of great importance. If doctors avoid prescribing medications indiscriminately and patients refrain from abusing drugs, the occurrence of drug reactions can be greatly reduced.
1. Before administering any medication, a clear diagnosis should first be established. Avoid using multiple drugs indiscriminately in an attempt to cover all possibilities before the condition is fully understood, as this can easily lead to unnecessary drug reactions.
2. The composition, properties, indications, contraindications, side effects, and prohibited combinations of the drugs used should be thoroughly understood and mastered to prevent misuse, incorrect use, or overuse of medications.
3. Before prescribing, a detailed inquiry should be made into the patient’s history of drug allergies, especially for those with an allergic constitution. For patients who have experienced allergic drug reactions, attention should be paid to the possibility of cross-sensitivity or polyvalent sensitivity reactions.
4. Medication should be administered in a planned manner, with doses not too large, types not too numerous, and duration not too prolonged. Regular monitoring is essential, particularly for drugs with certain toxicities, such as immunosuppressants and anticancer drugs. Close observation and frequent blood tests are necessary.
5. When certain organs have impaired function, they may be intolerant to specific drugs. For example, patients with kidney disease should use heavy metal drugs with caution.
6. During medication, warning signs or intolerance phenomena, such as cutaneous pruritus, erythema, or fever, should be closely monitored. If these occur, immediate discontinuation of the drug should be considered.
7. Patients who have experienced allergic drug reactions should be issued a drug contraindication card, specifying the name of the sensitizing drug and the type of reaction, for reference during follow-up visits.
8. National pharmaceutical regulatory authorities must strengthen drug administration. Before drugs are released to the market, they must undergo strict inspection to ensure high-quality standards.
