Case Report: First Report of Mucocutaneous Leishmaniasis in Algeria: Observations from a Case Report

ABSTRACT.

We present the first case of mucocutaneous leishmaniasis in Algeria, diagnosed in an immunocompetent 42-year-old man exhibiting an infiltrated and ulcerated plaque leading to macrocheilitis of the entire lower lip. He was a police officer who lived in a village in Ain El Hammam (Kabylie region, known as an active focus of zoonotic visceral leishmaniasis) without any history of travel for the previous 3 years. He suffered from cutaneous lesions for 22 months due to the misdiagnosis of a skin lesion resembling other diseases such as Crohn disease or sarcoidosis. A compilation of clinical, histopathological, parasitological, and molecular examinations revealed Leishmania infantum as the etiologic agent. The patient was treated with meglumine antimoniate, which resulted in the complete disappearance of the lesion 4 months after treatment.

INTRODUCTION

Leishmaniases are parasitic diseases caused by obligate intracellular protozoa of Leishmania genus (Trypanosomatida: Trypanosomatidae). They are transmitted by the bite of infected female sand flies to vertebrate animals, such as canids, rodents, and other mammals, as reservoirs. At present, 54 Leishmania species are known, with at least 21 species that are pathogenic to humans. Socioeconomic conditions, poverty, population mobility, environmental and climate changes, urbanization, and deforestation are among important factors that promote the incidence of disease.¹

Mucocutaneous leishmanisis (MCL), known as espundia, is an atypical presentation form produced by metastatic leishmanial dissemination through the mucous membranes. It is one of the clinical forms caused by Leishmania infection, which affects mucosal or cutaneous surfaces and leads to partial or total destruction of the upper respiratory tract, the mucous membranes of the nose, and the oral cavity. It appears to be frequent in the New World but rare in the Old World. More than 90% of mucocutaneous leishmaniasis cases occur in Bolivia, Brazil, Ethiopia, and Peru. Mucocutaneous leishmaniasis occurs when sand flies inoculate promastigotes onto the mucosal border of the nose and mouth, or due to the spread of parasites from nearby cutaneous lesions via direct extension, bloodstream, or lymphatics. Therefore, MCL develops as a complication of cutaneous leishmaniasis due to the extension of local skin disease into the mucosal tissue. The oral and nasal mucosae are frequently affected, with rare laryngeal and pharyngeal mucosa involvement. Herein, we present the first case of mucocutaneous leishmaniasis in an immunocompetent patient from Algeria.

CASE PRESENTATION

A 42-year-old man was referred in 2011 to the Nedir Mohamed Hospital (Tizi-Ouzou, Algeria) for a suspected parasitological skin infection. He was a police officer who lived in a village in Ain El Hammam, 150 km from Algiers, without any history of travel during previous 3 years. Based on medical records, he had a history of multiple treatments by general practitioners in private clinics using oral (methylprednisolone, 0.6 mg/kg/day) and intralesional (triamcinolone, 60 mg per injection) corticosteroid therapy without improvement.

On arrival, the initial clinical examinations revealed significant swelling of the lower lip evolving for 22 months, with morphological characteristics resembling other disorders such as Crohn disease or sarcoidosis. The clinical presentation was characterized by crusted ulceration, edema encompassing the entire lower lip extending toward the mucosal side, infiltrated and ulcerated plaque leading to macrocheilitis affecting the entire lower lip (Figure 1A). No evidence of infection was observed on the tongue and other parts of the body. According to the dermatological consultation, the patient benefited from local and systemic antibiotic and antifungal treatments for 15 days.

Figure 1.

Mucocutaneous leishmaniasis in an Algerian patient. (A) Ulcerative plaque leading to macrocheilitis involving whole lower lip. (B) Significant improvement of the lesion treated by meglumine antimonite. (C) Complete disappearance of the lesion 4 months post-treatment.

The second dermatological examination revealed the appearance of the lesion unchanged without improvement leading to the prescription of antiprotozoal and antiinflammation hydroxychloroquine (600 mg/day) for 6 weeks. No improvement in the patient’s lesion was observed, which led to the hospitalization. Biological examinations (e.g., blood cell counts, hemoglobin level and liver and renal function tests) were within the normal limits. The patient’s chest radiography revealed no abnormalities. An infection of the lesion by Staphylococcus aureus was reported in bacteriological examination. Histological analysis of a deep lower lip biopsy showed a tuberculoid, epithelio-giganto-cellular appearance without necrosis. Parasitological examination of the Giemsa-stained smear prepared from the patient’s lesion revealed Leishmania infection by microscopy. DNA extraction of Giemsa-stained smear and bidirectional sequencing of ITS1-rDNA fragment amplification using conventional polymerase chain reaction² revealed the infection by Leishmania infantum as the etiologic agent. The obtained sequence was deposited in GenBank under the accession number XN543729. The patient was treated with four intramuscular injections of meglumine antimonite (Glucantime^®) at a dose of 20 mg/kg/day for 15 days. A favorable evolution with complete healing of the ulcerations and partial drainage of the lip was observed 1 week after treatment (Figure 1B). Regarding the persistence of residual swelling of the lip 3 months after the initial infection, the same treatment was repeated and resulted in complete drainage of the lip 1 month later (Figure 1C).

DISCUSSION AND CONCLUSION

Algeria ranks second after Afghanistan in the global incidence of cutaneous leishmaniasis (CL), with more than 20,000 cases each year, making leishmaniasis a significant public health concern.³ Four clinical forms of 1) zoonotic cutaneous leishmaniasis (ZCL), 2) anthroponotic cutaneous leishmaniasis (ACL), 3) zoonotic visceral leishmaniasis (ZVL), and 4) sporadic cutaneous leishmaniasis (SCL) are prevalent in the country.⁴ Zoonotic cutaneous leishmaniasis, caused by Leishmania major, is prevalent in arid and semiarid areas over the northern Saharan border. Anthroponotic cutaneous leishmaniasis, caused by Leishmania killicki (syn: L. tropica), is restricted to some foci located mainly in Constantine, Annaba, Ghardaia, and Tipaza. Visceral leishmaniasis (VL), caused by L. infantum, is prevalent throughout the coastal regions in northwestern Algeria (Oran, Tlemcen), in the Algerian Tell (Tizi-Ouzou, Bouira, Bord Menail, Tipaza, Blida, and Algiers), and the extreme south of the country (Hoggar). Leishmania infantum is also responsible for SCL infection which is mostly widespread across the coastal regions of northern Algeria.⁴ The cutaneous form (ZCL, ACL, and SCL) is the most widespread clinical form in this country. Unlike cutaneous forms, mucosal involvement is uncommon. Ain El Hammam is a district in Tizi Ouzou (Kabylie region) in northern Algeria with 20,776 inhabitants. It is located on the mountainside of Djurdjura, up to 1,080 m above sea level, with an average rainfall of 720 mm per year. Although little is known about leishmaniasis in Ain El Hammam, Kabylie has long been known as an active focus of ZVL with L. infantum as the etiologic agent and Phlebotomus perniciosus and Phlebotomus perfiliewi as probable vectors. Regarding the bioclimatic, geomorphological, and vegetation factors, it offers diverse biotopes for the different species of sand flies and animal reservoirs, which is why for many years it had the largest number of VL cases recorded in Algeria.

Mucocutaneous leishmaniasis is a rare clinical form of tegumentary leishmaniasis in the Mediterranean region. A similar situation exists in North Africa. The literature review depicts a total of 11 reports on MCL in North Africa. They include six cases in Tunisia,^5–10 four in Morocco,^11–14 and one in Libya,¹⁵ with no cases recorded in Egypt. We report here the first case of MCL in Algeria with L. infantum as the etiologic agent. This parasite is commonly known as responsible for ZVL and CL in North Africa. In contrast, it has never been reported as a causative agent of MCL in Algeria. In North Africa, L. infantum followed by L. major, is the most widespread species causing MCL. This report is therefore in agreement with the introducing L. infantum as responsible for the MCL, alongside the ZVL and the AVL, in this region. MCL presents a significant complication of cutaneous leishmaniasis and can occur several months to years after skin ulcers heal. Regarding the serious clinical sequelae of MCL, early diagnosis is crucial to prevent further complications. MCL lesions are characterized by a chronic and hyperactive inflammatory immune response. MCL diagnosis is made by demonstrating the presence of Leishmania parasites in infected tissues. For this purpose, microscopic examination of biopsies taken from the lesion is effective for disease diagnosis. In our patient’s case, he suffered from cutaneous lesions for 22 months due to misdiagnosis of a skin lesion resembling other diseases such as Crohn disease and sarcoidosis. This failure to diagnose the etiologic agent accurately led to the prescription of multiple antimicrobial or corticosteroid medications without favorable outcomes, resulting in worsening of the lesion. Upon arrival at the hospital, the diagnosis was made based on a microscopic examination of the smears stained by Giemsa. Microscopic detection was further confirmed by molecular characterization targeting the ITS1-rDNA region.

Treatment of CL generally relies on peri/intralesional injections of meglumine antimoniate, systemic therapy by liposomal amphotericin B, or oral fluconazole, depending on the Leishmania species, number, topography, and extent of lesions. Miltefosine is another medication commonly prescribed as an oral treatment with established effectiveness in the treatment of cutaneous and visceral forms of leishmaniasis.^16,17 In the case of our patient, meglumine antimoniate was effective in his treatment with a satisfactory evolution observed 4 months after treatment.

This report underlines the occurrence of autochthonous MCL in Algeria and highlights the significance of this disease with cutaneous complications involving mucosal tissues. Clinicians therefore need to be aware of this parasitosis in Algeria, accurate diagnosis of the causative agent, and further effective treatments.