Paracoccidioidomycosis overview

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Danitza Lukac

Overview

Paracoccidioidomycosis (PCM) is a mycosis caused by the fungus Paracoccidioides brasiliensis or Paracoccidioides lutzii. Paracoccidioidomycosis may be classified based on the onset and duration of symptoms. Paracoccidioidomycosis may be classified into acute, subacute or chronic. The chronic form can be further subclassified into unifocal and multifocal.[1][2] Spores of Paracoccidioides spp. are commonly transmitted via the respiratory route to the human host. Following transmission, Paracoccidioides spp. particles invade the terminal bronchioles and alveoli where granulomas are formed, but can be inactive for up to 40 years.[2] On microscopic histopathological analysis, a "pilot's wheel" or a "Mickey mouse ears-like" appearance is a characteristic finding of PCM.[3][4][5] Among all infected patients 5% are acute with a more rapid and severe progression compared to the chronic subtype. Acute PMC primarily affects the reticuloendothelial system organs.[6][7] Meanwhile, chronic paracoccidioidomycosis represents 90% of infected patients and has a slower progression. Patients with chronic PCM frequently develops pulmonary symptoms.[8][9] Complications that can develop as a result of PCM are chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, bullae, pulmonary hypertension, dyspnea, adrenal gland insufficiency, dysphonia, laryngeal lesions (such as glottis estenosis), microstomia, seizures, and motor deficiency.[7][9][10] The prognosis of paracoccidioidomycosis is good with adequate treatment. Without treatment, death is due to PCM related complications.[11] Patients with acute paracoccidioidomycosis usually appear ill. Chronic PCM patients can appear healthy at early stages. Physical examination of patients with juvenile PCM is usually remarkable for lymphadenopathy and hepatosplenomegaly. The presence of pulmonary abnormalities and skin lesions on physical examination is suggestive of adult PCM.[8] The preferred pharmacologic regimens for both mild and moderate-to-severe include antifungals either azoles (such as itraconazole, ketoconazole, voriconazole) or amphotericin B and antimicrobials such as trimethoprim-sulfamethoxazole.[12] Surgical procedures are usually reserved for patients with PCM sequelae. There are no primary preventive measures available for paracoccidioidomycosis.

Historical Perspective

Paracoccidioidomycosis, also known as Lutz-Splendore-de Almeida disease, is named after Adolfo Lutz, Alfonso Splendore, and Floriano Paulo de Almeida, three physicians who first characterized the disease in Brazil in the early 20th century.[13]

Classification

Paracoccidioidomycosis may be classified based on the onset and duration of symptoms, paracoccidioidomycosis disease may be classified into: acute, subacute or chronic. The chronic form can be further subclassified into: unifocal and multifocal.[1][2]

Pathophysiology

Spores of Paracoccidioides spp. are commonly transmitted via the respiratory route to the human host. Following transmission, Paracoccidioides spp. particles invade the terminal bronchioles and alveoli where granulomas are formed, but can be inactive for approximately 40 years.[2] On microscopic histopathological analysis, a "pilot's wheel" or a "Mickey mouse ears-like" appearance is a characteristic finding of PCM.[14][4][5]

Causes

Paracoccidioidomycosis may be caused by either Paracoccidioides brasiliensis or Paracoccidioides lutzii.

Differential Diagnosis

Acute paracoccidioidomycosis must be differentiated from leukemia, lymphoma, toxoplasmosis and sarcoidosis.[4] Chronic paracoccidioidomycosis must be differentiated from tuberculosis, histoplasmosis and metastasis.[15]

Epidemiology and Demographics

Paracoccidioidomycosis has been reported as an autochthonous disease, that tends to affect agriculture workers from southern Mexico to northern Argentina. Paracoccidioidomycosis is prevalent in Brazil, Colombia, Venezuela, and Argentina, and is classically associated with individuals from rural areas. The typical patient is a man aged 30 to 50 years.[16] PCM affects men, more commonly than women. However, latent paracoccidioides infection can affect anyone.[2]

Risk Factors

Common risk factors in the development of paracoccidioidomycosis disease are: age, gender, poor hygiene, occupation, malnutrition, tabacco and alcohol consumption.[1][17]

Natural History, Complications and Prognosis

Acute paracoccidioidomycosis affects 5% of the patients, has a more rapid and severe evolution. Acute PCM primarily compromises the reticuloendothelial system organs.[6][7] Meanwhile, chronic paracoccidioidomycosis represents 90% of the patients and has a slower evolution. Chronic PCM frequently develops pulmonary symptoms which can leave severe sequela.[8][9] Complications that can develop as a result of PCM are: chronic obstructive pulmonary disease (COPD), pulmonary fibrosis, bullae, pulmonary hypertension, dyspnea, adrenal gland insufficiency, dysphonia, laryngeal lesions (such as glottis estenosis), microstomia, seizures and motor deficiency.[9][10][7] The prognosis of paracoccidioidomycosis is good with adequate treatment. Without treatment, PCM will result in death due to disease complications. The presence of late diagnosis and sequelae is associated with a particularly poor prognosis among patients with PCM.[11]

History and Symptoms

Primary infection is thought to be autolimited and almost asymptomatic as histoplasmosis or Valley Fever. In young people, there is a progressive form of the disease with high fever, generalized lymphadenopathy and pulmonary involvement with milliary lesions. The juvenile form has a more severe prognosis even with treatment. The most common form is the so called adult form of paracoccidioidomycosis that is almost certainly a reactivation of the disease. Chronic PCM has mainly pulmonary symptoms.[18]

Physical Examination

Patients with acute paracoccidioidomycosis usually have an ill appearing. Chronic PCM patients can appear healthy at early stages. Physical examination of patients with juvenile PCM is usually remarkable for lymph node swelling, hepatomegaly, and splenomegaly. The presence of pulmonary abnormalities and skin lesions on physical examination is suggestive of adult PCM.[8]

Laboratory Findings

Laboratory findings consistent with the diagnosis of acute PCM include anemia, Hypergammaglobulinemia, Eosinophilia, Hypoalbuminemia, Mild increase of AST and ALT and conjugated hyperbilirubinemia.[7]

Imaging Findings

Common chest x-ray findings in chronic PCM include bilateral and symmetric opacities, butterfly wing pattern, architectural distorsion, paracicatricial emphysema and traction bronchiectasis. There are not many chest x-ray finding in acute PCM, but it is characterized by mediastinal and hiliar lymphadenopathy and pleural effusions.[6] On thoraxic CT scan, chronic paracoccidioidomycosis is characterized by ground-glass attenuation, airspace consolidations, interlobular septal thickening, nodular pattern, fibrotic pattern, cavitary lesions, halo sign and reversed halo sign.[6][19][20][21]

Medical Therapy

Pharmacologic medical therapy is indicated in paracoccidioidomycosis. The preferred regimens for both mild and moderate-to-severe include antifungals either azoles (such as itraconazole, ketoconazole, voriconazole) or amphotericin B and antimicrobials such as trimethoprim-sulfamethoxazole.[12]

Surgery

Surgery is not the first-line treatment option for patients with paracoccidioidomycosis. Different surgical procedures are usually reserved for patients with PCM sequelae.

Prevention

There are no primary preventive measures available for paracoccidioidomycosis.

References

  1. 1.0 1.1 1.2 de Oliveira HC, Assato PA, Marcos CM, Scorzoni L, de Paula E Silva AC, Da Silva Jde F; et al. (2015). "Paracoccidioides-host Interaction: An Overview on Recent Advances in the Paracoccidioidomycosis". Front Microbiol. 6: 1319. doi:10.3389/fmicb.2015.01319. PMC 4658449. PMID 26635779.
  2. 2.0 2.1 2.2 2.3 2.4 Fortes MR, Miot HA, Kurokawa CS, Marques ME, Marques SA (2011). "Immunology of paracoccidioidomycosis". An Bras Dermatol. 86 (3): 516–24. PMID 21738969.
  3. Paracoccidioidomycosis. Wikipedia.https://en.wikipedia.org/wiki/Paracoccidioidomycosis. Accessed on January 12, 2016
  4. 4.0 4.1 4.2 Manns B.J, Baylis B.W, Urbanski S.J, Gibb A.P, Rabin H.R. Paracoccidioidomycosis: Case Report and Review. CID. 1996; 23: 1026-1032
  5. 5.0 5.1 Vargas J, Vargas R. Paracoccidiodomicosis. Rev. enferm. infecc. trop.2009(1):49-56
  6. 6.0 6.1 6.2 6.3 Barreto MM, Marchiori E, Amorim VB, Zanetti G, Takayassu TC, Escuissato DL; et al. (2012). "Thoracic paracoccidioidomycosis: radiographic and CT findings". Radiographics. 32 (1): 71–84. doi:10.1148/rg.321115052. PMID 22236894.
  7. 7.0 7.1 7.2 7.3 7.4 Brummer E, Castaneda E, Restrepo A. Paracoccidioidomycosis: An Update. 'Clin. Microbiol. Rev.1993;6(2):89-117
  8. 8.0 8.1 8.2 8.3 Vargas J, Vargas R. Paracoccidiodomicosis. Rev. enferm. infecc. trop.2009(1):49-56
  9. 9.0 9.1 9.2 9.3 Wanke B, Aidê M. Chapter 6 - Paracoccidioidomycosis. J. bras. pneumol. 2009; 35(12):1245-1249
  10. 10.0 10.1 Francesconi F, da Silva MT, Costa RL, et al. Long-term outcome of neuroparacoccidioidomycosis treatment. Rev Soc Bras Med Trop. 2011;44(1):22-25
  11. 11.0 11.1 Martinez, R.Epidemiology of Paracoccidioidomycosis. Rev. Inst. Med. trop. S. Paulo. 2015;57(19), 11-20
  12. 12.0 12.1 Marques SA (2013). "Paracoccidioidomycosis: epidemiological, clinical, diagnostic and treatment up-dating". An Bras Dermatol. 88 (5): 700–11. doi:10.1590/abd1806-4841.20132463. PMC 3798345. PMID 24173174.
  13. Paracoccidioidomycosis. Wikipedia. https://en.wikipedia.org/wiki/Paracoccidioidomycosis. Accessed on January 12, 2016
  14. Paracoccidioidomycosis. Wikipedia.https://en.wikipedia.org/wiki/Paracoccidioidomycosis. Accessed on January 12, 2016
  15. Manns B.J, Baylis B.W, Urbanski S.J, Gibb A.P, Rabin H.R. Paracoccidioidomycosis: Case Report and Review. CID. 1996; 23:1026-1032
  16. Paracoccidioidomycosis. Wikipedia.https://en.wikipedia.org/wiki/Paracoccidioidomycosis. Accessed on January 12, 2015
  17. Magalhães EM, Ribeiro Cde F, Dâmaso CS, Coelho LF, Silva RR, Ferreira EB; et al. (2014). "Prevalence of paracoccidioidomycosis infection by intradermal reaction in rural areas in Alfenas, Minas Gerais, Brazil". Rev Inst Med Trop Sao Paulo. 56 (4): 281–5. PMC 4131811. PMID 25076426.
  18. Paracoccidioidomycosis. Wikipedia.https://en.wikipedia.org/wiki/Paracoccidioidomycosis. Accessed on January 12, 2016
  19. Marchiori E, Valiante PM, Mano CM, Zanetti G, Escuissato DL, Souza AS; et al. (2011). "Paracoccidioidomycosis: high-resolution computed tomography-pathologic correlation". Eur J Radiol. 77 (1): 80–4. doi:10.1016/j.ejrad.2009.06.017. PMID 19608361.
  20. Funari M, Kavakama J, Shikanai-Yasuda MA, Castro LG, Bernard G, Rocha MS; et al. (1999). "Chronic pulmonary paracoccidioidomycosis (South American blastomycosis): high-resolution CT findings in 41 patients". AJR Am J Roentgenol. 173 (1): 59–64. doi:10.2214/ajr.173.1.10397100. PMID 10397100.
  21. Souza AS, Gasparetto EL, Davaus T, Escuissato DL, Marchiori E (2006). "High-resolution CT findings of 77 patients with untreated pulmonary paracoccidioidomycosis". AJR Am J Roentgenol. 187 (5): 1248–52. doi:10.2214/AJR.05.1065. PMID 17056912.