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Thinking in paracoccidioidomycosis: a delayed diagnosis of a neglected tropical disease, case report and review of clinical reports and eco-epidemiologic data from Colombia since the 2000

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Abstract

Background

Paracoccidioidomycosis is a neglected tropical disease, endemic in several countries of South America including Colombia. We report a case of a patient with Chronic Multifocal Paracoccidioidomycosis with long-standing symptoms and a delayed diagnosis caused by several barriers to achieve it. We did a review of the papers published in Colombia about this disease, focusing in clinical data and eco-epidemiology with the finding of a lack of new information on this topic since the 2000 in our region.

Case presentation

We present a 54-year-old man, farmer in his youth, with a chronic ulcerated lesion in the lower lip similar to a lip carcinoma, a deforming lesion in the nose, and respiratory symptoms with emphysematous lung. Lip biopsy with silver methenamine stain revealed small and large budding yeasts that resembles a “mariner’s wheel” confirming Chronic Multifocal Paracoccidioidomycosis. He was treated successfully but subsequently lost to follow up.

Conclusions

It is very important to focus attention, reinforce the search and create networks for the study of neglected tropical diseases. The presented case illustrates a usual clinical presentation, but with a delayed diagnosis due to the difficulties that still occur in some regions like ours for the early recognition of a case of chronic multifocal paracoccidioidomycosis.

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Background

Paracoccidioidomycosis (PCM) is a granulomatous systemic mycosis, endemic in South America from Mexico to Argentina, with the largest number of cases reported in Brazil, Venezuela, Colombia and Argentina [1,2,3,4]. It is caused by a fungus of the genus Paracoccidioides that has a dimorphic behavior. It has been isolated in the nine-banded armadillo (Dasypus novemcinctus) [5], the naked-tailed armadillo (Cabassus centralis), domestic animals, cattle, horses, sheep and monkeys [3, 6, 7]. In Colombia it is not a disease of obligatory notification and therefore its incidence and prevalence is not known with certainty.

Paracoccidioidomycosis is considered a neglected tropical disease [8]. We present a case of PCM from a region of Colombia with the objective of maintaining attention to a forgotten tropical disease with a usual clinical presentation but with a delayed diagnosis. The case reviewed illustrates the difficulties still present for the diagnosis of PCM in some regions like ours and the lack of awareness in the medical community for this type of disease.

Case presentation

A 54-year-old man from rural area of the department of Risaralda (Colombia), with a history of 3 years of a papule-like lesion in the lower lip that increased in size and then evolved to a deforming ulcer with extension towards the right labial commissure (Fig. 1). He presented a progressive deformity in the right nasal wing (Fig. 1), spontaneous loss of teeth, weight loss of 15 Kg, dry cough and dyspnea, without other B symptoms. He was a former smoker with a pack-year of 1.5 for 10 years and was receiving Metformin for a recent diagnosis of type 2 Diabetes Mellitus. He was a coffee farmer in his youth and then worked as a butcher for 30 years. Interestingly, we find that in his youth he had the habit of consuming armadillo meat and blood. He had several medical consultations, with difficulties for the follow-up caused by social aspects. A presumptive diagnosis of lip cancer was made for which a biopsy was performed.

Fig. 1
figure1

a Deforming and infiltrating ulcer in lower lip. b Deformity in the right nasal wing

An incisional biopsy of the lip showed pseudoepitheliomatous hyperplasia associated with suppurative granulomatous dermatitis, the silver methenamine stain revealed budding yeasts that resembles a “mariner’s wheel” confirming the diagnosis of Chronic Multifocal Paracoccidioidomycosis (Fig. 2). A Chest X-ray and then a HR-CT revealed emphysematous lung disease (Fig. 3), a HIV test and a VDRL were negative. A nasofiberoptic bronchoscopy was performed to rule out tuberculosis; during the study there was seen granulomatous lesions in upper airway and other ulcerated lesions covered by punctiform white secretion (Fig. 4). There was no presence of fungal structures in the routine stains of the bronchoalveolar lavage. The culture for fungal and Mycobacterial was negative, as so the PCR for Mycobacterium tuberculosis.

Fig. 2
figure2

Silver methenamine stain. Budding yeasts that resembles a “mariner’s wheel”

Fig. 3
figure3

a Chest x-ray showing interstitial opacities and fibrotic tracts in the lung bases. b High Resolution Tomography of the chest. Lung window showing centrilobular and paraseptal emphysematous foci

Fig. 4
figure4

Nasofiberoptic bronchoscopy. Granulomatous lesions and ulcerated lesions covered with punctiform white secretion in upper airway

Due to the severe constitutional commitment, he received amphotericin B for 7 days and then we made a change for Itraconazole 200 mg QD for 12 months, with successful recovery, but then lost the follow-up.

Discussion and conclusions

Paracoccidioidomycosis can manifest in an acute/subacute form in young patients or in a chronic form mainly in adults. The chronic form is more frequent and has an age of presentation between 30 and 60 years due to a prolonged incubation period, with multifocal compromise, mostly respiratory and mucocutaneous [8,9,10].. Given its heterogeneous nature, this disease is considered a “great imitator” and can be a diagnostic challenge in areas of low endemicity [11, 12]. The differential diagnosis of mucocutaneous commitment includes another tropical diseases like mucocutaneous Leishmaniasis, Sporotrichosis and Histoplasmosis; other conditions like squamous cell carcinoma, non-Hodgkin’s T/Nk cell lymphoma and vasculitis should be considered [13, 14]. In the case presented, it is noteworthy that pulmonary involvement was mainly emphysematous with formation of bullae and fibrotic tracts that are associated with residual forms of this condition. The differential diagnosis is with secular forms of Tuberculosis and Histoplasmosis, and it is hardly explained by the low smoke exposure of this patient; to achieve the clinical diagnosis, the clinician can be guided if there is a concomitant presence of mucocutaneous lesions and adenopathies forming a triad of characteristic symptoms of this disease [12, 15].

Paracoccidioidomycosis is considered a neglected tropical disease [16]. Of note, in Colombia, most of the information on the eco-epidemiology of the disease comes from publication until 2000, which allowed estimating the incidence and prevalence of the disease. To mention, the prevalence is 32.4 cases/year (period 1970–1999) [17] and the incidence rate is 0.1–2.4 cases/1.000.000 inhabitants per year [18]. We also know that there is a variation in the incidence according to the geographical area, and this is caused by certain ecological characteristics such as altitudes between 1000 to 1499 m above sea level, coffee plantations and rainfall between 2000 and 2999 mm/year [1]. All these estimates have serious limitations, mainly because this disease is not for mandatory notification to the health system, so there are no reliable sources of information even in the current days.

To know about the current state of the disease in Colombia we look for publications since 2000 focusing on eco-epidemiology and clinical information. We did a search with the words “Paracoccidioidomycosis” “Paracoccidioides” and “Colombia” on PUBMED, BIREME (a Latin American and Caribbean Center for Information in Health Sciences), an several representative journals of Colombia: Biomédica (Journal of the National Institute of health, e-ISSN: 0120–4157), Case Reports (Journal of the Universidad Nacional, e-ISSN: 2462–8522), CES MEDICINA (Journal of Universidad CES, e-ISSN 2215–9177), Revista Médica de Risaralda (Journal of Faculty of Universidad Tecnológica de Pereira, ISSN: 2539–5203), Colombia Médica (Journal of the Universidad del Valle, ISSN-1657-9534), Medicina U.P.B (Journal of the Universidad Pontificia Bolivariana, e- ISSN: 2357–6308), IATREIA and Hechos Microbiológicos (Journals of Universidad de Antioquia, e-ISSN 2011–7965 and ISSN:2145–8898 respectively). The findings are resume in Table 1. Of note, there is no any information about possible changes in eco-epidemiology given the development of some geographic areas of the country and transition phenomena caused by the population movements from rural to urban areas for violence, and vice versa given the transition to peace since the end of the war; in addition, we do not have information on possible imported cases caused by migratory movements in recent years from Venezuela, a country endemic to this disease, and this, of course, is a challenge considering the long latent period of this disease that would force us to seek the implementation of screening tests for migrants.

Table 1 Papers on clinical and eco-epidemiology of paracoccidioidomycosis in Colombia since 2000

The lack of new information in the last two decades on the eco-epidemiology and the clinical and social characterization of patients with Paracoccidioidomycosis reaffirms it as a neglected tropical disease, an aggravated situation during the last two decades despite the era of informatics, and also it is a call for physicians, institutions, and government to start working on this issue again. The main problems to recognize PCM seem to be 1) the apparent rare occurrence of the disease; 2) the difficulty to diagnose the disease in a timely manner; 3) the lack of interest of the clinicians to make it more visible, from the instances of the health system to the instances of medical education at the individual level. From this perspective, it seems that the way to begin to solve this problem could be to create a national network that involves leaders in the different medical schools.

Availability of data and materials

The datasets used and/or analysed during the current study available from the corresponding author on reasonable request.

Abbreviations

BAL:

Bronchoalveolar lavage

BMI:

Body mass index

HIV:

Human Immunodeficiency Virus

HR-CT:

High-resolution Computed Tomography

Kg:

Kilogram

PCM:

Paracoccidioidomycosis

PCR:

Polymerase chain reaction

QD:

“quaque die”, which means, in Latin, once a day

T2DM:

Type 2 Diabetes Mellitus

VDRL:

Venereal Disease Research Laboratory

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Acknowledgments

To the Instituto Liga Contra el Cáncer Seccional Pereira, Risaralda, where the initial assessment, biopsy and histochemistry were performed and allowed the diagnosis.

To the Hospital Universitario San Jorge de Pereira, Colombia, where the diagnosis and treatment of the patient was made.

Funding

The mentioned authors are not currently receiving and have not received any financial support for the development of the manuscript mentioned above. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Author information

DAR was the main responsible for the writing of the full article. JAA, AMGM and YAT analyzed and interpreted the patient data and made important contributions in the writing of the manuscript. LYAR contributed some ideas in the discussion and helped conduct several of the corrections requested in the peer review process. All authors read and approved the final manuscript.

Correspondence to Deving Arias Ramos.

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This article is of the case report type. We obtained informed consent from the patient to make the case report in accordance with the ethical responsibilities of the authors.

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We have obtained consent to publish from the participant to report individual patient data. Consent to publish was given in written format. The written consent for publication obtained from the patient was also inclusive of publishing identifying images.

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The authors declare that they have no competing interests.

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Arias Ramos, D., Alzate, J.A., Giraldo Montoya, Á.M. et al. Thinking in paracoccidioidomycosis: a delayed diagnosis of a neglected tropical disease, case report and review of clinical reports and eco-epidemiologic data from Colombia since the 2000. BMC Infect Dis 20, 119 (2020). https://doi.org/10.1186/s12879-020-4864-8

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Keywords

  • Paracoccidioidomycosis
  • Neglected tropical disease
  • Colombia
  • Pulmonary emphysema
  • Oral Cancer