What is the most likely diagnosis for a circular hypopigmented ulcer with a sharply demarcated dark‑red rim and necrotic slough, and what are the recommended diagnostic work‑up and first‑line treatment?

Cutaneous Leishmaniasis

The most likely diagnosis is cutaneous leishmaniasis, characterized by circular ulcerated lesions with raised, well-defined borders (often described as having a dark red or erythematous rim) and a necrotic or granulating base with slough. 1, 2

Clinical Presentation

The classic presentation includes:

• Circular, shallow ulcers with sharply demarcated, raised borders surrounding a central ulcerated area with granulation tissue or necrotic slough 1, 2
• Erythematous or dark red rim (the "raised border" with surrounding erythema) 1, 3
• Lesions typically begin as papules that evolve into nodules before ulcerating 2
• Regional lymphadenopathy may precede skin lesions by 1-12 weeks, particularly with Leishmania (Viannia) braziliensis 1
• Incubation period ranges from 2 weeks to several months after sandfly bite 1

Critical Differential Diagnoses to Exclude

Before confirming leishmaniasis, exclude these life-threatening conditions:

• Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN): Look for circular lesions with dark red centers surrounded by pink rings, but SJS/TEN presents with widespread purpuric macules, mucosal involvement, skin tenderness, positive Nikolsky sign, and rapid progression over 5-7 days 4
• Necrotizing fasciitis: Presents with systemic toxicity, hard "woody" feel to subcutaneous tissue extending beyond visible skin involvement, bullae, skin necrosis, and failure to respond to antibiotics within 24-48 hours 4
• Cutaneous malignancy: Any ulcer persisting >2 weeks requires biopsy to exclude malignancy 4, 5

Diagnostic Work-Up

For any ulcer persisting beyond 2 weeks, the following algorithmic approach is mandatory:

First-Line Testing 4, 5:

• Full blood count (to exclude hematologic disorders)
• Fasting blood glucose
• HIV antibody testing
• Syphilis serology

Definitive Diagnosis of Leishmaniasis 1, 2, 6:

1. Skin biopsy from the raised border (highest organism yield):

   • Hematoxylin & eosin staining
   • Giemsa stain (highlights amastigotes within histiocytes and vacuoles) 2, 3, 6
   • Look for amastigotes (2-4 μm oval bodies) within macrophages 2, 6

2. Tissue culture for promastigotes (gold standard but takes weeks) 1, 3

3. PCR with DNA sequencing for species identification (essential for treatment planning, available through CDC at no charge) 2, 3, 6

4. Leishmanin skin test becomes positive during disease course 1

Critical pitfall: Amastigotes can be confused with Histoplasma; use methenamine silver or PAS staining to differentiate (Histoplasma stains positive, Leishmania does not) 6

Species Identification Importance

Species identification is not academic—it directly impacts treatment choice and prognosis 7:

• Different species have varying drug sensitivities even within the same geographic region 7
• Certain species (L. braziliensis) carry substantial risk of mucosal involvement 1, 7
• Old World species (L. tropica) respond to physical modalities, while New World species require systemic therapy 7

First-Line Treatment

For New World Leishmaniasis (Latin America) 1, 7:

Pentavalent antimonials remain first-line:

• Meglumine antimoniate (Glucantime) OR
• Sodium stibogluconate
• Duration and dosing based on species and geographic origin 1, 7

For Treatment Failures or Severe Cases 1, 2, 3:

Liposomal amphotericin B:

• Intravenous administration for 6-7 days 2, 3
• Alternative for pentavalent antimony failures 1
• Demonstrated rapid resolution (within 3 weeks) 3

For Old World Leishmaniasis 7:

Physical modalities (cryotherapy, thermotherapy, intralesional therapy) are often sufficient and avoid systemic toxicity 7

Common Pitfalls

• Failing to obtain travel history: Leishmaniasis is not endemic to North America; always ask about travel to endemic regions (Latin America, Middle East, Mediterranean, Central Asia) even if remote 2, 6
• Missing organisms on histology: In 25% of cases, organisms may not be visible on routine staining; proceed with PCR if clinical suspicion is high 6
• Treating empirically without species identification: Different species require different treatment approaches and have different risks of visceral or mucosal spread 7
• Overlooking immunocompromised status: HIV-positive and immunosuppressed patients have propensity for diffuse cutaneous leishmaniasis requiring more aggressive management 7