Oral Leishmaniasis in HIV-Positive and HIV-Negative Patients: A Comparative Analysis with Two New Case Reports.

PURPOSE: This case report examines the clinical presentation, diagnosis, treatment, and outcomes of mucocutaneous leishmaniasis with primary oral involvement in HIV-positive and HIV-negative patients diagnosed in Brazil. METHODS: We discuss the clinical manifestations, diagnostic methods, and therapeutic strategies, highlighting the clinical and histopathologic diagnostic features and distinct progression patterns based on HIV status. Our findings are compared with patterns observed in other countries, emphasizing the differences between the Americas and Europe, Asia, and Africa. RESULTS: In the Americas, particularly in Brazil, mucocutaneous leishmaniasis often presents with localized oral lesions, even in the presence of systemic immunosuppression, whereas in the Europe, Asia, and Africa, oral involvement is typically associated with visceral leishmaniasis in immunocompromised patients. These differences were due to variations in the parasite species involved. CONCLUSION: This comparison underscores the importance of regional and immunological factors in diagnosing and managing this neglected infectious disease.

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

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.

Mucocutaneous Leishmaniasis Rhinology Complications: A Rare Presentation.

OBJECTIVE: This case report presents a unique manifestation of Mucocutaneous Leishmaniasis (MCL) in a 56-year-old woman with chronic nasal symptoms. Initially diagnosed with chronic sinusitis and septal perforation, the patient's history of a childhood sandfly bite and subsequent episodes of Leishmaniasis, revealed after nasal surgery, provided crucial information for accurate diagnosis. METHODS: A retrospective review was conducted on this patient's electronic medical record. RESULTS: The patient's life-long struggle with nasal obstruction, congestion, and a septal perforation initially masked the underlying MCL. Sinus surgery and persistent symptoms further complicated the diagnostic process. Only after postoperative complications, including grainy skin texture extending into the nasal passages, did the patient recall the sandfly bite, prompting reevaluation and diagnosis of MCL. The case highlights the challenges of diagnosing MCL due to its varied presentation and potential mimicry of other chronic nasal conditions. It emphasizes the importance of thorough patient history-taking, especially when symptoms are atypical or persistent. Additionally, the report underscores the potential for unexpected postoperative complications in MCL patients and the need for vigilance in recognizing and assessing them. CONCLUSION: This case contributes to the understanding of MCL's diverse clinical presentation and the importance of early diagnosis and multidisciplinary management for prompt intervention and improved outcomes.

Treatment of mucocutaneous leishmaniasis - A systematic review.

Mucocutaneous leishmaniasis is a severe infectious disease, predominantly endemic in Central and South America and is characterized by granulomatous, destructive mucosal lesions in the oral, nasal, and pharyngeal cavities. It is caused by protozoa of the genus Leishmania spp. transmitted to humans by sandflies. Mucocutaneous leishmaniasis occurs after untreated or inadequately treated cutaneous leishmaniasis and is more common in immunocompromised patients. The aim of this systematic review is to summarize all reported treatment options for mucocutaneous leishmaniasis. This review is based on all English, German, French, Spanish and Portuguese articles published in the databases "PubMed" and "Lilacs" from 1995 to 2020. Most of the medical literature is limited to case reports, small case series, retrospective studies, and a few randomized controlled trials. Various treatment options include pentavalent antimonates such as meglumine antimonate or sodium stibogluconate, amphotericin B (liposomal, deoxycholate, lipid complex, colloidal dispersion), miltefosine, and pentamidine. Other therapeutic options include itraconazole, fluconazole, ketoconazole, aminosidine sulfate, and azithromycin. The choice of drug depends primarily on its availability in the endemic area and the patient's comorbidities.

Case Report: In Situ and Systemic Immune Response to Mucosal Leishmaniasis in an HIV-Infected Patient.

In situ and systemic evaluations of the immune responses of HIV-infected patients to mucosal leishmaniasis have been poorly described. We describe a recently diagnosed HIV-infected patient with mucosal leishmaniasis who was characterized by a CD4 count of 85 cells/mm3 and nasal septum destruction resulting from pruritic and ulcerated nasal mucosa with crust formation and progression over 2 years. In situ and systemic immune evaluations of T cell activation, memory, and exhaustion were conducted using cytofluorometric assays, and sequencing of the Leishmania species was performed. The immune profile of HIV-infected patient with mucosal leishmaniasis shows a mixed Th1/Th2 pattern and an activated and exhausted status.

Clinicopathological characteristics of cutaneous and mucocutaneous leishmaniasis in patients treated with TNF-α inhibitors.

BACKGROUND AND OBJECTIVES: The increasing use of biologics in the treatment of inflammatory diseases has led to more cases of leishmaniasis in patients subjected to iatrogenic immunosuppression. The main objective was to describe the characteristics of the patients with cutaneous (CL) or mucocutaneous (MCL) leishmaniasis who were receiving a biological therapy at the time of diagnosis. PATIENTS AND METHODS: A multicenter retrospective study was design based on a cohort of patients diagnosed with CL or MCL. All patients who were being treated with biologicals were included. For each case, two matched non-exposed patients were included for comparison. RESULTS: 38 patients were diagnosed with CL or MCL while being treated with tumor necrosis factor alpha (TNF-α) inhibitors. Leishmaniasis presented more frequently as a plaque (58.3%) with a larger median lesion size (2.5 cm), ulceration (92.1%), and required a greater median number of intralesional meglumine antimoniate infiltrations (3 doses) (P < 0.05) than in non-exposed patients. We found no systemic involvement in patients being treated with anti-TNF-α. We did not find differences regarding the treatment characteristics whether biologic therapy was modified or not. CONCLUSIONS: Although management should be individualized, maintenance of biologic therapy does not seem to interfere with treatment of CL or MCL.

Fever with perinasal and tongue lesions: A diagnostic challenge.

The diagnosis may be challenging, and high suspicion index should be maintained in immunosuppressed patients with unusual mucocutaneous lesions, even in non-endemic areas for mucocutaneous leishmaniasis.

Mucosal Leishmaniasis of the lip: Report of an Exuberant case in a Young man.

BACKGROUND: Leishmaniasis is a tropical disease caused by protozoan parasites of the genus Leishmania. Mucosal leishmaniasis has been described as secondary to the cutaneous form; however, isolated mucosal involvement can also occur. Specifically, mucosal leishmaniasis of the lip is poorly described and its diagnosis challenges clinicians. METHODS: We herein report a case of mucosal leishmaniasis affecting the lower lip without cutaneous involvement in a 20-year-old Venezuelan man. The patient had no relevant past medical history. Clinically, a mass-like lesion with ulcerations and crusts was observed. RESULTS: Microscopically, the lesion was composed of granulomatous inflammation along with macrophages containing intracytoplasmic inclusions similar to round-shaped Leishmania. The species Leishmania (Viannia) braziliensis was confirmed. Treatment with meglumine antimonate was effective. The lesion healed satisfactorily, and no side effects or recurrences were observed. CONCLUSION: Clinicians should be aware of isolated forms of mucosal leishmaniasis of the lip, even in cases where the cutaneous lesion is undetected or clinically manifests as self-limiting. Knowing the endemic areas in the scenario of the dynamics of the ecoepidemiology of leishmaniasis is also essential for surveillance and counselling of the population.

Clinical criteria for Mucosal Leishmaniasis diagnosis in rural South America: A systematic literature review.

BACKGROUND: Mucosal Leishmaniasis (ML), a neglected tropical disease caused by Leishmania parasites, impairs the quality of life of under-resourced populations in South America. If not treated promptly, this disease progresses to facial deformities and death. The low sensitivity of microscopy results and the unavailability of other accurate tests hamper the diagnosis. As clinical criteria are readily available in any setting, these may be combined in a syndromic algorithm, which in turn can be used as a diagnostic tool. We explore potential clinical criteria for a syndromic diagnostic algorithm for ML in rural healthcare settings in South America. METHODOLOGY/PRINCIPAL FINDINGS: The protocol for this systematic review was pre-registered in PROSPERO with the number: CRD42017074148. In patients with ML, described in case series identified through a systematic retrieval process, we explored the cumulative ML detection rates of clinical criteria. Participants: all patients with active mucosal disease from an endemic area in South America. Any original, non-treatment study was eligible, and case reports were excluded. PUBMED, EMBASE, Web of Science, SCIELO, and LILACS databases were searched without restrictions. The risk of bias was assessed with the JBI checklist for case series. We included 10 full texts describing 192 ML patients. Male gender had the highest detection rate (88%), followed by ulcer of the nasal mucosa (77%), age >15 (69%), and symptom duration >4 months (63%). SIGNIFICANCE: Within this selection of patients, we found that the male gender, ulcer of the nasal mucosa, age >15, and symptom duration >4 months lead to the highest detection rates. However, higher detection comes -naturally- with a higher rate of false positives as well. As we only included ML patients, this could not be verified. Therefore, the criteria that we found to be most promising should be validated in a well-designed prospective study.

A trespasser from a foreign land? A case report of primary mucosal leishmaniasis.

BACKGROUND: We report a clinically challenging and unusual case of L. donovani oral mucosal leishmaniasis. CASE PRESENTATION: Israeli resident with a former travel to central and North Africa, with no documented or prior cutaneous lesions presented with oral lesions of the maxillary gingiva and the upper lip. A delay in diagnosis and treatment have led to progression of the maxillary gingival lesions towards the hard palatal and the soft palate that could have potentially compromised the upper airway. CONCLUSIONS: This case highlights the importance of early diagnosis of leishmaniasis in patients with oral lesions and the laboratory workup necessary to appropriately characterize and treat the disease.

Gestión de diagnóstico de leishmaniasis cutánea y mucocutánea en Ecuador 2019- 2020 / Diagnostic management of cutaneous and mucocutaneous leishmaniasis in Ecuador-2020

La leishmaniasis es un síndrome clínicamente heterogéneo causado por parásitos protozoarios intracelulares del género Leishmania. El espectro clínico de la leishmaniasis abarca la infección subclínica (no aparente), localizada (lesión cutánea) y diseminada (cutánea, mucocutánea y visceral). Un diagnóstico erróneo puede conducir a un resultado desfavorable. Utilizando los resultados del estudio microscópico, histológico y / o por métodos inmunológicos, se puede establecer un diagnóstico de leishmaniasis e iniciar el tratamiento. El manejo apropiado requiere un diagnóstico preciso, que a menudo incluye la identificación de la especie etiológica específica. Se realizó un estudio descriptivo de corte transversal para conocer la gestión de diagnóstico de leishmaniasis cutánea y mucocutánea en Ecuador. En el año 2019 se reportaron 1104 casos, 1084 tipo cutánea y 20 mucocutánea; hasta la semana epidemiológica 53 del año 2020, se notificaron 924 casos (894 cutáneo y 30 mucocutáneo). Este estudio abre el camino para una mayor investigación sobre la transmisión de la leishmaniasis en Ecuador, incluida la vigilancia de vectores y reservorios, así como para la intensificación de las actividades de investigación y control contra la leishmaniasis cutánea y la mucocutánea en la región(AU)

Leishmaniasis is a clinically heterogeneous syndrome caused by intracellular protozoan parasites of the genus Leishmania. The clinical spectrum of leishmaniasis encompasses subclinical (not apparent), localized (skin lesion), and disseminated (cutaneous, mucocutaneous, and visceral) infection. A misdiagnosis may lead to an unfavorable outcome. Using microscopic examination, histologic, and/or or by immunological methods study results, a diagnosis of leishmaniasis can be established and treatment initiated. Appropriate management requires an accurate diagnosis, which often includes identification of the specific etiologic species. A descriptive cross-sectional study was carried out to understand the diagnostic management of cutaneous and mucocutaneous leishmaniasis in Ecuador. In 2019, 1104 cases were reported, 1084 cutaneous and 20 mucocutaneous; Up to epidemiological week 53 of 2020, 924 cases were reported (894 cutaneous and 30 mucocutaneous). This study opens the path for further research on the transmission of leishmaniasis in Ecuador including vector and reservoir surveillance as well as for intensification of investigation and control activities against cutaneous and mucocutaneous leishmaniasis in the región(AU)

Potential antigenic targets used in immunological tests for diagnosis of tegumentary leishmaniasis: A systematic review.

Immunological tests may represent valuable tools for the diagnosis of human tegumentary leishmaniasis (TL) due to their simple execution, less invasive nature and potential use as a point-of-care test. Indeed, several antigenic targets have been used with the aim of improving the restricted scenario for TL-diagnosis. We performed a worldwide systematic review to identify antigenic targets that have been evaluated for the main clinical forms of TL, such as cutaneous (CL) and mucosal (ML) leishmaniasis. Included were original studies evaluating the sensitivity and specificity of immunological tests for human-TL, CL and/or ML diagnosis using purified or recombinant proteins, synthetic peptides or polyclonal or monoclonal antibodies to detect Leishmania-specific antibodies or antigens. The review methodology followed PRISMA guidelines and all selected studies were evaluated in accordance with QUADAS-2. Thirty-eight original studies from four databases fulfilled the selection criteria. A total of 79 antigens were evaluated for the detection of antibodies as a diagnostic for TL, CL and/or ML by ELISA. Furthermore, three antibodies were evaluated for the detection of antigen by immunochromatographic test (ICT) and immunohistochemistry (IHC) for CL-diagnosis. Several antigenic targets showed 100% of sensitivity and specificity, suggesting potential use for TL-diagnosis in its different clinical manifestations. However, a high number of proof-of-concept studies reinforce the need for further analysis aimed at verifying true diagnostic accuracy in clinical practice.

Challenges in diagnosis of genital ulcers: a genital leishmaniasis case series.

Leishmaniasis is a tropical infectious disease caused by Leishmania spp. protozoa and is transmitted by insects from the Phlebotominae subfamily. It can manifest as cutaneous leishmaniasis, a painless ulcer that can develop into a more serious systemic affliction as the protozoa spreads lymphatically or hematogenously, depending on the host's immunity. In this case series, the authors present a rare form of genital mucocutaneous leishmaniasis, with consideration of epidemiologic characteristics, clinical presentation, differential diagnosis, and treatments offered.

Immunoproteomics characterization of Leishmania panamensis proteins for potential clinical diagnosis of mucosal Leishmaniasis.

Diagnosis of leishmaniasis based on antibodies detection represents a challenge due to cross-reaction of sera with other infectious agents, which co-exist in endemic areas of Leishmania sp, especially patients with Trypanosoma cruzi. This work is aimed at searching for immunogenic proteins in sera from patients with cutaneous and mucosal leishmaniasis that may be potential candidates for the development of diagnostic tests and/or vaccines that help control the infection. Total protein extracts of L. panamensis promastigotes were put in contact with sera from patients with cutaneous and mucosal leishmaniasis (immunoblots). Immunoreactive proteins were identified by mass spectrometry and bioinformatics tools. 81 proteins were identified. One of these was uniquely recognized by the sera from patients with ML but not from sera from either CL or Chagas disease patients. MS analysis of this band pointed to the putative leishmanial 3-oxoacyl-(Acylcarrierprotein) reductase.

Tongue Nodule as Primary Manifestation of American Cutaneous Leishmaniasis in an Immunocompetent Patient.

Leishmaniasis is a parasitic disease considered an endemic public health problem in developing countries, where it is a reportable disease. Isolated oral manifestation is rare, and its clinical manifestations are variable. In this paper we describe an unusual case of an immunocompetent patient, 57-year-old man with a painless reddish submucosal nodule located on the tongue dorsum. Microscopical analysis showed chronic inflammatory infiltrate with macrophages containing leishmania in cytoplasmic vacuoles. PCR assays confirmed the diagnosis and patient was treated with meglumine antimoniate for 30 days. Absence of the parasite was confirmed by PCR. Thirteen years after treatment, a scar fibrosis persisted on the tongue dorsum. The case reported reveals that leishmaniasis should be considered in the diagnosis of tongue nodules in immunocompetent patients.