Drug Eruption

Introduction

Drug eruption refers to a cutaneous reaction to a medication, often presenting as a rash or other skin lesions. These reactions can range from mild, self-limiting rashes to severe, life-threatening conditions. Drug eruptions are common and account for a significant number of adverse drug reactions. Identifying the causative drug and discontinuing it is crucial in managing the condition.

Aetiology and Pathophysiology

Drug eruptions are caused by an adverse reaction to medications. The pathophysiology varies depending on the type of reaction:

• Immune-Mediated Reactions: These are the most common and involve an immune response to the drug or its metabolites. They are often classified into Type I to Type IV hypersensitivity reactions:
  • Type I (Immediate Hypersensitivity): Mediated by IgE antibodies, leading to conditions like urticaria or anaphylaxis.
  • Type II (Cytotoxic Hypersensitivity): Involves IgG or IgM antibodies, leading to conditions like drug-induced thrombocytopenia.
  • Type III (Immune Complex-Mediated Hypersensitivity): Involves immune complexes, leading to conditions like serum sickness or vasculitis.
  • Type IV (Delayed Hypersensitivity): T-cell mediated reactions, leading to conditions like contact dermatitis or Stevens-Johnson syndrome.
• Non-Immune-Mediated Reactions: These reactions do not involve the immune system and may result from drug toxicity, cumulative dosage, or interactions with other medications.

Clinical Presentation

Drug eruptions can present with a variety of skin manifestations, ranging from mild rashes to severe, systemic reactions:

• Exanthematous (Morbilliform) Rash: The most common type of drug eruption, presenting as a widespread, symmetrical red rash with small, raised spots. It typically appears 1-2 weeks after starting the offending drug.
• Urticaria: Characterised by raised, red, itchy welts on the skin, often appearing within minutes to hours of drug exposure. Urticaria may be associated with angioedema.
• Fixed Drug Eruption: Presents as a single or few well-demarcated, erythematous plaques that recur at the same site each time the drug is taken.
• Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN): Severe, life-threatening conditions characterised by widespread skin blistering, mucosal involvement, and epidermal detachment. These reactions are medical emergencies and require immediate hospitalisation.
• Photosensitivity Reactions: Present as sunburn-like rashes on sun-exposed areas of the skin, triggered by drugs that increase sensitivity to UV light.
• Vasculitis: Small vessel vasculitis can present with palpable purpura, often on the lower limbs, and may be associated with systemic involvement.

Diagnosis

The diagnosis of a drug eruption is primarily clinical, supported by the patient's history and the temporal relationship between drug intake and the onset of the rash. Key steps in diagnosis include:

• Detailed Drug History: Review all medications taken by the patient, including over-the-counter drugs, herbal supplements, and recent changes in medication. Note the timing of drug initiation relative to the onset of the rash.
• Physical Examination: Assess the distribution, morphology, and severity of the skin lesions. Look for signs of systemic involvement, such as fever, lymphadenopathy, or mucosal involvement.
• Differential Diagnosis: Consider other causes of rashes, such as viral exanthems, autoimmune diseases, or infections, especially if the patient has a complex medical history.
• Laboratory Tests: While not always necessary, tests such as full blood count (FBC), liver function tests (LFTs), and renal function tests may be helpful in severe cases or when systemic involvement is suspected. In cases of suspected SJS/TEN, a skin biopsy may be warranted.
• Patch Testing: In cases where the diagnosis is uncertain, or for delayed hypersensitivity reactions, patch testing by a dermatologist may help identify the causative agent.

Management

The primary goal in managing a drug eruption is to identify and discontinue the offending drug. The management strategy will depend on the severity of the reaction:

1. Discontinuation of the Offending Drug

• Immediate Cessation: Stop the suspected drug immediately. This is especially critical in severe reactions such as SJS/TEN or anaphylaxis.
• Substitution: If the drug is essential (e.g., an antibiotic), consider substituting with a different class of medication.

2. Symptomatic Treatment

• Antihistamines: Oral antihistamines (e.g., cetirizine, loratadine) can be used to manage pruritus and urticaria.
• Topical Corticosteroids: For mild to moderate exanthematous rashes, topical corticosteroids (e.g., hydrocortisone 1%, betamethasone 0.1%) can reduce inflammation and itching.
• Systemic Corticosteroids: In more severe cases, particularly when systemic symptoms are present, short courses of oral corticosteroids (e.g., prednisolone) may be required. This should be done under medical supervision.
• Supportive Care: Maintain adequate hydration, and provide analgesics and antipyretics as needed. For patients with extensive involvement, hospitalisation may be necessary for monitoring and supportive care.

3. Management of Severe Reactions

• SJS/TEN: These conditions require immediate referral to a burn unit or intensive care unit (ICU) for supportive care, including wound care, fluid management, and prevention of secondary infections. Intravenous immunoglobulin (IVIG) or systemic corticosteroids may be considered in some cases, though their use is controversial.
• Anaphylaxis: Anaphylaxis is a medical emergency requiring immediate administration of intramuscular adrenaline (epinephrine), followed by airway management, intravenous fluids, and additional supportive measures.

4. Patient Education and Documentation

• Patient Education: Educate the patient on the importance of avoiding the offending drug in the future and the potential for cross-reactivity with similar medications.
• Medical Records: Document the drug eruption and the offending medication clearly in the patient's medical records to prevent future exposure.
• MedicAlert Bracelet: For patients with severe reactions, recommend wearing a MedicAlert bracelet that lists the offending drug(s).

When to Refer

Referral to a dermatologist or specialist is recommended in the following situations:

• Severe Reactions: Any suspicion of SJS/TEN, drug hypersensitivity syndrome (DRESS), or anaphylaxis warrants immediate referral and hospitalisation.
• Diagnostic Uncertainty: If the diagnosis is unclear or if multiple drugs are potential culprits, referral for further investigation, including patch testing, may be necessary.
• Refractory Cases: If the drug eruption does not improve with standard management or if the patient experiences recurrent eruptions, specialist input may be required.

References

1. British Association of Dermatologists (2024) Guidelines for the Management of Drug Eruptions. Available at: https://www.bad.org.uk (Accessed: 26 August 2024).
2. National Institute for Health and Care Excellence (2024) Drug Reactions: Diagnosis and Management. Available at: https://www.nice.org.uk/guidance/ng196 (Accessed: 26 August 2024).
3. British National Formulary (2024) Systemic and Topical Treatments for Dermatological Conditions. Available at: https://bnf.nice.org.uk/ (Accessed: 26 August 2024).