MYCOSES 38, 369-37 1 (1995) ACCEPTED:MAY 15, 1995

CASE REPORT

Arthritis without grains caused by

Myzetische Arthritis ohne Drusenbildung durch Pseudallescheria boydii

Gabriele Ginter', G. S. de Hoog', Andrea Pschaid3, M. Fellinger3,A. Bogiatzis3, C. Berghold3, E.-M. Reich3 and F. C. Odds4

Key words. Pseudallescheria boydii, apwspennum, Scedosporium prol$cans, arthritis. ScHiisselworter. Pseudallescheria boydii, Scedosporium apiospemzum, Scedosporium prol$cans, Arthritis.

I

Summary. Severe infection of the knee joint by Introduction Pseudallescheria boydii in a 23-year-old female resulted in complete destruction of the cartilagi- Pseudallescheria boydii (Shear) McGinnis et al. nous surface. The possibility of entry of the [: ; anamorph: Scedo- through mild abrasions of unperforated skin is sporium apiospermum (Sacc.) Sacc.] is one of the discussed. The clinical appearance is compared classical agents of human white-grain mycetoma with that of Scedosporium prolgcans. Antimy- [ 13. More recently it has emerged as an agent of cotic miconazole-itraconazole treatment, applied opportunistic systemic mycoses, frequently show- during a period of 4 months, was successful; no ing neurotropism [2]. The related anamorph side-effects were noted. species Scedosporium prol$icans (Hennebert & Desai) GuCho & de Hoog [3] is particularly known to Zusammenfassung. Bericht uber eine schwere cause focal invasive arthritis after traumatic inocu- Infektion eines Kniegelenks durch Pseudallescheria lation; grains remain absent. Here we report a boydii bei einer 23-jahrigen gesunden Frau. Als case of arthritis without grains caused by P. boydii. Endzustand resultierte eine komplette Zerstorung Criteria for differentiation of the two species are der knorpeligen Gelenksanteile. Durch eine discussed in view of their markedly different sus- antimykotische Kombinationsbehandlung mit ceptibility to antifungal agents. Miconazol-Itraconazol iiber 4 Monate konnte eine Heilung erzielt werden. Signifikante Nebenwir- kungen wurden nicht beobachtet. Das klinische Case report Erscheinungsbild erinnert an Infektionen durch Scedosporium prol$cans. Die Moglichkeit eines Erre- A 23-year-old nurse acquired a bruise of the left gereintritts durch ein kutanes Minitrauma muR in knee without open wound through a fall. Because Erwagung gezogen werden. of the development of a painful swelling, a fine- needle aspiration of the traumatized area was performed a few days afterwards. The local subcut- aneous changes were diagnosed as oedema and bursa haematoma. One month later the swelling appeared chronic. An arthroscopic lavage was performed and a synovial biopsy specimen was Department of Dermatology, University of Graz, Austria, Centraalbureau voor Schimmelcultures, Baarn, The taken. Arthroscopically a diffuse synovitis was Netherlands, Institute of Hygiene, University of Graz, observed, and a massive amount of clear serous Austria, Janssen Research Foundation, Beerse, Belgium. fluid was aspirated. Synovial biopsy showed no evidence of fungal elements. Despite this inter- Correspondence: Dr Gabriele Ginter, Department of Dermatology, University of Graz, Auenbruggerplatz 8, vention, recurrent painful arthritis developed, for A-8036 Graz, Austria. which repeated aspirates were judged necessary. 370 GABRIELEGINTER ET AL.

In addition, Peroxinorm, xylocaine and a corticoid crystalline suspension were installed, and an open synovectomy was performed. The synovial cavity was seen to be swollen, somewhat flu@ and covered by fibrotic membranes. Histologically the diagnosis of a non-specific fibrotic arthritis was made. No fungal elements were observed in unstained or in specifically stained preparations; fungal grains were absent. Repeated culturing remained unsuccessful. Erythrocytes and leuco- cytes were found repeatedly in the increasing amounts of floccose, opaque, serous exudate. Finally an extended glassy, diffuse synovitis with fourth-grade destruction of all bony parts devel- oped. A leucocytosis (33500mm-3) and an increased erythrocyte sedimentation rate were noted, as well as a hypochromic anaemia. After the patient developed a fever a fungus was repeatedly isolated in culture from the Redon drain as well as from synovial fluid taken intrasurg- ically under sterile conditions. Cultures grew easily within a few days at room temperature on potato- glucose agar and on Griitz-Kimmig agar.

Mycology Figare 1. Scanning electron micrograph of Pseudallescheria bydii anamorph with ovoidal conidia produced on cylindrical annellated Colonies (strain deposit CBS 445.93) grew rapidly zones showing annellations of irregular length ( x 10 000). on the above-mentioned media, and were lanose, initially whitish, soon becoming smoke grey to brown. Conidiogenous cells were scattered along- aspirate remained free of fungal growth at the end side hyaline hyphae or arranged terminally in of treatment. small groups. Conidia, produced in slimy heads from elongating annellated zones (Fig. I), were one-celled, obovoidal, subhyaline to pale brown, Discussion with a truncate base. Susceptibility testing showed the strain to Pseudallescheria boydii grows with hyphae in tissue be resistant to amorolfine, amphotericin B, 5- in the case of systemic mycoses [2] or colonization fluorocytosine, fluconazole, griseofulvin and of cavities such as lungs [4] or external ears [5]. terbinafine, but sensitive to the imidazoles Cases of keratitis also remain localized [6, 71. miconazole, clotrimazole, econazole, itraconazole, However, subcutaneous, traumatic inoculation ketoconazole, miconazole and tioconazole. leads to mycetoma, characterized by extensive tissue erosion, formation of draining fistulas and the presence of white grains [ 1, 81. Therapy The patient described here exhibited severe chronic arthritis finally resulting in complete Antimycotic miconazole-itraconazole combi- destruction of the cartilaginous surface. Draining nation therapy was applied for a period of 4 fistulas, grains or other fungal elements were not months. Miconazole was given intravenously at found. Similar reports of post-traumatic arthritis 600 mg per day for the first 12 days, followed by of the knee joint caused by P. boydii, in which the 1200 mg miconazole orally and 400 mg itracona- presence of fistulas is variable and grains remained zole orally for a further 4 weeks. Itraconazole absent, have been published [9-121. Grains may monotherapy was given at 200mg orally for 3 be absent from mycetoma-like infections [ 131. De months. No side-effects were noted. After cessation Hoog et al. [ 131 suggested that the kind of fungal of antifungal therapy, clinical signs had decreased growth in tissue might be dependent on the species, and joint function gradually improved during sub- but previous cases of P. boydii arthritis suggest that sequent physiotherapy. Repeated cultures of joint the site of inoculation may also be significant.

mycoses 38, 369-371 (1995) ARTHRITISDUE TO PSEUDALLESCHERIABOYDII 371

Cases of P. boydii arthritis are remarkably similar medical species of Pseudalleschm'a and Scedosponum. 3. Mycol. to focal infections caused by the related species, Mid. 1, 3-9. 4 Chabasse, D., Bouchara, J. P., Chazalette, J. P. et al. Scedosporium prol$cans, which has a predilection for (1991) Mucoviscidose et colonisation fongique a Scedospor- cartilage and joint areas [ 141. S. prol$cans does not ium apiospmum. 3. Mycol. Mid. 1, 152-155. produce any fungal grains either. Cases of arthritis 5 Rippon, J. W. & Carmichael,, J. (1976) Petriellidiosis caused by the two species are thus nearly indis- (Allescheriosis): four unusual cases and review of the tinguishable. Even mixed infections in the knee literature. Mycopathologia 58, 117- 124. 6 Rubens, S. (1991) Pseudallescheria boydii keratitis. Acta by both species have been reported [ 151. Culture Ophthalmol. 69, 684-686. of the causative agent(s) is essential, given the 7 Del Palacio, A., Perez-Blazquez, E., Cuetara, M. S. et al. extreme tolerance to antimycotics of S. prol$cans. (1991) Case report. Keratomycosis due to Scedosporium In vitro, S. prol$cans can be distinguished by the apiospermum. mycoses 34, 483-487. local presence of inflated conidiogenous cells [ 161 8 Rippon, J. W. (1988) Medical Mycolo~, 3rd edn. Philadelphia: W. B. Saunders, pp. 651-680. and by the absence of growth with sucrose, ribitol, 9 Gener, F. A., Kustimur, S., Sultan, N., Sever, A. (1991) xylitol and L-arabinitol [ 171. Uber eine Pilz-induzierte Arthritis durch Scedosporium apio- The natural occurrence of the two species is spermum (Pseudallescherza boydzi). Ziitschr. Rheumatol. 50, somewhat different. Pseudalleschm'a boydii is associ- 219-221. ated with nitrate-rich environments such as pol- 10 Hung, L. H. & Nonvood, L. A. (1993) Osteomyelitis due to Pseudallescheria boydiz. South. Med. 3. 86, 23 1-234. luted water, manure and agricultural soil, while 11 Piper, J. P., Golden, J., Brown, D., Broestler, J. & Scedosporium prol$cans occurs in soil. Mild abrasions Grant, D. (1990) Successful treatment of Scedosponum may be sufficient for infection [ 14, 181. Th'is was apiospmum suppurative arthritis with itraconazole. Pediatr. the case in our patient, in whom the skin was Insect. Dzs. 3. 9, 674-675. largely undamaged. A minor trauma must be 12 Chatte, G., Boibieux, A,, Bailly, M. P. et al. (1993) Osteo- arthrite du genou B Scedosporium apiospennum: succks de assumed in our case, although the possibility of l'itraconazole. 3. Mycol. Mid. 3, 1 1 1 - 113. infection through repeated aspirations and arthro- 13 De Hoog, G. S., Buiting, A., Tan, C. S. et al. (1993) scopic surgery cannot be excluded. Diagnostic problems with imported cases of mycetoma in There is no consensus on the appropriate treat- The Netherlands. mycoser 36, 81-87. ment of Pseudallescheria infections; several antimy- 14 Wilson, C. M., O'Rourke, E. J., McGinnis, M. R. & Salkin, I. F. (1990) Scedosporzum znzatum: clinical spectrum cotics have been used with varying success. of a newly recognized pathogen. 3. Infect. D~J.161, Because of the organism's almost invariable 102- 107. resistance to amphotericin B, the agents currently 15 Wild, B. E., Clements, B. S., Holt, M. J. G., Gray, A. & recommended for therapy include miconazole and Gatus, B. J. (1994) Successful treatment of Scedosporium itraconazole. Miconazole readily penetrates the injatum and Scedosporzum apiospennum osteomyelitis in 2 children. MI.ISHAM Congress, 13.-183. 1994, Adelaide inflamed joints. The minimal inhibitory concen- (Abstract No. D 38). tration (MIC) for P. boydii is <0.8 [19] to 16 Salkin, I. F., McGinnis, M. R., Dykstra, M. J. & Rinaldi, 1 mg ml-' [20]. The recommended daily dose M. G. ( 1988) Scedosporzurn inJlatum, an emerging pathogen. depends on the severity and localization of the 3. Clzn. Microbiol. 26, 498-503. infection and on the general condition of the 17 De Hoog, G. S., Marvin-Sikkema, F. D., Lahpor, G. A., Gottschal, J. C., Prins, R. A. & Gukho, E. (1994) Ecology patient and ranges between 10 and 30 mg kg-'. and physiology of Pseudalleschma boydii, an emerging oppor- tunistic fungus. mycoses 37, 71-78. 18 Cremer, G., Bournerias, I., Mhalla, S. et al. (1994) References ScCdosporiose cutanee non-mycktomateuse chez un patient immunodtprimC. 3. Mycol. MLd. 4, 1 1 1-1 14. Ajello, L. (1952) The isolation of Allescheria boydii Shear, 19 Jones, D. B. (1975) Sensitzv@ Zstzng gMicona

mycoses 38, 369-371 (1995)