What is the approach to a suspected case of drug eruption, including history, clinical examination, investigations, and management plan?

Approach to Suspected Drug Eruption

Immediately discontinue all suspected medications upon recognition of a drug eruption, as this is the cornerstone of management and directly impacts prognosis and mortality. 1, 2

History Taking

Symptom Documentation

• Document the index date (when the first symptom or sign appeared—sore throat, rash, skin pain, sore eyes/mouth) and track progression of the eruption daily 1
• Ask specifically about prodromal illness: fever, malaise, upper respiratory tract symptoms, painful rash initially on face and chest 1
• Inquire about mucosal involvement: eyes, mouth, nose, genitalia, noting symptoms like dysuria or retention 1
• Assess for respiratory symptoms: cough, dyspnea, bronchial hypersecretion, hemoptysis 1
• Ask about gastrointestinal involvement: diarrhea, abdominal distension 1

Comprehensive Drug History

• Obtain a complete medication timeline covering the previous 2 months, including all prescription drugs, over-the-counter medications, complementary/alternative therapies, and document exact dates when each was started, escalated, or stopped 1, 2
• Use multiple sources: patient, relatives, general practitioner, pharmacist to ensure accuracy 1
• Consider using web-based tools like www.drugrash.co.uk for timeline analysis 1
• Identify the latent period: 5-28 days following drug initiation is most likely for first exposure; shorter latency occurs with re-exposure 1
• Estimate drug presence in the body at reaction onset by considering pharmacokinetic parameters (half-life), renal/hepatic dysfunction, and drug interactions 1
• Document any previous exposures to each drug and any prior adverse reactions 1
• Assess each drug's notoriety for causing drug eruptions (particularly SJS/TEN, fixed drug eruption, or other patterns) 1

Past Medical History

• Record previous or ongoing medical problems, specifically asking about recurrent HSV infections and chest infections 1
• Document any previous drug allergies with details of reaction type 1

Clinical Examination

Vital Signs and General Assessment

• Record baseline body weight, vital signs, and measure oxygen saturation with pulse oximeter 1

Skin Examination

• Look for specific morphologic patterns: target lesions (particularly atypical targets), purpuric macules, blisters, areas of epidermal detachment, papulopustular rashes, or fixed hyperpigmented lesions 1, 3
• Record extent of erythema and epidermal detachment separately on a body map using the Lund and Browder chart 1
• Estimate percentage of body surface area (BSA) involved for each parameter; detachment includes detachable epidermis (Nikolsky positive) plus already detached epidermis 1
• Note that extent of detachment (not erythema) has prognostic value 1

Mucosal Examination

• Examine all mucosal sites systematically: oral cavity, eyes, nose, genitalia, looking for mucositis, blisters, and erosions 1

Investigations

Laboratory Studies

• Full blood count, erythrocyte sedimentation rate, C-reactive protein 1
• Urea and electrolytes, magnesium, phosphate, bicarbonate, glucose 1
• Liver function tests, coagulation studies 1
• Mycoplasma serology (particularly important when causative drug cannot be identified) 1

Imaging

• Chest X-ray to assess for respiratory involvement 1

Skin Biopsy

• Take a biopsy from lesional skin just adjacent to a blister and send for routine histopathology 1
• Take a second biopsy from periblister lesional skin and send unfixed for direct immunofluorescence to exclude immunobullous disorders 1
• Histopathology typically shows multiple apoptotic keratinocytes throughout full thickness of epidermis with subepidermal split in severe cases like SJS/TEN 1

Microbiologic Studies

• Swabs from lesional skin for bacteriology 1
• Consider bacterial/viral/fungal cultures if superinfection is suspected, particularly in pustular eruptions 2

Documentation

• Organize photographs of the skin to show type of lesion and extent of involvement 1

Management Plan

Immediate Actions

• Discontinue any potential culprit drug immediately 1, 2, 4
• Establish peripheral venous access through nonlesional skin when possible 1
• Commence appropriate intravenous fluid resuscitation if clinically indicated and initiate a fluid chart 1
• Insert urinary catheter when urogenital involvement causes significant dysuria or retention, and for accurate output monitoring 1

Severity Assessment

• Calculate SCORTEN within first 24 hours for severe cases (SJS/TEN) to predict mortality risk 5, 6
• Transfer patients with >10% BSA epidermal detachment to specialized burn unit or ICU 5

Treatment Based on Severity

Mild/Localized Eruptions

• Apply topical moderate-to-high potency corticosteroids (mometasone furoate 0.1% or betamethasone valerate 0.1% ointment) twice daily to affected areas 2
• Oral antihistamines for pruritus: second-generation agents like loratadine 10 mg daily for daytime, or first-generation agents like diphenhydramine 25-50 mg or hydroxyzine 25-50 mg for nighttime sedation 2

Widespread/Intense Eruptions

• Continue topical high-potency corticosteroids 2
• Add GABA agonists as second-line therapy for persistent pruritus: pregabalin 25-150 mg daily or gabapentin 900-3600 mg daily 2
• Consider systemic corticosteroids (prednisone 0.5-1 mg/kg body weight) for severe cases, though use cautiously as they may be deleterious in advanced toxic epidermal necrolysis 2, 4

Specific Patterns

Papulopustular Rashes (from targeted cancer therapies):

• Initiate oral antibiotics for 6 weeks: doxycycline 100 mg twice daily, minocycline 50 mg twice daily, or oxytetracycline 500 mg twice daily 2
• Combine with topical low-to-moderate potency steroids 2

Fixed Drug Eruptions:

• Recognize that cotrimoxazole is the most common cause, followed by tetracycline, metamizole, phenylbutazone, and NSAIDs 7
• Discontinue offending drug; lesions typically recur at same sites with re-exposure 7

Blistering Eruptions (pemphigus-like):

• Stop thiol drugs, phenol drugs, or other implicated agents 2
• Recognize that 50% resolve with drug withdrawal alone (drug-triggered pemphigus), while 50% require treatment as idiopathic pemphigus 2

Severe Cases (SJS/TEN)

• Arrange ophthalmology consultation within 24 hours of diagnosis 5
• Use silicone dressings for eroded areas 5
• Consider cyclosporine as potential treatment option under specialist supervision 5, 6
• Avoid overaggressive fluid resuscitation which may cause pulmonary, cutaneous, and intestinal edema 5
• Do not administer prophylactic systemic antibiotics as this may increase skin colonization, particularly with Candida albicans 5

Nutritional Support

• Ascertain if patient can maintain adequate hydration and nutrition orally 1
• If not possible, insert nasogastric tube and institute nasogastric feeding 1

Monitoring

• Daily assessment of vital signs and organ function 5
• Regular monitoring for infection (most common cause of mortality in severe cases) 5
• Daily review of mucosal sites (oral, ocular, urogenital) to prevent complications 5

Common Pitfalls to Avoid

• Delayed transfer to specialized unit increases mortality risk in severe cases 5
• Failure to obtain complete drug history including over-the-counter and complementary medications 1
• Not considering drug pharmacokinetics when assessing causality 1
• Overlooking infectious causes, particularly mycoplasma in children and young adults 1, 5
• Neglecting eye care may result in permanent visual impairment 5
• Using prophylactic antibiotics in severe cases, which increases colonization risk 5
• Continuing suspected drug while "monitoring" in severe or progressive cases 1

Follow-up and Documentation

• Provide written information about drug(s) to avoid and encourage wearing MedicAlert bracelet 5, 6
• Document drug allergy in patient's notes and inform all healthcare providers 5, 6
• Report the episode to pharmacovigilance authorities 5
• Arrange follow-up with dermatology and ophthalmology within weeks of discharge for severe cases 5
• Consider referral for diagnostic testing to specialist center with expertise in drug allergy in severe cases 6
• Note that routine drug hypersensitivity testing is not recommended following SJS/TEN, and oral provocation studies are not ethical due to risk of life-threatening reactions 6