A review of lobomycosis and lobomycosis-like skin disease in cetaceans worldwide, with new data from the Gulf of Guayaquil, Ecuador.

Lobomycosis, also called paracoccidioidomycosis ceti, is a chronic mycotic cutaneous disease affecting odontocetes. Lobomycosis-like disease (LLD) has a clinical presentation consistent with lobomycosis but lacks a histological and molecular diagnosis. We review the literature on lobomycosis aetiology, clinical signs and pathogenesis, species affected and geographic distribution and examine the factors influencing the presence, transmission and prevalence of the disease, to better understand its ecology. In addition, we provide unpublished information on LLD in two common bottlenose dolphin (Tursiops truncatus) communities inhabiting the Gulf of Guayaquil, Ecuador. Lobomycosis and LLD occur in Delphinidae from the Atlantic, Pacific, and Indian Oceans between 33°N and 35°S. Primary risk factors include habitat, sex, age, sociality, and pollution. In dolphins from the Americas and Japan, lobomycosis is caused by Paracoccidioides ceti, family Ajellomycetaceae. The disease is characterized by cutaneous granulomatous lesions that may occur anywhere on the body, grow to large size, and may ulcerate. Histologically, the lesions consist of acanthosis and histiocytic granulomas between the skin and subcutaneous tissues, with inflammatory changes that extend deep into the dermis. Multiple yeast cells with a double refringent layer stained positive using Gomori-Grocott methenamine silver in the dermis of a T. truncatus from Ecuador diagnosed with LLD since 2011, a first record for the Southeast Pacific. Injuries may enable the entry of P. ceti into the dermis while skin contact likely favours transmission, putting males at higher risk than females. Lobomycosis and LLD may have a negative impact on small communities already threatened by anthropogenic factors.

We review lobomycosis and lobomycosis-like disease in cetaceans and give new information for bottlenose dolphins (Tursiops truncatus) from the Gulf of Guayaquil, Ecuador. Caused by Paracoccidioides ceti, the disease affects several dolphin species worldwide, including in Ecuador, for which we present a first record.

Macrophage immunophenotypes in Jorge Lobo's disease and lepromatous leprosy - a comparative study

Jorge Lobo's disease (JLD) and lepromatous leprosy (LL) share several clinical, histological and immunological features, especially a deficiency in the cellular immune response. Macrophages participate in innate and adaptive inflammatory immune responses, as well as in tissue regeneration and repair. Macrophage function deficiency results in maintenance of diseases. M1 macrophages produce pro-inflammatory mediators and M2 produce anti-inflammatory cytokines. To better understand JLD and LL pathogenesis, we studied the immunophenotype profile of macrophage subtypes in 52 JLD skin lesions, in comparison with 16 LL samples, using a panmacrophage (CD68) antibody and selective immunohistochemical markers for M1 (iNOS) and M2 (CD163, CD204) responses, HAM56 (resident/fixed macrophage) and MAC 387 (recently infiltrating macrophage) antibodies. We found no differences between the groups regarding the density of the CD163, CD204, MAC387+ immunostained cells, including iNOS, considered a M1 marker. But HAM56+ cell density was higher in LL samples. By comparing the M2 and M1 immunomarkers in each disease separately, some other differences were found. Our results reinforce a higher M2 response in JLD and LL patients, depicting predominant production of anti-inflammatory cytokines, but also some distinction in degree of macrophage activation. Significant amounts of iNOS + macrophages take part in the immune milieu of both LL and JLD samples, displaying impaired microbicidal activity, like alternatively activated M2 cells

Human Lobomycosis Caused by Paracoccidioides (Lacazia) loboi, Panama, 2022.

We report a patient from Panama who had lobomycosis caused by Paracoccidioides (Lacazia) loboi. We used combined clinical-epidemiologic and phylogenetic data, including a new gene sequence dataset on this fungus in Panama, for analysis. Findings contribute useful insights to limited knowledge of this fungal infection in the Mesoamerican Biologic Corridor.

Fungal Density in Lobomycosis in French Guiana: A Proposal for a New Clinico-Histological and Therapeutic Classification.

BACKGROUND: Lobomycosis is a rare cutaneous tropical neglected disease caused by the fungal agent Lacazia loboi, recently renamed Paracoccidioides lobogeorgii. Our objectives were to present all cases of lobomycosis diagnosed in French Guiana, to offer a precise description of their histopathological features and to propose a new clinico-histological prognostic classification. METHODS: All cases of lobomycosis diagnosed in French Guiana between 1959 and 2022 were included. We looked for associations between the occurrence of relapses and the clinic-histological form. RESULTS: 31 patients diagnosed with lobomycosis were included. An epidemiological shift was observed in the 2000s as Brazilian patients became the most important ethnic group. Gold mining, forestry and fishing/sailing were reported as professional exposures. New histological features, such as inflammatory "rosettes" formations were described. We describe two clinic-histological patterns: a major form (high fungal density and/or multifocal lesions) and a minor form (low fungal density, unifocal lesions, association with fewer relapses). CONCLUSIONS: The changing epidemiology of lobomycosis in French Guiana is characterized by a shift towards Brazilian patients, mostly gold miners. Minor forms should be treated with surgery, major forms with a combination of surgery followed by nultiple drug therapy (MDT) or posaconazole.

Lobomycosis Epidemiology and Management: The Quest for a Cure for the Most Neglected of Neglected Tropical Diseases.

Lobomycosis is a chronic disease caused by Lacazia loboi, which is endemic to the Amazon rainforest, where it affects forest dwellers in Brazil. There is no disease control program and no official therapeutic protocol. This situation contributes to an unknown disease prevalence and unmet needs of people disabled by this disease who seek access to treatment. This review provides an update on the subject with an emphasis on therapeutic advances in humans. All relevant studies that addressed epidemiology, diagnosis, or therapeutics of lobomycosis were considered. Seventy-one articles published between 1931 and 2021 were included for a narrative literature review on the epidemiology and quest for a cure. An effective therapy for lobomycosis has been found following decades of research led by the State Dermatology Program of Acre in the Amazon rainforest, where the largest number of cases occur. This discovery opened new avenues for future studies. The main recommendations here, addressed to the Brazilian Ministry of Health, are for lobomycosis to become a reportable disease to ensure that disease prevalence is measured, and that it be prioritized such that affected individuals may access treatment free-of-charge.

Jorge Lobo's disease with malignant degeneration to squamous cell carcinoma: case report

Abstract Jorge Lobo's disease (JLD) is a chronic, granulomatous fungal infection caused by the traumatic implantation of the fungus Lacazia loboi in the cutaneous and subcutaneous tissues, with the presence of isolated nodular and coalescent keloidal lesions. Malignant degeneration is rare. This case report describes a 64-year-old male patient with JLD for 30-years who showed a change in the aspect of a lesion in the left lower limb. Histopathological examination confirmed the progression to well-differentiated squamous cell carcinoma (SSC). JLD is highly prevalent in tropical and subtropical regions, requiring monitoring concerning the transformation into SSC in long-term lesions.

Jorge Lobo's disease with malignant degeneration to squamous cell carcinoma: case report.

Jorge Lobo's disease (JLD) is a chronic, granulomatous fungal infection caused by the traumatic implantation of the fungus Lacazia loboi in the cutaneous and subcutaneous tissues, with the presence of isolated nodular and coalescent keloidal lesions. Malignant degeneration is rare. This case report describes a 64-year-old male patient with JLD for 30-years who showed a change in the aspect of a lesion in the left lower limb. Histopathological examination confirmed the progression to well-differentiated squamous cell carcinoma (SSC). JLD is highly prevalent in tropical and subtropical regions, requiring monitoring concerning the transformation into SSC in long-term lesions.

Lobomycosis epidemiology and management: the quest for a cure for the most neglected of neglected tropiocal diseases

Lobomycosis is a chronic disease caused by Lacazia loboi, which is endemic to the Amazon rainforest, where it affects forest dwellers in Brazil. There is no disease control program and no official therapeutic protocol. This situation contributes to an unknown disease prevalence and unmet needs of people disabled by this disease who seek access to treatment. This review provides an update on the subject with an emphasis on therapeutic advances in humans. All relevant studies that addressed epidemiology, diagnosis, or therapeutics of lobomycosis were considered. Seventy-one articles published between 1931 and 2021 were included for a narrative literature review on the epidemiology and quest for a cure. An effective therapy for lobomycosis has been found following decades of research led by the State Dermatology Program of Acre in the Amazon rainforest, where the largest number of cases occur. This discovery opened new avenues for future studies. The main recommendations here, addressed to the Brazilian Ministry of Health, are for lobomycosis to become a reportable disease to ensure that disease prevalence is measured, and that it be prioritized such that affected individuals may access treatment free-of-charge.

Lobomycosis: exuberant presentation with malignant transformation

Abstract Lobomycosis is a chronic granulomatous infection caused by the yeast Lacazia loboi, typically found in tropical and subtropical geographical areas. Transmission occurs through traumatic inoculation into the skin, especially in exposed areas, of men who work in contact with the soil. Lesions are restricted to the skin and subcutaneous tissue, with a keloid-like appearance in most cases. The occurrence of squamous cell carcinoma on skin lesions with a long evolution is well known; however, there are scarce reports of lobomycosis that developed into squamous cell carcinoma. The authors report a patient from the Brazilian Amazon region, with lobomycosis and carcinomatous degeneration, with an unfavorable outcome, due to late diagnosis.

Lobomycosis: exuberant presentation with malignant transformation.

Lobomycosis is a chronic granulomatous infection caused by the yeast Lacazia loboi, typically found in tropical and subtropical geographical areas. Transmission occurs through traumatic inoculation into the skin, especially in exposed areas, of men who work in contact with the soil. Lesions are restricted to the skin and subcutaneous tissue, with a keloid-like appearance in most cases. The occurrence of squamous cell carcinoma on skin lesions with a long evolution is well known; however, there are scarce reports of lobomycosis that developed into squamous cell carcinoma. The authors report a patient from the Brazilian Amazon region, with lobomycosis and carcinomatous degeneration, with an unfavorable outcome, due to late diagnosis.

Case for diagnosis. Keloidal cord-like lesion on the leg

Abstract We report a 74-year-old male presented to an outpatient dermatology clinic in Manaus, Amazonas, with a one-year history of pruritic, keloidal lesions on his left lower extremity. Histopathology showed round structures in reticular dermis. Grocott methenamine silver stain revealed numerous round yeasts with thick double walls, occurring singly or in chains connected by tubular projections. The diagnosis was lobomycosis. Although the keloidal lesions presented by this patient are typical of lobomycosis, their linear distribution along the left lower limb is unusual.

What is your diagnosis? Keloidal cord-like lesion on the leg.

We report a 74-year-old male presented to an outpatient dermatology clinic in Manaus, Amazonas, with a one-year history of pruritic, keloidal lesions on his left lower extremity. Histopathology showed round structures in reticular dermis. Grocott methenamine silver stain revealed numerous round yeasts with thick double walls, occurring singly or in chains connected by tubular projections. The diagnosis was lobomycosis. Although the keloidal lesions presented by this patient are typical of lobomycosis, their linear distribution along the left lower limb is unusual.

Epidemiologic and Clinical Progression of Lobomycosis among Kaiabi Indians, Brazil, 1965-2019.

Lobomycosis is a rare granulomatous skin disease with a high prevalence in the Amazon region. The Kaiabi Indians are an especially affected group. We studied the current epidemiologic and clinical progression of lobomycosis among the Kaiabi in Brazil, from initial case reports in 1965 through 2019. A total of 60 lobomycosis cases had been reported among the Kaiabi, and we identified 3 new cases in our review. Of 550 cases of lobomycosis ever reported worldwide, 11.5% were among the Kaiabi. We note a high incidence among female Kaiabi and a precocious onset of disease in this indigenous population. Male Kaiabi frequently are infected with the multicentric form and women more frequently exhibit the localized form. Ulcerated lesions are observed more often in the multicentric form. The prevalence among this indigenous group could be explained by genetic susceptibility and lifestyle, which exposes them to a particular agent in the habitats in which they live.

An atypical keloid in a Brazilian man.

Case report from French Guiana of an atypical keloid in a Brazilian man: Lobomycosis. Lobomycosis is a rare fungal skin infection, endemic to the Amazon basin. Its clinical manifestations are slow-growing keloid-like nodules, with a granulomatous reaction on histopathology. The etiological agent, Lacazia loboi, has never been isolated in the environment or cultured in a laboratory. Diagnosis is based on the typical appearance on microscopy. Treatment is disappointing, with a high recurrence rate. We report a new case in French Guiana and review the literature. Only 10 cases have been reported outside of the endemic area, 2 involving no travel; the mean time to diagnosis was 21 years. Phylogenetic analysis has recently proved that lobomycosis in dolphins is caused by a fungus more closely related to Paracoccidioides brasiliensis than to L. loboi (two very closely related species). Molecular diagnosis is possible in a few centers. Climate change may result in spreading lobomycosis to currently disease-free areas of the world.

Role of social behaviour in the epidemiology of lobomycosis-like disease (LLD) in estuarine common bottlenose dolphins from Ecuador.

Lobomycosis-like disease (LLD) is a chronic granulomatous skin disorder that affects Delphinidae worldwide. LLD has been observed in common bottlenose dolphins Tursiops truncatus from the Gulf of Guayaquil, Ecuador, since 1990. Although exogenous factors such as salinity and pollution may play a role in the pathogenesis of this disease in estuarine and coastal dolphin communities, we hypothesized that demography and social behaviour may also influence its epidemiology. To address this issue, the role of social behaviour in the distribution and prevalence of LLD was assessed through hierarchical cluster analysis and spatial distribution analysis in 7 dolphin communities inhabiting the inner estuary. Individuals with LLD lesions were observed in 5 of the 7 dolphin communities, with 13 of the 163 (8%) animals being positive, all adults. Among 8 dolphins of known sex, LLD affected mostly males (86%), who usually were found in pairs. Prevalence was low to moderate (5.1-13%) in dolphin communities where low-rank males had LLD. Conversely, it was high (44.4%, n = 9) in a small community where a high-rank male was infected. LLD affected both dolphins in 2 of the 4 male pairs for which large time series data were available, suggesting horizontal transmission due to contact. Thus, association with LLD-positive males seems to be an important risk factor for infections. Additionally, low-rank males had larger home ranges than high-rank males, indicating that low-status LLD-affected dolphins are likely responsible for the geographic dissemination of the disease in this population.

Lobomycosis in Soldiers, Colombia.

Lobomycosis is a disease that is endemic to the Amazon rainforest and is caused by the still uncultured fungus Lacazia loboi. This disease occurs in loggers, farmers, miners, fishermen, and persons living near coastal rivers of this region. We report 6 soldiers in Colombia in whom lobomycosis developed after military service in the Amazon area. The patients had nodular and keloid-like lesions on the face, neck, trunk, and limbs. The duration of illness ranged from 2 years to 15 years. The initial diagnosis was leishmaniasis on the basis of clinical manifestations and direct smear results, but biopsies confirmed the final diagnosis of lobomycosis. Treatment with surgical excision, itraconazole and clofazimine was satisfactory. However, the follow-up time was short. Healthcare professionals responsible for the diagnosis and treatment of skin diseases need to be able to recognize the clinical signs of lobomycosis and differentiate them from those of cutaneous leishmaniasis.

Cirurgia plástica e o tratamento de doenças infectocontagiosas: lobomicose / Plastic surgery for the treatment of contagious diseases: lobomycosis

Introdução: Lacaziose é uma doença rara que afeta principalmente trabalhadores de áreas tropicais, sendo descritos aproximadamente 500 casos no mundo. A lacaziose é um doença parasitária causada pelo fungo saprófita Lacazia loboi, para o qual não existe um tratamento específico. A cirurgia é o tratamento mais eficiente para as deformidades causadas pela doença. Entretanto, é um tratamento temporário, uma vez que as recidivas são frequentes. Lacazia loboi acomete duas espécies de golfinhos, o Tursiops truncates e o Sotalia guianensis. A literatura aborda o tratamento cirúrgico de maneira superficial, pois não existem trabalhos específicos descrevendo o tratamento cirúrgico para essa doença. Métodos: Descrevemos aqui nossos 8 anos de experiência no Hospital de Base de Porto Velho-Rondônia com 22 casos submetidos a tratamento cirúrgico e acompanhados. Resultados: A maioria dos pacientes (91%) já se submeteram a pelo menos um tratamento cirúrgico associado ao tratamento antifúngico. Os pacientes apresentavam lesões com tempo de evolução entre 5 meses e 6 anos previamente ao tratamento cirúrgico. Apenas dois casos eram virgens de tratamento. Conclusão: Nossos pacientes foram acompanhados, mas apenas 11 dos 22 pacientes retornaram para acompanhamento. Recorrências foram observadas em 9 dos 11 pacientes, com um período de latência de 5 meses (AU)

Introduction: Lacaziosis is a rare disease that mainly affects workers in tropical areas, with approximately 500 cases reported worldwide. Lacaziosis is a parasitic disease caused by the saprophytic fungus Lacazia loboi; there is no specific treatment for this disease. Surgery is the most effective treatment for the deformities caused by the disease. However, it is a temporary treatment, since disease recurrence is frequently observed. Lacazia loboi affects two species of dolphin, Tursiops truncates and Sotalia guianensis. The available literature discusses the surgical treatment in a superficial way , because there are no specific studies describing the surgical treatment for this disease. Methods: Here, we describe our 8 years of experience with lacaziosis at the Hospital de Base de Porto Velho - Rondônia; a total of 22 patients underwent surgical treatment and were followed-up. Results: The majority of the patients (91%) had already submitted to at least one surgical treatment together with antifungal treatment. The patients presented with lesions with disease progression ranging from 5 months to 6 years prior to surgical treatment. Only two patients were treatment-naive. Conclusion: Our patients were followed-up; however, only 11 of the 22 patients returned for follow-up. Recurrences were observed in 9 of the 11 patients, with a latency period of 5 months.(AU)

Lobomycosis-like disease in common bottlenose dolphins Tursiops truncatus from Belize and Mexico: bridging the gap between the Americas.

Lobomycosis and lobomycosis-like diseases (LLD) (also: paracoccidioidomycosis) are chronic cutaneous infections that affect Delphinidae in tropical and subtropical regions worldwide. In the Americas, these diseases have been relatively well-described, but gaps still exist in our understanding of their distribution across the continent. Here we report on LLD affecting inshore bottlenose dolphins Tursiops truncatus from the Caribbean waters of Belize and from the eastern tropical Pacific Ocean off the southwestern coast of Mexico. Photo-identification and catalog data gathered between 1992 and 2017 for 371 and 41 individuals, respectively from Belize and Mexico, were examined for the presence of LLD. In Belize, 5 free-ranging and 1 stranded dolphin were found positive in at least 3 communities with the highest prevalence in the south. In Guerrero, Mexico, 4 inshore bottlenose dolphins sighted in 2014-2017 were affected by LLD. These data highlight the need for histological and molecular studies to confirm the etiological agent. Additionally, we document a single case of LLD in an adult Atlantic spotted dolphin Stenella frontalis in southern Belize, the first report in this species. The role of environmental and anthropogenic factors in the occurrence, severity, and epidemiology of LLD in South and Central America requires further investigation.

Lobomycosis: a therapeutic challenge

Abstract: Lobomycosis or lacaziosis is a chronic granulomatous fungal infection caused by Lacazia loboi. Most cases are restricted to tropical regions. Transmission is believed to occur through traumatic inoculation in the skin, mainly in exposed areas. It is characterized by keloid-like nodules. There are only a few hundred cases reported. The differential diagnoses include many skin conditions, and treatment is difficult. The reported case, initially diagnosed as keloid, proved to be refractory to surgical treatment alone. It was subsequently approached with extensive surgery, cryotherapy every three months and a combination of itraconazole and clofazimine for two years. No signs of clinical and histopathological activity were detected during follow-up.