Paracoccidioidomycosis manifested by sarcoidosis-like cutaneous lesions and caused by Paracoccidioides brasiliensis sensu stricto (S1a)* * Work conducted at the Department of Dermatology and Radiotherapy, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista, Botucatu (SP), Brazil.

Sílvio Alencar Marques Marilia Formentini Scotton Jorge Marluce Francisca Hrycyk Sandra de Moraes Gimenes Bosco About the authors

Abstract:

Molecular studies have shown more than one species of the genus Paracoccidioides to be the causal agent of paracoccidioidomycosis. Efforts have been made to correlate the identified species with epidemiological and clinical data of patients, aiming to determine the real meaning and impact of new species. Bearing this objective in mind, the authors report a clinical case of paracoccidioidomycosis, from São Paulo state, Brazil, that manifested as uncommon sarcoid-like cutaneous lesions and was caused by Paracoccidioides brasiliensis sensu stricto (S1a). The patient was treated with itraconazole 200mg/day for 12 months, with complete clinical remission.

Keywords:
Paracoccidioidomycosis; Sarcoidosis; Skin diseases; Skin manifestations

Paracoccidioidomycosis (PCM) is a systemic mycosis caused by thermally dimorphic fungi of the genus Paracoccidioides. Recently, molecular studies have shown that P. brasiliensis (S1a, S1b) and related species P. americana (S2), P. restrepiensis (S3),P. venezuelensis (S4) and P. lutzii are possible etiological agents.11 Turissini DA, Gomez OM, Teixeira MM, McEwen JG, Matute DR. Species boundaries in the human pathogen Paracoccidioides. Fungal Genet Biol. 2017;106:9-25. Airborne infections occur mainly in rural areas, and the primary complex develops in the lungs.22 Marques SA. Paracoccidioidomycosis: epidemiological, clinical, diagnostic and treatment up dating. An Bras Dermatol. 2013;88:700-11. Clinical manifestation in adult patients typically includes oral, cutaneous and pulmonary involvement. Cutaneous lesions are reported to occur in 30% to 61.2% of studied patients.33 Marques SA, Cortez DB, Lastoria JC, Camargo RMP, Marques MEA. Paracoccidioidomycosis: frequency, morphology, and pathogenesis of tegumentary lesions. An Bras Dermatol. 2007;82:411-7. Most frequently, skin lesions result from hematogenous spread of fungi. The most common forms of lesion are ulcerative and ulcerous-vegetative, reported in up to 42.8% of cases in one series.33 Marques SA, Cortez DB, Lastoria JC, Camargo RMP, Marques MEA. Paracoccidioidomycosis: frequency, morphology, and pathogenesis of tegumentary lesions. An Bras Dermatol. 2007;82:411-7. Conversely, an infiltrative pattern similar to the plaque-type lesion of cutaneous sarcoidosis is very uncommon.44 Abreu MAMM, Lastória JC, Mattos ALA, Alchorne MMA. Paracoccidioiodomycosis with sarcoid-like lesions: a diagnostic challenge. Rev Soc Bras Med Trop. 2017;50:273-6. The authors report a male patient with an unusual and extensive cutaneous involvement of a sarcoid-like skin lesion caused by P. brasiliensis sensu stricto (S1a).55 Hrycyk MF, Garcia Garces H, Bosco SMG, de Oliveira SL, Marques SA, Bagagli E. Ecology of Paracoccidioides brasiliensis, P. lutzii and related species: infection in armadillos, soil occurrence and mycological aspects. Med Mycol. 2018; Epub ahead of print.

A 53-year-old male patient, from a rural area in the municipality of São Manuel (SP), was referred for evaluation of a facial skin lesion that had evolved over one year. Fever, weight loss, pulmonary complaints and comorbidities were denied, as was alcohol and tobacco use. On examination, we observed an infiltrative sarcoid-like skin lesion on the face (Figures 1 and 2). With the hypothesis of B-cell lymphoma or PCM, the lesion was submitted to a punch biopsy. The histopathology revealed a dense, granulomatous inflammatory dermal infiltrate of histiocytes and multinucleated giant cells with rare fungal cells, viewed in greater specificity with silver staining (Figures 3 and 4). Culture from a biopsy fragment incubated on Mycosel ® at 35ºC showed yeast cells diagnostic of Paracoccidioides genus. The isolate was molecularly characterized as P. brasiliensis sensustricto (S1a) by sequencing ITS rDNA and gp43 exon 2 loci.55 Hrycyk MF, Garcia Garces H, Bosco SMG, de Oliveira SL, Marques SA, Bagagli E. Ecology of Paracoccidioides brasiliensis, P. lutzii and related species: infection in armadillos, soil occurrence and mycological aspects. Med Mycol. 2018; Epub ahead of print. PCR-RFLP (Restriction Fragment Length Polymorphism) of tub1 gene was also carried out to enable differentiation among Paracoccidioides spp.55 Hrycyk MF, Garcia Garces H, Bosco SMG, de Oliveira SL, Marques SA, Bagagli E. Ecology of Paracoccidioides brasiliensis, P. lutzii and related species: infection in armadillos, soil occurrence and mycological aspects. Med Mycol. 2018; Epub ahead of print.,66 Roberto TN, Rodrigues AM, Hahn RC, de Camargo ZP. Identifying Paracoccidioides phylogenetic species by PCR-RFLP of the alpha-tubulin gene. Med Mycol. 2016;54:240-7. A thin-slice computed tomography of the thorax and abdomen showed no abnormalities. Laboratory data were within normal limits, with exception of ESR of 20 mm/h. Antibody screens for HIV, HBV, HCV and Paracoccidioides spp. (IDD) tested negative. Itraconazole 200 mg/day was used for 12 months, with complete clinical remission.

Figure 1
Paracoccidioidomycosis: erythematoviolaceous, infiltrated, sarcoidosis-like lesions on the face

Figure 2
Paracoccidioidomycosis: detail of infiltrated lesion and shallow ulcer

Figure 3
Paracoccidioidomycosis: well-formed epithelioid granuloma with giant cell and no visible fungus. Hematoxylin & eosin, x100

Figure 4
Paracoccidioidomycosis: isolated fungus cell with discrete multiple sporulation amid epithelioid granuloma. Grocott-Gomori, x100

In PCM, sarcoid-like lesion is an expression of equilibrium between infectious agent and host defense. The histological presentation comprises a well-developed epithelioid granuloma and multinucleated giant cells with scarce fungal elements, posing a diagnostic challenge even when using specific stain.77 Marques SA, Lastória JC, Putinatti MSMA, Camargo RMP, Marques MEA. Paracoccidioidomycosis: infiltrated, sarcoid-like cutaneous lesions misinterpreted as tuberculoid leprosy. Rev Inst Med Trop São Paulo. 2008;50:47-50. In such circumstances, cases can be clinically and histologically misinterpreted as leprosy or another infectious disease, or even as non-infectious granulomatous dermatosis.77 Marques SA, Lastória JC, Putinatti MSMA, Camargo RMP, Marques MEA. Paracoccidioidomycosis: infiltrated, sarcoid-like cutaneous lesions misinterpreted as tuberculoid leprosy. Rev Inst Med Trop São Paulo. 2008;50:47-50. Another unusual aspect of this case was the apparent absence of pulmonary involvement, which is the rule in adult male individuals. Itraconazole has been effective in PCM, as observed in this patient.88 Shikanai-Yasuda MA, Mendes RP, Colombo AL, Queiroz-Telles F, Kono ASG, Paniago AMM, et al. Brazilian guidelines for the clinical management of paracoccidioiodomycosis. Rev Soc Bras Med Trop. 2017;50:715-40. Efforts have been made in every case, using molecular tools, to identify the correct species of genus Paracoccidioides and to correlate it with geographical origin, clinical aspects and response to treatment, to determine the real meaning and impact of the new species.99 Munõz JF, Farrer RA, Desjardins CA, Gallo JE, Sykes S, Sakthikumar S, et al. Genome Diversity, Recombination, and Virulence across the Major Lineages of Paracoccidioides. mSphere. 2016;1. pii: e00213-16. q

  • *
    Work conducted at the Department of Dermatology and Radiotherapy, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista, Botucatu (SP), Brazil.
  • Financial support: None.

REFERENCES

  • 1
    Turissini DA, Gomez OM, Teixeira MM, McEwen JG, Matute DR. Species boundaries in the human pathogen Paracoccidioides. Fungal Genet Biol. 2017;106:9-25.
  • 2
    Marques SA. Paracoccidioidomycosis: epidemiological, clinical, diagnostic and treatment up dating. An Bras Dermatol. 2013;88:700-11.
  • 3
    Marques SA, Cortez DB, Lastoria JC, Camargo RMP, Marques MEA. Paracoccidioidomycosis: frequency, morphology, and pathogenesis of tegumentary lesions. An Bras Dermatol. 2007;82:411-7.
  • 4
    Abreu MAMM, Lastória JC, Mattos ALA, Alchorne MMA. Paracoccidioiodomycosis with sarcoid-like lesions: a diagnostic challenge. Rev Soc Bras Med Trop. 2017;50:273-6.
  • 5
    Hrycyk MF, Garcia Garces H, Bosco SMG, de Oliveira SL, Marques SA, Bagagli E. Ecology of Paracoccidioides brasiliensis, P. lutzii and related species: infection in armadillos, soil occurrence and mycological aspects. Med Mycol. 2018; Epub ahead of print.
  • 6
    Roberto TN, Rodrigues AM, Hahn RC, de Camargo ZP. Identifying Paracoccidioides phylogenetic species by PCR-RFLP of the alpha-tubulin gene. Med Mycol. 2016;54:240-7.
  • 7
    Marques SA, Lastória JC, Putinatti MSMA, Camargo RMP, Marques MEA. Paracoccidioidomycosis: infiltrated, sarcoid-like cutaneous lesions misinterpreted as tuberculoid leprosy. Rev Inst Med Trop São Paulo. 2008;50:47-50.
  • 8
    Shikanai-Yasuda MA, Mendes RP, Colombo AL, Queiroz-Telles F, Kono ASG, Paniago AMM, et al. Brazilian guidelines for the clinical management of paracoccidioiodomycosis. Rev Soc Bras Med Trop. 2017;50:715-40.
  • 9
    Munõz JF, Farrer RA, Desjardins CA, Gallo JE, Sykes S, Sakthikumar S, et al. Genome Diversity, Recombination, and Virulence across the Major Lineages of Paracoccidioides. mSphere. 2016;1. pii: e00213-16.

Publication Dates

  • Publication in this collection
    Nov/Dec 2018

History

  • Received
    14 Mar 2018
  • Accepted
    06 Apr 2018
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