Drug Eruption

Drug eruptions are skin reactions that happen when your body responds to a medication. While most are mild and disappear after stopping the medicine, some can become serious and even life-threatening, requiring immediate medical attention.

Table of contents

• What is a drug eruption?
• Other names
• Medical identification codes
• Types of drug eruptions
• Who gets drug eruptions?
• What causes drug eruptions?
• Signs and symptoms
• Complications
• How are drug eruptions diagnosed?
• Treatment
• Prevention

What is a drug eruption?

A drug eruption is a skin reaction caused by taking a medication. These reactions happen when your body responds negatively to a medicine you’ve taken by mouth, injection, or other ways. Drug eruptions can also be called drug rashes or drug reactions^[1].

Drug eruptions are one of the most common types of adverse drug reactions (unwanted effects from medicines). They account for about 30% to 45% of all bad reactions to medications^[5]. These skin reactions range from mild rashes that go away on their own to severe, life-threatening conditions that need emergency care^[1].

Any medicine—whether bought over the counter, prescribed by a doctor, or even herbal—can trigger a drug eruption^[6]. Most drug eruptions are mild and disappear when the medicine is stopped^[3].

Other names

Cutaneous drug reaction, Adverse cutaneous reaction to drug, Adverse cutaneous reaction to medicine, Drug rash, Drug-induced rash, Dermatitis medicamentosa, Eruptions due to drugs

Medical identification codes

L27; L27.0; L27.1

Types of drug eruptions

The two most common types of drug eruptions are mild and usually not dangerous^[1]:

• Morbilliform eruption (also called exanthematous or maculopapular drug eruption): This is the most common type. It appears as a red rash with flat and slightly raised spots, similar to measles. It usually shows up 1 to 2 weeks after starting a new medication^[2].
• Urticarial rash: This is the second most common type. It appears as itchy, raised, ring-shaped patches that move around on the skin (hives). These usually appear within hours of taking the medicine^[2].

There are also many other types of drug eruptions. Some are mild, while others are severe and require immediate medical attention^[1]:

• Acute generalized exanthematous pustulosis (AGEP): A rapidly spreading rash with small pus-filled bumps
• Serum sickness: A reaction that causes hives, fever, joint pain, and swollen lymph nodes
• Fixed drug eruption: Single or multiple spots that blister and come back in the same place each time you take the drug
• Lichenoid drug eruption: A rash that looks like a skin condition called lichen planus
• Drug-induced photosensitivity: Increased sensitivity to sunlight, causing sunburn-like reactions or eczema in sun-exposed areas
• Bullous drug eruptions: Large fluid-filled blisters on the skin

The most serious types are called severe cutaneous adverse reactions (SCARs). These are rare but can be life-threatening^[1]:

• Drug hypersensitivity syndrome (also called DRESS syndrome): A serious reaction with fever, rash, and organ involvement
• Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN): Very serious conditions where the skin blisters and peels off

Who gets drug eruptions?

Drug eruptions can happen to anyone taking medication. On average, about 2 out of every 100 prescriptions for a new medication lead to a drug eruption^[1]. About 2% of hospitalized patients develop drug eruptions^[5].

Certain factors make drug eruptions more likely^[1][4]:

• Gender: Women are more likely than men to develop drug eruptions
• Age: Drug eruptions occur more often in people older than 65 years
• Genetic factors: Some people inherit genes that make them more likely to react to certain drugs
• Weakened immune system: People with HIV, cancer, or those taking medications that suppress the immune system are at higher risk
• Underlying viral infections: Active infections can influence how the body reacts to drugs
• Multiple medications: Taking more than three medicines daily increases risk
• Previous drug reactions: Having had a drug reaction before increases the risk of another one

Certain medications are more commonly associated with drug eruptions^[2][4]:

• Antibiotics, especially penicillin and sulfa drugs
• Anti-inflammatory medicines like ibuprofen, naproxen, and aspirin
• Seizure medications (anticonvulsants) such as phenytoin or carbamazepine
• Chemotherapy drugs
• Medicines for psychiatric illnesses
• Blood pressure medications, especially diuretics and ACE inhibitors
• Gout medication (allopurinol)
• HIV medications
• X-ray contrast dye containing iodine

What causes drug eruptions?

Drug eruptions happen through several different mechanisms. Understanding these can help explain why some reactions occur^[1][5].

True allergy is caused by an immunological reaction, where your immune system mistakenly identifies the drug as harmful:

• Immediate reactions occur within an hour of taking the drug. They are caused by IgE antibodies (proteins your immune system makes) and can cause hives or a severe reaction called anaphylaxis.
• Delayed reactions occur between 6 hours and several weeks after first taking the drug. These may be caused by different immune system responses involving antibodies or special immune cells called T cells.

Other causes of drug eruptions that are not true allergies include^[1]:

• Predictable reactions based on how the drug works: These are known side effects of the medication
• Drug intolerance: Reactions related to the dose of the drug
• Pseudoallergy: A reaction that looks like an allergy but is actually caused by the drug directly releasing chemicals from certain immune cells, rather than through an immune response. This can happen with opioid pain medications and NSAIDs.

In many cases, a complex interaction between your inherited genetics, how your body processes the drug, and your immune response leads to a drug eruption^[3].

Signs and symptoms

Drug eruptions can appear in many different ways. The symptoms depend on the type of reaction and can range from mild to severe^[2][4].

Common skin symptoms include:

• Red, flat spots or slightly raised bumps (papules)
• Hives (raised, itchy welts that move around)
• Small blisters (vesicles)
• Small pus-filled bumps (pustules)
• Large blisters (bullae)
• Increased sensitivity to sunlight
• Itching

The rash can appear anywhere on the body. It may cover the entire skin surface or be limited to certain areas. Most often, the rash appears in skin fold areas such as the underarms or groin, on the trunk, or on the arms and legs. Drug eruptions are usually symmetric, meaning they appear on both sides of the body in a similar pattern^[4].

In people with darker skin colors, the redness may be harder to see^[4].

Additional symptoms that may accompany the rash include^[1][4]:

• Fever
• Feeling generally unwell (malaise)
• Swelling of the face, hands, or other body parts
• Swollen lymph nodes

Warning signs that indicate a severe, potentially life-threatening drug reaction include^[2][4]:

• Sores inside the mouth or on the genitals
• Blisters or skin peeling
• Tender or painful skin
• Swelling of the tongue or throat
• Difficulty breathing
• Fast or irregular heartbeat
• High fever
• Dizziness or feeling faint
• Low blood pressure
• Loss of consciousness

If you experience any of these severe symptoms, call emergency services immediately or go to the nearest emergency room.

Complications

Most drug eruptions are mild and resolve without complications once the medicine is stopped. However, drug eruptions can lead to several problems^[1]:

If the wrong drug is identified as the cause, patients may be deprived of a useful medication that could help them. They may also avoid a safe medication unnecessarily. On the other hand, if a drug eruption is not recognized, taking the same drug again can lead to another reaction, possibly more severe^[1].

Severe drug eruptions can be life-threatening. Patients with severe reactions may die from the condition^[1]. Stevens-Johnson syndrome and toxic epidermal necrolysis can cause permanent scarring. This scarring can lead to blindness if the eyes are affected, or physical deformity if large areas of skin are involved^[1].

Drug eruptions can also lead to prolonged hospital stays, increased medical costs, and time lost from school or work^[5].

How are drug eruptions diagnosed?

Diagnosing a drug eruption can be challenging because there are many possible causes and no single test can confirm the diagnosis in most cases. The diagnosis relies heavily on the patient’s history and physical examination^[1][2].

Your doctor will ask you detailed questions about^[2]:

• All medications you are taking, including prescription drugs, over-the-counter medicines, supplements, and herbal remedies
• When you started each medication
• When the rash first appeared
• Whether you have had any drug reactions in the past
• Any recent infections or other illnesses
• Family history of drug reactions

During the physical examination, your doctor will carefully look at your skin to assess the type, pattern, and distribution of the rash. They will also check your mouth, eyes, and genital areas for sores or blisters. A general physical examination will look for fever, swollen lymph nodes, or signs of organ involvement^[1][2].

For mild, straightforward cases, the history and physical examination may be enough to make the diagnosis^[2].

For more severe or unclear cases, your doctor may order additional tests^[1][2][4]:

• Skin biopsy: A small sample of skin is removed and examined under a microscope. This is the most reliable way to diagnose certain types of drug eruptions.
• Blood tests: These can check for signs of an allergic reaction, such as increased numbers of certain white blood cells (eosinophils), or check how well your organs (liver, kidneys) are working.
• Allergy testing: Skin tests or blood tests may be done to identify specific drug allergies, though these are not available for all medications.

Testing for potential allergens can include patch testing (placing small amounts of the drug on the skin), prick testing (pricking the skin with a tiny amount of the drug), or intradermal testing (injecting a small amount under the skin). However, these tests cannot confirm drug causality in many cases^[1].

Identifying the specific drug causing the eruption requires a careful analysis of the timing of when each drug was started, the type of rash, and other clinical features^[1].

Treatment

The most important step in treating a drug eruption is to stop taking the medication that is causing it. However, never stop taking a prescription medication without talking to your doctor first, especially if the medication is essential for treating a serious condition^[4][9].

After stopping the medication, it may take 5 to 10 days to see improvement in the skin, and up to 3 weeks for the rash to resolve completely^[4].

For mild drug eruptions, treatment focuses on relieving symptoms^[4][9]:

• Cool compresses: Applying cool, wet cloths to the rash or taking cool showers can help reduce itching and discomfort.
• Calamine lotion: This can soothe itchy skin.
• Antihistamines: Oral antihistamine pills, such as diphenhydramine, hydroxyzine, cetirizine, or loratadine, can help relieve itching.
• Mild topical corticosteroids: Creams or lotions containing cortisone (such as hydrocortisone or desonide) can reduce inflammation and itching.
• Moisturizing lotions: These are especially helpful during the late stage when the skin is peeling.

Severe drug eruptions require hospitalization^[9]. Treatment may include:

• Intensive supportive care: Patients with severe skin reactions like toxic epidermal necrolysis are best managed in specialized burn units. Care includes careful monitoring of fluid and electrolyte balance, preventing infection, and protecting damaged skin.
• Eye care: An eye doctor (ophthalmologist) must examine patients with severe reactions because adhesions can develop in the eyes and cause blindness.
• Oral corticosteroids: Medications such as prednisone may be prescribed for severe eruptions or drug hypersensitivity syndrome.
• Intravenous immunoglobulin (IVIG): This treatment may improve outcomes for patients with toxic epidermal necrolysis.
• Cyclosporine: This medication may also have a role in treating toxic epidermal necrolysis.

In some cases, patients can continue taking a medication even if they develop a mild rash, especially if the medication is essential. The eruption often resolves on its own, particularly if antihistamines are used. However, all patients with rashes should be watched carefully for signs that the reaction is becoming more severe^[9].

Prevention

The best way to prevent drug eruptions is to avoid medications that have caused reactions in the past. It is important to^[1][4]:

• Keep a list of all medications you are allergic to or have had bad reactions to
• Inform all your healthcare providers about your drug allergies before starting any new treatment
• Wear a medical alert bracelet or necklace that lists your drug allergies
• Be cautious with related medications, as cross-reactions can occur

For people with known allergies to penicillin, special precautions are needed. These patients should avoid carbapenems (a related type of antibiotic). Cephalosporins (another related antibiotic) should also be used with caution in people with penicillin allergy^[15].

For people who need X-rays with contrast dye and have had reactions before, pretreatment with medications can help limit future reactions. This typically includes prednisone (a corticosteroid), diphenhydramine (an antihistamine), and either ephedrine or another type of antihistamine^[15].

When starting a new medication, it is helpful to be aware of early signs of a drug eruption so you can seek medical attention promptly if needed.