Brief overview
- What is drug exanthema? A skin reaction to a drug that is sometimes allergic in nature.
- Symptoms: Variable-looking skin rash, sometimes occurring only in small areas, but sometimes covering almost the entire body. In severe cases, often other symptoms such as fever, swollen lymph nodes. Involvement of internal organs, if applicable.
- Forms: Including maculopapular exanthema, fixed drug exanthema, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell syndrome), DRESS syndrome.
- Causes: The drug rash is often an allergic reaction, but sometimes it is another form of hypersensitivity.
- Diagnosis: Doctor-patient consultation, physical examination, blood test, skin tests, if necessary further examinations such as provocation test.
- Treatment: If possible, discontinuation of the triggering medication (after medical consultation!). If necessary, antihistamines and/or cortisone to alleviate the symptoms (usually applied locally, if necessary also as tablets or infusions). In severe cases, inpatient treatment (possibly in intensive care).
Drug exanthema: description
Drug exanthema (“drug rash”) is an allergic or pseudoallergic skin rash caused by a drug used internally or externally. It is among the most common drug side effects.
In most cases, antibiotics are the trigger of drug exanthema, especially penicillins. For example, a pseudoallergic rash can develop during treatment with ampicillin (ampicillin exanthema). Other drug groups that can cause drug exanthema include anti-inflammatory painkillers from the NSAID group (such as ASA, ibuprofen, diclofenac) as well as epilepsy and gout medications.
Often, the active drug ingredient itself is responsible for drug-induced exanthema. In other cases, excipients of the drug trigger the rash, for example preservatives or dyes.
Drug exanthema: symptoms
Drug exanthema can occur on almost any part of the body, including mucous membranes. However, it typically develops on the extremities (arms, legs) and trunk (chest, abdomen, back). Sometimes, medicinal exanthema spreads from the trunk; in other cases, it extends from the extremities to the trunk of the body.
Appearance
Drug eruption is a very diverse skin manifestation. It can easily be confused with the large-spotted rash of measles, the small-spotted rash of rubella, or the skin lesions of scarlet fever or syphilis.
In most cases, drug exanthema presents as a reddish elevation, often similar to a mosquito bite. Also wheals (urticaria = hives) are a frequent symptom of drug exanthema. Sometimes blisters form, some of which are large and burst (bullous form).
Other symptoms
In more serious cases, allergic drug exanthema is accompanied by other symptoms such as diarrhea, nausea, vomiting, and swelling of the mucous membranes in the mouth and throat. This is then associated with a more or less pronounced feeling of illness, occasionally also with fever. In addition, nearby lymph nodes may swell. In the case of a very severe allergic reaction, the cardiovascular system is also affected.
Special forms of drug-induced skin rash
Special forms of drug-induced rash include:
Fixed drug exanthema.
The so-called fixed drug exanthema usually develops within two weeks the first time. When the drug in question is used again, healed foci on the skin can reactivate within as little as 30 minutes to 12 hours.
The rash usually appears as a single focal area. It is round to oval in shape, sharply demarcated, and reddish in color. Over time, it may become darker in color. Fixed drug exanthema is often found, for example, on the arms, legs, or genital area (including the mucous membrane).
Maculopapular exanthema.
This is a blotchy, nodular skin rash that may be accompanied by the formation of blisters, hives (urticaria), and hemorrhages into the skin (purpura). Preferably, this drug exanthema forms on the trunk of the body. The head, palms, and soles of the feet are always left out.
A maculopapular exanthema can develop, for example, after taking certain antibiotics (such as sulfonamides, penicillins) or epilepsy drugs. It usually appears about ten days after the start of therapy. Occasionally, it develops later or even a few days after the end of therapy.
Maculopapular exanthema is the most common form of drug reaction.
Acute generalized exanthemic pustulosis (AGEP).
Acute generalized exanthemic pustulosis (AGEP), also called toxic pustuloderma, is another special type of drug-induced skin reaction. The first time it develops within three weeks after the start of drug use (various antibiotics). Later, it may occur within a few days.
Generally, this form of drug exanthema heals within two weeks with the formation of fine scales.
Erythema exsudativum multiforme
Erythema exsudativum multiforme can be triggered not only by drugs but also, for example, by infections (such as with herpes simplex viruses or streptococci).
Patients develop disc-shaped, weeping foci with red edges and a bluish center. The extensor sides of the hands and arms are usually affected, sometimes also the mucous membranes. Affected patients may also have a severely impaired general condition.
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).
These are rare but severe forms of drug exanthema. Large areas of skin and mucous membrane can detach and die. This often looks like scalded skin. In Steven-Johnson syndrome, less than ten percent of the body surface is affected; in toxic epidermal necrolysis (also known as Lyell syndrome), at least 30 percent is affected.
In addition to the severe skin reaction, both variants also manifest themselves in symptoms of the liver, intestines and lungs, as well as through fever.
DRESS syndrome
DRESS syndrome (DRESS = drug reaction with eosinophilia and systemic symptoms) is also a rare but severe form of drug reaction. It begins a few weeks after use of the triggering drug with high fever, muscle pain, and a patchy, nodular skin rash. Accompanying facial swelling, pharyngitis, and swollen lymph nodes occur.
In the further course, symptoms develop in the area of internal organs, for example in the form of liver inflammation (hepatitis), kidney inflammation (nephritis), heart muscle inflammation (myocarditis) or pneumonia (pneumonia). The condition of the affected person can deteriorate rapidly.
DRESS syndrome may develop, for example, as a reaction to certain drugs for epilepsy (phenytoin, carbamazepine) or the gout drug allopurinol.
Drug-induced exanthema: causes and risk factors
In most cases, drug exanthema is an allergic reaction to a drug. Less commonly, it is not allergic in origin but is a pseudoallergy.
Allergic drug-induced exanthema
On first contact with a new drug, it usually takes several hours to days for the drug rash to develop. Sometimes weeks pass (sometimes the drug rash only forms after the drug is discontinued). If the drug is used again later, the skin reactions usually start earlier – often after hours or a few days.
The first contact with a drug does not always trigger sensitization, i.e. classification by the immune system as a supposedly dangerous substance. Sometimes a drug is first used a few times without any problems before the immune system suddenly sees it as dangerous and begins to act against it.
Some risk factors favor allergic reactions to drugs (for example, in the form of allergy-related drug exanthema). For example, the risk of a drug allergy increases when a drug is administered as an infusion or injection (syringe) or applied to the skin. The same applies if a drug is used repeatedly.
In addition, certain genetic factors may increase the risk of hypersensitivity reactions to drugs. However, this is largely still the subject of research.
Pseudoallergic drug rash.
A drug rash can also develop without an allergic reaction from the immune system. For example, cortisone preparations can cause an acne-like rash. The same is true for medications containing lithium, which are prescribed for certain mental illnesses.
Some medications make the skin more sensitive to UV rays. During treatment, the skin may therefore become painfully red (phototoxic reaction) or even allergic (photoallergic reaction) when exposed to sunlight or in a solarium. This can happen, for example, during treatment with certain antibiotics (such as tetracyclines) and with the dehydrating agent (diuretic) furosemide. Read more about phototoxic and photoallergic reactions in the article Sun allergy.
Drug exanthema: examinations and diagnosis
If you develop an unclear skin rash – especially (shortly) after using a new medication – you should definitely see a doctor. It is best to contact the doctor who may have prescribed the medication in question. However, a specialist in skin diseases (dermatologist) is also a suitable contact person.
The doctor will first obtain important background information about your medical history (anamnesis) in a detailed discussion. Possible questions include:
- What prescription and over-the-counter medications are you currently using or have you recently used? Is there a new medication?
- How has the skin reaction developed?
- Were you particularly stressed or had an acute infection when the rash appeared?
- Are there any other symptoms such as itching or general complaints?
- Have you had any previous adverse reactions to a medication?
- Do you have any known allergies or food intolerances? Do you have asthma or any other underlying condition?
After the interview, the doctor will examine the rash in more detail. He may also take blood samples and send them to the laboratory for analysis. It is possible that abnormal findings such as changes in the blood count will be found, which will be helpful in clarifying the rash.
The information from the history interview and the look at the rash are sometimes enough for the doctor to suspect a drug exanthema. If necessary, he or she will recommend discontinuing a drug that is probably responsible on a trial basis (if it is not absolutely necessary). If the rash then improves, this confirms the suspicion of drug-induced exanthema.
Do not discontinue a medication prescribed by a doctor on your own! First consult the doctor treating you.
Tests
Various tests can help to find the trigger for a drug-induced exanthema and, if necessary, to clarify the underlying mechanism. Doctors usually perform such tests after the symptoms have subsided.
A negative test result does not rule out an allergic drug rash! Conversely, a positive skin test is not always proof of an allergic drug rash. Especially since validated skin tests are available for only a few drug groups, including X-ray contrast media and beta-lactam antibiotics.
For a few drugs, there are standardized in vitro tests (“in vitro” means “in glass,” i.e., in laboratory vessels) that are suitable for diagnosing drug hypersensitivity. For example, a penicillin allergy can be detected by detecting specific antibodies in the blood.
Another in vitro method is the lymphocyte transformation test. In this allergy test, one looks for specific immune cells against the suspected trigger of the rash in a blood sample from the patient. However, the procedure is difficult and costly. It is therefore not routinely used to clarify allergic drug exanthema.
To rule out other possible causes for the rash, it is sometimes necessary to take a tissue sample from the changed skin area (skin biopsy) and examine it more closely in the laboratory.
Physicians always interpret test results in conjunction with information from the medical history interview and physical examination.
Drug-induced exanthema: treatment
In general, the drug that (presumably) causes the rash should be discontinued after medical consultation (!) – unless the drug exanthema is only very mild. If necessary, the doctor will prescribe a better tolerated substitute drug.
Sometimes a (triggering) drug is indispensable for the treatment of an existing disease and must therefore not be discontinued – even if it causes a pronounced allergic drug rash. Then the doctor may give cortisone and antihistamines as a preventive measure before taking the drug to attenuate the allergic reaction.
Drug treatment
To relieve the symptoms of drug-induced exanthema, physicians may prescribe an antihistamine or cortisone. In milder cases, local treatment, such as with an ointment, is sufficient.
Severe forms of drug reactions such as toxic epidermal necrolysis (Lyell syndrome) and DRESS syndrome can be life-threatening. Affected patients must therefore be treated and monitored in hospital or an intensive care unit.
Drug-induced exanthema: course of disease and prognosis
In most cases, drug-induced exanthema resolves soon after the triggering drug is discontinued. However, very severe courses, such as toxic epidermal necrolysis, can be fatal.
In most cases, however, the prognosis for drug-induced exanthema is good. Apart from discoloration of the skin as in fixed drug exanthema, drug exanthema leaves no permanent damage in the vast majority of cases. Exceptions are severe cases of illness, where, for example, mucosal adhesions may occur.
Allergy passport
In any case, the patient should avoid the triggering drug if at all possible. It is also best to make a note of the name of the drug and carry this note with you in your wallet, for example. In this way, he or she can quickly draw the attention of any physician to the allergic drug rash that occurred earlier in the event of renewed treatment. This is important because when the trigger is administered again, the allergic reaction is often more severe than the first time.
