Definition

Drug eruption refers to a skin reaction triggered by medication. Two common types of drug eruptions are exanthematous drug eruption (EDE) and fixed drug eruption (FDE).

• Exanthematous Drug Eruption (EDE)

EDE, particularly morbilliform drug eruption, is the most prevalent type, accounting for approximately 95% of drug eruption cases. Skin reactions may persist even after discontinuing the causative medication.

• Fixed Drug Eruption (FDE)

Fixed drug eruption (FDE) is characterized by rash symptoms that reappear at the same location upon re-exposure to the causative drug. Although less common than exanthematous drug eruptions (EDE), FDE is still one of the most frequent drug-induced skin reactions. Repeated exposure to the drug can lead to the development of new skin rashes.

On average, around 2% of new drug prescriptions lead to drug eruptions in patients. However, it's important to note that some symptoms may be mistakenly attributed to drugs.

Causes

Several factors can lead to drug-induced skin reactions.

• Allergy: This occurs due to the body's immune response and can be mediated by antibodies and immune cells. There are two main types of allergic reactions:
• Immediate allergic reactions: These occur within an hour after exposure to the causative drug.
• Delayed allergic reactions: These occur between 6 hours and several weeks after the initial exposure to the drug.
• Side effects: Some skin reactions may arise from medication use.
• Drug intolerance: This includes reactions related to drug dosage and may manifest as skin symptoms.

Examples of causative drugs

Certain drugs, particularly antibiotics and antiepileptic medications, are more likely to cause drug eruptions compared to other classes of medications, such as those used for heart conditions.

Exanthematous Drug Eruption (EDE) is commonly associated with the following medications:

• Penicillin antibiotics and sulfa drugs.
• Phenytoin antiepileptic medication.
• Chlorpromazine antipsychotic medication.
• Captopril antihypertensive medication.
• Other medications, including allopurinol, naproxen, piroxicam, penicillamine, and chemotherapy and immunotherapy drugs.

On the other hand, Fixed Drug Eruption (FDE) can be triggered by various medications, with the frequency varying in each country depending on drug availability and usage rates. Common medications associated with FDE include:

• Antibiotics such as penicillin, trimethoprim-sulfamethoxazole, tetracycline, quinolones, or dapsone.
• Antiepileptic drugs like barbiturates and carbamazepine.
• Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, naproxen, and mefenamic acid.
• Acetaminophen or paracetamol.
• Antimalarials such as quinine.
• Sildenafil, used for erectile dysfunction.
• Phenothiazine antipsychotic medications.

Risk factor

Approximately 20% new drug prescriptions can result in drug eruptions. Several factors contribute to the risk of experiencing drug eruptions.

• Gender: Allergic reactions to certain medications are slightly more common in women than men.
• Genetic Factors: Some individuals may have genetic predispositions that make them more susceptible to drug eruptions. These genetic differences can affect drug metabolism and increase the likelihood of drug intolerance.
• Age: Fixed drug eruption (FDE) can occur across a wide age range, from 1.5 years to 87 years, with an average occurrence between 30 and 31 years of age.
• Viral Infections and Diseases: Certain viral infections or underlying medical conditions can influence the body's response to medications.
• History of Allergic Reactions: Individuals with a history of allergic reactions or drug intolerance are at a higher risk of experiencing drug eruptions.
• Polypharmacy: The risk of allergies and adverse drug reactions increases with the number of prescribed medications.

Symptoms

Symptoms of Exanthematous Drug Eruption (EDE)

EDE symptoms commonly include a rash characterized by red spots or patches on the skin, often starting on the back and spreading symmetrically to the torso and both arms. In severe cases, these rashes may merge, leading to erythroderma, a condition marked by widespread redness and peeling of the skin affecting over 90% of the body area.

Additionally, the palms, soles of the feet, and mucous membranes can be affected. Itching is a prevalent complaint among individuals with EDE, and in severe reactions, fever may occur.

Skin rashes and spots typically emerge within 7 to 14 days after initiating treatment. Importantly, drug reactions can persist even after discontinuing the causative medication.

Symptoms of Fixed Drug Eruption (FDE)

Fixed Drug Eruption (FDE) typically presents as round or oval-shaped spots with well-defined borders, varying in color from reddish-black to brown or black. These spots may evolve into plaques, sometimes accompanied by fluid-filled blisters. Skin complaints can manifest anywhere on the body, including the lips, genital area, anus, hands, or feet. Commonly affected areas include the hips, lower back, or upper extremities.

Along with the skin complaints, patients may experience itching, burning sensations, or stinging. Fever and malaise are typically absent. Ulcers may develop in the mouth or genital area.

Symptoms of FDE typically manifest within 30 minutes to 8 hours after drug consumption, although they can also occur up to 2 weeks after drug exposure. These symptoms may persist for several weeks before gradually disappearing, leaving behind dark spots.

Re-exposure to the causative drug can trigger new skin complaints and reactivate existing lesions. Skin inflammation can occur within 30 minutes to 16 hours after exposure.

Diagnosis

To diagnose drug eruptions and assess their severity, your doctor will begin by gathering detailed information about your medical history and the symptoms you're experiencing. A thorough discussion about your medication history is crucial, including all types of drugs consumed and their method of administration, whether orally or by injection. It's essential to inform your doctor if you've encountered similar issues.

During the physical examination, the doctor will inspect the affected skin and may look for specific patterns or characteristics indicative of drug eruptions. While mild cases can often be diagnosed based on physical examination alone, identifying the specific drug triggering the reaction can sometimes be challenging.

For severe or persistent eruptions, further evaluation may be necessary. Common diagnostic tests that may be employed include:

• Skin prick test: This test detects immediate allergic reactions, particularly to penicillin antibiotics and certain other drugs.
• Patch test: This test involves applying suspected drugs to the skin. It helps identify delayed allergic reactions. It is typically performed on the area where the rash occurred previously, although interpretation can be complex.

Management

The primary approach to managing drug eruptions involves promptly identifying the causative drug and discontinuing its use. It's crucial to consult with a healthcare professional before initiating any medication. If a drug eruption is suspected, immediate discontinuation of the suspected medication is recommended.

In cases of fixed drug eruption, the skin abnormalities typically resolve spontaneously, although they may leave behind dark spots on the skin. To prevent recurrence, it's important to avoid drugs known to have caused previous drug eruptions. Inform your doctor about any history of drug eruptions for further guidance on medication management.

Therapeutic options for managing drug eruptions include:

• Corticosteroid creams or ointments, though their use remains controversial and is generally reserved for more severe cases. These medications, when used short-term, can help alleviate symptoms.
• Emollients or moisturizers, which can be applied liberally and frequently to soothe the skin.
• Antihistamines, which may provide relief from drug-induced skin rashes.

It's worth noting that some individuals may tolerate drugs previously suspected to cause eruptions. This tolerance could stem from various reasons:

• The drug may not have been the actual cause of the eruption.
• Sensitivity to the drug might have diminished over time.
• The initial drug reaction could have been linked to a resolved medical condition. In such cases, the drug reaction subsides once the underlying condition is treated.

Complications

In most instances of drug eruptions, patients typically achieve full recovery without encountering complications. Notably, there have been no documented fatalities directly attributed to exanthematous drug eruptions (EDE) or fixed drug eruptions (FDE). However, drug eruptions can manifest as widespread skin rashes across the body.

Prevention

Preventing drug eruptions entails steering clear of medications known to trigger such reactions. Whenever feasible, these medications should be substituted with alternatives. It's crucial to avoid unnecessary medications whenever possible.

It is essential to maintain awareness of the names of drugs associated with allergies. Informing healthcare providers about known drug allergies each time medication is prescribed can help mitigate the risk of adverse reactions.

When to see a doctor?

You should consult with your doctor about the medications you're taking, be aware of any side effects you experience, and promptly seek medical advice if you suspect symptoms of a drug eruption.

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