Drug

Drug Eruption: Description

Medicines can cause a variety of side effects. More than 80 percent of all side effects of the drugs are on the skin – including the mucous membrane. Two to three percent of hospital patients experience skin reactions to medication. Of these, every fifth response is potentially life-threatening. The skin reactions may be due to immune (e.g., allergic) as well as toxic, by interactions with other drugs, or by drug-induced photosensitivity.

The drug rash, a skin rash, is allergic and is one of the most common side effects. About one third of all drug eruptions are caused by penicillin. Up to ten percent of penicillin-treated patients report skin reactions after application of the antibiotic.

In addition to skin changes, the allergic reaction to antibiotics and other medicines can also lead to general symptoms such as nausea, vomiting, diarrhea, swelling of the mucous membranes and cardiovascular disorders (systemic symptoms).

Drug Eruption: Symptoms

Usually, the drug eruption occurs on first contact in the first days to two weeks after the start of drug administration. If sensitization has already occurred, the drug eruption usually occurs minutes to 48 hours after administration of the drug. It can also occur with repeated ingestion delayed.

It is also possible that a so-called cross reaction occurs. This means that previously sensitization by chemically similar substances took place and thus an immediate reaction is possible.

localization

A drug eruption can occur in almost all parts of the body, including the mucous membrane. Typically, however, it is found on the extremities and on the trunk of the body (chest, abdomen and back.) The drug eruption can either spread from the trunk or extend from the extremities to the body trunk.

Appearance

The drug eruption is a very diverse skin condition. So it can easily be confused with the large spot rash in measles, with the spotless rubella, or with scarlet fever or syphilis. In most cases, the drug eruption is a reddish elevation, often similar to a mosquito bite. The second most common drug eruption is wheal (urticaria). The formation of partly large and bursting bubbles is possible (bullous form). From the nature of the rash so it can not be concluded for sure whether it is a drug eruption. The severity of drug xantem varies greatly. Menacing forms of drug eruption are associated with detachment and death of large areas of skin.

Other symptoms

Diarrhea, nausea, vomiting and swelling of the mucous membranes in the mouth and throat sometimes occur in the skin reaction. This is associated with a more or less pronounced feeling of illness, occasionally with fever. In addition, lymph nodes nearby may also be swollen. In very severe cases, the cardiovascular system is also affected.

Special forms of the drug-related rash:

The so-called fixed drug eruption Although it can occur on the whole body, with the repeated taking of the triggering drug, it always occurs exactly “fix” in the same place. It is usually a roundish, blistered, about two centimeters large rash with gray color. Often the mucous membrane in the mouth, on the tongue and on the penis affected. The first fixed drug eruption usually occurs as a single rash one to two weeks after the first dose, but again after 24 hours and often in several places.

Also the rheumatic disease Systemic lupus erythematosus can be triggered in ten percent of cases by medication (drug-induced lupus syndrome). In addition to the rash it comes to joint pain and fever. However, when the trigger is released, the symptoms usually return.

Another special form of drug-related skin reactions is the toxic pustoloderm(Acute generalized exanthemic pustulosis). There is a sudden red discoloration with pustules, which may resemble a psoriasis. Typically, the pustules are located in the flexures and the inter-finger and inter-toe spaces. The rash may burn or itch.

Redness of most of the skin is called Erythroderma. This drug reaction is usually accompanied by fever, swollen lymph nodes and a poor general condition. In severe cases, erythroderma can be life-threatening. However, erythroderma is usually triggered not by medication but by skin diseases.

The Erythema exudative multiforme is a sudden, circular, weeping and bright red skin reaction triggered mainly by infections and medications. Usually it is found on the extensor sides of the hands and arms, but also on the mucous membrane. It can lead to severe disturbances of the general condition.

The strongest manifestations of the erythema exsudativum multiforme are the Toxic epidermal necrolysis (TEN) and the Steven-Johnson syndrome (SJS).These are rare. This leads to a skin reaction with detachment and death of large areas. This also affects the mucous membrane, including the conjunctiva of the eye (conjunctivitis). The lesion resembles a second-degree burn. When less than ten percent of the skin is affected, this is called Steven-Johnson syndrome. With a skin involvement of over 30 percent, this is called toxic epidermal necrolysis. In addition to the strong skin reaction sufferers suffer from fever, liver, intestinal and pulmonary symptoms.

Other special forms are vascular inflammation (vasculitis), erythema annulare centrifugum, pruritus sine materia (pruritus without skin rash), angioedema and allergic contact dermatitis. In cancer treatment with certain drugs, the so-called “EGFR inhibitor rash” may occur.

Differentiation to ampicillinxanthem

Often a drug eruption occurs in connection with the administration of the antibiotic ampicillin (ampicillinxanthem) with simultaneous viral infections such as glandular fever (infectious mononucleosis) or CML infections. In nearly 100 percent of cases, it develops after the administration of ampicillin in a Pfeiffer’s glandular fever. Other risk factors include the concomitant use of the gout drug allopurinol, kidney failure and chronic lymphocytic leukemia. However, this is not an allergic reaction, therefore, the drug can be given further. This is an important difference to the allergic skin reactions of other medicines. Since the ampicillinxanthem is very similar to the drug eruption, it is called a pseudoallergic reaction.

Drug Eruption: Causes and Risk Factors

The drug eruption is one of the major group of allergic reactions. This means that the body sees the drug as a foreign body and fights it. Drug eruption can be triggered by various mechanisms. One differentiates roughly reactions of the immediate type and delayed reactions.

Allergic reactions are divided into four groups according to Coombs and Gell. Medications can trigger all four types of allergies, the drug eruption is usually assigned to the group IV, which is mediated by immune cells.

Drug eruptions are common in a number of medications. These include:

• Analgesic (NSAID): e.g. Naproxen, ibuprofen, diclofenac, acetylsalicylic acid
• Antibiotics: penicillins, sulfonamides, cephalosporins
• antiepileptics
• Allopurinol (gout medication)
• Anesthesia: local anesthetics, muscle relaxants
• Antibodies (immunoglobulins)
• heparins
• Cardiovascular drugs: e.g. ACE inhibitors
• vaccines
• insulin
• contrast agents
• thyroid hormones

Risk factors for a drug eruption are female gender, old age, concurrent viral infections, immune system disorders and cancers. If drug reactions are already known in the family or in the past, the risk of an adverse reaction is also increased (genetic predisposition). Also dysfunctions of liver and kidney favor the occurrence of a drug eruption.

The type of medication also influences the likelihood of drug allergy. Regular use promotes tolerance, while irregular intake (intermittent) leads to more frequent allergic reactions. The administration of a variety of drugs or a significant dose increase are unfavorable. With regard to the type of application, it should be noted that the delivery route (oral, local, intravenous, etc.) also plays a role.

Drug Eruption: Investigations and Diagnosis

If an unclear skin rash occurs, especially after the start of taking a new drug, a doctor should be consulted. The contact person should first be the attending physician who has prescribed the medication that may trigger it. The specialist in diseases of the skin is the dermatologist. The doctor will ask questions such as:

• Are you taking a new drug recently?
• How has the skin reaction developed?
• Are there other symptoms such as itching or general symptoms?
• Did you or a family member already have adverse reactions to a drug?

Since the drug eruption can be similar to a variety of other diseases, the medical discussion and thus the clarification of the connection with a drug intake is of particular importance. In addition, simple skin examinations such as the Nikolski sign can be helpful. This sign is positive if the healthy skin can easily be detached.

In obvious cases, a strong suspicion is already sufficient to diagnose a drug rash and begin treatment. As a rule, accurate tests are only performed after the symptoms have resolved. A treatment success is usually already a sufficient indication. In about half of the blood tests, there is an increase in a subset of white blood cells called eosinophils.

Before starting any further diagnostics, other causes of the rash should be ruled out. Not always is a more specific diagnosis useful, this should be discussed with the doctor.

There are a variety of allergy tests that you choose depending on the type of drug reaction. There are roughly two types of tests. On the one hand, suspected allergens can be applied to or into the skin and the skin reaction can be observed (in vivo), on the other hand, one can also try to detect an allergy in the blood (in vitro). The skin tests carry the risk of a variety of side effects.

A drug eruption is a so-called pseudoallergic reaction, which is not due to the immune system, but directly caused by the drug (for example, the ampicillin rash) to distinguish.

Drug Eruption: Treatment

First, the (presumably) triggering drug should be discontinued immediately. In the case of a mild course and special medical importance of the drug, however, may be considered to pass the drug. When choosing a replacement medicine, it must be remembered that there may be cross reactions. This is especially true in the search for a replacement antibiotic.

If the skin reaction is localized and itchy, even an ointment containing an antihistamine or cortisone may provide adequate relief. In more severe cases, cortisone or antihistamines may also be given as a tablet or infusion. In particularly threatening cases, the infusion of immunoglobulins is considered.

If additional suspicion of bacterial infection of damaged skin exists, antibiotic therapy should be started in parallel. Because when the damaged by the drug eruption skin infected, the bacteria can spread in the tissue and in bad cases in the blood (sepsis).

Steven Johnson syndrome and so-called toxic epidermal necrolysis are diseases that require intensive care treatment and monitoring. These are life-threatening courses of a drug reaction, but may also have other triggers.

In rare cases, a so-called hyposensitization can be performed. However, this is rarely done and in the case of extremely important medicines without replacement options. Examples include PJP prophylaxis (a pneumonia caused by a fungus) in AIDS, insulin in diabetes mellitus and certain antibiotics.

Before taking an essential allergy-inducing medicine, one can take preventive cortisone and antihistamines to alleviate the allergic reaction.

Drug eruption: disease course and prognosis

In most cases, a drug eruption returns within a few days after discontinuation of the triggering drug. However, very severe events such as Steven-Johnson syndrome or toxic epidermal necrolysis can be fatal. The cause of this is usually an infection that penetrates the bloodstream via the skin (sepsis).

After a drug eruption and the completion of allergy diagnostics should be issued an allergy pass and the patient to be informed about the trigger and possible cross-reactions. In any case, the triggering drug should be avoided. It is best to note the name of the drug and, for example, Document in the leaflet to alert physicians immediately in case of re-treatment. Because with the renewed administration of the trigger, the reaction usually turns out to be more intense than the first time. Alternative drugs that are listed as a recommendation in the Allergy Pass should ideally be tested in advance.

Apart from a discoloration of the skin, as in a fixed drug eruption in gray color, leaves Drug in the vast majority of cases no permanent damage. Exceptions are severe courses, which can also lead to adhesions of the mucous membrane.