Palpebral paracoccidioidomycosis

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Mycopathologia 140: 29–33, 1997. c 1997 Kluwer Academic Publishers. Printed in the Netherlands.

Palpebral paracoccidioidomycosis Sergio Vanetti Burnier & Ana Estela Sant’Anna Ophthalmology Department, S˜ao Paulo Federal University, Paulista School of Medicine (EPM), Brazil Received 1 April 1997; accepted in final form 19 August 1997

Abstract This paper describes two cases of eyelid paracoccidioidomycosis (South American blastomycosis) in which it was the first signal of the disease. In both cases the first clinical diagnosis made was not a fungal infection, but a neoplastic disease that was not confirmed by the pathology study. In the first patient we suspected a primary infection on the eyelid, because there was no other systemic signs of the disease, and in the second patient we noted a very advanced pulmonary lesions caused by the Paracoccidioides brasiliensis. We believe that, in endemic areas, the histopathological study should be made before every excisional procedures to avoid unnecessary palpebral mutilation. Key words: eyelid, palpebra, paracoccidioidomycosis, South American blastomycosis Introduction Paracoccidioidomycosis has synonyms: South American blastomycosis, Lutz-Splendore and Almeida mycosis and paracoccidioido granuloma. This is an granulomatous infectious disease, caused by Paracoccidiodes brasiliensis, with a progression frequently subacute or chronic, rarely acute. First described in Brazil, by Adolfo Lutz in 1908, it is endemic in rural zones, and found only in South and Central America (except Chile). We have cases reported in every country from Mexico to Argentina, with the majority coming from Brazil (south, central and southeast regions). The disease is more common in male adults, rural workers, and the proportion of male : female is 9–15: 1, at the age of 20 to 40 years old, mainly in its chronic form, which is the most common. In the subacute and acute forms, are found mainly in youths and children, with no difference between sexes. It is caused by the fungus Paracoccidioides brasiliensis, and can be cultivated in Sabouraud agar and blood agar. At room temperature it develops a filament form, and in an incubator at 37 C it shows a yeast form. This fungus is charaterized by developing these two forms in a reversible manner. P. brasiliensis lives

in nature, soil, vegetation or water, and transmission from patients to healthy humans is unknown. The most common way of penetration in human body is through the lungs, with later lymphhematogenic dissemination to others organs, skin or mucosas. It can also penetrate through the mucosas: buccal, pharyngeal, intestinal (anal hygiene with vegetable leafs), and rarely by inoculation into the skin. Depending on individual immunity, number and virulence of the parasite, it will develop as paracoccidioidomycosis infection or paracoccidioidomycosis disease. Incubation period can range from two months or reactivation up to 37 years [1]. In the Medellin Meeting (1986) a committee created criteria for a classification: Paracoccidioidomycosis-Infection People who have a positive specific skin test reaction, with no clinical sign or symptom. Paracoccidioidomycosis-Disease Acute Form (Young Type) Usually severe, affecting young persons. Divided in two sub types. Grave, with a rapid onset and progression, with poor general conditions. Affects lymph nodes, liver, spleen and bone marrow. Moderate, with

30 a less rapid onset and progression than the grave type, with better general conditions, and affecting only one system or lymph channels. Chronic Form (Adult Type) Long lasting, slow onset, gradual changes in general condition. Attacks mainly males, 30 years old or more. May be slight, moderate or grave. Divided also in two sub types. Unifocal, that affects only one organ or system, and the multifocal, that affects more than one organ or system Residual Forms or Succession Shows signs or symptoms related with scars of old actives wounds. Methods We describe retrospectively on this report 2 cases of paracoccidioidomycosis of the eyelids, that were first clinically diagnosed as neoplastic lesions of the eyelid. Case Report – 1 R.L.S., white male, 68 years old, retired gardener, was attended by Doctor Ana Estela Sant’Anna, complaining of a tumor in his left superior eyelid that started 1 month before. The patient related a few eyelid lumps in his eye that healed spontaneously. Within 1 month, one lump started growing, which didn’t heal, in his left superior eyelid (LSE). At examination the LSE showed infiltrated, edematous, thickened, and without lashes (Figure 1). The superior tarsal conjunctiva had a white plaque with an ulcerated center that was extended until the palpebral margins, measuring 5 mm horizontally and entire high of the superior tarsus (Figure 2). No other changes were noted at the ophthalmological examination. A few diagnostic hypotheses were made and the one most accepted was the Sebaceous Gland Carcinoma. The chosen procedure was an “in bloc” ressection, in pentagon manner, with simple reconstruction of palpebral margins. Case Report – 2 J.B.A., white, male, 37 years old, attended by Doctor Sergio Vanetti Burnier. The patient complained about a “little wound” in inner canthus of the right eye, that had grown for 7 months. It had a slow progression, without

pain or itch, only a little discharge from lesion, with no previous treatment and no similar cases in family. The patient had a inner canthus lesion of 1.0  0.5 cm on right eye, with an erythematous-crusty border, regular, a small infiltration, with a little purulent discharge (Figure 3). There was no other lesion on skin or mucosa, and no changes in physical and ophthalmological examination. The most accepted clinical diagnostic hypothesis for this case was ulcerated basal cell tumor. It was decided to biopsy the lesion.

Results In both cases a first clinical diagnoses of neoplastic disease were made which changed completely after the histopathological study. The slides of these cases showed Paracoccidioides brasiliensis in a very typical pattern, with the direct visualization of the fungi in the microabscesses and giant cells, and confirmed with silver staining (Figure 4). After this first examination a few others were made to confirm the diagnosis: A – Complement Fixation Case 1 – Reactive in 1/32 Case 2 – Reactive in 1/256 B – Contraimunoeletrophoresis Case 1 – Reactive in 1/8 Case 2 – Reactive in 1/128 C – Mantoux Case 1 – Absent Case 2 – Absent D – Culture Case 1 - Not done Case 2 - Absent E – Chest X-Ray Case 1 – Normal Case 2 – Pulmonary infiltration bilateral This results allowed us to make the diagnosis of: Case 1 – Unifocal Chronic Paracoccidioidomycosis – Adult type Case 2 – Multifocal Chronic Paracoccidioidomycosis – Adult type The treatment, for both patients, were made with Ketoconazole 400 mg PO/day, for 3 months with good results, there was no sign of recurrences. We asked for new examinations to control the disease, but both patients did not return to follow-up.

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Figure 1. Left superior eyelid infiltrated, edematous, thickened, and without lashes.

Figure 2. The inner aspect of the lesion, showing the intire high of the superior tarsus compromised.

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Figure 3. The “little wound” in the inner canthus of the right eye, that has grown for 7 months.

Figure 4. Paracoccidioides brasiliensis in a very typical pattern, with direct visualization of the fungi into the microabscesses and giant cells.

33 Discussion Ocular paracoccidioidomycosis is very rarely described in international literature, we can find some report tables that try to summarize all cases described [2, 3]. There were 44 cases until 1988 [2]. By contrast, Vida and Moel in 1974 [4], related the eyelid involvement in about 25% of the cases with systemic infection by Blastomyces dermatitidis, a number contested by Bartley [5], who, after the review of 79 patients of Mayo Clinic, found only one patient (1.27%) with ocular lesions. All authors seems to agree that infection by direct inoculation of P. brasiliensis into the skin is even more rare [1, 2, 6–10]. The first clinical manifestation may be ocular, and then the systemic infection is noted, being almost impossible to specify where the primary inoculation was, since the hematogenic and lymphatic dissemination had already been demonstrated in experimental studies [11]. In Case 1, here described, no systemic lesions were found after the diagnosis of eyelid paracoccidioidomycosis, which led us to think in the primary inoculation on skin. This disease, that sometimes can start like a blepharitis or a hordeolum, can lead to deformations or even blindness [2]. The diagnoses may be very difficult, like in these two cases described, because of their clinical resemblance with carcinoma’s lesions [1, 2, 9, 10, 12], even in histopathological examinations. Other differential diagnoses are trachoma, leishmaniasis, sporotrichosis, lupus erythematosus, tuberculosis and secondary lues. Margo [12] points out the utility of fungal autofluorescence to help in diagnostic of fungus like: Blastomyces, Candida, Cryptococus, Aspergillus, Coccidioides, and Histoplasma, using slides that were even already stained by hematoxylin and eosin, with good results. Another important topic of consideration is the treatment and the cure. For treatment sulfamethoxazole, ketoconazole, amphotericin B or itraconazole have been used, for a period that ranged from 3 to 6 months, making compliance with the treatment very poor, as we observed in both cases here described. Moreover there is no definitive exam for the therapeutic control [5]. We would like to point out an interesting paper about therapeutic follow-up with 67 Ga, where they observed the disease in a few systems of patients that were considered clinical and histopathologically cured [13].

All these peculiar difficulties lead us to think that there are many ocular paracoccidioidomycosis lesions that are not diagnosed or not properly treated, in compliance with the opinion of Conti-Diaz [11], that based in some experimental studies showed the great frequency and intensity of the ocular findings after systemic inoculation of this fungus, and of Silva [2], who recommends more attention to this diagnosis in endemic areas, mainly in men over 30 years, that have a frequent contact with soil and vegetables.

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Address for correspondence: Sergio V. Burnier, MD, Rua Coronel Quirino, 1457/141, Campinas - SP - CEP: 13025-002, Brazil Phone/Fax: (55)-(19)-251-2894