Case Report: An Atypical Case of Post-Kala-Azar Dermal Leishmaniasis with Ulcers and Verrucous Lesions: Clinical and Therapeutic Implications.

About 75% cases of post-kala-azar dermal leishmaniasis (PKDL) occur in India. Although the classic description of PKDL is the progression from initial hypopigmented macular lesions to papules to plaques and nodular lesions, atypical morphologies are also seen and are easily missed or misdiagnosed. We report a case of a 27-year-old man who presented to us with multiple acral ulcers and verrucous lesions for 5 years. A diagnosis of PKDL was made based on slit skin smear, histopathology, and quantitative polymerase chain reaction. The patient was given combination therapy with four doses of liposomal amphotericin B and miltefosine 50 mg twice daily for 45 days. In this report, we discuss unusual morphologies of PKDL, the pathway to the diagnosis, and the therapeutic options available along with their efficacy.

A case report on para-kala-azar dermal leishmaniasis: an unresolved mystery.

BACKGROUND: Post-kala-azar dermal leishmaniasis (PKDL) is a dermatosis that occurs 2-3 years after an apparently successful treatment of visceral leishmaniasis (VL). In rare cases, PKDL occurs concurrently with VL and is characterized by fever, splenomegaly, hepatomegaly or lymphadenopathy, and poor nutritional status and is known as Para-kala-azar dermal leishmaniasis (Para-KDL). Co-association of active VL in PKDL patients is documented in Africa, but very few case reports are found in South Asia. We present a case of Para-kala-azar Dermal Leishmaniasis (Para-KDL) in a 50-year-old male patient with a history of one primary Visceral Leishmaniasis (VL) and 2 times relapse of Visceral Leishmaniasis (VL). The patient presented with fever, skin lesions, and hepatosplenomegaly. Laboratory tests revealed LD bodies in the slit skin smear and splenic biopsy. The patient was treated with two cycles of Amphotericin B with Miltefosine in between cycles for 12 weeks to obtain full recovery. CONCLUSION: This case report serves as a reminder that Para-kala-azar dermal leishmaniasis can develop as a consequence of prior visceral leishmaniasis episodes, even after apparently effective therapy. Since para-kala-azar is a source of infectious spread, endemics cannot be avoided unless it is effectively recognized and treated.

Clinical Manifestation of Cutaneous Leishmaniasis Following a Mechanical Trauma.

Unusual skin ulcers frequently represent a diagnostic challenge. When the most common disease entities such as arterial, venous or diabetic ulcers have been excluded, the question of further differential diagnoses and procedures arises. Other possible causes include chronic inflammatory diseases, neoplasia, self-inflicted wounds, primary infectious diseases and physical/chemical damage to the skin. To narrow down the differential diagnoses, a detailed history of the patient is essential, which also needs to include events further back in time.

Amputation of a type II diabetic patient with cutaneous leishmaniasis due to Leishmania major.

BACKGROUND: Leishmaniases are neglected tropical diseases of public health concern in Algeria. The immunocompromised patients with HIV, autoimmune diseases, or chronic alcohol abuse are at a higher risk of leishmaniasis. Herein, we present the case of an immunocompetent diabetic patient infected by Leishmania major, leading to life-threatening consequences. CASE PRESENTATION: An Algerian diabetic patient developed a cutaneous lesion with large polymorphous inflamed granuloma and pyoderma gangrenosum in the left foot, following L. major infection. A delayed follow-up led to a treatment failure, resulting in the amputation. CONCLUSIONS: This report highlights the absence of timely treatment of Leishmania infection as a life-threatening point among high-risk diabetic patients. Clinicians should be aware of this parasitosis leading to severe complications in diabetic patients.

An 18-year-old man with tropical verrucous syndrome: Leishmaniasis or sporotrichosis? / [Hombre de 18 años con síndrome verrugoso tropical: ¿leishmaniasis o esporotricosis?]

The tropical verrucous syndrome includes infectious, chronic, and granulomatous skin conditions appearing with plaques, nodules, or ulcers with a warty surface which gives name to the syndrome. It includes forms of chromoblastomycosis, sporotrichosis, paracoccidioidomycosis, lobomycosis, leishmaniasis, and tuberculosis verrucosa cutis with ample distribution in tropical and subtropical areas. The diagnoses may be difficult and confused among them, especially between sporotrichosis and leishmaniasis. Clinical, epidemiologic, intradermal reactions, direct smears, skin biopsies, cultures, immunofluorescence, and PCR are used to differentiate them, although several of these methods are not commonly used. We present an 18-year-old man with extensive verrucous plaques in one knee interpreted by clinic, epidemiology, and biopsy as verrucous cutaneous leishmaniasis. He was treated with Glucantime® for 20 days without improvement. A new biopsy was made that was also interpreted as cutaneous leishmaniasis. The revision of both biopsies showed inflammation with abscessed granulomas and asteroid sporotrichotic bodies at the center of the granulomas that led to the diagnosis of sporotrichosis later confirmed by the fungus culture. The patient responded to the treatment with itraconazole. As clinical and epidemiological findings of leishmaniasis and sporotrichosis can be similar, skin biopsy and other paraclinical studies are necessary to establish a proper diagnosis. The asteroid sporotrichotic body is pathognomonic of this mycosis. We review here the essential concepts of leishmaniasis and sporotrichosis and the criteria to differentiate them.

El síndrome verrugoso tropical comprende condiciones cutáneas infecciosas, crónicas y granulomatosas que cursan con placas, nódulos o úlceras verrugosas, de ahí su nombre. Este síndrome incluye la cromoblastomicosis, la esporotricosis, la paracoccidioidomicosis, la lobomicosis, la leishmaniasis y la tuberculosis cutánea verrugosa, todas ellas enfermedades de amplia distribución en áreas tropicales y subtropicales. Sus diagnósticos pueden ser difíciles y confundirse entre sí, lo cual es más frecuente entre la esporotricosis y la leishmaniasis. Para distinguirlas se recurre a criterios clínicos y epidemiológicos, y a métodos diagnósticos como intradermorreacción, examen directo, biopsia, cultivo, inmunofluorescencia y PCR, algunos de los cuales no son de uso común. El diagnóstico preciso conduce al tratamiento adecuado. Se presenta el caso de un hombre de 18 años con extensas placas verrugosas en una rodilla, inicialmente interpretadas como leishmaniasis verrugosa por la clínica, la epidemiología y la biopsia. Se le trató con Glucantime® durante 20 días, pero no presentó mejoría, por lo que se tomó una nueva biopsia que también se interpretó como leishmaniasis cutánea. La revisión de ambas biopsias evidenció inflamación con granulomas abscedados y presencia de cuerpos asteroides esporotricósicos, que condujeron al diagnóstico de esporotricosis, el cual se confirmó luego con el cultivo del hongo. Las lesiones remitieron con la administración de itraconazol. La clínica y la epidemiología de la leishmaniasis y las de la esporotricosis pueden ser semejantes, por lo que la biopsia y los estudios de laboratorio son esenciales para establecer el diagnóstico. El cuerpo asteroide esporotricósico es patognomónico de esta entidad.

Sandfly Fever Sicilian Virus-Leishmania major co-infection modulates innate inflammatory response favoring myeloid cell infections and skin hyperinflammation.

BACKGROUND: The leishmaniases are a group of sandfly-transmitted diseases caused by species of the protozoan parasite, Leishmania. With an annual incidence of 1 million cases, 1 billion people living in Leishmania-endemic regions, and nearly 30,000 deaths each year, leishmaniasis is a major global public health concern. While phlebotomine sandflies are well-known as vectors of Leishmania, they are also the vectors of various phleboviruses, including Sandfly Fever Sicilian Virus (SFSV). Cutaneous leishmaniasis (CL), caused by Leishmania major (L. major), among other species, results in development of skin lesions on the infected host. Importantly, there exists much variation in the clinical manifestation between individuals. We propose that phleboviruses, vectored by and found in the same sandfly guts as Leishmania, may be a factor in determining CL severity. It was reported by our group that Leishmania exosomes are released into the gut of the sandfly vector and co-inoculated during blood meals, where they exacerbate CL skin lesions. We hypothesized that, when taking a blood meal, the sandfly vector infects the host with Leishmania parasites and exosomes as well as phleboviruses, and that this viral co-infection results in a modulation of leishmaniasis. METHODOLOGY/PRINCIPAL FINDINGS: In vitro, we observed modulation by SFSV in MAP kinase signaling as well as in the IRF3 pathway that resulted in a pro-inflammatory phenotype. Additionally, we found that SFSV and L. major co-infection resulted in an exacerbation of leishmaniasis in vivo, and by using endosomal (Toll-like receptor) TLR3, and MAVS knock-out mice, deduced that SFSV's hyperinflammatory effect was TLR3- and MAVS-dependent. Critically, we observed that L. major and SFSV co-infected C57BL/6 mice demonstrated significantly higher parasite burden than mice solely infected with L. major. Furthermore, viral presence increased leukocyte influx in vivo. This influx was accompanied by elevated total extracellular vesicle numbers. Interestingly, L. major displayed higher infectiveness with coincident phleboviral infection compared to L. major infection alone. CONCLUSION/SIGNIFICANCE: Overall our work represents novel findings that contribute towards understanding the causal mechanisms governing cutaneous leishmaniasis pathology. Better comprehension of the potential role of viral co-infection could lead to treatment regimens with enhanced effectiveness.

[Generalized old world leishmaniasis: first Moroccan case in an immunocompetent adult?] / Leishmaniose généralisée de l'Ancien monde : Premier cas marocain chez un adulte immunocompétent ?

Background: Post-kala-azar dermal Leishmaniasis (PKDL) is a rare skin syndrome observed after treatment of visceral Leishmaniasis (VL) with pentavalent antimonial organic salts, never described in Morocco before. Here we report a case in an immunocompetent adult. Case: A 36-year-old-man from Tata in southern Morocco, with a history of visceral Leishmaniasis 2 years before and treated with meglumine antimoniate and amphotericin B with good clinical course, was hospitalized in dermatology for an erythematous papulo-nodular closet of the face. Six months ago, he presented oral mucosa involvement, then 3 months later, cutaneous lesions appeared on the face. The dermatological examination revealed a papulo-nodular erythematous closet extending to the nose and both cheeks, crusty and lupoid lesions on the forehead, around the eyes and chin, associated with an ulcerative and painless lesion on the heeL. The examination of the oral mucosa revealed an ulceration of the posterior third of the tongue and a papillomatous aspect of the soft palate. The skin biopsy and smear found some amastigote forms of Leishmania bodies. ITS1 PCR was positive (genus Leishmania). The HIV serology was negative. The diagnosis of PKDL was then evoked. The patient received intra-muscular injections of meglumine antimoniate with good progress. Conclusion: To our knowledge, this is the first case of generalised leishmaniasis suggesting PKDL reported in a Moroccan immunocompetent adult.

Treatment of tegumentary leishmaniasis in two hemodialysis patients with end-stage renal disease using two series of pentamidine

Abstract In this study, we present two cases of cutaneous leishmaniasis in patients with end-stage renal disease, who were treated solely with intramuscular pentamidine. In such cases, treatment implies a fine line between therapeutic efficacy and toxicity. This is suggestive of a knowledge gap; however, findings indicate that this is still the fastest and safest alternative to the treatment with antimonials. Also, it can help avoid the side effects that occur upon using antimonials.

The co-infection of Buruli ulcer and cutaneous leishmaniasis in Sudanese patient: An association by choice or by chance?

Buruli ulcer and cutaneous leishmaniasis both have the similar cutaneous clinical presentation. Therefore, relying on clinical diagnosis can be challenging. We present a case of 45 years old woman diagnosed with cutaneous leishmaniasis, confirmed by skin biopsy. She received different modalities of anti-leishmanial treatment (fluconazole 450mg daily for 4 weeks, sodium stibogluconate (SSG) followed by thermal therapy, SSG/IV 20mg/kg for 30 days combined with paromomycin 15mg/kg IM for 17 days). These treatments were associated with partial improvement of the ulcer and failure of healing. A second biopsy demonstrated the presence of Mycobacterium ulcerans and hence the diagnosis of Buruli ulcer as a cause of the delayed healing of the ulcer. M. ulcerans releases a toxin known as mycolactone, which decreases immune system function and results in tissue death. M. ulcerans, is regarded as the third most prevalent Mycobacterium after M. tuberculosis and M. leprae. Treatment with streptomycin intramuscular injections 1g daily and rifampicin 600mg daily for 8 weeks was associated with complete healing of the ulcer. To our knowledge, this is the first report that describes the co-infection of Buruli ulcer and cutaneous leishmaniasis in Sudan.

Non-Ablative Fractional 1,540-nm Er:Glass Laser in the Treatment of Atrophic Cutaneous Leishmaniasis Scars.

OBJECTIVES: To evaluate the efficacy of nonablative fractional 1,540 nm laser to treat the atrophic scars caused by the cutaneous leishmaniasis (CL). METHODS: This clinical trial with a pre- and a posttreatment measurement was conducted on patients with atrophic CL scars. The lesions were treated with nonablative fractional 1,540 nm laser. We evaluated the patients initially and then monthly, before each treatment session. The final follow-up was done 6 months after the end of study for all patients. Patient assessment was performed by two physicians using the modified Manchester Scar Scale (MSS) as well as the interpretation of captured digital photographs. Moreover, the patients performed a self-assessment by filling in a researcher-made questionnaire. The data were statistically analyzed by SPSS software. P < 0.05 was considered statistically significant. RESULTS: Thirty patients with 37 skin lesions participated in the study. The pairwise comparison demonstrated a statistically significant difference between the modified MSS parameters (P < 0.05); however, no significant difference was observed between the modified MSS of the third and fourth (P = 0.82) as well as fourth and fifth (P = 0.636) sessions. The lesions improvement was significant based on the physician's evaluation (P < 0.001). Furthermore, patients' level of satisfaction was significantly increased in all six follow-ups (P < 0.001). No persistent complication was found. CONCLUSIONS: Nonablative fractional 1,540 nm laser is an effective and safe therapeutic choice for atrophic CL, even in darker skins. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Tegumentary leishmaniasis mimicking visceralization in a cirrhotic patient: atypical cutaneous lesions and local immunological features

Abstract Tegumentary leishmaniasis (TL) diagnosis is challenging due to the lack of a gold standard diagnostic tool. The diagnosis is significantly harder in regions where visceral leishmaniasis (VL) is also prevalent since immunological tests may present cross-reactivity. A cirrhotic patient from an endemic Brazilian region for TL and VL presented with atypical cutaneous lesions, a usual clinico-laboratory feature of VL (including a positive rk39 test result), but he was diagnosed with TL histopathologically; VL was ruled out by necropsy. Physicians working in co-prevalent areas should be aware of atypical features, unusual clinical course, and unexpected laboratory findings of leishmaniasis.

Neurohistoplasmosis y leishmaniasis cutánea en paciente inmunocompetente / Neurohistoplasmosis and cutaneous leishmaniasis in an immunocompetent patient

La histoplasmosis y la leishmaniasis son enfermedades olvidadas, endémicas en Argentina, y generalmente se asocian a inmunocompromiso. Presentamos el caso de un varón de 16 años, inmunocompetente, con histoplasmosis del sistema nervioso central y leishmaniasis cutánea. Inicialmente, el paciente presentó una lesión en la pierna de un mes de evolución seguida de paraparesia leve, diagnosticada como un proceso de desmielinización mediante estudios de imágenes. El cuadro fue tratado con altas dosis de corticoides y en 72 horas evolucionó a paraparesia grave con lesiones nodulares en las vértebras cervicales, observadas en las imágenes de resonancia magnética nuclear. Se aisló Histoplasma capsulatum de líquido cefalorraquídeo, genotípicamente identificado como perteneciente a la especie filogenética LamB. El paciente recibió tratamiento intravenoso con anfotericina B deoxicolato durante 30 días y posteriormente fluconazol e itraconazol oral durante un año. A los tres meses de iniciado el tratamiento con antifúngicos se reactivó la lesión de la pierna y en el examen directo se observaron amastigotes de Leishmania. La leishmaniasis cutánea fue tratada con antimoniato de meglumina intramuscular. La respuesta clínica al tratamiento de ambas enfermedades fue favorable.

Histoplasmosis and leishmaniasis are neglected and endemic diseases in Argentina, and generally are found associated with immunosuppression. We report the case of an immunocompetent 16-years-old man with simultaneous occurrence of central nervous system histoplasmosis and cutaneous leishmaniasis. Upon admission, the patient showed a one-month old skin lesion in a leg and mild paraparesis. Imaging studies detected thickening and edema in the spinal cord and the cerebrospinal fluid analysis was within normal range. The case was diagnosed as a demyelinating disorder and treated with high-dose short-term steroids. Seventy-two hours later the patient showed severe paraparesis and nuclear magnetic resonance imaging revealed nodular lesions in the spinal cord. Histoplasma capsulatum belonging to the phylogenetic species LamB was isolated from cerebrospinal fluid samples. The patient received intravenous antifungal therapy with amphotericin B for 30 days, followed by oral fluconazole and itraconazole for one year. Three months after initiation of antifungal treatment, the cutaneous lesion recrudesced and Leishmania amastigotes were observed on microscopic examination. The cutaneous leishmaniasis was treated with intramuscular meglumine antimoniate. The patient´s outcome was favorable after treatment for both diseases.

Combined chemotherapy manifest less severe immunopathology effects in helminth-protozoa comorbidity.

BACKGROUND: Co-infection with Leishmania major and Schistosoma mansoni may have significant consequences for disease progression, severity and subsequent transmission dynamics. Pentavalent antimonials and Praziquantel (PZQ) are used as first line of treatment for Leishmania and Schistosoma infections respectively. However, there is limited insight on how combined therapy with the standard drugs impacts the host in comorbidity. The study aimed to determine the efficacy of combined chemotherapy using Pentostam (P) and PZQ in murine model co-infected with L. major and S. mansoni. METHODS: A 3 × 4 factorial design with three parasite infection groups (Lm, Sm, Lm + Sm to represent L. major, S. mansoni and L. major + S. mansoni respectively) and four treatment regimens [P, PZQ, P + PZQ, and PBS designating Pentostam (GlaxoSmithKline UK), Praziquantel (Biltricide®, Bayer Ag. Leverkusen, Germany), Pentostam + Praziquantel and Phosphate buffered saline] as factors was applied. RESULTS: Significant changes were observed in the serum Interferon gamma (IFN-γ), and Macrophage inflammatory protein-one alpha (MIP-1α) levels among various treatment groups between week 8 and week 10 (p < 0.05). There was increased IFN-γ in the L. major infected mice subjected to PZQ and PBS, and in L. major + S. mansoni infected BALB/c mice treated with P + PZQ. Subsequently, MIP-1α levels increased significantly in both the L. major infected mice under PZQ and PBS and in L. major + S. mansoni infected BALB/c mice undergoing concurrent chemotherapy with P + PZQ between 8 and 10 weeks (p < 0.05). In the comorbidity, simultaneous chemotherapy resulted in less severe histopathological effects in the liver. CONCLUSION: It was evident, combined first line of treatment is a more effective strategy in managing co-infection of L. major and S. mansoni. The findings denote simultaneous chemotherapy compliments immunomodulation in the helminth-protozoa comorbidity hence, less severe pathological effects following the parasites infection. Recent cases of increased incidences of polyparasitism in vertebrates call for better ways to manage co-infections. The findings presented necessitate intrinsic biological interest on examining optimal combined chemotherapeutic agents strategies in helminth-protozoa concomitance and the related infections abatement trends vis-a-vis host-parasite relationships.

Clinical and Pathological Aspects of Canine Cutaneous Leishmaniasis: A Meta-analysis.

PURPOSE: In the present study, we described the most prevalent clinical symptoms, the most affected organs, and the macro and microscopic lesions associated with cutaneous leishmaniasis. METHODS: Two independent researchers performed an extensive systematic review of the literature in four stages (identification, screening, eligibility, and inclusion) to identify studies published between January 2002 and November 2018 from the following electronic databases: Web of Science, PubMed, SciELO, Science Direct, and Google Scholar. Meta-analysis was conducted in "Metaprop" package of R 3.4.2 software. RESULTS: The electronic search yielded 3896 results, out of which 155 were further analyzed based on the full-text. Data extracted from 16 articles were included in the meta-analysis, representing a total of 430 leishmaniasis cases. Only 43% of all animals were identified to exhibit the clinical and cutaneous changes characteristic of leishmaniasis based on the observation that skin lesions were the most prevalent clinical sign and were present in 86% of all cases. Other less prevalent symptoms included weight loss, cachexia, apathy and lymph node enlargement. Histopathological analysis showed that the skin was the most affected organ, affecting 64% of cases, followed by lymph nodes (12%), spleen (8%) and liver (7%). CONCLUSIONS: Therefore, our current findings suggest that cutaneous leishmaniasis could lead to visceral disease. Notably, our findings indicated no clinical manifestation patterns in cutaneous leishmaniasis, since the same host species may present different clinical conditions.

American tegumentary leishmaniasis: severe side effects of pentavalent antimonial in a patient with chronic renal failure

Abstract: Pentavalent antimonials are the first-line drug treatment for American tegumentary leishmaniasis. We report on a patient with chronic renal failure on hemodialysis who presented with cutaneous lesions of leishmaniasis for four months. The patient was treated with intravenous meglumine under strict nephrological surveillance, but cardiotoxicity, acute pancreatitis, pancytopenia, and cardiogenic shock developed rapidly. Deficient renal clearance of meglumine antimoniate can result in severe toxicity, as observed in this case. These side effects are related to cumulative plasma levels of the drug. Therefore, second-line drugs like amphotericin B are a better choice for patients on dialysis.

The color of skin: orange diseases of the skin, nails, and mucosa.

Cutaneous disease can present with lesions of all colors of the visible spectrum. Lesions of the skin, nail, and mucous membranes with an orange color can be due to a variety of etiologies. The conditions may appear as purely orange, yellow-orange, red-orange, tan, or brown with an orange hue. The orange color may also present as a transient phase of a disease process. As with all dermatologic pathology, a key way to distinguish orange-colored lesions is by distribution and morphology. The sclera, palate, lips, gingiva, and nails may also be involved. A literature review using PubMed with keywords, including orange, skin, mucosa, cutaneous, xanthoderma, and granuloma, was conducted to gather all dermatologic conditions that can present with an orange color. The relevant diseases were categorized by etiology and include inflammatory, infectious, neoplastic, and exogenous causes.