What is the best course of action for a patient with a history of a positive Antinuclear Antibody (ANA) titer and suspected lupus, who has developed itchy and burning flat red elliptical rashes on the back of her leg and upper abdomen after starting doxycycline (doxycycline), and has a concurrent cancer diagnosis?

Discontinue Doxycycline Immediately and Evaluate for Drug-Induced Lupus

The most critical action is to stop doxycycline immediately, as this patient is experiencing a drug-induced photosensitive rash that mimics or exacerbates lupus, particularly given her positive ANA and prior dermatologic concern for lupus. 1, 2

Why Doxycycline Must Be Stopped

• Doxycycline causes photosensitivity reactions in susceptible patients, manifesting as exaggerated sunburn-like eruptions that should prompt immediate discontinuation at the first sign of skin erythema 1
• The FDA label explicitly warns that photosensitivity reactions occur with tetracyclines and treatment must be discontinued at first evidence of skin erythema 1
• Doxycycline can trigger dual cutaneous adverse reactions, including both photosensitivity and morbilliform exanthems simultaneously, which matches this patient's presentation of flat red elliptical rashes 2
• Tetracyclines have been associated with drug-induced lupus-like syndromes, particularly concerning in a patient with pre-existing positive ANA 3

Immediate Management Steps

First 48 Hours

• Stop doxycycline immediately and document this as a drug allergy in the medical record 1, 2
• Initiate topical corticosteroids (prednicarbate cream 0.02% or hydrocortisone 1%) to affected areas twice daily for symptomatic relief 3, 2
• Start oral antihistamines (cetirizine 10mg daily or fexofenadine 180mg daily) for pruritus control 3
• Apply emollient moisturizers liberally and frequently to all affected areas, avoiding alcohol-containing formulations 3, 4

Within 1-2 Weeks

• Reassess skin lesions; doxycycline-induced photosensitivity typically resolves within 2 weeks of discontinuation with supportive care 2
• If rash persists beyond 2 weeks or worsens, urgent dermatology referral is mandatory to differentiate drug reaction from active cutaneous lupus 3, 4

Critical Diagnostic Considerations

Distinguish Drug Reaction from Lupus Flare

• ANA-positive lupus patients can present with prominent photosensitive dermatitis, making differentiation from drug-induced photosensitivity challenging 5
• The temporal relationship (rash onset after doxycycline initiation) strongly suggests drug causation rather than spontaneous lupus flare 2
• Consider checking anti-Ro(SSA) and anti-La(SSB) antibodies, as these are found in 25% of lupus patients and associated with photosensitive dermatitis, particularly in ANA-positive patients 5

Monitor for Systemic Involvement

• Check complete blood count with differential to assess for eosinophilia, as doxycycline can rarely trigger DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms) 2-8 weeks after exposure 6
• Obtain liver function tests to exclude hepatic involvement, which would indicate DRESS rather than simple photosensitivity 6
• Monitor for fever, lymphadenopathy, or facial edema, which would escalate concern for DRESS and require immediate hospitalization 6

What NOT to Do

Avoid These Common Pitfalls

• Never restart doxycycline or any tetracycline-class antibiotic in this patient, as cross-reactivity is likely 3, 1
• Do not use alcohol-containing topical preparations (gels, lotions with alcohol), as these worsen xerosis and irritation 3, 4
• Avoid topical corticosteroids as monotherapy without concurrent emollients and sun protection, as this provides incomplete management 4
• Do not delay dermatology referral if the rash fails to improve within 2 weeks or if systemic symptoms develop 3, 4

Sun Protection is Mandatory

• Strict sun avoidance is essential during recovery, as photosensitivity persists for weeks after drug discontinuation 1
• Apply broad-spectrum sunscreen (SPF 30 minimum, zinc oxide or titanium dioxide-based) to all exposed skin daily, regardless of weather 3
• Recommend protective clothing, wide-brimmed hats, and avoidance of peak sun hours (10 AM to 4 PM) 3

Coordination with Oncology

• Communicate with the patient's oncology team about this drug reaction, as many cancer treatments can also cause photosensitivity or rash 3
• If the patient is receiving EGFR inhibitors for cancer treatment, the management algorithm differs entirely and requires oncology-dermatology co-management 3
• Document doxycycline allergy prominently to prevent inadvertent re-exposure during cancer treatment, where tetracyclines are sometimes used for EGFR inhibitor-induced rash 4

When to Escalate Care

• Immediate dermatology consultation if rash progresses to blistering, mucosal involvement, or skin necrosis 3
• Emergency department evaluation if fever >38.5°C, facial swelling, or respiratory symptoms develop, suggesting severe hypersensitivity 6
• Rheumatology referral after acute reaction resolves to establish definitive lupus diagnosis and determine if systemic treatment is needed 5, 7