Abstract
Diffuse cutaneous leishmaniasis is a rare chronic infectious disease, associated with Leishmania mexicana and L. amazonensis, presenting as multiple non-ulcerative painless nodules, with a tendency to relapse soon after treatment. We report a case of a 56-year-old Mexican woman exhibiting nodular lesions, plaques, crusts and scars involving the whole body. A solitary nodule was present at the junction between hard and soft palates. Diffuse cutaneous leishmaniasis is a disfiguring disease resulting in severe scarring if untreated.
Keywords
Case report
A 56-year-old Mexican woman attended an oral cancer prevention campaign in Coahuila state (northern Mexico), with multiple nodular lesions involving the skin of the whole body, particularly the face. The upper and lower extremities presented mainly erosive lesions and crusts, while the trunk, neck and face had mainly nodular lesions. Besides these, the facial skin showed scaly plaques, crusts and scars, which were also present on both lips, and a solitary nodule at the junction of hard and soft palates was seen. This was biopsied (Figure 1). The skin lesions had been present since her childhood but she had not remarked on the oral lesions. No definitive treatment had been previously sought, although ointments had been used for relief of pruritis.
Clinical aspects of DCL in a 56-year-old Mexican woman. (a) Multiple non-ulcerative nodular lesions on the skin of the face. (b) Crusty lesions on both lips and a nodular lesion extending to the soft palate at the junction between hard and soft palates.
Microscopically, an intense infiltrate of amastigote-filled vacuolated macrophages was present beneath the surface epithelium, extending deeply into the connective tissue. Large parasitophorous vacuoles (PV) were seen within the cytoplasm of heavily parasitized macrophages, with scant surrounding lymphocytes. At high power magnification, blue-grey amastigotes attached to PV membranes were observed. Immunohistochemically, macrophages were diffusely positive for CD-68 and the scant lymphocytic infiltrate was positive for LCA, CD-3 and CD-8, but negative for CD-20 and CD-4. Anti-Leishmania confirmed the large number of amastigotes throughout the lesion, also highlighting the peripheral disposition of the protozoa within PV (Figure 2).
Histopathological (left) and immunohistochemical (right) aspects of DCL. (a, b) Macrophagic infiltrate (CD-68 positive) in the palatal mucosa, showing pseudoepitheliomatous hyperplasia (orig. mag. 100×). (c, d) Sparse lymphocytes (CD-8 positive) surrounding the parasite-laden vacuolated macrophages (orig. mag. 200×). (e, f) Macrophages containing several amastigotes (anti-Leishmania positive) disposed contiguously to the parasitophorous vacuole membrane (orig. mag. 1000×).
Scanning electron microscopy analysis showed multiple amastigotes measuring approximately 2 µm inside the macrophagic PV (Figure 3). These clinical and microscopical findings confirmed a diagnosis of diffuse cutaneous leishmaniasis (DCL) with oral involvement. Intravenous meglumine (20 mg/kg per day) for 20 days was given, with partial regression of the lesions. As the patient requested voluntary discharge, she did not complete the course of treatment.
(a) Scanning electron microscopy showing Leishmania amastigotes inside macrophages. (b) Higher magnification illustrating that each macrophage contained several amastigotes, measuring approximately 2 µm.
Discussion
Leishmaniasis is a neglected tropical disease, endemic in 98 countries or territories, often related to poverty, with >350 million people at risk. 1 In the Americas, 18 countries are endemic for cutaneous leishmaniasis (CL) and mucocutaneous leishmaniasis (MCL), with the highest frequencies registered in Brazil, Colombia, Nicaragua and Peru. 2 On the other hand, transmission rates are considered low in Mexico, with 5.97/100,000 cases, with the vast majority of cases occurring in the Yucatán peninsula. 3 In the north-eastern region, leishmaniasis is extremely rare, with only isolated case reports. 4
New world DCL is a rare clinical form that represents an uncontrolled infection caused by deficient cell-mediated immunity. 5 When compared to the localized form of disease, DCL patients’ CD8 T lymphocytes display low cytotoxicity and low IFNγ production against macrophages infected with Leishmania mexicana, which may explain the continuous uncontrolled spread of the parasite. 6 Consequently, multiple non-ulcerative nodular lesions affect the skin diffusely; these patients eventually show parasite invasion of the nasopharyngeal and oral mucosa. 6 In contrast to other Leishmania species, each macrophage infected by L. mexicana complex harbour numerous amastigotes, usually attached to PV membranes. 7 Antimonial drugs are used as first-line therapy, and amphotericin, miltefosine, or pentamidine in cases of resistance, with mixed results. 8
DCL is a rare chronic slowly progressive disease, with limited treatment options, causing extensive scarring. Early diagnosis is imperative to accelerate cure, prevent mucosal involvement and reduce disfigurement.
Footnotes
Declaration of conflicting interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Ethical Approval
The written permission was given by the patient for her photograph to appear in this article.
Funding
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES) – Finance Code 001.