Diagnostic and therapeutic challenges of cutaneous leishmaniasis in Canada: A case report

Abstract

Cutaneous leishmaniasis is increasingly reported in non-endemic areas due to international travel. This case describes a 17-year-old male from Western Canada who developed localized cutaneous leishmaniasis (Leishmania mexicana) after visiting the Yucatán Peninsula, Mexico. His persistent skin ulcers initially failed to respond to supportive wound care, thermotherapy, and systemic antimicrobials. Skin biopsy revealed granulomatous inflammation, and polymerase chain reaction confirmed L. mexicana species. Limited access to first-line treatments (e.g. miltefosine) in Canada complicated management. While intravenous liposomal amphotericin B provided partial improvement, complete healing occurred only after obtaining miltefosine. This case highlights the challenges of diagnosing and treating cutaneous leishmaniasis in non-endemic regions.

Introduction

Cutaneous leishmaniasis (CL) remains the most prevalent form of leishmaniasis and a significant global health concern. ¹ It is caused by Leishmania protozoa, transmitted through infected female sandfly bites. ² Recent trends show a steady increase in the incidence of pediatric CL, ³ with localized cutaneous leishmaniasis (LCL) in children often presenting as solitary lesions on exposed areas like the face and extremities due to outdoor exposure. ³ The initial lesion starts as a small red papule, enlarging up to 2 cm with central ulceration. ² While generally painless and capable of spontaneous resolution, lesions frequently heal with scarring.^1,2 Complex CL is characterized by larger, numerous, or cosmetically significant lesions, often in challenging locations where local or intralesional treatment is not feasible. ⁴ Unlike simple CL, complex cases may present with large regional adenopathy, subcutaneous nodules, or lesions ⩾5 cm in diameter often requiring systemic therapy. ⁴

Endemic to tropical and subtropical regions, CL is rarely seen in non-endemic countries like Canada. However, globalization and increased travel have led to more imported cases, posing diagnostic and therapeutic challenges. A Canadian tropical disease center documented nearly double the annual CL cases from 2008 to 2018. ⁵ With an incubation period of 2 weeks to 6 months, CL’s presentation can further obscure diagnosis, and limited antiparasitic availability in non-endemic areas often delays treatment. ⁶

This report presents a pediatric case of complex New World LCL due to Leishmania mexicana following travel to the Yucatán Peninsula in Mexico, a region with increasing rates of CL, ⁷ highlighting the difficulties in the treatment and management of this infection in Western Canada.

Case report

A 17-year-old male presented with non-healing skin ulcers (Figure 1) 3 months after returning from the Yucatán Peninsula. He developed erythematous papules on his anterior neck that progressively ulcerated and expanded, with a secondary lesion on his left scapula. Despite treatment with topical mometasone, a combination steroid-antibacterial-antifungal cream (triamcinolone acetonide, nystatin, neomycin sulfate, and gramicidin), and two courses of oral cephalexin, the lesions worsened.

Figure 1.

(a) Initial presentation of cutaneous leishmaniasis ulcers on the anterior neck, measuring approximately 6 × 3 cm on the right side and 5.5 × 3 cm on the left side. (b) Re-epithelialization of the lesion after a 4-week course of miltefosine, demonstrating significant healing and resolution of the ulcer 4 months after completion of miltefosine.

Punch biopsy revealed granulomatous inflammation with patchy necrosis and neutrophils (Figure 2). Giemsa staining showed numerous parasitized intracellular nucleated microorganisms arranged around the periphery of the histiocytes cytoplasm with eccentric nuclei (“marquee sign”), confirming Leishmania infection. Eight months after presentation, polymerase chain reaction identified L. mexicana as the causative species.

Figure 2.

Skin biopsy of cutaneous leishmaniasis, Hematoxylin & Eosin (H&E) stain, 40×. Intracytoplasmic Leishmania mexicana (red arrows) are observed, with Giemsa staining highlighting the parasites positioned along the edges of intracellular histiocyte vacuoles, characteristic of the “marquee sign.”

Initial treatment with oral fluconazole (400 mg daily for 42 days) did not resolve the lesions. He was subsequently treated with two courses of systemic intravenous liposomal amphotericin B (170 mg daily, cumulative total of 2380 mg). The first course lasted 7 days, and the second course, administered 4 months later, was given according to the World Health Organization’s (WHO) recommended schedule, with doses on days 1–5 and additional doses on days 14 and 21. While initially improving, the lesions began to progress further and were complicated by a methicillin-sensitive Staphylococcus aureus suprainfection requiring three courses of cephalexin and one of doxycycline. Concomitantly, the patient was using thermotherapy at home one session every 2 days. Additional therapies, such as cryotherapy, were declined by the family at the time, while photodynamic therapy was not available at our center.

Management was complicated by limited access to first-line therapies. Topical pentavalent antimonials and systemic agents like meglumine antimoniate and miltefosine are only available through Health Canada’s Special Access Program (SAP). Additionally, while paromomycin-containing creams are available through compounding pharmacies, they are very cost-prohibitive. Miltefosine was eventually approved through Health Canada’s SAP 18 months after onset. A 4-week course (50 mg TID) ultimately led to full re-epithelialization with minimal side effects.

Discussion

This case highlights the diagnostic and therapeutic challenges of managing LCL in non-endemic regions like Canada. Our patient had a significant delay (8 months) from symptom onset to diagnosis due to the unfamiliarity of this condition among healthcare providers in non-endemic settings. Diagnostic delay has also been shown in other Canadian and non-endemic centers highlighting the importance of physician awareness of this condition and eliciting pertinent travel and exposure history. ⁵

A significant challenge in this case was the unavailability of first-line antileishmanial therapies, such as miltefosine, for treating complex LCL. Miltefosine, included on the WHO’s Model List of Essential Medicines, remains inaccessible in many non-endemic regions, complicating treatment. ⁸ This list identifies medications essential for key health needs, chosen for their proven efficacy, safety, and cost-effectiveness. While these drugs are more accessible in endemic regions, they are not approved for use in Canada. To obtain these treatments, healthcare professionals typically must apply to Health Canada’s SAP, which can lead to delays in management. Health Canada’s SAP provides access to unapproved drugs for patients with serious or life-threatening conditions when available treatments are ineffective or unsuitable.

Prior to diagnosis, treatment with topical steroids may have worsened the lesions, as corticosteroids and other immunosuppressants increase susceptibility to leishmaniasis. ⁹ Once diagnosed, the patient was treated with two courses of liposomal amphotericin B for a total of 2380 mg. This treatment is commonly used for LCL, particularly in non-endemic centers, due to availability and prescriber familiarity. ⁵ However, liposomal amphotericin B has shown low efficacy in pediatric LCL cases and carries a high risk of adverse events, such as acute kidney injury.^5,10 Despite initial improvement with this treatment, the lesions regressed, reflecting the critical need for timely access to alternate therapies.

Once miltefosine was administered, the patient experienced complete healing, demonstrating the drug’s efficacy even with delayed treatment. This outcome supports miltefosine’s established role in treating LCL, particularly cases caused by L. mexicana in adolescents. While L. mexicana is a less virulent species, typically leading to a more indolent course, ¹¹ this patient experienced a prolonged and severe progression. This may be due to factors such as the highly vascularized cervical area, where the lesions were located. The increased blood supply in this region could have facilitated more extensive spread or prolonged the inflammation, contributing to the slow healing process. This highlights the complexity of LCL and the potential for varying disease progression even with less virulent species.

In conclusion, LCL presents significant diagnostic and therapeutic challenges in non-endemic regions. This case emphasizes the importance of increased awareness among healthcare professionals and the need for more efficient access to treatments for tropical diseases. Streamlining the regulatory process for obtaining medications, combined with heightened clinical suspicion for tropical diseases in travelers, is essential for improving patient health outcomes.