The Eye Has It!

A previously healthy 12-month-old male presented in May 2022 to an Urgent Care Center with a 1-month history of a right eyelid lesion acquired during migration. His parents had first noted a small red dot on the upper eyelid, thought to be a bug bite, while in Mexico City. The family had traveled by foot and ground transportation over 6 months from Foz do Iguaçu in Brazil, through Bolivia, Peru, Ecuador, Colombia, Central America, and Mexico before arriving in Houston, Texas. On initial evaluation, a 1 cm area of redness with a central golden crust and mild induration was noted at the right upper eyelid and sub brow region. His physical examination was otherwise normal. His parents denied fever, eye redness, or discharge. Cephalexin was prescribed for presumed cellulitis. Due to lack of improvement, he was seen at an Emergency Center 10 days later. He appeared to be well and did not seem to be in pain (Figure 1A). He was prescribed trimethoprim/sulfamethoxazole, without improvement. Over the subsequent 2 months, the lesion increased in size, and he developed several erythematous nodules on the right side of his face.

Figure 1.

A, Eyelid lesion at initial evaluation in May 2022. B, Eyelid lesion in July 2022 after 2 courses of oral antibiotics.

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He was referred to the Oculoplastics Service where magnetic resonance imaging (MRI) of the face revealed diffuse right upper eyelid edema without abscess or post-septal extension, as well as nodular lesions suggestive of lymphadenopathy along the malar eminence. Given persistent findings and progression of the lesion, he was admitted to the hospital in July 2022, and the Infectious Disease service was consulted. Examination revealed a firm, non-fluctuant, crusted lesion measuring approximately 0.5 × 1.5 cm on the right eyelid (Figure 1B). There was surrounding erythema but no tenderness to palpation. He had 2 nontender, mobile soft subcutaneous nodular lesions on the right cheek, each less than 1 cm in diameter. He had full extraocular motility and no conjunctival erythema or mucosal lesions.

What is your diagnosis?

Diagnosis: Cutaneous leishmaniasis.

The patient underwent incisional biopsy under anesthesia. Biopsy specimens revealed lymphoplasmacytic and histiocytic inflammation with granulomas and intracytoplasmic round organisms concerning for Leishmania species amastigotes (Figure 2A). The Centers for Disease Control and Prevention (CDC) confirmed the diagnosis of leishmaniasis by polymerase chain reaction (PCR) testing. The sample was not sufficient for speciation. He underwent flexible laryngoscopy, and there was no evidence of mucosal involvement of the nasal cavities, oropharyngeal mucosa, or larynx down to the vocal folds.

Figure 2.

A, Histopathology of skin biopsy displaying intracellular round organisms consistent with amastigotes (arrow). Hematoxylin and eosin (H&E) staining, magnification 400×. B, Eyelid lesion 4 mo after completing therapy.

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Cutaneous leishmaniasis has an annual incidence of 700 000 to 1 million cases worldwide and is endemic in many South American, Asian, African, and European countries [1]. Infection is acquired when a female sand fly takes a blood meal and introduces promastigotes into the skin of the host. Promastigotes turn into amastigotes inside macrophages where they replicate. Lack of recognition of this entity in the United States makes timely diagnosis challenging. A chronic lesion that evolves from an erythematous macule to papule, then nodule and eventually a painless ulcerative skin lesion is highly suggestive of the diagnosis. Patients can also present with hyperkeratotic eschars, verrucous or psoriasiform lesions that are usually painless unless superinfected. Given the variety of presentations, a chronic painless skin lesion of any type in an area of exposed skin in a patient with history of travel to an endemic region should raise concern for cutaneous leishmaniasis [2]. Bacterial infection with common pathogens causing cellulitis, such as Staphylococcus aureus and Streptococcus pyogenes, usually presents with pain and tenderness on exam. Our patient had no tenderness, and the lesion did not improve with antibiotics, making bacterial superinfection unlikely.

Patients with mucosal involvement can present with epistaxis, nasal congestion, and erythema or ulcerative lesions in the nasal or oropharyngeal mucosa that can progress to perforation, disfiguration and difficulty breathing. These symptoms present months to years after cutaneous lesions appear [3].

The diagnosis of leishmaniasis requires tissue sampling via skin scraping or biopsy for histopathologic examination and molecular testing for speciation [4]. In young children, this often requires sedation. PCR is the most sensitive diagnostic tool, but it is available only in specialty laboratories [5]. Speciation is important to guide therapy as some species are prone to metastasizing. Rapid diagnostic tests have not shown an advantage due to low sensitivity in some regions [6].

Lesions that involve sensitive areas such as the face and genitals are considered complex and should be treated with systemic therapy, as local therapy or observation without intervention can lead to unfavorable scarring [7]. Children with cutaneous leishmaniasis have facial involvement more frequently than adults and, consequently, will require systemic therapy more often [2]. Upper eyelid lesions are extremely rare as the eyes tend to be open during the day time, precluding the bite from occurring unless a person is sleeping in a setting with vectorial exposure. Oral miltefosine and intravenous liposomal amphotericin B are the only treatment options routinely available for complex lesions within the United States. Oral miltefosine is Food and Drug Administration (FDA) approved only for those older than 12 years of age and weighing at least 30 kg. Meglumine antimoniate is available outside the United States and can be obtained for intravenous use [7].

Our patient traveled through countries endemic for leishmaniasis, where species that can metastasize such as Leishmania braziliensis, Leishmania guyanensis, and Leishmania panamensis and species less likely to, such as Leishmania mexicana, can present similarly. He could have acquired infection in Brazil or during migration, as incubation can range from weeks to many months. Given facial involvement and to cover for species that can metastasize, he received a 7 day course of intravenous liposomal amphotericin B (3 mg/kg daily) rather than local therapy, and examination to rule out mucosal extension was completed. At follow-up 4 months after completing therapy, he had substantial clinical improvement with only 1 remaining skin nodule and mild scarring of his eyelid (Figure 2B).

In conclusion, cutaneous leishmaniasis should be suspected in travelers and migrants from endemic regions with chronic painless skin lesions. Development of diagnostic tests that can identify leishmaniasis without the need for invasive procedures is needed. Non-invasive cytology-brush PCR is a promising modality [8]. New therapeutic strategies targeting younger pediatric patients should be prioritized, as they are at greater risk than adults for a complex presentation.

Notes

Acknowledgments. The authors thank Dr Julia Shelburne and her Pediatric Hospital Medicine team at Texas Children's Hospital for assistance in caring for this patient and Dr Denver Niles for providing the pathology image displayed. They thank Dr Andrew Abbott at the CDC for advice concerning treatment.

References

Author notes