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.

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.

OBJECTIVE: To document a case of lobomycosis and to discuss its epidemiology & diagnosis.
METHODS: A 53-year-old male presented with a history of nasal congestion, nasal discharge, and epistaxis following Covid 19 infection. On physical examination, there was necrotic slough in the nasal vestibule near the inferior turbinate. Scrapings and punch biopsy were taken from the lesion. Hematoxylin-eosin-stained sections showed necrotic and mucoid areas with mixed inflammatory cell infiltration and numerous budding yeasts 3- 7μm diameter in singles, and small clusters with single narrow based budding as well as multiple budding including sequential budding forming \"chains of yeasts\". A diagnosis of Lobomycosis was made. Yeasts of lobomycosis are often confused with other yeasts such as P. brasiliensis, Candida spp., B. dermatitidis, and Cryptococci, but characteristic \'sequential budding\' with a \'chain of yeasts\" aid in the final diagnosis. Demonstration of yeasts with characteristic chains either in tissue sections or in potassium hydroxide (KOH) preparation of scraped material, exudate, or exfoliative cytology is the mainstay in the diagnosis as the organisms are uncultivable in vitro in culture medium.

Fibrosis is a common pathophysiological response of many tissues and organs subjected to chronic injury. Despite the diverse aetiology of keloid, lacaziosis and localized scleroderma, the process of fibrosis is present in the pathogenesis of all of these three entities beyond other individual clinical and histological distinct characteristics. Fibrosis was studied in 20 samples each of these three chronic cutaneous inflammatory diseases. An immunohistochemical study was carried out to explore the presence of α-smooth muscle actin (α-SMA) and vimentin cytoskeleton antigens, CD31, CD34, Ki67, p16; CD105, CD163, CD206 and FOXP3 antigens; and the central fibrotic cytokine TGF-β. Higher expression of vimentin in comparison to α-SMA in all three lesion types was found. CD31- and CD34-positive blood vessel endothelial cells were observed throughout the reticular dermis. Ki67 expression was low and almost absent in scleroderma. p16-positive levels were higher than ki67 and observed in reticular dermis of keloidal collagen in keloids, in collagen bundles in scleroderma and in the external layers of the granulomas in lacaziosis. The presence of α-actin positive cells and rarely CD34 positive cells, observed primarily in keloids, may be related to higher p16 antigen expression, a measure of cell senescence. Low FOXP3 expression was observed in all lesion types. CD105-positive cells were mainly found in perivascular tissue in close contact with the adventitia in keloids and scleroderma, while, in lacaziosis, these cells were chiefly observed in conjunction with collagen deposition in the external granuloma layer. We did not find high involvement of CD163 or CD206-positive cells in the fibrotic process. TGF-β was notable only in keloid and lacaziosis lesions. In conclusion, we have suggested vimentin to be the main myofibroblast general marker of the fibrotic process in all three studied diseases, while endothelial-to-mesenchymal transition (EndoMT) and mesenchymal stem cells (MSCs) and M2 macrophages may not play an important role.

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Lacaziosis is a cutaneous mycosis caused by the fungus Lacazia loboi, described in different countries of Latin America and prevalent in the Amazon region. The ineffective immune response against the agent seems to be related to a Th2 pattern of cytokines. There are few reports exploring elements of the humoral response in these lesions. Our aim was to investigate some elements focusing on B cells, plasma cells and local expression of IgG and IgM antibodies. Forty skin biopsies of lower limbs were selected. The diagnosis of lacaziosis was based on direct mycological examination and histological analysis. The visualization of fungal cells was improved by using Gridley\'s staining. An immunohistochemical protocol was performed to detect the expression of B cells, plasma cells, IgG and IgM. A double staining was performed to explore the presence of yeasts in the cytoplasm of keratinocytes, using an anti-AE1 AE3 antibody over Gridley\'s staining. The inflammatory infiltrate consisted of macrophages, multinucleated giant cells, lymphocytes, and fibrosis. Fungal cells were frequent in the stratum corneum and in both, the dermis and, in 50% of the specimens, also in the epidermis. Cells expressing IgG were more abundant when compared to cells expressing IgM. B cells and the presence of IgG might indicate that the humoral response promotes a Th2 immune response resulting in an anti-inflammatory phenotype. Our results lead us to suggest a possible role of B cells and immunoglobulins in the mechanisms of lacaziosis pathogenesis.

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Lacaziosis is a cutaneous chronic mycosis caused by Lacazia loboi. Macrophages are important cells in the host immune response in fungal infections. The macrophage population exhibits strong plasticity that varies according to the stimuli in the microenvironment of lesions M1 profile promotes a Th1 pattern of cytokines and a microbicidal function and M2 is related to Th2 cytokines and immunomodulatory response. We investigated the population of M1 and M2 polarized macrophages in human cutaneous lesions. A total of 27 biopsies from human lesions were submitted to an immunohistochemistry protocol using antibodies to detect M1 and M2 macrophages (Arginase-1, CD163, iNOS, RBP-J and cMAF). We could observe high number of cells expressing Arginase1, CD163 and c-MAF that correspond to elements of the M2 profile of macrophage, over iNOS and RBP-J (elements of the M1 profile). The results suggest a predominant phenotype of M2 macrophages, which have an immunomodulatory role and probably contributing to chronicity of Lacaziosis.