6 JClin Pathol 1994;47:764-766

Chronic Brucella infection of the supra-patellarbursa with sinus formation

M McDermott, B O'Connell, T E Mulvihill, E C Sweeney

AbstractA case of supra-patellar bursitis with theformation of discharging sinus isdescribed. B abortus was isolated fromresected bursal tissue. Vhile osteoarticu-lar complications of bruceliosis are com-mon and a number of different clinicalsyndromes are now recognised, disease ofthe bursae is rare and as far as is knownsinus formation has not been describedbefore in this setting.

(7 Clin Pathol 1994;47:764-766)

Department ofHistopathology,Trinity College Dublinand St James'sHospital, DublinM McDermottE C SweeneyDepartment ofMicrobiologyB O'ConnellT E MulvihillCorrespondence to:Dr E C Sweeney,Department ofHistopathology, St James'sHospital, Dublin, IrelandAccepted for publication28 February 1994

Case reportA 39 year old man presented with a smallinfected skin lesion above the left knee, whichwas treated successfully with flucloxacillin. Hepresented four months later with a recurrence

of the lesion and associated inguinal adenopa-thy and fever. A full blood count was normaland the monospot test was negative, butBrucella sp antibody serology titres wereincreased with a Coombs test result of1/5120. A tentative diagnosis of Brucella infec-tion was made, although the exact nature ofthe skin lesion remained unclear. There was

no history of occupational exposure to farmanimals, but the patient had occasionally con-sumed unpasteurised milk from neighbouringfarms.

Figure 1 Axial magnetic resonance image scan of knee demonstratingfluidfilled space(short arrow) anterior to lower end of thefemur with lateral subcutaneous extension to thesite of the discharging sinus (long arrow).

Three years later, he developed a discharg-ing sinus which required surgical excision of ablind-ending subcutaneous tract above theleft knee. There was no obvious infection inthe knee joint. Histological examination of theresected material confirmed the presence of asinus tract, lined by granulation tissue withadjacent chronic inflammation and necrosis.The features were felt to represent aninflamed bursa and the patient was dischargedwithout additional treatment.

Seven years after initial presentation, a fur-ther purulent discharging sinus developed atthe same site. Clinically, erythema, oedema,and tenderness were present in the area but,as on previous admission, there was no limita-tion of movement. Culture of the purulentexudate grew no organisms. Repeat Brucellaserology using B abortus antigen (MurexDiagnostics, Hartford, England) produced astandard agglutination test of 1/1280 and aCoombs test result of 1/5120. Magnetic reso-nance imaging demonstrated a multioculatedsoft tissue swelling above and anterior to theknee (fig 1). Surgical exploration was under-taken with drainage of a multiloculatedabscess and resection of large quantities ofgranulation tissue from the soft tissues aroundthe knee. Histologically, the resection speci-men consisted of chronically inflamed hyper-plastic synovium with surface fibrinousexudate. No lymphoid aggregates were identi-fied, but there were numerous, poorly formednecrotising granulomata in the surroundingconnective tissue (fig 2). Ziehl-Neelsen andGram stains were negative. Culture ofresected material, after three weeks of incuba-tion, grew Brucella abortus biotype 1. Thepatient was started on oral tetracycline 500mg four times a day and has made a goodrecovery.

DiscussionBrucella infection is associated with arthritis in10-25% of patients' 2 and may precede,accompany, or follow systemic infection.3Four clinical patterns of joint disease aredescribed, listed in order of frequency: (i)sacroiliitis; (ii) peripheral arthritis, usuallymonoarticular, affecting knee, hip, ankle andshoulder; (iii) mixed forms; (iv) and spondy-litis, the most frequently destructive form.4Arthritis may be seen in association withacute, undulant, or chronic systemic disease.5Spondylitis is strongly associated with chronicdisease and tends to occur in a more elderlypopulation, while sacroiliitis and peripheralarthritis are more frequently acute or subacute

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Chronic Brucella infection of the supra-pateUlar bursa with sinus formation

Figure 2 Section of resected bursa showing severe chronic inflammation and a largenecrotising granuloma.

illnesses of children and young adults.45Brucella may, less frequently, affect othermusculoskeletal sites, producing tendinitis,enthesopathies, and osteomyelitis.5 Infectionin the bursae has been described6 but isunusual, and skin and soft tissue disease israre.7Where Brucella arthritis is the presenting

feature and represents a localised form of thedisease, constitutional symptoms may beabsent.2 50% of cases, however, are associatedwith an acute Brucella syndrome and typifiedby fever, sweating, and fatigue.2 Headache,anxiety, depression and insomnia are the mostcommon systemic symptoms seen withchronic Brucella arthritis.2

Laboratory findings are variable, with a

normal white cell count seen in 80%2although leucocytosis, leucopenia, relativelymphocytosis, anaemia, pancytopenia andthrombocytopenia have all been described.8The erythrocyte sedimentation rate isincreased in 30%.8

Synovial fluid examination usually indi-cates a modest increase in white cell countwith a predominance of mononuclear cells, anunusual finding in infective arthritis.5 Proteinis mildly increased and glucose concentrationsare variable.5

Diagnosis of Brucella infection is madedefinitively by isolation of organisms fromblood, tissue, or fluid specimens, although itshould be noted that isolation of B melitensisfrom blood cultures is easier than isolation ofBabortus.9 The Castaneda method has tradi-tionally been used for blood culture isolationand is considered by many to be the gold stan-dard, although other media, including digestbroth, are suitable.'0 Interestingly, newerautomated or semi-automated methodologymay increase the yield from blood cultures.Lysis-centrifugation has been reported as

being more successful than the Castanedamethod" and similarly continuous monitoringis promising.'2

The isolation of Brucella spp, in particularB abortus, from synovial fluid is difficult(authors quoting success rates of 35-92%),3and depends to a large extent on a clinicalsuspicion and a high level of vigilance atbench level. This difficulty may be due to therelative paucity of organisms present in clini-cal specimens as it has been shown that apartfrom B abortus biotype 2 and B suis biotype 3brucellae are not fastidious organisms.'0Various media are suitable for Brucella isola-tion including chocolate agar, which was suc-cessful in this case.

Because of the poor yield from culture ofBabortus, which is almost invariably thepathogen in the United Kingdom, many relyon a combination of clinical presentation andserological tests to arrive at a diagnosis. Thestandard agglutination test is the most widelyused serological procedure, with a titre of >1/160 considered by many to be diagnostic inacute infection. However, these tests need tobe interpreted with caution as no single titremay be taken to indicate active disease, espe-cially in a rural population where a significantdegree of exposure and subclinical infectionoccurs. In the Republic of Ireland, where bru-cellosis remains endemic in cattle, it has beenshown that over 40% of blood donors in arural community have standard agglutinationtitres of >1/80, whereas only 14% of blooddonors from an urban community have simi-lar titres (personal communication, Mr LiamEnglish, Department of Microbiology, StJames's Hospital, and unpublished data).

Histological changes associated withBrucella infection of synovial lined spaces arevariable but are principally those of a chronicinflammation, with hyperplasia of lining cells.Lymphocytes, plasma cells, and histiocytesare the predominant cell types, with occa-sional giant cells and granuloma formation.'Granulomata may undergo central necrosis'but are sparse and therefore infrequentlyfound.46 Some authors feel that the non-spe-cific histological picture means that synovialbiopsy is not a diagnostically useful procedurein this setting.2 However, the finding of granu-lomata significantly narrows the range of diag-nostic possibilities and, if not pathognomonicof Brucella infection, may at least add furtherweight to an established clinical suspicion.As such, biopsy will continue to have arole, particularly where the diagnosis hasproved difficult. Biopsy also provides materialfor immunocytochemical identification ofBrucella organisms. Immunoperoxidase anti-bodies are commercially available (Wellcome)and are used extensively in the veterinaryindustry. However, the small numbers oforganisms typically associated with humandisease mean that the diagnostic yield will below and in this case no organisms were identi-fied using this method.The high percentage of cases in which

Brucella has not been cultured from synovialfluid has been used as an argument for theexistence of a "reactive" Brucella arthritis aswell as an "infective" form.5 This suggestion issupported by the non-specific histological

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McDermott, O'ConneUl, Mulvihill, Sweeney

picture, the non-destructive nature ofmany ofthese infections, and the resolution of caseswithout anti-microbial treatment.5 Manyauthors have also documented the existenceof immunological abnormalities in Brucellaarthritis, including IgG agglutinating anti-Brucella antibodies in synovial fluid of suchpatients, and point to the similarity of thecondition with other "reactive" arthritidessuch as those following Shigella and Yersiniainfection.4 However, isolation of organismsfrom the joint in such cases, improved byusing appropriate media and conditions,immediately moves cases of otherwise typical"reactive" arthritis into the "infective" cate-gory. Further improvements in organismdetection are likely to follow the application ofmolecular biological techniques to the field,such as PCR amplification of Brucella DNA.The current case illustrates the lengthy

delay in reaching a firm diagnosis in muscu-loskeletal brucellosis. The rarity of the condi-tion, the "non-infectious" synovial fluidpicture, and the difficulty in culturing theorganism all militate against prompt diagnosisand treatment.4 These factors were com-pounded in this case by the absence of any ofthe more traditional risk factors for the illness,such as farming or abattoir work (the patienthad had a number of occupations, but was acourier at the time of initial presentation).The predominant bursal location of theinflammatory process without evidence ofdirect articular disease which allowed normalrange of movement throughout the seven yearhistory of the lesion was also perplexing.Bursal disease is uncommon, with the three

cases described by Johnson and Weed repre-senting the largest series to date. Bursitis andtendinitis were not separated as clinical syn-dromes in the series reported by Mousa et al,7but the combination represented only 1 2% ofthe 169 cases of osteoarticular brucellosis theydescribed, and bursitis is not recorded inother large series.2' The formation of a sinustract in this setting has also not beendescribed before.

We acknowledge the technical assistance of Margaret Lynch,Department of Microbiology, St James' Hospital.

1 Walker AN, Fechner RE. Granulomatous inflammation ofbones and joints. Pathology of granulomas, New York:Raven Press 1983: 421-48.

2 Khateeb MI, Araj GF, Majeed SA, Lulu AR. Brucellaarthritis: A study of 96 cases in Kuwait. Ann Rheum Dis1990;49:994-8.

3 Lulu AR, Araj GF, Khateeb MI, Mustafa MY, Yusuf AR,Fenech FF. Human brucellosis in Kuwait: A prospectivestudy of 400 cases. QYMed 1988;249:39-54.

4 Gotuzzo E, Alarcon GS, Bocanegra TS, Carrillo C,Guerra JC, Rolando I, et al. Articular involvement inhuman brucellosis: A retrospective analysis of 304 cases.Semin Arthritis Rheum 1982;12:245-55.

5 Alarcon GS, Bocanegra TS, Gotuzzo E, Espinoza LR. Thearthritis of brucellosis: A perspective one hundred yearsafter Bruce's discovery. J Rheumatol 1987;14: 1083-5.

6 Johnson WE, Weed LA. Brucellar bursitis. J BoneJnt Surg1954;364: 133-41.

7 Young EJ. Human brucellosis. Rev Infect Dis 1983;5:821-42.

8 Mousa ARM, Mutaseb SA, Almudallal DS, Khodeir SM,Marafie AA. Osteoarticular complications of brucellosis:A study of 169 cases. Rev Infect Dis 1987;9:531-43.

9 Spink WW. The nature of brucellosis. Minneapolis:University of Minnesota Press, 1956:145-90.

10 Robertson L, Farrell ID, Hinchcliffe PM, Quaife RA.Benchbook on Brucella. PHLS Monograph Series,London: HMSO: 1980.

11 Etamadi H, Raissadat A, Pickett MJ, et al. Isolation ofBrucella spp from clinical specimens. Y Clin Microbiol1984;20:586.

12 Solomon HM, Jackson D. Rapid diagnosis of Brucellamelitensis in blood: some operational characteristics ofthe BACT/ALERT. Y Clin Microbiol 1992;30:222-4.

J Clin Pathol 1994;47:766-768

Cushing's syndrome associated with recurrentendometrioid adenocarcinoma of the ovary

Cancer MedicineResearch Unit,University ofBradfordand Department ofOncology, AiredaleGeneral Hospital,KeighleyS M CrawfordDepartment ofHistopathology,Airdale GeneralHospitalR D PyrahDepartment ofPathology, UniversityofWales College ofMedicine, CardiffS M IsmailCorrespondence toDr S M Crawford, CancerMedicine Research Unit,University of Bradford,Bradford, West YorkshireBD7 lDPAccepted for publication14 December 1993

S M Crawford, R D Pyrah, S M Ismail

AbstractEctopic production of adrenocortico-trophic hormone (ACTH) by malignantneoplasms is a well recognised cause ofCushing's syndrome but is extremelyrare in ovarian carcinoma. A patient whounderwent surgery for ovarian carci-noma followed by a course of chemother-apy is reported. The tumour was abilateral moderately differentiated endo-metrioid adenocarcinoma and containednumerous chromogranin inmmunoreac-tive endocrine cells as well as small foci ofACTH immunoreactivity. She subse-

quently presented with Cushing's syn-drome in association with extensivepelvic recurrence of the tumour.

(7 Clin Pathol 1994;47:766-768)

Cushing's syndrome due to ectopic adreno-corticotrophic hormone (ACTH) productionhas been described in a wide range of ovariantumours including sex cord stromal tumours,'carcinoid tumours,'-' and teratomas.4 How-ever, ovarian tumours of common epithelialtype are an extremely uncommon cause of

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