Case Presentation: A 34-year-old male smoker with no significant medical history presented to the ED with fever and bilateral inguinal lymph node swelling and pain for one week duration. Patient recently emigrated from China two months prior and traveled through the rainforests of Colombia, where he resided for two days, then El Salvador, Honduras, Nicaragua, and through Mexico before reaching the United States. Unsure if bitten by bugs, he recalled a rash on his legs with purulent drainage, which has since resolved. Preliminary laboratory testing revealed ESR 35 mm/hr, CRP 1.89 mg/dL, and malaria antigen testing was positive for Plasmodium falciparum with 0.2% parasitemia and normal G6PD levels. Patient completed a course of Artemether/Lumefantrine 80-480 mg twice daily for 3 days. Despite treatment, the patient experienced worsening of his skin lesions and was subsequently treated with oral antibiotics for one month, which also provided no improvement. He had a punch biopsy of his lesions, which revealed benign skin with dermal perivascular and vasculopathic reactions, favoring arthropod bites. Additionally, reverse transcription-polymerase chain reaction (RT-PCR) was negative for all Plasmodium sp. Further parasitology testing revealed that he was positive for Leishmaniasis sp., both Hsp70 (heat shock protein) and amino acid permease 3 (AAP3) by RT-PCR. The patient was subsequently treated with Amphotericin B.

Discussion: Cutaneous leishmaniasis (CL) is a neglected tropical disease caused by protozoa of the Leishmania species, transmitted to humans by the bite of an infected sandfly. CL is characterized by skin ulcers on exposed parts of the body and can present with systemic features that resemble other infections, potentially delaying appropriate diagnosis and treatment. Current diagnostic methods for CL are far from optimal, with punch biopsy being commonly the most performed, which can take days to weeks for results to be reported. In our case, Malaria was suspected given clinical presentation and positive malaria rapid diagnostic test (RDT). Malaria RDT targets a histidine-rich protein 2 and pan-malerial antigen, which may cross-react with antigens from the Leishmania parasite, leading to a false-positive malaria result. Leishmaniasis is considered the second most-deadly parasitic infection in humans after malaria. For this reason, accurate and qualitative detection and identification of Leishmaniasis are the keys to seeking prompt intervention and successful treatment of infection. Therefore, tissue samples were sent to the New York State Department of Health Wadsworth Center, where RT-PCR utilized the Hsp70 gene and AAP3 coding sequence useful for detection of Leishmania species.

Conclusions: With the increase in travel and migration from endemic regions, it is important to include CL in the differential diagnosis when seeing patients with suggestive lesions. This report highlights a unique case of cutaneous leishmaniasis initially misdiagnosed as malaria due to overlapping clinical symptoms and a false-positive malaria antigen test, underscoring the importance of maintaining a broad differential diagnosis. A literature review revealed scarce case reports on this diagnostic challenge, highlighting a need to further consider more definitive diagnostic strategies when encountering such patients.