What is the best course of action for a patient who develops an itchy, burning lesion on the back of their leg after starting doxycycline (antibiotic), without any sun exposure?

Doxycycline-Induced Cutaneous Reaction Without Sun Exposure

Discontinue doxycycline immediately and treat this as a drug-induced hypersensitivity reaction, not phototoxicity, since the lesion occurred without sun exposure. 1

Understanding the Clinical Presentation

This patient's itchy, burning lesion on the back of the leg without sun exposure is critical—this rules out the classic phototoxic reaction that doxycycline typically causes. 2, 3 The FDA drug label explicitly warns about photosensitivity manifesting as "exaggerated sunburn reaction" in sun-exposed areas, but this patient's leg was not exposed to sunlight. 1

Instead, this presentation is consistent with:

• Symmetrical Drug-Related Intertriginous and Flexural Exanthema (SDRIFE): A delayed hypersensitivity reaction presenting as symmetric, pruritic, erythematous eruptions in flexural and intertriginous areas, occurring days to weeks after doxycycline initiation. 4
• Non-phototoxic drug eruption: Doxycycline can cause cutaneous reactions independent of UV exposure through allergic mechanisms. 5, 6

Immediate Management Algorithm

Step 1: Discontinue Doxycycline

• Stop the medication immediately—the FDA label states treatment should be discontinued at the first evidence of skin eruption. 1
• Do not rechallenge with doxycycline, as this represents a hypersensitivity reaction. 4

Step 2: Symptomatic Treatment

• Topical corticosteroids: Apply a potent topical corticosteroid (e.g., triamcinolone 0.1% or betamethasone dipropionate 0.05%) twice daily to the affected area. 5, 4
• Oral antihistamines: For pruritus control, use non-sedating antihistamines (e.g., cetirizine 10 mg daily or loratadine 10 mg daily). 4

Step 3: Monitor for Resolution

• Lesions typically resolve within days to weeks after drug discontinuation with topical steroid therapy. 4
• If the eruption worsens or spreads despite discontinuation, consider systemic corticosteroids (prednisone 0.5-1 mg/kg for 5-7 days). 5

Alternative Antibiotic Selection

If the patient requires continued antibiotic therapy for the original indication:

• For Lyme disease or tick-borne illness: Switch to amoxicillin 500 mg three times daily for 14 days or cefuroxime axetil 500 mg twice daily for 14 days. 7
• For other infections: Avoid all tetracyclines (minocycline, tetracycline) due to cross-reactivity risk. 5, 6
• Cephalexin is preferred if there are photosensitivity concerns, though this patient's reaction is not phototoxic. 2

Critical Pitfalls to Avoid

• Do not assume this is phototoxicity just because the patient is on doxycycline—the absence of sun exposure makes this diagnosis impossible. 1, 5
• Do not continue doxycycline while treating the rash symptomatically—the FDA label explicitly states to discontinue at first evidence of skin eruption. 1
• Do not rechallenge with doxycycline after resolution, as hypersensitivity reactions can recur and potentially worsen. 4
• Avoid topical antibiotics as they may cause additional contact dermatitis. 7

When to Escalate Care

• If the eruption involves mucosal surfaces, consider Stevens-Johnson syndrome/toxic epidermal necrolysis and refer urgently to dermatology. 5
• If systemic symptoms develop (fever, lymphadenopathy, eosinophilia), consider drug reaction with eosinophilia and systemic symptoms (DRESS) and hospitalize. 5, 6
• If the rash does not improve within 1-2 weeks of discontinuation and topical steroids, refer to dermatology for further evaluation. 4