On-line version ISSN 1806-4841
An. Bras. Dermatol. vol.79 no.1 Rio de Janeiro Jan./Feb. 2004
Ocular paracoccidioidomycosis: report of two cases and review of literature*
Roberto Lopes GerviniI; Gerson VettoratoII; Sergio Martinez LecompteIII; Tatiana Basso BiasiIII; Fernanda Goulart RuthnerIII; Fernando Leite KronbauerIV
of Dermatology Service /UFRGS. Complexo Hospitalar Santa Casa. Porto Alegre,
Rio Grande do Sul, Brazil
IIM.D., Dermatologist, responsible for the Mycology sector, Dermatology Service /UFRGS. Complexo Hospitalar Santa Casa. Porto Alegre, Rio Grande do Sul, Brazil
IIIResidents M.D., Dermatology Service /UFRGS. Complexo Hospitalar Santa Casa. Porto Alegre, Rio Grande do Sul, Brazil
IVResident M.D., Ophthalmology Service. Complexo Hospitalar Santa Casa. Porto Alegre, Rio Grande do Sul, Brazil
is an endemic disease in Brazil that commonly affects multiple organs, although
ocular involvement is rare. The ocular form of this disease affects predominantly
the eyelids and conjunctiva, highlighting the importance for dermatologists
to consider this disease in the differential diagnosis for lesions within the
orbital area. Even with localized forms of the disease, a complete systemic
examination should be done bearing in mind that the exclusive ocular form of
paracoccidioidomycosis can frequently hide a multi-systemic disease.
We describe two cases of the ocular form of paracoccidioidomycosis with a revision of 55 cases described in the literature.
Key-words: conjunctiva; eyelid diseases; epidemiology; paracoccidioidomycosis.
Paracoccidioidomycosis is systemic mycosis caused by the dimorphic fungi Paracoccidioides brasiliensis, originally described by Adolfo Lutz (Brazil) in 1908.1,2 The disease occurs above all in adults from 30 to 60 years of age and is rare in children and young adults.2-5 It is more frequent in the male sex, with a male/female ratio in endemic areas of 13:1.3,6,7
In most cases (between 70 and 80%) paracoccidioidomycosis is a multifocal disease.4,5 However, when unifocal, lung involvement is predominant and mucocutaneous involvement or other foci are somewhat infrequent.8 Extrapulmonary locations occur in general in the skin of the face and in the oral, pharyngeal, laryngeal and nasal mucous membranes.2,9 There is rarely involvement of other mucous membranes, such as the anal, genital or occular membranes.10 Involvement of the lymph nodes is also frequent and the cervical and supraclavicular lymph nodes are the most commonly affected.2,4,11
This work presents two cases reports of the disease with ocular location and also a revision of the cases of paracoccidioidomycosis with ocular involvement described in the literature.
Patient male, 67 years old, farmer, resident in Encantado, Rio Grande do Sul. He complained of the appearance of small ulcerated lesions, with six months of evolution, located in the right inferior eyelid and left forearm, both of slow growth. He presented a prior history of smoking and alcoholism.
Dermatological exam showed in the right inferior eyelid a small, shallow ulcerated lesion with infiltrated base, discreet vegetation and stippled hemorrhage in the surface (Figure 1). In the left forearm there were small ulcerated lesions, with center covered by hemorrhagic crust and fibrinous exudate. Ophthalmologic exam revealed palpebral-conjunctival involvement, with consequent right temporal lagophthalmic and keratitis of inferior exposure. Examination of the eyeball showed no abnormalities. Direct mycological exam of the cutaneous lesion detected round, birefringent cells with several branches compatible with Paracoccidiodes brasiliensis (Figure 2). Culture confirmed the diagnosis. Histopathologic exam of the palpebral lesion revealed a granulomatous inflammatory infiltrate with the presence of fungi. No alterations were found in the chest x-ray. Serology using the double immunodiffusion in agar-gel technique resulted positive for paracoccidioidomycosis. Other laboratorial exams, such as blood count and tests of hepatic and renal function, did not present any alterations. Treatment was initiated with itraconazole, 200mg/day for three months and subsequent decrease of the dose to 100mg/day at the end of the sixth month of treatment, with disappearance of the mucous and cutaneous lesions.
Patient, 46 years old, male, resident in an urban area (Esteio, RS), with appearance four months earlier of asymptomatic papular lesions in the right superior eyelid. At dermatological exam he presented ulcerated lesion with discreetly vegetative bed, hemorrhagic points and infiltrated, round and translucent borders, in the superior and inferior right eyelids (Figure 3). Ophthalmologic exam revealed involvement of the palpebral and superior conjunctival margin, with consequent inferior exposure keratitis and ciliary madarosis. Direct mycological exam showed numerous round cells with multiple branches. Culture in Sabouraud's agar, after 30 days, was negative. Histopathologic exam of the cutaneous lesion demonstrated inflammatory granulomatous infiltrate and the presence of Paracoccidioides brasiliensis. Laboratory exams (blood count, electrolytes, renal and hepatic function, fast glycemia, anti-HIV and VDRL test) were all normal. Chest x-ray showed opacities presumably consolidant in the right median and inferior lobes and probable lung hyperinflation, suggestive of chronic bronchopulmonary obstructive disease. Direct mycological exam of the spittle and cultivation at 25°C were negative. Treatment was instituted with itraconazole at 200mg/day for one month, later being reduced to 100mg/day, which was maintained for five months. Initially this was associated with prednisone at 60mg/day, which was suspended after 15 days following significant reduction in the inflammatory process. A rapid regression of the lesions was acheived without sequels (Figure 4).
Ocular impairment in paracoccidioidomycosis is rare, since being described for the first time by Terra in 1923,12 only 55 cases have been reported in the world literature (source: Medline and Lilacs) and of these, most were in Brazil. The present work offers a synthesis of these cases and in particular two paracoccidioidomycosis reports, the first manifestation of which occurred in the ocular area (Table 1).
The areas most frequently involved in the ocular region are the eyelids and conjunctiva, while other locations are rarely affected. 10 In both case reports there was involvement of the eyelids and conjunctival mucous membrane. Analysis of the 55 cases reported to date showed that exclusive palpebral involvement occurred in 23; palpebral involvement and of other ocular structures in 21; and exclusive involvement of ocular structures other than the eyelid in 11 cases. The other structures in which ocular involvement has already been described include the cornea, conjunctive, sclera, choroidea, uvea and retina. The findings point to the fact that, faced with a diagnosis of paracoccidioidomycosis with palpebral involvement, a complete ophthalmologic evaluation is necessary to certify whether other structures are affected.
In general, involvement of the eyeball and enclosures is accompanied by the compromising of other organs.10 In the cases described here, neither of the patients presented pulmonary radiological alterations, albeit that additional exams of greater sensitivity were not performed, which does not corroborate with the multifocal involvement that the disease usually presents. However, Patient 1 also presented lesions in the arm, which can suggest a possible hematogenic dissemination.
In the ocular region, the lesions commonly begin as an erythematosus papule in the palpebral border that courses with progressive growth and tendency to central ulceration. The ulcers present raised borders and bed with fine granulation and characteristic stippled hemorrhage, which in the oral mucous membrane is known as "moriforme" stomatitis.47 The lesions can develop with destruction of the tear ducts and of all the layers of the eyelid or with the formation of palpebral coloboma, including involvement of the bulbar conjunctiva and the cornea by contiguity.47 The pre-auricular lymph nodes can be palpable.40
The differential diagnosis should be made in the initial phase with hordeolum and bacterial blepharitis, while in the chronic phase, when the lesions are more extensive, with basal cell and squamous cell carcinomas, trachoma, leishmaniosis, histoplasmosis, sporotrichosis, chronic discoid cutaneous lupus erythematosus, tuberculosis and secondary syphilis.40,41 Bearing in mind the high frequency of paracoccidioidomycosis in Brazil, one should always consider this disease in the differential diagnosis of ulcerated lesions in the palpebral area, especially among male patients over 30 years old and history of contact with rural environments.2
Diagnostic confirmation can be accomplished by direct mycological exam of the exudate of the lesions or tissue sample, in which the fungi can be identified by its characteristic "ship's wheel" aspect.2,3,4 Microscopic exam of the culture in chocolate-agar and blood-agar at 37°C, after a period of seven to 10 days, presents the classic forms of Paracoccidioides brasiliensis. In Sabouraud's agar cultivated at room temperature for 20 to 30 days, hyphae and chlamydiaspores .3,5,11 can be observed. Histopathological exam is also quite useful, especially when there are few microorganisms.2,3,4 A granulomatous reaction rich in epithelioid cells and gigantocytes is observed, inside which Paracoccidioides brasiliensis can be found.54
Treatment can be accomplished using systemic medications, with several possibilities, including sulfamides, imidazoles and amphotericin B. These are the most frequently used and itraconazole is considered the drug of choice by some authors, due to the shorter treatment duration in relation to other orally administered drugs (from three to six months) as well as less frequent occurrence of side effects and recurrence (between 3 and 5%).3,4,55,56 Recently the successful use of terbinafine was described in a patient with cutaneous and mucous lesions in the genital area, at a dose of 250mg twice daily for six months.57
It was concluded that ocular involvement in paracoccidioidomycosis is uncommon, but when present most frequently affects the eyelids and conjunctiva. In spite of being a rare location, it should be considered in the differential diagnoses of ulcerated lesions of the eyelid, since it is an endemic disease in Brazil. The importance is also emphasized for a systemic evaluation, as the disease is usually multifocal. Likewise, a complete ophthalmologic exam is recommended, in view of the cases described with involvement of other ocular structures and that the disease can progress to more serious forms with visual impairment.
1. Padilha-Gonçalves A. Paracoccidioidomicose. An Bras Dermatol 1985; 60(1):271-80. [ Links ]
2. Rios-Fabra A, Moreno AR, Istúriz RE. Fungal Infection in Latin American Countries. Infect Dis Clin North Am 1994; 8(1):129-54. [ Links ]
3. Brummer E, Castaneda E, Restrepo A. Paracoccidioidomycosis: an Update. Clin Microbiol Rev 1993; 6(2):89-117. [ Links ]
4. Negroni R. Paracoccidioidomycosis (South American Blastomycosis, Lutz's Mycosis). Int J Dermatol 1993; 32(12):847-59. [ Links ]
5. Severo LC. Paracoccidioidomicose. In: Silva LCC. Compêndio de Pneumologia.2a edição. São Paulo: BYK; 1993. p.601-6 [ Links ]
6. Restrepo A. The ecology of Paracoccidioides brasiliensis: a puzzle still unsolved. J Med Vet Mycol 1985; 23:323-34. [ Links ]
7. Restrepo A, Greer DL. La epidemiologia de la paracoccidioidomicosis. Bol Of Sanit Panam 1977; 83:428-45. [ Links ]
8. Montenegro MRG. Formas Clínicas da Paracoccidioidommicose. Rev Inst Med Trop S Paulo 1986; 28(3):203-4. [ Links ]
9. Fisher F, Cook NB. Fungos Sistêmicos. In: Fisher F, Cook NB. Micologia Fundamentos e Diagnostico. 1° Edição. Rio de Janeiro: Revinter; 2001 p.227-250. [ Links ]
10. Del Negro G. Outras lesões. Formas de ocorrência rara e associações a outros processos. In: Del Negro G, Lacaz CS, Fiorillo AM, eds. Paracoccidioidomicose (Blastomicose sul-americana). São Paulo: Saraiva, EDUSP, 1982: 229-243. [ Links ]
11. Lacaz CS, Porto E, Martinho JEC. Paracoccidioidommicose. In: Lacaz CS, Porto E, Martinho JEC. Micologia Médica: fungos, actinomicetos e algas de interesse médico. 7a edição. São Paulo: Sarvier; 1984. p.189-216. [ Links ]
12. Terra F. Três casos de Blastomycose. Brasil-med 1923; 32: 41-4. [ Links ]
13. Ferguson AS, Blastomycosis of eye and face secondary to lung infection. Brit Med J 1928; 1:442-443. [ Links ]
14. Belfort F. Um caso de 'blastomycose' conjuntical. S Paulo méd 1929/1930; 2:777-786. [ Links ]
15. Campos E, Silva Filho JF. Localização palpebro-conjuntival da blastomycose. Ann Oculist 1930; xx:221-222. [ Links ]
16. Silva F. Comentários em torno de alguns casos de Blastomycose por Paracoccidiodes brasiliensis observados na Bahia. Brasil-med 1936; 50:706-715. [ Links ]
17. Andrade C. Manifestações oculares nas doenças tropicais. Arq Clin Oftal Oto-rino-laringol 1937; 4:50-52. [ Links ]
18. Almeida A. Blastomicose palpebral. Arq Inst P Burnier (Campinas) 1939; 5:324. [ Links ]
19. Andrade C. Micoses. Oftalmologia Tropical (Sul-americana). Rio de Janeiro, Rodrigues e cia, 1940; 131-150. [ Links ]
20. Queiroz S. Blastomicose palpebral. Bol Soc Méd Cirurg, (Campinas) 1943; 3:130. [ Links ]
21. Sales M, Queiroz S. Blastomicose ocular (palpebral). Arq Inst P Burnier (Campinas) 1945; 7:260-261. [ Links ]
22. Lacaz CS. Blastomicose sul-americana. Na Inst Pinheiros 1948; 11:23-53. [ Links ]
23. Niño FL. Siete nuevas observaciones de granuloma paracoccidiodico em la Republica Argentina. Bol Inst Clin quir (B.Aires) 1950; 26:272-305. [ Links ]
24. Rocha M. Micosis em Oftalmologia. Arq Inst P Burnier (Campinas) 1952;9:28-69. [ Links ]
25. Azevedo PC. Algumas considerações sobre a blastomicose sul-americana e seu agente etiológico. Belém 1954: 95 p.(Thesis-Cathedral-School of Odontology of Pará). [ Links ]
26. Gaipa M. Su di caso di granulomatose paracoccidioidea con localizzazione congiuntivale. Rev Ital Trac 1957;9:6-13. [ Links ]
27. Gonzales Ochoa A, Domínguez Soto L. Blastomicosis sulamericana. Casos mexicanos. Rev Inst Salubr Enferm Trop (Méx), 1957; 17:97-104. [ Links ]
28. Haedo AA, Boggino J, Mercado M. Um caso de paracoccidiodomicosis conjuntival. Arq brás Oftal 1957; 20:450-457. [ Links ]
29. Blodi FC, Huffman WC. Cicatricial ectropion caused by cutaneous blastomycosis. Arch Ophthal 1958; 59:459-462. [ Links ]
30. Campos EC. Micose de Lutz (blastomicose sul-americana). Contribuição ao seu estudo no estado do Rio Grande do Sul. Porto Alegre, 1960: 220p. (Thesis-School of Medicine University of Rio Grande do Sul, Brasil). [ Links ]
31. Machado Filho J, Miranda JL. Considerações relativas à blastomicose sul-americana. Localizações, sintomas iniciais, vias de penetração e disseminação em 313 casos consecutivos. Hospital (Rio de J.) 1960; 58:129-137. [ Links ]
32. Conti-Diaz IA. Lesiones oculares em la blastomicosis sudamericana. Hospital (Rio de J.) 1960; 58:903-914. [ Links ]
33. Servino V, Proto F. Contributo alla conoscenza delle lesioni oculari da Paracoccidiodes brasiliensis. Boll Ocul 1966; 45:811-819. [ Links ]
34. Negroni R. Observaciones personales sobre la micosis de Lutz (blastomicosis sudamericana) en la Argentina. Buenos Aires, 1968: 78p.(Thesis-Doctorate, School of Medicine, University of Buenos Aires). [ Links ]
35. Brass K. Observaciones sobre la anatomia patológica, patogénesis y evolucion de la paracoccidioidomicosis. Mycopathologia 1969; 37: 119-138. [ Links ]
36. Brick M. Ocular involvement in lymphatic paracoccidioidomycosis. Acta Ophtal (Kbh.) 1969; 47:991-997. [ Links ]
37. Dantas AM, Curi R, Costa JD, Azulay RD, Quevedo LP, Manhães LF. Sobre um caso de Blastomicose sul-americana com lesão ocular. Rev Bras Oftal 1971; 30:83-91. [ Links ]
38. Dantas AM, Curi R, Silva JBC, Paiva LM. Blastomicose sul-americana. Relato de um caso com uveíte granulomatosa e oftalmoplegia externa incompleta. Rev Bras Oftal 1973; 32:61-68. [ Links ]
39. Albornoz MB. Paracoccidiodomicosis. Pan Amer Hlth Org Sci Publ 1972; 254:142-145. [ Links ]
40. Belfort JR, Fischman O, Camargo ZP, Almada A. Paracoccidioidomycosis with palpebral and conjuntival involvement. Mycopathologia 1975; 56(1): 21-4. [ Links ]
41. Sampaio SAP, Rivitti EA. Micoses Profundas. In: Sampaio SAP, Rivitti EA. Dermatologia. 2a edição. São Paulo: Editora Artes Médicas; 1998. p.535-561. [ Links ]
42. Bonomo PP, Belfort Jr R, Tsunechiro JY, G Filho O. Choroidal granuloma caused by Paracoccidiodes brasiliensis. A clinical and angiographic study. Mycopathologia 1982; 77:37-41. [ Links ]
42. Cechella MS, Melo CR, Melo IS, Londero AT, Barreto SM, Gaiger AM. Paracoccidiodomycose genital masculine. Rev Inst Med trop São Paulo 1982; 24:240-245. [ Links ]
44. Jannke HA, Lopez FS, Abrahão MCY, Thofern P, Duarte AL, Holthausen ET. Blastomicose sul-americana palpebral. Rev bras Oftal 1983; 42:87-90. [ Links ]
45. Arruda WO, Canto MAS, Loddo G, Rebuffi VF, Cardoso MA. Paracoccidioidomicose ocular. Relato de um caso com corioretinite posterior. Rev Inst Med Trop São Paulo 1986; 28:190-193. [ Links ]
46. Pinheiro SRAA, Oréfice F, Mason EM. Blastomicose sul-americana: descrição de um caso com lesões cutâneas, nasais e envolvimento do trato uveal posterior. Arq Bras Oftal 1987; 50:66-69. [ Links ]
47. Silva MRBM, Mendes RP, Lastória JC, Barraviera B, Marques SA, Kamegasawa A. Paracoccidioidomycosis: Study of six cases with ocular involvement. Mycopathologia 1998; 102: 87-96. [ Links ]
48. Salinas LF, Pereira DM, Costa ER, Seixas J, Alves MR. Paracoccidioidomicose Ocular. Bras Méd 1989; 26(1-4):7-8. [ Links ]
49. Lottemberg C, Neves RA, Belfort Jr. R, Lowen MS, Colombo A, Rehder JR. Paracoccidioidomycosis chorioretinitis in a patient with Aids, Arq Bras Oftal 1992;55:13-14. [ Links ]
50. Carneiro EJS, Couto Júnior AS, França VP, Miranda D. Paracoccidioidomicose com envolvimento palpebral e conjuntival. Relato de 4 casos e revisão da literatura. Rev Bras Oftal 1995;54(10): 786-90. [ Links ]
51. Noronha RMJ, Perez NT, Fortes HM, Hueb M, Fontes CJF. Paracoccidioidomicose ocular: relato de um caso de doença multifocal com envolvimento da pálpebra. Arq Bras Oftal 1998; 61(5):590-592. [ Links ]
52. Tobon AM, Orozco B, Estrada S, Jaramillo E, De Bedout C, Arango M. Paracoccidioidomycosis and AIDS: Report of the first two Colombian cases. Rev Inst Med Trop São Paulo 1998; 40(6): 377-81. [ Links ]
53. Ferraz E, Cella W, Rocha E, Caldato R. Paracoccidioidomicose primária da pálpebra e conjuntiva. Arq Bras Oftal 2001; 64(3): 259-61. [ Links ]
54. Talhari S, Neves RG. Dermatologia tropical. 1° ed São Paulo: MEDSI, 1985: 147-65. [ Links ]
55. San-Blas G. Paracoccidioidomycosis and its etiologic agent Paracoccidiodes brasiliensis. J Med Vet Mycol 1993; 31:99-113. [ Links ]
56. Del Negro G. Avanços terapêuticos em micoses profundas, com ênfase à paracoccidioidomicose. An bras Dermatol 1987; 62(4):209-12. [ Links ]
57. Ollague JM, Zuritta AM, Calero G. Paracoccidioidomycosis (South American blastomycosis) successfully treated with terbinafine: first case report. Br J Dermatol 2000; 143: 188-91. [ Links ]
Sergio Martinez Lecompte
Bocagrande Cra. 5ta # 5-98
in August, 13th of 2001
Approved by the Consultive Council and accepted for publication in May, 24th of 2002.
* Work done at "Complexo Hospitalar Santa Casa de Porto Alegre, Serviço de Dermatologia/UFRGS".