Case
On May 8th, 2023, a previously healthy 27-year-old female visited our office, complaining of a severe ulcerative lesion and pain on her left external ear that had persisted for one month. The upper half of the left pinna was edematous, with crust and yellowish discharge.
Due to our suspicion of acute perichondritis, she was hospitalized and received intravenous ceftazidime for 7 days. Inflammatory markers (white blood cell, erythrocyte sedimentation rate, C-reactive protein) in the initial lab results were not significantly elevated, but there was mild eosinophilia. The patient was applied mupirocin ointment targeting Staphylococcus aureus. After treatment and dressing, the wound showed slight improvement.
However, on the follow-up treatment date, her symptoms and the lesion were similar to the previous admission. A swab culture during admission revealed Methicillin-resistant Staphylococcus capitis, leading us to start oral TMP-SMX. We switched from mupirocin to fusidic cream based on swab culture results which indicated resistance to mupirocin ointment and susceptibility to fusidic-acid. As there was still no improvement, on May 28th, 2023, she was re-hospitalized and received intravenous vancomycin for 7 days. The wound did not improve even after receiving antibiotics covering gram-positive and negative organisms. Eventually, we suspected cutaneous tuberculosis.
Tuberculosis is endemic in South Korea, but there is limited data about the treatment of cutaneous tuberculosis. We performed a biopsy on the lesion, consulted the Infectious Diseases Department, and initiated the HERZ treatment regimen empirically (H-isoniazid, E-ethambutol, R-rifampin, Z-pyrazinamide).
However, even after taking anti-tuberculosis medication for one week, there was no change in the lesion. Real-time polymerase chain reaction (PCR) of Mycobacterium tuberculosis and non-tuberculosis mycobacteria on the biopsy revealed negative results.
Upon thorough history-taking, the patient reported visiting Mexico and the Galapagos Islands during the Christmas season. Although she did not remember being bitten by any insects, we suspected CL considering this travel history.
She was re-hospitalized and underwent debridement and biopsy under local anesthesia on June 15th. The sample was stained using Giemsa’s method and immuno-histochemical staining using with CD1a antibodies. But pathology and swab reports done in our hospital showed no leishmania amastigote. We sent samples to the Korea Disease Control and Prevention Agency for real-time PCR of Leishmania spp. Sequencing targeting ITS1 was conducted, and L. mexicana was finally diagnosed.
The first-line treatment for Leishmaniasis is pentavalent antimoniate, and fortunately, meglumine antimoniate (Glucantime®, Sanofi Aventis) was available at the National Medical Center. From June 30th, she received an intramuscular injection of meglumine antimoniate at 20mg/kg for 20 days and underwent daily dressing. After 3 weeks of using meglumine antimoniate, a skin rash and pain developed along the left buttock which resolved upon discontinuation of the drug. Fig. 1 shows the clinical progression of the auricular lesion from initial presentation through treatment. The lesion showed a dramatic improvement one month after the end of antileishmanial treatment.
Ethics Committee Approval for the study was obtained from the Institutional Review Board of the Medical Center (IRB Number: 2020AN0488).
Discussion
Leishmaniasis is a vector-borne infection caused by the protozoan parasite of the genus Leishmania. The vectors are female sandflies (Phlebotomus and Lutzomyia). Depending on the Leishmania species, the disease can cause three main clinical manifestations: 1) localized CL characterized by cutaneous ulcers, 2) muco-cutaneous leishmaniasis involving mucosa and underlying connective tissue such as cartilage structures; and 3) visceral leishmaniasis (VL) affecting internal organs like liver spleen and bone marrow [3].
In Mexico and Central America, localized CL involving the ear is known as ‘Chiclero’s ulcer.’ The term is derived from workers who gather chicle latex for gum. These workers lived in the forest for long durations, increasing their exposure to the sandfly vector [4].
In South Korea, there have been only 29 cases of leishmaniasis including this case. 5 cases were VL and except these cases are CL. But there is no evidence to indicate the occurrence of leishmaniasis vectors in the Republic of Korea, thereby limiting the risk of introduction and autochthonous transmission [5].
Chiclero’s ulcer may manifest as an erythematous-edematous auricle or ulcer with discharge and rolled border. Differential diagnoses include perichondritis or carcinoma [3]. In our case, we initially suspected perichondritis, which is more common according to age and sex.
The diagnosis of CL is the demonstration of the parasite by histology and culture or molecular analysis via PCR. Even though CL is self-limiting, irreversible disfiguring scar formation often occurs, so medical treatment is usually required [3]. Parenteral pentavalent antimoniate and amphotericin B, oral azoles, and miltefosine have activity against CL [6]. Although several antileishmanial drugs have been used during the past few decades, antimonials remain the first-line treatment for CL. Sodium stibogluconate and meglumine antimoniate are the two major formulations of antimonials in current use to CL [7]. Meglumine antimoniate can cause local and general side effects. Local reactions included pain, burning sensation, edema, redness and skin reactions. The most important and serious side effect, which fortunately occurred the least frequently was anaphylactic shock [8]. Amphotericin B is commonly used as an alternative drug with a broad spectrum of antiparasitic or antifungal activities with leishmaniasis resistance to antimonials [7]. But amphotericin B has hepatotoxicity, so it should be used with caution. In South Korea, the National Medical Center stocks meglumine antimoniate.
Protection against sandfly bites, including the avoidance of outdoor activities from dusk to dawn and wearing appropriate clothing in endemic countries, is crucial for disease prevention.
This case highlights the importance for clinicians to consider overseas infectious diseases in patients refractory to conventional treatments. Although a diagnosis of leishmaniasis may not always be feasible in non-endemic regions, the risk can be mitigated by raising awareness of this emerging problem among physicians [3]. Also, physicians should recognize that there is a Real-time PCR kit and meglumine antimoniate available in South Korea.