J Clin Pathol 1984;37:78-82

Disseminated petriellidiosis (allescheriasis) in a patientwith refractory acute lymphoblastic leukaemiaLY SHIH, N LEE*

From the Division of Haematology, Department of Internal Medicine and the *Department of Pathology,Chang Gung Memorial Hospital, 199 Tung-Hwa North Road, Taipei, Taiwan, 105

SUMMARY A case of disseminated petriellidiosis is presented. This complication occurred in a

patient with refractory acute lymphoblastic leukaemia, who was receiving repeated courses ofcytotoxic drugs, antibiotics and prolonged corticosteroid therapy. The diagnosis of infection byPetriellidium boydii was established by pathological and microbiological studies of a specimenobtained at open lung biopsy. The portal of entry was probably through the lung spreading latervia the blood stream to the brain, thyroid and kidneys. The present case once again emphasises theimportance of specific microbiological identification in definitive diagnosis. To our knowledge, onlythree cases of disseminated petriellidiosis have been reported and this case appears to be the firstcase with renal involvement.

Recent advances in the treatment of acute leukaemiahave contributed to prolonged survival, but thesehave been offset by a substantial increase in thefrequency of opportunistic fungal infections.' 2Petriellidium (Allescheria) boydii is well known as acausative agent of Madura foot in the United States.3Extracutaneous sites of infection with this organismare relatively infrequent and disseminated infection isextremely rare.The purpose of this report is to describe a patient

with refractory acute lymphoblastic leukaemia com-plicated by a disseminated petriellidiosis. To ourknowledge, this is only the fourth case of disseminatedpetriellidiosis ever reported in the English literature.

Case report

A 20-year-old male Taiwanese was first seen on 21December 1980 with the complaints of fatigue, exer-tional dyspnoea and lower sternal pain. Diagnosis ofacute lymphoblastic leukaemia was established afterbone marrow and blood examination. Completeremission was achieved on 28 January 1981 afterinduction therapy with vincristine and prednisolonewhich was followed by prophylactic cranialirradiation and intrathecal methotrexate. Remissionwas maintained with 6-mercaptopurine and oralmethotrexate. "Pulses" of vincristine and predni-solone were given at three monthly intervals for

Accepted for publication 1 September 1983

reinforcement. He continued on this regimen until 27February 1982 when he had his first bone marrowrelapse. A second remission was achieved withadriamycin, vincristine and prednisolone, and thenfollowed by the same maintenance therapy. After asecond marrow relapse on 30 June 1982, remissionwas again induced by adriamycin, vincristine andprednisolone. Unfortunately the remission onlylasted four weeks. A further marrow relapse occurredat the end of August 1982 and there was nosubsequent remission despite various courses ofchemotherapy consisting of adriamycin, vincristine,cytosine arabinoside, cyclophosphamide, high dosemethotrexate and prednisolone. During the course,there were several episodes of infections includingupper respiratory tract, oropharynx and perianalinfections, which were all successfully treated byantibiotics.On 2 December 1982 he was readmitted for

treatment of his refractory leukaemia. Physicalexamination on admission was within normal limitsexcept for a marked sternal tenderness. Adriamycinand cytosine arabinoside were reinstituted. Profoundgranulocytopenia and high fever developed on 13December. Empirical antibiotics with carbenicillinand tobramycin was given. Fever resolved on 15December but again arose to 39 40C two days later,associated with cough and occasional headacheduring febrile episodes; cefamandole was then added.Chest x-ray examination showed bilateral upperpulmonary infiltrates with evidence of cavitation inthe left upper lung (Fig. 1). The roentgenogram in

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Fig. I Chest x-ray showing bilateral upper infiltrates witha cavity in the left upper lung.

October revealed clear lung fields. Urine culture andseveral blood cultures were unrevealing. Sputumsmears and cultures for acid fast bacilli or otherbacteria and fungi were all negative. The patientremained persistently febrile. Blood streaked sputumand left pleuritic pain developed on 21 December andthe follow-up chest film showed progression of pul-monary lesions. Open lung biopsy from the left upperlobe was performed on 24 December. Pathologicalexamination revealed suppurative inflammation withpresence of branching septate fungal hyphae in thenecrotic lung tissue and overlying pleura. The findingswere initially thought to be consistent with asper-gillosis. Subsequently the fungus was identified onculture as Petriellidium boydii. Blurred vision, weak-ness of the left extremities and left central type facialpalsy developed on 27 December. A lumbar puncturerevealed an opening pressure of 80 mm H20. Thecerebrospinal fluid showed 81 x 106/1 with 93%segmented cells, 6% monocytes and 1% lymphocytes,glucose was 56 mg/dl (simultaneous blood glucose95 mg/dl) and protein was 51 mg/dl. No leukaemiccells were found. Smears for acid-fast bacilli, Gram'sstain, potassium hydroxide and India ink prepara-tions were negative, as were cultures for bacteria andfungi of cerebrospinal fluid. A computerised tomo-graph scan of the brain showed non-enhancinghypodensity at right basal ganglia, right thalamic andright deep frontal regions. Unfortunately his neuro-logical condition deteriorated rapidly and hedeveloped uncontrollable seizures and coma. He diedon 30 December.

POSTMORTEM FINDINGSAt necropsy, there was a 150 ml serous pleuraleffusion in each pleural cavity and a 100 ml yellowishclear pericardial effusion. Adhesions were found in theright upper pleural space, between left upper andlower lobes of lung and adjacent pleurae. On sec-tioning, right upper lung contained a 2-5 cm x 2-5 cmcavity which was filled with laminated yellowish-blackpieces of fungus ball-like mass. An abscess measuring2 cm x 15 cm was present in the left upper lung andcontained soft grey material. Microscopically, theright intracavitary mass consisted of concentric ringsof tangled hyphal strands and spores (Fig. 2). The leftlung abscess was lined by granulation tissue and con-tained clumps of branching septate hyphae bearingoccasional terminal brownish conidia along withnecrotic debris and inflammatory cells. The fungi werealso found in the abscess wall as well as in the bloodvessel wall. The fungi were seen faintly inhaematoxylin and eosin stained preparations, butwere better demonstrated in periodic acid-Schiff andGomori methenamine silver nitrate stained prepara-tions. Aspergillus conidiophores were not observed.Fungal involvement of pleura with fibrinoid pleuritiswas noted. No leukaemic infiltration of pulmonaryparenchyma was seen. Foci of bronchopneumoniawere present. The remainder of the lung was con-gested and oedematous.The brain weighed 1450 g and the right cerebral

hemisphere was swollen. There was a large abscess,measuring 3 cm x 2 cm x 4-5 cm, extending from the

Fig. 2 Section of the mass in the cavity in the right upperlung showing clumps of septate hyphae and spores. Periodicacid-Schiffstain x 400.

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Fig. 3 A single glomerulus showing fungal invasion.Gomori methenamine silver stain x 200.

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Fig. 4 Renal blood vessel showing fungal invasion of vesselwall and lumen. Gomori methenamine silver stain x 400.

Shih, Lee

right lower frontal lobe (near anterior commissure)through the basal ganglia, thalamus and midbrain.The abscess was not walled off. Microscopicalexamination revealed extensive necrosis, neutrophilicinfiltration and numerous fungi scattered throughoutthe abscess. There was mild reactive gliosissurrounding the abscess. Many blood vessels showedthe presence of thrombi. The fungi were seen withinthe lumen and wall of vessels. The fungi weremorphologically identical with those seen in the lung.There was no evidence of leukaemic infiltration inleptomeninges and brain parenchyma. The spinalcord was not examined.The thyroid gland contained multiple tiny whitish

lesions, the largest measuring 017 cm in diameter.Many yellowish nodules, approximately 0 5 cm toI cm in diameter and wedge-shaped infarcted areaswere found on the cortical region of bilateral kidneys.The abscesses, both in the thyroid and kidneys alldisplayed identical microscopical features as thoseseen in the lung and brain. Fungal invasion of theglomeruli and renal blood vessels was well demon-strated (Figs. 3 and 4).The gross findings in other organs were

unremarkable. Microscopically, the bone marrow,bilateral adrenals, bilateral kidneys and spleen wereinfiltrated by leukaemic cells.For legal reasons, at least eight hours must elapse

from the time of death before a necropsy may becarried out. Bacteria were grown in large numbersfrom necropsy material taken from heart blood, lungand the kidney abscess. The heavy bacterial over-growth inhibited fungal isolation. The brain was notsuitable for culture due to previous formalin fixationand a culture of the thyroid abscess was not obtained.

MYCOLOGYThe lung biopsy tissue was cultured on Sabouraud'sdextrose agar at room temperature. White to light-grey colonies were noted after three days' incubation,which later became smoky-grey with a dark brown onthe reverse side. Microscopical examination usinglactophenol cotton blue stain of the fungi in the origi-nal isolates and their subcultures revealed branchingseptate hyphae bearing brownish ovoid conidia at theends or on short sides of conidiophores (Fig. 5). Theconidia measuring 3-7 um x 6-10 um in size, usuallyoccurred singly, but occasionally in groups of 2 to 3.The hyphae measured 1-5 pm in width. The initialisolates were those of the asexual form, Monosporiumapiospermum. After three-month incubation onSabouraud's agar, dark brown, thin-walled peritheciacontaining large numbers of brown ellipticalascospores were produced (Fig. 6), characteristic ofsexual form of Allescheria (Petriellidium) boydii. The

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Disseminated petriellidiosis

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Fig. 5 Branching septate hyphae with terminal or lateralconidia from slide culture grown on Sabouraud dextroseagar. Lactophenol cotton blue preparation x 400.

Fig. 6 Perithecia containing ascospores x 200.

perithecia, measuring 25 to 150 gm in diameter, when

ruptured, released ascospores which were quiteconstant in size, averaging 3-5 pm x 6-0 pm.

Discussion

Monosporium apiospermum and Petriellidium boydiiare the asexual and sexual forms of the same fungus

4

respectively.4 Malloch has proposed the new genus

Petriellidium for the organism.' This fungus usuallyenters the body by penetrating injury and causes infec-

tion in cutaneous and subcutaneous tissues of the

foot. Extracutaneous sites of petriellidiosis are rare.

We have found 16 reported cases of pulmonary

81

infection which mostly occurred in farmers withunderlying structural lung diseases and usually in thenon-invasive form of an opportunistic intracavitarymycetoma.6 -21 Although rarely, this organism hasbeen implicated in sinusitis,22 23 endophthalmitis,24joint infection,24 parotitis,18 prostatitis,25 pachy-meningitis,26 and brain abscess.9 2 7Almost all seriously invasive petriellidioses have

occurred in compromised hosts or in patients withpredisposing underlying conditions. Our patient hadrefractory acute lymphoblastic leukaemia and hadreceived multiple courses of many cytotoxic drugs,prolonged corticosteroid therapy and various sys-temic antibiotics. He was therefore highly vulnerableto opportunistic fungal infection. In our case theoriginal infection was assumed to have originated inthe lung by inhalation and later to have disseminatedvia the blood stream to the brain, thyroid and kidneysas evidenced by the presence of fungi in the lumen andwall of vessels.

Disseminated petriellidiosis is extremely rare. Toour knowledge, only three cases have been reported.The first case was reported by Rosen et at28 in 1965from Canada in a patient with subacute glomeru-lonephritis and treated with corticosteroid andazathioprine. Brain and thyroid abscesses caused byP boydii were found at necropsy. Forno andBillingham29 subsequently described the second caseof probable air borne pulmonary infection with sys-temic dissemination to the brain and thyroid in a caseof steroid-treated systemic lupus erythematosus. Thethird similar case was reported by Walker et at30 in arenal allograft recipient taking methylprednisoloneand azathioprine. Interestingly, brain and thyroidhave been involved in all three reported disseminatedcases as well as in the present case. All four hadreceived systemic antibiotic therapy and immuno-suppressive drugs before the development of the Pboydii infection. The case described here is the onlycase of systemic petriellidiosis in which renalinvolvement has been demonstrated.The present case as well as the cases reported by

Louria et al," Arnett and Hatch,16 and Walker etat30 would have been diagnosed mistakenly as asper-gillosis if culture had not been obtained. While in thecases reported by Winston et al9 and Gluckman etal,22 tissue sections initially suggested a diagnosis ofphycomycosis. Since P boydii and other mycosesespecially the Aspergillus species produce septatehyphae, their appearance in tissue sections alone willnot be diagnostic. Appropriate culture is the onlyreliable means to an accurate diagnosis.

We are grateful to Miss Chu-Lam Wu for technicalassistance and Miss Hsiu-Jen Hung for typing themanuscript.

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References

'Bodey GP, Bolivar R, Fainstein V. Infectious complications inleukemic patients. Semin Hematol 1982;19:193-226.

Schimpff SC. Infections in patients with acute leukemia. In:Mandell GL, Douglas RG, Bennett JE, eds. Principles andpractice of infectious disease. New York: John Wiley and Sons,1979:2263-78.

3 Green WO, Adams TE. Mycetoma in the United States. Am J ClinPathol 1964;42:75-91.

4 Emmons CW. Allescheria boydii and Monosporium apiospermum.Mycologia 1944;36:188-93.

Malloch D. New concepts in the microascaceae illustrated by twonew species. Mycologia 1970;62:727-40.

6 Creitz J, Harris HW. Isolation of Allescheria boydii from sputum.Am Rev Tuberc 1955;71:126-30.

Tong JL, Valentine EH, Durrance JR, Wilson GM, Fischer DA.Pulmonary infection with Allescheria bovdii: Report of a fatalcase. Am Rev Tuberc 1958;78:604-9.

8 Scharyj M, Levene N, Gordon H. Primary pulmonary infectionwith Monosporium apiospermum: Report of a case with clinical,pathologic and mycologic data. J Infect Dis 1960;106:141-8.

9 Winston DJ, Jordan MC, Rhodes J. Allescheria boydii infections inthe immunosuppressed host. Am J Med 1977;63:830-5.

0Alture-Werber E, Edberg SC, Singer JM. Pulmonary infection withAllescheria boydii. Am J Clin Pathol 1976;66:1019-24.

Louria DB, Lieberman PH, Collins HS, Blevins A. Pulmonarymycetoma due to Allescheria boydii. Arch Intern Med1966;1 17:748-51.

12 Reddy PC, Christianson CS, Gorelick DF, Larsh HW. Pulmonarymonosporosis: An uncommon pulmonary mycotic infection.Thorax 1969;24:722-8.

13 Rosen P, Adelson HT, Burleigh E. Bronchiectasis complicated bythe presence of Monosporium apiospermum and Aspergillusfumi-gatus. Am J Clin Pathol 1969;52:182-7.

'4Travis RE, Ulrich EW, Phillips S. Pulmonary allescheriasis. AnnIntern Med 1961;54:141-52.

15 Hainer JW, Ostrow JH, Mackenzie DWR. Pulmonarymonosporosis: Report of a case with precipitating antibody.Chest 1974;66:601-3.

16 Arnett JC, Hatch HB. Pulmonary allescheriasis: Report of a caseand review of the literature. Arch Intern Med 1975;135:1250-3.

Shih, Lee

1' Belitsos NJ, Merz WG, Bowersox DW, Hutchins GM. Allescheriaboydii mycetoma complicating pulmonary sarcoid. JohnsHopkins Med J 1974;135:259-67.

18 Rippon JW, Carmichael JW. Petriellidiosis (Allescheriosis): Fourunusual cases and review of literature. Mycopathologia1976;58:117-24.

19 Bakerspigel A, Wood T, Burke S. Pulmonary allescheriasis: Reportof a case from Ontario, Canada. Am J Clin Pathol1977;68:299-303.

20 Kathuria SK, Rippon J. Non-aspergillus aspergilloma. Anm J ClinPathol 1982;78:870-3.

2 Severo LC, Londero AT, Picon PD, Rizzon CFC, Tarasconi JC.Petriellidium boydii fungus ball in a patient with active tuber-culosis. Mycopathologia 1982;77:13-7.

22 Gluckman SJ, Ries K, Abrutyn E. Allescheria (Petriellidium)boydii sinusitis in a compromised host. J Clin Microhiol1977;5:481-4.

23 Hecht R, Montgomerie JZ. Maxillary sinus infection withAllescheria boydii (Petriellidium boydii). Johns Hopkins Med J1978;142:107-9.

24Lutwick LI, Galgiani JN, Johnson RH, Stevens DA. Visceralfungal infections due to Petriellidium boaydii (Allescheria boydii):In vitro drug sensitivity studies. Am J Med 1976;61:632-40.

2 Meyer E, Herrold RD. Allescheria boydii isolated from a patientwith chronic prostatitis. Am J Clin Pathol 1961;35:155-9.

26Selby R. Pachymeningitis secondary to Allescheria boydii. JNeurosurg 1972;36:225-7.

27Bell WE, Myers MG. Allescheria (Petriellidium) boadii: Brainabscess in a child with leukemia. Arch Neurol 1978;35:386-8.

28 Rosen F, Deck JHN, Rewcastle NB. Allescheria bovdii-Uniquesystemic dissemination to thyroid and brain. Can Med Assoc J1965;93:1125-7.

29 Forno LS, Billingham ME. Allescheria bovdii infection of thebrain. J Pathol 1972;106:195-8.

30Walker DH, Adamec T, Krigman M. Disseminated Petriellidiosis(Allescheriosis). Arch Pathol Lab Med 1978;102:158-60.

Requests for reprints to: Dr LY Shih, Division of Haema-tology, Department of Internal Medicine, Chang GungMemorial Hospital, 199 Tung-Hwa North Road, Taipei,Taiwan, 105.

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