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.

submitted for histologic examination showed an extensive chronic granulomatous sclerosing inflammatory reaction, with abundant large and refractile yeast-like structures arranged in chains, consistent with lobomycosis (Figure 1).
In August 2022, the patient was given itraconazole (200 mg orally 1×/d).However, in November 2022, the patient had pyrosis, dyspepsia, and increased liver enzyme levels, leading to the decision to taper her dose of itraconazole to 100 mg/day, resulting in slight improvement of lesions.In June 2023, it was decided to increase the dose of itraconazole to 200 mg/ day because of slow improvement of lesions while waiting for adjuvant cryotherapy.Despite showing a slow and minor regression of her nodules, the patient reported a noticeable improvement of dysesthesias associated with the lesions.

Conclusions
Lobomycosis is a puzzling disease caused by the dimorphic Onygenale fungus P. loboi (8).One of the intriguing aspects of this organism is its inability to grow in laboratory cultures and its resistance to specific antifungal treatments (1).Lobomycosis was documented in the 1930s when Brazilian dermatologist Jorge Lobo described a patient with skin lesions resembling keloids (2).Although the fungus is believed to be primarily in soil and vegetation, its presence in marine mammals has been increasingly observed (1).Furthermore, human infections have been linked to water proximity, leading to the hypothesis that P. loboi might be a hydrophilic microorganism that enters the skin through traumatic means (9).
Because of challenges of culturing the fungus in vitro, nomenclature has been a highly debated aspect among mycologists, resulting in diverse classifications of the organism.Proposed taxonomic designations have included Glenosporella loboi, Glenosporopsis amazonica, Blastomyces loboi, Loboa loboi, and the family Lobomyces (1).In 1999, Taborda et al. proposed a new genus, Lacazia, and renamed the agent as Lacazia loboi (10).Subsequent studies by Mendoza et al. contributed to resolving the taxonomic puzzle surrounding this agent.By conducting amplification of the 18S small subunit rDNA and 600 bp of the chitin synthetase gene, the organism was placed within the group of Onygenales dimorphic fungi (11    was previously inferred on the basis of their morphologic and antigenic similarities (1).More recently, DNA sequence analyses of dolphins samples have shown that the samples align with those of Paracoccidioides species (12).This discovery has resulted in grouping of this pathogen within a monophyletic cluster, positioned as a close relative to P. americana and other Paracoccidioides species (3,7).Consequently, the taxonomy of the dolphin pathogen has been updated, now referred to as P. cetii, and the designation of the human-infecting pathogens remains classified as P. loboi (3,7,12,13).This recent amendment in the taxonomy reflects newfound understanding of the relationships between these pathogens.
Lesions of lobomycosis show various morphologic patterns; 5 well-known subtypes have been identified: infiltrated, keloidal, gummatous, ulcerative, and verrucoid (1).Among these subtypes, the keloid subtype is the most common, characterized by well-defined, infiltrative papules and nodules with a shiny, pink surface with overriding telangiectasias (1).Nodules are firm to the touch and can merge together.Lobomycosis lesions can appear hyperchromic, hypochromic, or achromic and are typically painless or accompanied by dysesthesia (1,14).Distinguishing lobomycosis from other infectious causes, such as leishmaniasis, leprosy, sporotrichosis, paracoccidioidomycosis, cryptococcosis, and blastomycosis, can be challenging (1).Verrucoid lesions, observed in advanced stages, are commonly found on the legs and show a gray-white coloration mimicking chromoblastomycosis (1).Ulcerated lesions resemble those seen in leishmaniasis and mycetomas, further complicating differential diagnosis (1).
No antifungal treatment has been consistently effective against P. loboi.Some drugs have shown partial effectiveness, including amphotericin B, imidazoles, triazoles, expanded spectrum azoles, and clofazimine, but complete remission is rare.Surgical excision remains the most effective option, although multiple or disseminated lesions often recur after surgery (1).
Little is known about the ecoepidemiologic and biogeographic aspects of lobomycosis in Panama.This disease was reported in Panama in 1972, followed by 2 additional cases in 1978 (15) (Appendix Figure 2).An addendum to the study from 1978 reports 11 additional cases diagnosed and reported by a pathologist in the Chiriquí region (in northern Panama close to the border with Costa Rica) (15).Our case-patient came from Capira, which is ≈386 km from Chiriqui in southwestern Panama, suggesting that lobomycosis is endemic to Panama, might be more widespread than previously suspected, and might be underreported (Appendix Figure 2).Increased awareness and further research are needed to better understand the endemicity of this fungal disease in Panama.
DNA sequences have been deposited and are available in the European Nucleotide Archive under bio project no.PRJEB64904 (ERA26631335).

Figure 1 .
Figure 1.Lesions from an 87-year-old woman from Capira in western Panama, determined to be lobomycosis caused by infection with the fungus Paracoccidioides (Lacazia) loboi.A, B) Multiple keloid-like nodules on the left leg extending through the mid-distal third of the posterior aspect of the left thigh of the patient who had lobomycosis.Shown are the classic confluent arrangement and hyperpigmented aspect of lesions.C) Tissue stain showing classic oval-to-round-shaped cells with connecting tubular projections arranging in a string-of-pearls pattern, both in pairs and individually.Gömöri methenamine silver stain; original magnification ×100.

Figure 2 .
Figure 2. Phylogenetic relationship of ADP-rf, Gp43, and internal transcribed spacer (ITS) 1 and 2 genes from patient in Panama who had lobomycosis with other Paracoccidioides species.Trees indicate phylogenetic analysis inferred by maximum-likelihood method of the ADP-rf (A), Gp43 (B), and ITS1-ITS2 (C) genes.Analyses included sequences obtained from research conducted by Vilela et al. (7) and the Panama case analyzed in this study (red).Each color in the trees represent different clusters identified: yellow, Paracoccidioides cetti; white, P. restrepiensis/ venezuelensis; gray, P. brasiliensis; green, P. americana; light blue, P. lutzii; and light purple, P. loboi.Gray triangles indicate genomes of the same clade belonging to P. restrepiensis, P. venezuelensis, or P. brasiliensis (to the ADP-rf gene, 49 genomes; to the Gp43 gene, 32 genomes; and to ITS1-ITS2 gene, 52 genomes).Histoplasma capsulatum and Ajellomyces capsulatus DNA sequences were used as outgroups for ADP-rf and ITS genes, respectively.Scale bars indicate nucleotide substitutions per site.
Dr. Suárez is a clinician research scientist in the Panamanian Investigation System and CIDES, Panama City, Panama, and a professor at the International University SEK-Ecuador, Quito, Ecuador, and the University of Panama, Panama City.Panama.His primary research interests are tropical medicine and fungal diseases.