How should painful oral ulcers be managed in an adult with DRESS caused by cefuroxime?

Management of Painful Oral Ulcers in DRESS Syndrome

For painful oral ulcers in an adult with cefuroxime-induced DRESS, immediately discontinue cefuroxime, initiate systemic corticosteroids (IV methylprednisolone 1-2 mg/kg/day), and provide topical high-potency corticosteroids (dexamethasone 0.1 mg/ml mouth rinse or clobetasol 0.05% gel) combined with adequate pain management using viscous lidocaine 2% and oral antihistamines. 1, 2, 3

Immediate Management Steps

Drug Discontinuation and Systemic Therapy

• Discontinue cefuroxime immediately as the first and most crucial step, since cefuroxime has been documented as a causative agent of DRESS syndrome 4
• Initiate systemic corticosteroids with IV methylprednisolone 1-2 mg/kg/day, as systemic corticosteroids are first-line therapy for DRESS syndrome 1, 2
• Plan for a minimum 4-week steroid taper to prevent relapse, as DRESS involves T-cell immune-directed toxicity with long-lasting memory responses 1, 5
• Obtain prompt dermatology consultation for all suspected DRESS cases 2, 5

Topical Corticosteroid Management for Oral Ulcers

• Use dexamethasone mouth rinse (0.1 mg/ml) when multiple locations of the oral cavity are involved or ulcerations are difficult to reach 3
• Apply clobetasol gel or ointment (0.05%) for limited locations and easy-to-approach ulcers 3
• Increase frequency of bland non-alcoholic sodium bicarbonate containing mouthwash up to each hour if needed 3

Pain Management Algorithm

Mild to Moderate Pain

• Start with viscous lidocaine 2% as an anesthetic mouthwash for immediate topical pain relief 3
• Apply coating agents before using other mouthwashes if the patient finds them painful 3
• Add oral antihistamines such as loratadine 10 mg once daily for symptomatic pruritus management 1
• Consider first-generation antihistamines (diphenhydramine 25-50 mg or hydroxyzine 25-50 mg) for nighttime itch due to sedative properties 1

Moderate Pain Escalation

• Consider topical NSAID (amlexanox 5% oral paste) for moderate pain 3
• If NSAIDs are not tolerated, use acetaminophen (paracetamol) as maintenance therapy 3
• Combine with immediate-release oral opioid or fast-acting fentanyl preparation (50 μg fentanyl nasal spray) for short-term relief before meals 3

Severe or Persistent Pain

• Implement more aggressive pain management following the WHO pain management ladder 3
• Consider alternative administration routes (transdermal or intranasal) since oral complaints can complicate oral drug administration 3
• The systemic corticosteroids already initiated for DRESS will help control severe ulceration 1, 2

Advanced Interventions for Refractory Ulcers

If Ulcers Do Not Resolve with Initial Therapy

• Consider intralesional steroid injection (triamcinolone weekly; total dose 28 mg) in conjunction with topical clobetasol gel or ointment (0.05%) 3
• For highly symptomatic or recurrent ulcers, the systemic corticosteroids already prescribed for DRESS management should be adequate 3

Steroid-Unresponsive DRESS Cases

• Consider intravenous immunoglobulin (IVIG) at 1-2 g/kg total dosage if the patient does not respond to systemic steroids 1, 2
• Cyclosporine may also be considered in severe or steroid-unresponsive cases 1, 2

Critical Monitoring and Supportive Care

Comprehensive Workup Required

• Complete blood count with differential to assess eosinophilia 1, 2
• Comprehensive metabolic panel evaluating liver function (ALT, AST, alkaline phosphatase, bilirubin) and kidney function (BUN, creatinine) 1, 2
• Urinalysis to evaluate for nephritis 1, 2
• Blood cultures if febrile to rule out infectious mimics 1

Admission Criteria

• Admit to burn unit or ICU for severe DRESS with significant organ involvement or extensive mucosal involvement 1, 2
• Consult appropriate specialists based on organ involvement, including otolaryngology for extensive oral mucosal involvement 2

Important Pitfalls to Avoid

Steroid Tapering

• Never taper steroids prematurely (minimum 4 weeks required), as relapse occurs in 12% of cases 1, 5
• Prolonged immunosuppression may be necessary due to T-cell immune-directed toxicity 2
• Start proton pump inhibitor for gastrointestinal prophylaxis during corticosteroid therapy 1

Drug Rechallenge

• Never rechallenge with cefuroxime, as DRESS involves severe T-cell-mediated delayed reactions with long-lasting memory responses 1, 5
• Drug challenge is contraindicated except in extreme circumstances 1
• The patient in the referenced case report developed recurrence after re-challenge with the culprit drug 6

Diagnostic Testing Timing

• Do not perform patch testing or delayed intradermal testing until at least 6 months after complete resolution and at least 4 weeks after discontinuing systemic steroids (>10 mg prednisone-equivalent) 1, 5
• Early testing is contraindicated due to risk of systemic relapse 1

Clinical Context for Oral Ulcers in DRESS

• Erosive cheilitis and oral mucosal involvement can be early manifestations of DRESS syndrome, as documented in allopurinol-induced cases 6
• Oral ulcerations in DRESS typically appear as part of the complex hypersensitivity reaction occurring 2-6 weeks after drug exposure 1, 7
• The morbilliform rash in DRESS typically involves >30% of body surface area and is accompanied by fever, eosinophilia, and multi-organ involvement 1, 5