SUBCUTANEOUS PHEOHYPHOMYCOSIS CAUSED BY Phoma cava: REPORT OF A CASE AND REVIEW OF THE LITERATURE

SUBCUTANEOUS PHEOHYPHOMYCOSIS CAUSED BY Phoma cava . REPORT OF A CASE AND REVIEW OF THE LITERATURE

Clarisse ZAITZ ^{( 1 )} , Elisabeth Maria HEINS-VACCARI ^{( 2 )} , Roseli Santos de FREITAS ^{( 2 )} , Giovana Letícia Hernández ARRIAGADA ^{( 3 )} , Ligia RUIZ ^{( 4 )} , Silvia A.S. TOTOLI ^{( 5 )} , Ana Cristina MARQUES ^{( 4 )} , Gisele G. REZZE ^{( 6 )} , Helena MÚLLER ^{( 7 )} , Neuza Sakai VALENTE ^{( 8 )} & Carlos da Silva LACAZ ^{( 9 )}

ZAITZ, C.; HEINS-VACCARI, E.M.; FREITAS, R.S. de; ARRIAGADA, G.L.H.; RUIZ, L.; TOTOLI, S.A.S.; MARQUES, A.C.; REZZE, G.G.; MÚLLER, H.; VALENTE, N.S. & LACAZ, C. da S. – Subcutaneous pheohyphomycosis caused by Phoma cava. Report of a cause and review of the literature. Rev. Inst. Med. trop. S. Paulo, 39(1):000-000, 1997.

SUMMARY

We report a case of subcutaneous pheohyphomycosis observed in a male patient presenting pulmonary sarcoidosis and submitted to corticosteroid treatment. He presented nodular erythematous-violaceous skin lesions in the dorsum of the right hand. Histopathological examination of the biopsied lesion revealed dematiaceous hyphae and yeast-like cells, with a granulomatous tissual reaction. The isolated fungus was identified as Phoma cava. A review of the literature on fungal infection caused by different Phoma species, is presented. The patient healed after therapy with amphotericin B, followed by itraconazole.

KEYWORDS: Pheohyphomycosis; Phoma cava; Subcutaneous mycosis.

INTRODUCTION

The fungi of the genus Phoma (Saccardo 1812)^* [=Peyronellaeae Guidanich ex Guidanichi, 1946] are part of a complex of species designated Pleurophoma by Hönel (1914). Are primarily soil inhabiting fungi, living on plant debris, but they are also phytopathogens and, eventually, pathogenic for man and animals.

A genus similar to Phoma is Pyrenochaeta, created by Notaris in 1894 which also has dark pycnidia with papillae and with a single ostiole, but with septate setae, usually concentrated around the ostiole. The conidia are hyaline, frequently guttulate, unicellular, cylindric or elliptic. The species of Pyrenochaeta considered thus far in the fungal taxonomy are: Pyrenochaeta romeroi Borelli, 1951, isolated in Venezuela from a black grain foot eumycetoma (this species was named in honor of Prof. Jesus Romero by Dante Borelli), Pyrenochaeta mackinnonii Borelli, 1976, also isolated in Venezuela from a black grain eumycetoma of the foot by Dante Borelli, and Pyrenochaeta unguis-hominis Punithalingan et English, 1975, isolated from a case of onychomycosis. According to Romero & Mackenzie (1989), there is a marked resemblance between Pyrenochaeta romeroi and Madurella grisea. In a case of subcutaneous pheophyphomuycosis recorded by YOUNG et al. (1973)¹², the fungus isolated and identified as Phoma strongly resembled Pyrenochaeta romeroi.

Human lesion caused by species of the genus Phoma may be superficial or deep, attacking the skin, cornea, subcutaneous cell tissue, and lungs. In the last case, mycelial filaments and dematiaceous round cells are detected inside the inflamatory process, similar to those observed in other cases of pheohyphomycosis. There are no cases of eumycetoma caused by Phoma, in contrast to what occurs with the genus Pyrenochaeta. Lesions in other animals have been reported. GORDON et al. (1975)⁷ isolated P. cava from skin lesions of a white-tailed deer (Odoileus virginianus). Lesions of the skin of the ears caused by P. glomerata (Peyronellaeae glomerata DAWSON & LEPPER, 1970⁴) have been reported in goats (Capra hircus) and sheep. This is the reason why GORDON et al. (1975)⁷ refer to Phoma as a pathogen fungus.

Phoma or related fungi belonging to the Pleurophoma complex are frequent agents of lesions in different plants, mainly attacking potatoes. Insects may also be parasitized by fungi of the genus Phoma. Of interest to human and veterinary pathology is the fact that several antifungal drugs act in vitro on Phoma "strains". ROSEN et al. (1966)¹⁴, studying the minimum inhibitory concentration (MIC, µg/ml) of some fungistatic agents on a Phoma (Pleurophoma) strain isolated from a skin lesion, obtained the following results: itraconazole – £ 0.0018; ketoconazole – 0.2; fluconazole – 5.0; griseofulvin – 0.5. BAKER et al. (1981)¹ in a study of a Phoma minutela "strain" isolated from a case of subcutaneous pheohyphomycosis, obtained MIC values of 0.625 µg/ml for amphotericin B and 0.06 µg/ml for 5-FC. GORDON et al. (1975)¹⁴, in a study on Phoma cava isolated from a skin lesion of a deer, referred to an article by GALLO & GALLO (1961) in which the autors recorded the sensitivity of this species to nistatin and griseofulvin, without citing the results obtained for the MIC of these agents.

CASE REPORT

E.C., a 63 year-old white male, from Barretos (SP), presenting with dyspnea and a palpable cervical lymph node was examined at the Dermatology Clinic of the Faculty of Medical Sciences, Santa Casa de São Paulo. A biopsy of the lymph node was performed and the diagnosis of sarcoidosis was achieved. The patient was submitted to corticoid therapy. One month later nodular and slightly erythematous-violaceous lesions appeared. On physical examination nodules measuring 1 to 1.5 cm in diamenter were palpable in infiltrated skin on the dorsum of the right hand and on the sternal region (Fig. 1). A chest X-ray revealed a diffuse interstitial infiltrate. Bacilloscopy and PPD were negative. Pulmonary scintigraphy was normal. A chest tomography revealed hilar and mediastinal lymphadenomegalies. An uncharacteristic pneumopathy was detected. A lung fragment obtained by transbronchial lung biopsy did not revealed bacilli and fungi. Sections of a biopsy of the skin revealed the epidermis thickened by acanthosis and elongated cristae. The dermis showed a small area of necrosis surrounded by an inflamatory reaction consisting of mononuclear cells and tending to form a granulomatous arrangement. PAS stain revealed hyphal fragments and yeast-like cells isolated or in small chains (Fig. 2). A search for acid fast bacilli was negative. In culture grew up a dematiaceous fungus, initially identified as Phoma sp. Corticoid therapy was gradually discontinued and amphotericin B was administered in a cumulative dose of 610 mg. The patient was kept maintained on itraconazole 400 mg/day. Skin lesions healed.

 

Fig. 1 – Slightly erythematous-violaceous nodular lesions located on the dorsum of the right hand

Fig. 2 – Phoma cava. Histological section stained with PAS. Note septate hyphae and yeast-like cells isolated, clustered or arranged in small chains. a, c) 400 X; b, d) 500 X.

MYCOLOGIC STUDY

The isolated fungus was identified as Phoma cava on the basis of the following characteristics: a fast growing colony, ash grey-olive in color, and becoming black. Sparse and reverse brown mycelium (Fig. 3). Pycnidia were observed after 30 days on Sabouraud-agar and potato-agar at room temperature. They were globose to subglobose, brown, ostiolate, releasing large amounts of conidia. Pycnoconidia were straight and slightly curved, light brown in color and occasionally guttulate. Setae and chlamydoconidia were absent (Fig. 4).

 

Fig. 3 – Phoma cava. Colony on Sabouraud-agar after 7 days of growth at room temperature.

 

Fig. 4 – Phoma cava. Globose brown pycnidia: a, b) 100 X; c) 400 X; d) abundant cylindric pycnoconidia released from the pycnidia (1000 X).

DISCUSSION

Cases of pheohyphomycosis caused by dematiaceous fungi of the genus Phoma have been rarely reported in the literature. YOUNG et al. (1973)¹⁷ observed a case of subcutaneous cystic lesion located in the posterior region of Achilles tendon in a black male submitted to renal transplantation. The histopathological picture of this lesion was closely similar to that detected in cystic lesions provoked by Exophiala jeanselmei or Phiallophora richardsiae. No grain formation was observed upon histopathological examination. Dematiaceous hyphae and yeast-like cells were present and ostiolate pycnidia were detected in culture. Table 1 list the lesions caused by fungi of the genus Phoma on the skin or in other locations, according to ROSEN et al. (1996)¹⁴, modified.

The systematic of fungi assigned to the genus Phoma has not been fully established McGINNIS (1980)¹¹ accepts as valid the species P. hibernica and P. glomerata. HOOGS & GUARRO (1995)⁹ consider the following species of Phoma to be pathogenic for man and other animals: P. cava, P. cruris-hominis, P. eupyrena (type species created in 1812 by Saccardo), P. glomerata, P. herbarum (= P. hibernica according to Grimis, O’Connor et Cummins, 1932) P. minutella, P. minutispora, P. oculo-hominis and P. sorghina.

These fungi belonging to the subdivision Deuteromycotina, Coelomycetes class, which comprises two order. Sphaeropsidales, which form pycnidia, structures constituted by a sexual fruiting bodies containing pycnoconidia born on short phialides or directly from the cells of the peridium, and Melanconiales, which produce saucer-shaped acervules (also called conidiomas or sporocarps) in whose basal portion (hymenium) are found conidiophores arranged in rows giving origin to conidia. This order is of great interest in Phytopathology. In the genus Phoma, created by Saccardo in 1812, the picnidia are ostiolate, black or ash grey in color and measure 40 to 200 µm. They contain elongated or curved, and eventually guttulate pycnoconidia. The ostiole cannot always be identified in the pycnidium since it may be obliterated by compact paraphyses. Aerial mycelium may or not be present. Chlamycoconidia are detected in Phoma eupyrena and Phoma glomerata. Some of them of moriform, aspect and intercalary the mycelial filaments, catenulate or not. The pycnidia may or not be sub-mersed in the medium. They are rounded or piriform and some of them are flasks like shape with a usually short "neck" on Sabouraud-agar. Phoma colonies (teleomorph Pleospora) grow slowly at room temperature and are gray to back in color. To characterize the various species of Phoma, the structure and shape of pycnidia as also are the morphology and size of pycnidioconidia and the presence and arrangement of chlamydoconidia, is fundamental importance.

Phoma minutella was isolated from subcutaneous lesions on the left foot (dorsal region) of a farmer from the Dominican Republic who had myasthenia gravis and who was being treated with corticoids. In observations of Indian patients reported by RAI (1989)¹³, skin lesions were superficial, with on particular dermatologic characteristics and were provoked by Phoma minutispora (SHUKLA et al., 1984)¹⁵ and by Phoma sorghina. Corneal lesions were observed in a case reported by PUNITHALINGHAM (1979)¹².

Phoma cava was isolated by GORDON et al. (1975) from superficial skin lesions located above the ear of a child. The same species was also isolated from a dermatitis observed in a deer.

TABLE 1

Skin and other lesions caused by fungi of the genus Phoma according to Rosen et al. (1996), modified.

Author(s) Isolated fungus Lesions Immunodepression 1. JANKE (1956)
2. BAKERSPIGEL (1970)
3. YOUNG et al. (1973)
4. GORDON et al. (1975)
5. PUNITHALINGAN (1979)
6. BADERSPIEGEL et al. (1981)
7. SHUKLA et al. (1984)

8. BAKER et al. (1987)
9. STONE et al. (1988)
10. DOOLEY et al. (1989)
11. RAI (1989)

12. HIRSH & SCHIFF (1986)
13. ROSEN et al. (1996)
14. ZAITZ et al. (1996) Phoma (peyronellaea sp.)
Phoma hibernica
Phoma sp.
Phoma cava
Phoma cruris-hominis
Phoma eupyrena
Phoma minutispora
Phoma minutispora
Phoma minutella

Pleurophoma pleurospora
Phoma sorghina
Phoma sorghina
Phoma sp.
Pleurophoma sp.
Phoma cava Pulmonary
Deep (leg)
Deep (heel)
Superficial above the ear
Deep
Superficial (perioral lesion)
Superficial (face)
Superficial (neck)
Deep (foot)
Deep (forearm)
Deep (legs and arms)
Superficial (face neck and hands)
Superficial (face)
Deep (hands)
Deep (face)
Deep (hand) –
Topical steroids
Azathioprine, prednisone (renal transplant)
–
–
–
Typhoid fever
Oral steroids
Corticoids. Diabetes
–
Cyclosporin, prednisone (heart transplant)
–
–
–
Topical steroids
Oral corticoids

RESUMO

Feo-hifomicose subcutânea causada por Phoma cava . Relato de caso e revisão da literatura

O presente trabalho registra um caso de feo-hifomicose subcutânea em paciente do sexo masculino com o diagnóstico de sarcoidose pulmonar, submetido à terapêutica por corticosteróides quando apresentou no dorso da mão direita lesões cutâneas nodulares, eritêmato-violáceas, de aspecto infiltrado, exigindo biópsia para o diagnóstico. O exame histopatológico revelou processo granulomatoso, com a presença de hifas e células arredondadas demácias. Cultivo positivo para fungo identificado com Phoma cava. Os Autores fizeram revisão da literatura sobre as infecções fúngicas provocadas por diversas espécies de Phoma, mostrando a raridade desta observação. A evolução foi favorável com a administração da anfotericina B (via venosa) seguida do itraconazol (via oral).

REFERENCES

1. BAKER, J.G.; SALKIN, I.F.; FORGACS, P.; HAINES, J.H. & KEMMA, M.E. – First report of subcutaneous phaeohyphomycosis of the foot caused by Phoma minutella. J. clin. Microbiol., 25:2395-2397, 1987.

2. BAKERSPIEGEL, A. – The isolation of Phoma hibernica from a lesion on a leg. Sabouraudia, 7:261-264, 1970.

3. BAKERSPIEGEL, A.; LOWE, & ROSTAS, A. – The isolation Phoma eupyrena from a human lesion. Arch Derm., 117:362-363, 1981.

4. DAWSON, C.O. & LEPPER, A.W.D. – Peyronellaea glomerata infection of the ear pinna in gots. Sabouraudia, 8:145-148, 1970.

5. DOOLEY, D.P.; BECKIUS, M.L.; JEFFERY, B.S. et al. – Phaeohyphomycotic cutaneous disease caused by Pleurophoma in a cardiac transplant patient. J. infect. Dis., 159:503-507, 1989.

6. ENGLISH, M.P. – Infection of the finger-mail by Pyrenochaeta unguis-hominis. J. Derm., 103:91-93, 1980.

7. GORDON, M.A.; SALKIN, I.F. & STONE, W.B. – Phoma (Peyronellaea) as zoopathogen. Sabouraudia, 13:329-333, 1975.

8. HIRSH, A.H. & SCHIFF, T.A. – Subcutaneous phaeohyphomycosis caused by an unusual pathogen: Phoma species. J. Amer. Acad. Derm., 34:679-680, 1996.

9. HOOG, G.S. de & GUARRO, J. – Ed. Atlas of clinical fungi. Baarn, Centrallbureau voor Schimmelcultures; Reus Universit, Rovira i Virgili, 1995.

10. JANKE, D. – Über eine menschenpathogene, aus lungenveränderungen gezüchetete neue spezies von Peyronellaea. Mycopathologia (Den Haag), 7:229-240, 1956.

11. McGINNIS, M.R. – Laboratory handbook of medical mycology. New York, Academic Press, 1980.

12. PUNITHALINGAM, E. – Sphaeropsidales in culture from humans. Nova Hedwigia, 31:119-158, 1979.

13. RAI, M.K. – Phoma sorghina infection in human geing. Mycopathologia (Den Haag), 105:167-170, 1989.

14. ROSEN, T.; RINALDI, M.J.; TSCHEN, J.A.; STERN, J.K. & CERNOCK, P. – Cutaneous lesions due to Pleurophoma (Phoma) complex. Sth. med. J. (Bgham, Ala.), 89: 431-433, 1996.

15. SHUKLA, N.P.; RAJAK, R.K.; AGARWAL, G.P. & GUPTA, D.K.– Phoma minutispora as a human pathogen. Mykosen, 27:255-258, 1983.

16. STONE, M.S.; ROSEN, T. & CLARRIDGE, J. – Phaeohyphomicosis due to Coelomycetes organisms. Int. J. Derm., 27:404-405, 1988.

17. YOUNG, N.A.; KWON-CHUNG, K.J. & FREEMAN, J. – Subcutaneous abscess caused by Phoma sp. resembling Pyrenochaeta romeroi: unique fingal infection occurring in immunosuppressed recipient of renal allograft. Amer. J. clin. Path., 59:810-816, 1973.

Recebido para publicação em 12/11/996

Aceito para publicação em 17/02/1997

(1

) Associated Professor. Faculty of Medical Sciences. Santa Casa de São Paulo, São Paulo, SP, Brasil.

(2

) Mycologist, I.M.T.S.P. and LIM/53. Clinical Hospital. FMUSP, São Paulo, SP, Brasil.

(3

) Trainee. FUNDAP, São Paulo, SP, Brasil.

(4

) Dermatologist. Santa Casa de São Paulo, São Paulo, SP, Brasil.

(5

) Instructor. Faculty of Medical Sciences. Santa Casa de São Paulo, São Paulo, SP, Brasil.

(6

) Resident. Santa Casa de São Paulo, São Paulo, SP, Brasil.

(7

) Pathologist. Faculty of Medical Sciences. Santa Casa de São Paulo, São Paulo, SP, Brasil.

(8

) Pathologist. Dermatology Clinic of the Clinical Hospital. FMUSP, São Paulo, SP, Brasil.

(9

) Head of the Medical Mycology Laboratory, I.M.T.S.P. and LIM/53. Clinical Hospital. FMUSP, São Paulo, SP, Brasil.

Correspondence to: Prof. Dr. Carlos da S. Lacaz. Lab. Micologia Médica. Instituto de Medicina Tropical, Av. Dr. Enéas de Carvalho Aguiar 500, 05403-000 São Paulo, SP, Brasil.

*

Pier Andrea Saccardo (1845-1920) was a Professor of Botany in Padua (Italy), and one of the most active mycologist of this time who left his name indelibly linked to this specialty. He was the author of the famous opus

Sylloge fungorum hucusque cognitorum (1882-1925), among others.

Publication Dates

• Publication in this collection
  14 Oct 1998
• Date of issue
  Jan 1997

History

• Accepted
  17 Feb 1997
• Received
  12 Nov 1996