Description of the dermatoscopic features observed in sporotrichosis and American cutaneous leishmaniasis in a reference center in Rio de Janeiro, Brazil.

BACKGROUND: The evaluation of American cutaneous leishmaniasis (CL) and sporotrichosis (SP) with dermoscopy may improve the diagnosis accuracy and clinical monitoring. OBJECTIVES: To describe the dermoscopic findings and patterns of skin lesions of patients with CL and SP followed up at the Laboratory of Clinical Research and Surveillance in Leishmaniasis (LaPClinVigiLeish), Evandro Chagas National Institute of Infectious Diseases (INI), Oswaldo Cruz Foundation, Rio de Janeiro, Brazil. METHODS: The authors included patients with a diagnosis of CL or SP, who attended at INI/ Fiocruz, between 2019‒2021. All patients had 3 dermoscopic examinations (DermLite DL4): before treatment (T0), during treatment (T1), and after healing (T2). Up to three lesions per patient were evaluated. RESULTS: The authors studied 47 patients with CL (74 lesions), and 19 patients with SP (24 lesions). The authors described dermoscopic structures such as rosettes, white lines, white dots, brown focal structureless areas, brown lines and dots, white perilesional circles, perilesional hyperchromic circles, microulcerations and the rainbow patterns. The authors created specific patterns; in CL: CL-T0 "central yellow scales with a white perilesional circle pattern", CL-T1 "diffuse structureless white area pattern" and CL-T2 "white and brown focal structureless areas pattern". In SP: SP-T0 the "pustule with erythema pattern"; SP-T1 the "focal structureless white areas with erythema pattern" and SP-T2 the "white linear pattern". STUDY LIMITATIONS: This study does not correlate dermoscopic findings with time of disease evolution at the first medical examination. CONCLUSIONS: The recognition of CL and SP dermoscopy patterns may be helpful tool for the differential diagnosis and monitoring of disease evolution.

Dermoscopy of cutaneous granulomatous disorders: A study of 107 cases.

BACKGROUND: Cutaneous granulomatous disorders (CGDs) can share some features, but an accurate assessment of various findings and their pattern can be useful in differentiating them. In addition to common dermoscopic findings for CGDs, some peculiar dermoscopic characteristics can be helpful in distinguishing them. OBJECTIVE: Herein, we aimed to evaluate dermoscopic findings in patients with CGDs and determine the dermoscopic criteria that could suggest the type of granulomatous disorder. MATERIAL AND METHODS: A total of 107 cases including 75 (70.09%) males and 32 (29.90%) females with an established diagnosis of cutaneous leishmaniasis (n = 49), cutaneous sarcoidosis (n = 23), granuloma annulare (GA) (n = 18), and tattoo granuloma (n = 17) confirmed by clinical and pathological studies were included. Based on the previous studies available in the literature, we wrote a checklist containing dermoscopic features of CGDs. Afterward, two dermatologists independently reviewed all dermoscopic images for the presence or absence of each item on the checklist. Descriptive analysis, fisher exact, chi-square, and t-test were used. The granulomatous disorders with larger sample sizes were selected for further analysis, including the univariate and conditional multivariate logistic regressions. RESULTS: The most prevalent nonvascular findings in all of our CGD patients were white scaling (N = 67%, 62.61%), diffuse or localized orange structureless areas (N = 53%, 49.53%), and diffuse erythema (N = 48%, 44.85%). Furthermore, the most frequent vascular findings in all of our CGD cases were branching and arborizing vessels (N = 30%, 28.03%), linear irregular (N = 30%, 28.03%), and dotted vessels (N = 27%, 25.23%). CONCLUSION: For differentiating leishmaniasis from sarcoidosis by dermoscopy, white scaling and white scarring areas are more suggestive of cutaneous leishmaniasis, whereas the presence of arborizing vessels would be more in favor of sarcoidosis. When comparing GA to cutaneous leishmaniasis, the latter significantly shows more linear irregular vessels, hairpin vessels, white scaling, and white scarring areas. In the case of differentiating sarcoidosis from GA, the presence of hairpin vessels would be suggestive of sarcoidosis.

Biophysical and ultrasonographic changes of acute Old World cutaneous leishmaniasis skin lesions in comparison with uninvolved skin: A possible tool for non-invasive early detection and treatment outcome assessment.

Cutaneous leishmaniasis (CL) is a skin disease caused by intracellular protozoa, which is endemic in Iran. The goal of this study was to compare biophysical characteristics in CL lesions with uninvolved skin. Stratum corneum hydration, transepidermal water loss, surface friction, pH, sebum, melanin, erythema, temperature, elasticity parameters (R0, R2, and R5), thickness and echo-density of epidermis and dermis were measured on the active erythematous indurated part of a typical CL lesion in 20 patients, and compared with the same location on the other side of the body as control. Paired t-test was used for statistical analyses and a p < 0.05 was considered significant. Melanin content, R2 and echo-density of dermis were significantly lower, whereas transepidermal water loss, friction index, pH, erythema index, temperature, and the thickness of dermis were significantly higher in CL lesions. There was no significant difference in stratum corneum hydration, sebum, R0, R5, thickness of epidermis, and density of epidermis between CL and normal skin. CL lesions are characterized by certain changes in biophysical and ultrasonographic properties, which are mostly correlated with histological features. These changes are likely to be useful in the non-invasive early detection of CL and also as treatment outcome measures for clinical trials of new treatment modalities for CL in the future.

Ultrasound patterns of localized cutaneous leishmaniasis and clinical correlations.

A single-center retrospective study reviewed the following sonographic features of 18 confirmed cases of localized cutaneous leishmaniasis to identify shared presentation patterns: echotexture, lesion borders, hypodermal involvement, soft-tissue changes, and vascular pattern. A second objective was to correlate these patterns with clinical characteristics, including sex, age, anatomical location, nodule vs. plaque presentation, raised borders, granulation tissue, swelling, hyperkeratotic crusting, disease onset, and healing time. Two main patterns were identified with high-frequency ultrasonography. The first pattern was characterized by a high level of inflammation and deep hypodermal involvement, while the second variant showed involvement limited to the dermis, with minimal inflammation. The "inflammatory pattern" showed ill-defined borders, mixed echotexture, prominent vascularity with central distribution, and was correlated with clinical signs of ulceration, granulation tissue, raised borders, and longer healing time (p < 0.05). The "pauci-inflammatory pattern" presented a well-defined structure with decreased echogenicity, reduced or absent vascularity with minimal soft-tissue changes, and was associated with a shorter healing time (p < 0.05).

Image Processing for mHealth-Based Approach to Detect the Local Tissue Inflammation in Cutaneous Leishmaniasis: A Proof of Concept Study.

Skin lesions are a feature of many diseases including cutaneous leishmaniasis (CL). Ulcerative lesions are a common manifestation of CL. Response to treatment in such lesions is judged through the assessment of the healing process by regular clinical observations, which remains a challenge for the clinician, health system, and the patient in leishmaniasis endemic countries. In this study, image processing was initially done using 40 CL lesion color images that were captured using a mobile phone camera, to establish a technique to extract features from the image which could be related to the clinical status of the lesion. The identified techniques were further developed, and ten ulcer images were analyzed to detect the extent of inflammatory response and/or signs of healing using pattern recognition of inflammatory tissue captured in the image. The images were preprocessed at the outset, and the quality was improved using the CIE L∗a∗b color space technique. Furthermore, features were extracted using the principal component analysis and profiled using the signal spectrogram technique. This study has established an adaptive thresholding technique ranging between 35 and 200 to profile the skin lesion images using signal spectrogram plotted using Signal Analyzer in MATLAB. The outcome indicates its potential utility in visualizing and assessing inflammatory tissue response in a CL ulcer. This approach is expected to be developed further to a mHealth-based prediction algorithm to enable remote monitoring of treatment response of cutaneous leishmaniasis.

Usefulness of ultrasound for treatment and follow-up of cutaneous leishmaniasis.

PURPOSE: Local therapy is the preferred option of treatment for most cutaneous leishmaniasis (CL); however, local therapy could be challenging, depth and size of the skin lesions are not always clinically evident and treatment response evaluation could occasionally be misleading. High frequency ultrasound is a non-invasive imaging tool which allows initial depth assessment ultrasound-guided infiltrations and ultrasound monitoring until resolution. METHODS: We present two cases of CL treated with ultrasound-guided infiltrations and ultrasound monitoring until resolution. RESULTS: Ultrasound imaging allowed a more accurate diagnosis of CL, defining more precisely the depth and size of the skin lesions. During follow-up, progressive decrease in dermal involvement, marked attenuation of the echogenicity of subcutaneous cellular tissue and a decrease in vascularization in the color Doppler mode was observed, which aided in evaluation of treatment response. Hypodermal inflammation observed through sonography was addressed with image-guided infiltration. CONCLUSION: We would like to highlight the usefulness of skin ultrasound (both B-mode and color Doppler mode) in the diagnosis, depth assessment, imaging guided treatment, and follow-up in CL.

Three-Dimensional Optical Scanning in Post-kala-azar Dermal Leishmaniasis (PKDL).

Post-kala-azar dermal leishmaniasis may occur after successful treatment of visceral leishmaniasis and is characterized by macules, papules, or nodules in the skin, with varying size. The response to antileishmanial therapy remains difficult to assess because there are presently no reliable biomarkers. To date, skin lesions are clinically assessed for decrease in size or change in color, which is invariably subjective. Novel 3-dimensional optical scanning devices offer safe and field-adapted methods to objectively assess skin lesions for changes over time in size and color that can be quantified with great accuracy.

Visualization of Leishmania tropica Infection in BALB/c Mice by Bioluminescence Imaging

Background: Leishmania tropica is the cause of more than one form of leishmaniasis and lacks a known reservoir animal. This study compares the potential infectivity of recombinant and wild-type L. tropica in BALB/c mice. Methods: The potential infectivity of recombinant L. tropicaEGFP or L. tropicaEGFP-LUC by two different, the subcutaneous and intradermal, routes was compared using a range of classical detection methods and bioluminescence imaging (BLI). Results: In addition to the results obtained from classical diagnostic approaches, the BLI signals were detected in footpads and ears of L. tropica-infected animals. The BLI revealed that a bioluminescence signal can be observed at the inoculation site. The stability of the BLI remained constant in the footpad, but the signal was detectable for only three months in the pinna due to the decline in infection over time. Conclusion: The presented data are a precise verification of the assumption that BALB/c mice could be used as an experimental model for L. tropica infectivity.

Antimoniato de meglumine perilesional en leishmaniasis cutánea con falla terapéutica sistémica: serie de casos / Perilesional meglumine antimonate in cutaneous leishmaniasis with systemic therapeutic failure: series of cases

En Bolivia, los medicamentos utilizados para el tratamiento de la leishmaniasis cutánea son los antimoniales, de aplicación sistémica en dosis/kg peso, los cuales provocan efectos adversos por la aplicación en largos periodos y grandes volúmenes. La aplicación perilesional de antimonio tiene similar eficacia terapéutica que la sistémica. Sin embargo, no se cuenta con información documentada respecto a la eficacia del tratamiento perilesional en pacientes con falla terapéutica, posterior al tratamiento sistémico. El objetivo de esta serie de casos fue evaluar el tratamiento perilesional con glucantime, en pacientes con leishmaniasis cutánea y falla terapéutica, posterior a un primer ciclo de tratamiento sistémico con antimoniales. El estudio se realizó con once pacientes con leishmaniasis cutánea con falla terapéutica, posterior a la administración de un primer ciclo de tratamiento sistémico con glucantime procedentes de la zona tropical de Bolivia. Se consideró como falla terapéutica la persistencia de la lesión y presencia de parásitos obtenidos de los bordes de la lesión. La intervención perilesional consistió en la aplicación día por medio de glucantime en cinco sesiones. La inoculación se realizó sobre el borde de la lesión y la dosificación del medicamento se calculó multiplicando el área de la lesión por el factor 0.008. Todos los pacientes presentaron dolor local durante el momento de inoculación del medicamento, así como también presentaron un ligero agrandamiento del área de la lesión después de la primera aplicación del medicamento En las siguientes inoculaciones se observó la reducción progresiva del área de la lesión hasta su completa cicatrización.

In Bolivia, the drugs used for the treatment of cutaneous leishmaniasis are the antimonials by systemic application in doses/kg/weight, which cause adverse effects due to the applications in long periods and large volumes. The perilesional application of antimony has similar therapeutic efficacy than the systemic one. However, there is no documented information regarding the efficacy of perilesional treatment in patients with therapeutic failure after systemic treatment. The aim of this series of cases was to evaluate the perilesional treatment with Glucantime, in patients with cutaneous leishmaniasis and therapeutic failure, after a first cycle of systemic treatment with antimonials. The study was conducted with eleven patients with cutaneous leishmaniasis and therapeutic failure, after the administration of a first cycle of systemic treatment with Glucantime. From the tropical zone of Bolivia. The persistence of the lesion and the presence of parasites at the edge of the lesion were considered as therapeutic failure. The perilesional intervention consisted in the application past one day of glucantime in five sessions. The inoculation was performed on the edge of the lesion and the dosage of the medication was calculated by multiplying the area of the lesion by the factor 0.008. All the cases presented local pain during the time of inoculation of the drug, as well as a slight enlargement of the area of the lesion after the first inoculation of the drug. In the following inoculations the progressive reduction of the area of the lesion was observed until its complete healing.

Dermatoscopy of Granulomatous Disorders.

Although diagnosis of cutaneous granulomatous disorders (CGDs) is usually suspected based on morphologic findings, localization, and anamnestic data, clinical differentiation from each other and from similar dermatoses may be challenging. Recently, dermatoscopy has been demonstrated to be a useful tool for assisting the recognition of several CGDs. This article provides a current overview of the dermatoscopic features of the main noninfectious and infectious CGDs, including sarcoidosis, necrobiosis lipoidica, granuloma annulare, rheumatoid nodules, and leishmaniasis. Other, less common, CGDs are briefly addressed, including granulomatous rosacea, acne agminata, and leprosy.

A new chimeric triple reporter fusion protein as a tool for in vitro and in vivo multimodal imaging to monitor the development of African trypanosomes and Leishmania parasites.

Trypanosomiases and leishmaniases, caused by a group of related protist parasites, are Neglected Tropical Diseases currently threatening >500 million people worldwide. Reporter proteins have revolutionised the research on infectious diseases and have opened up new advances in the understanding of trypanosomatid-borne diseases in terms of both biology, pathogenesis and drug development. Here, we describe the generation and some applications of a new chimeric triple reporter fusion protein combining the red-shifted firefly luciferase PpyREH9 and the tdTomato red fluorescent protein, fused by the TY1 tag. Expressed in both Trypanosoma brucei brucei and Leishmania major transgenic parasites, this construct was successfully assessed on different state-of-the-art imaging technologies, at different scales ranging from whole organism to cellular level, both in vitro and in vivo in murine models. For T. b. brucei, the usefulness of this triple marker to monitor the entire parasite cycle in both tsetse flies and mice was further demonstrated. This stable reporter allows to qualitatively and quantitatively scrutinize in real-time several crucial aspects of the parasite's development, including the development of African trypanosomes in the dermis of the mammalian host. We briefly discuss developments in bio-imaging technologies and highlight how we could improve our understanding of parasitism by combining the genetic engineering of parasites to the one of the hosting organisms in which they complete their developmental program.

Evaluation of (131)I-pentamidine for scintigraphy of experimentally Leishmania tropica-infected hamsters.

We aimed to assess the ability of (131)I-Pentamidine scintigraphy to detect the lesions of Leishmania tropica infection. An experimental model of cutaneous leishmaniasis was developed. The presence of cutaneous leishmaniasis was confirmed. Pentamidine was radioiodinated with (131)I. The radiolabeled pentamidine was validated by the requisite quality control tests to check its radiolabeling efficiency, in vitro stability. (131)I-Pentamidine (activity: 18.5 MBq/100 µl) was injected intracardiacally into infected hamsters. Static whole body images of the hamsters were acquired under the gamma camera at 5 and 30 min, 2, 6 and 24 h following the administration. On the scintigrams, anatomically adjusted regions of interest (ROIs) were drawn over the right feet (target) and left feet (not-target) and various organs. Accumulation of (131)I-Pentamidine at sites of infection is expressed as the target to non-target (T/NT) ratio. The results T/NT ratio decreased with time. In concluding the (131)I-Pentamidine has poor sensitivity in detection of L. tropica infection.

Unusual location of cutaneous leishmaniasis on the hallux in a Brazilian patient.

A 70-year-old white Brazilian woman from a rural area had a 2-year history of a painful lesion on her left toe. The lesion increased progressively in size followed by toenail destruction. She was treated with systemic antibiotics for secondary bacterial infection several times without any clinical response. Physical examination showed an erythematous swelling on the first toe with an irregular 2.5 cm ulcer with a raised edge that was infiltrating and destroying the toenail. The bottom of the ulcer was granular and partially covered with a crust (Fig. 1). Laboratory studies showed a strong positive Montenegro intradermal reaction (2.5 mm). Other intradermal reactions were also performed, such as purified protein derivative (PPD) and sporotrichin, which were negative. On X-ray examination of the left foot, bone destruction of the distal phalanx of the first toe and a soft tissue swelling were observed (Fig. 2). A biopsy was taken and the histologic picture showed a chronic inflammatory change with tuberculoid-type granuloma and necrosis suggesting leishmaniasis, although parasites were not observed. Based on the clinical, histologic, and immunologic aspects, we concluded that this was a case of leishmaniasis. Methylglucamine (Glucantime) was introduced at a total dose of 17 g of the salt (10 mg/kg daily for 40 days). Immediately after the start of treatment, the lesion began to improve, and 4 months later the lesion had healed completely and the dystrophic nail had started to grow (Fig. 3).

[2 infectious granulomatous diseases (leprosy and cutaneous and mucous leishmaniasis) by scintigraphic methods]. / Contribution au début de l'étude de deux maladies infectieuses granulomateuses (la lèpre et la leishmaniose cutanée et muqueuse) par des méthodes scintigraphiques.

Leprosy is a multiform chronic infectious granulomatous disease caused by Mycobacterium leprae, that affects over 12 million people in the world. Cutaneous and mucous leishmaniasis (CML) is also a chronic granulomatous infectious disease, caused by Leishmania brasiliensis and transmitted to man by the mosquitoes of the Phlebotominae family. It is a worldwide spread disease. We studied one case of Borderline-wirchowian leprosy and 2 cases of CML with Gallium-67 (GA-67) scintigraphy. Ga-67 is a radiopharmaceutical known for its property of concentrating in inflammatory sites. In the leprosy patient, Ga-67 accumulated in the skin in a moderate, homogeneous and disseminated way (outlined skin); in the area of the face, the uptake was important and homogeneous (image in beard). Several internal organs accumulated Ga-67. As for the 2 CML patients, Ga-67 accumulated focally, in different degrees, in the affected anatomical areas. The leprosy patient was not under treatment and the 2 CML were under treatment (20 and 40 days, respectively). In the 3 cases, all affected areas accumulated Ga-67. Intensity differences of uptake may be explained both by different degrees of inflammatory processes (between leprosy and CML) and by treatment lasting. It is possible that Ga-67 scintigraphy may be useful for the evaluation of these 2 diseases extent and also for the therapy follow-up.