A 32-year-old woman presents with a single, well-demarcated, dusky red macule on the dorsum of her right hand that appeared 48 hours after she took trimethoprim-sulfamethoxazole for a urinary tract infection. She reports that the lesion is mildly itchy and tender. On examination, the lesion measures 2 cm × 1.5 cm and has a slightly raised, edematous border. She recalls a similar lesion at the exact same site 6 months ago after taking the same antibiotic, which resolved spontaneously within 2 weeks. What is the most likely diagnosis?

Explanation

## Diagnosis: Fixed Drug Eruption (FDE) ### Clinical Features Supporting FDE **Key Point:** Fixed drug eruption is characterized by the appearance of a lesion at the SAME anatomical site upon re-exposure to the offending drug. - **Temporal relationship**: Lesion appeared 48 hours after drug ingestion — typical onset window for FDE is 30 minutes to 8 days - **Recurrence at identical site**: The patient explicitly recalls an identical lesion at the same location 6 months ago after re-exposure to TMP-SMX — this is pathognomonic for FDE - **Solitary lesion**: FDE typically presents as a single lesion, though multiple lesions can occur (generalized FDE) - **Morphology**: Well-demarcated, dusky red macule with edematous border is classic - **Causative agent**: TMP-SMX is one of the most common culprits for FDE [cite:Fitzpatrick's Dermatology 9e Ch 23] ### Pathophysiology 1. Initial sensitization to drug metabolite 2. Hapten formation at specific anatomical site (often genital, oral, or acral areas) 3. Recruitment of cytotoxic T cells (CD8+) to the epidermis 4. Keratinocyte apoptosis → localized inflammation 5. Upon re-exposure, rapid recall response at the same site (within 48 hours) ### Differential Diagnosis | Feature | FDE | Contact Dermatitis | Erythema Multiforme | Urticaria | |---------|-----|-------------------|---------------------|----------| | **Recurrence at same site** | Yes (pathognomonic) | No | No | No | | **Onset after re-exposure** | 30 min–8 days | 24–72 hrs (sensitized) | 3–14 days | Minutes to hours | | **Morphology** | Solitary macule/plaque | Vesicles, weeping | Target lesions | Transient wheals | | **Distribution** | Localized, often acral | Exposed areas | Symmetric, acral | Generalized | | **Pruritus vs. pain** | Tender/burning | Pruritic | Pruritic | Pruritic | | **Resolution** | 2–3 weeks | Days–weeks | 1–4 weeks | Hours–days | **Clinical Pearl:** The history of recurrence at the EXACT same anatomical site is the gold standard for diagnosis and makes FDE the only defensible answer. ### Management 1. **Immediate**: Discontinue TMP-SMX 2. **Topical**: Mild corticosteroid (hydrocortisone 1%) for symptomatic relief 3. **Systemic**: Oral corticosteroids (prednisolone 0.5–1 mg/kg/day) if extensive or severe 4. **Patient education**: Strict avoidance of the offending drug; document allergy in medical records 5. **Resolution**: Typically within 2–3 weeks; post-inflammatory hyperpigmentation may persist **High-Yield:** TMP-SMX, NSAIDs, acetaminophen, oral contraceptives, and antimalarials are the most common triggers for FDE in clinical practice.