Isolated cutaneous lesions in paracoccidioidomycosis: a suggestive case of acquisition through cutaneous inoculation

Porto Alegre, December 3^rd, 2020

Dear Editor

Paracoccidioidomycosis, an infection caused by the dimorphic fungus of the species Paracoccidioides brasiliensis and P. lutzii, is endemic in the American continent, with a high number of reports in South America. It is believed that its incidence in endemic areas ranges from three to four new cases per million each year¹. The lung is the major “gateway” to PCM infections, and direct cutaneous inoculation is extremely rare². We report a rare case of paracoccidioidomycosis with isolated cutaneous involvement, with no evidence of primary pulmonary complex or infection in other organs.

A 66-year-old male patient, reported a previous history of hypertension, smoking and skin lesions that appeared one year before on the left lower limb, after stepping on an anthill in the municipality of Sao Sebastiao do Cai, Rio Grande do Sul State, Southern Brazil, where he has worked as a farmer and has always lived. The patient reported that the lesions appeared after some time at the site of the ant bites, at most three months after the injuries. The physical examination revealed hyperkeratotic erythematous plaques with hemorrhagic areas and ulcerations, with a linear ascending pattern on the left lower limb affecting the sole, dorsum of the foot, knee and thigh (Figure 1). Cervical, axillary and inguinal lymph nodes were examined, and no abnormalities were detected. Two skin biopsies were performed. The first histopathological exam was suggestive of a squamous cell carcinoma. Due to the incompatible clinical presentation, a fresh biopsy was performed which showed the presence of epithelial hyperplasia, intraepithelial microabscesses (Figure 2A) and multiple budding yeasts in Grocott's staining (Figure 2B). Culture of the biopsy tissue revealed typical findings with appearance of “popcorn popped” (Figure 3), compatible with Paracoccidioides spp., ruling out the previous diagnosis of squamous cell carcinoma. No serological test was performed. Magnetic resonance imaging of the abdomen and pelvis and two chest X-ray (performedtwice, in 2018 and 2019) were normal. The first 2018 X-ray was performed when the patient had already had the confirmed diagnosis through the second biopsy and the direct mycological examination. The second one, performed in 2019, was a follow-up chest X-ray. Hepatic and renal functions were also normal, and the patient had no associated symptoms related to PCM. The treatment was performed with itraconazole 200 mg/day for six months, until complete remission of lesions.

Figure 1
Ulcerated hyperkeratotic plaques on the foot and left thigh.

Figure 2
Pseudoepitheliomatous hyperplasia with intraepithelial microabscesses; HE staining, 4x magnification (A). Yeast with multiple buds; Grocott's staining, 40x magnification (B).

Figure 3
White, wrinkled, slow growing filamentous colonies, with appearance of “popcorn popped”. Mycosel cultivation at 25 °C.

Paracoccidioidomycosis most commonly affects adult males between 30 and 50 years of age and can be classified into two clinical forms: the acute-subacute form and the chronic form¹. The adult chronic form is subdivided into the unifocal form, with involvement of a single organ or system, usually the lungs, and the multiple form, with more than one affected organ and system, usually the skin and lungs. Cutaneous lesions are present in more than half of the patients³. The causative fungus is present in the soil of high humidity environments². Agricultural activity is the major risk factor for the infection. Smoking and alcoholism are also associated with an increased risk of contracting the disease. Paracoccidioidomycosis is endemic in Rio Grande do Sul State, mainly in the Northern region and around the metropolitan region of Porto Alegre, the State capital, where is located the municipality of Sao Sebastiao do Cai^4–6. However, we did not find any other case report in this specific municipality in the literature.

The main source of infection is inhalation, controlled by the cellular immune response, which may or may not progress to other organs involvement through hematogenous dissemination¹. There are few reports of infections caused by direct fungal inoculation, which is questionable due to the small inoculum of subcutaneous fungal particles following minor trauma^7–9. In our case report, the first and only clinical manifestation were the cutaneous lesions occurring after a history of stepping on an anthill. However, it is important to note that the chest X-ray may not have shown subtle pulmonary injuries, making it difficult to exclude a pulmonary involvement. Nevertheless, in recently published guidelines for the clinical management of paracoccidioidomycosis in Brazil, the X-ray was indicated as an exam to be performed for the diagnosis of PCM¹.

The absence of pulmonary injuries, according to the X-ray, and other related symptoms of PCM, led us to consider the possibility of a direct inoculation as the mode of transmission. Infections with fungus-contaminated material, such as branches and plants, have also been suggested in other studies^8,10,11. However, isolating Paracoccidioides species directly from the environment is not simple¹, making it difficult to confirm the presence of the fungus in a certain place or object, such as the anthill in our case report.

The clinical presentation of the patient did not differ from the polymorphic lesions described in the literature, characterized by papules, ulcers and hyperkeratotic lesions¹². In addition, the farming and the smoking habits were relevant aspects for suspecting this diagnosis. An initial confounding factor was the first histopathological examination results compatible with squamous cell carcinoma, which may have occurred due to the finding of pseudoepitheliomatous hyperplasia, common in both pathologies. The last biopsy showed epithelial hyperplasia and intraepithelial microabscesses and the microbiological culture revealed the presence of white wrinkled and filamentous colonies, characteristic of Paracoccidioides spp. Therefore, we emphasize the importance of considering this differential diagnosis, since the patient could have been subjected to an unnecessary surgical intervention. This case highlights the fact that although there is little evidence in favor of an infection acquired by direct inoculation, this possibility cannot be ruled out^7,8,10. Finally, it is important to note that our case report has limitations, such as the lack of a CT scan and other specific exams. The approach should be individualized, as the clinical manifestations of paracoccidioidomycosis are diverse and can represent diagnostic challenges.

REFERENCES

• ¹
  Shikanai-Yasuda MA, Mendes RP, Colombo AL, Queiroz-Telles F, Kono AS, Paniago AM, et al. Brazilian guidelines for the clinical management of paracoccidioidomycosis. Rev Soc Bras Med Trop. 2017;50:715-40.
• ²
  Mendes RP, Cavalcante RS, Marques AS, Marques ME, Venturini J, Sylvestre TF, et al. Paracoccidioidomycosis: current perspectives from Brazil. Open Microbiol J. 2017;11:224-82.
• ³
  Marques SA, Camargo RM, Cortez DB, Marques ME, Lastória JC. Paracoccidioidomicose: frequência, morfologia e patogênese de lesões tegumentares. An Bras Dermatol. 2007;82:411-7.
• ⁴
  Londero AT, Ramos CD. Paracoccidioidomicose: estudo clínico e micológico de 260 casos observados no interior do Estado do Rio Grande do Sul. J Pneumol. 1990;16:129-32.
• ⁵
  Londero AT, Ramos CD, Lopes JO. Progressive pulmonary paracoccidioidomycosis a study of 34 cases observed in Rio Grande do Sul (Brazil). Mycopathologia. 1978;63:53-6.
• ⁶
  Verli FD, Marinho AS, Souza SC, Figueiredo MA, Yurgel LS. Perfil clínico-epidemiológico dos pacientes portadores de paracoccidioidomicose no Serviço de Estomatologia do Hospital São Lucas da Pontifícia Universidade Católica do Rio Grande do Sul. Rev Soc Bras Med Trop. 2005;38:234-7.
• ⁷
  Castro RM, Cuce LC, Fava Netto C. Paracoccidioidomicose: inoculação acidental “anima nobile”: relato de um caso. Med Cutan Ibero Lat Am. 1975;4:289-92.
• ⁸
  Rassi TN, Passos RR, Kumagai KM, Soranz Filho JE, Freitas JA. Paracoccidioidomicose crônica multifocal tendo como primeira manifestação o envolvimento palpebral: relato de caso. Arq Bras Oftalmol. 2009;72:822-5.
• ⁹
  Martinez R. Epidemiology of paracoccidioidomycosis. Rev Inst Med Trop Sao Paulo. 2015;57 Suppl 19:11-20.
• ¹⁰
  García Bustínduy M, Guimerá FJ, Arévalo P, Castro C, Sáez M, Alom SD, et al. Cutaneos primary paracoccidioidomycosis. J Eur Acad Dermatol Venereol. 2000;14:113-7.
• ¹¹
  Albornoz MB. Paracoccidioidiomycosis. In: Paracoccidioidomycosis: proceedings of the First Pan American Symposium, 25-27 October 1971, Medellin, Colombia. Medellin: Pan American Health Organization; 1971. p.142.
• ¹²
  Fortes MR, Miot HA, Kurokawa CS, Marques ME, Marques SA. Immunology of paracoccidioidomycosis. An Bras Dermatol. 2011;86:516-24.

Publication Dates

• Publication in this collection
  24 Mar 2021
• Date of issue
  2021

History

• Received
  03 Dec 2020
• Accepted
  02 Mar 2021