Candida Arthritis A Manifestation

of Disseminated Candidiasis

HENRY W. MURRAY, M.D. MARK A. FIALK, M.D. RiCHARD B. ROBERTS, M.D. New York, New York

Fungai infections infrequently invoive the joints. Review of the iiterature reveals that Candkla arthritis is rare, that it is usuaity a complication of dtssemtnated candtdiasis and that it occurs as a primary joint infection without spread from adjacent osteomyeiitis. in the patient we describe Candtda arthrttts and buMts of separate jotnts developed as a late manifestatkn of -ted infection foilowing “transient” C. tropkatis fungemta. Treatment consisting of asptration and parentera amphoterktn B eradkated the joint infection without the need for surgery. Bursectomy, however, was required to eradicate the bursai infection. Awareness of this as weti as other late complications of candkkmia whkh signtfy disseminated infection Is important. Optimal therapy will be determined onty by further clinical experience with this unusual manifestation of Candida infection. Fungal infections are uncommon causes of infective arthritis. The mycoses most frequently associated with arthritis are coccidiiidomycosis, North American biastomycosis and systemic sporotrichosis. Primary joint involvement with the other deep-seated mycases is rare [ 11. Arthritis caused by infection with Candiia species is similarly uncommon. Review of the English literature reveals only 11 reports of ante- or postmortem isolation of Candida species from synoviai tissue or fluid [2-121. In eight of the nine well-described cases, joint infection resulted from hematogeneous spread to the synovium. C. albicans was the responsible organism in the cases of hematogeneous joint infection, whereas C. guiiiiermondii was isolated in the one case of infection caused by direct inoculation. Wi the recent increasing incidence of fungemia, especially associated with Candida species [ 13-171, recognition of the potential for joint involvement by this fungus is important since antifungal and/or surgical therapy can eradicate the joint infection as demonstrated in each of the reported cases diagnosed antemortem. In the patient we describe Candida arthritis and bursitis developed several weeks after resolution of asymptomatic, transient C. tropicalis fungemia. The patient’s hospital course illustrates the necessity for careful, prolonged observation of all patients with l

From the Department of Medicine, Division of infectious Diseases, The New York HospttalCornell Medical Center, New York, New York. Requests for reprints shoukt be addressed to Dr. Richard B. Roberts, Department of Medii tine, Cornell University fb%dttl CoJfege. New York, New York 10021. Manuscript accepted September 5, 1975.

*The term “transient candiimia” or “transient fungemia” is used to describe the finding of positive biocd cuitures for Candkta in patients with no clinical evtdence of invasive, systemic fungal infection [l&19]. By definitton, candkfemia is brief [ 181 and spontaneously resolves with efiminatiin of iatrogenic predisposing factors, typically, intravenous catheters [ 18-221.

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587

CANDIDA

ARTHRITIS-MURRAY

ET AL.

transient candidemia for delayed manifestations signifying disseminated infection. This case, which is the first report of joint infection caused by C. tropicalis, also serves to reemphasize the pathogenicity of Candida species other than C. albicans.

CASE REPORT A 77 year old retired chauffeur was admitted to The New York Hospital for evaluation of shortness of breath and anemia. His past history was unremarkable. Physical examination revealed an anxious, afebrile white man with a blood pressure of 120165 mm Hg and a pulse rate of 120 beats/min. Except for a grade 216 systolic murmur and a ventricular gallop, the remainder of the examination was within normal limits. Pertinent laboratory data included a white blood cell count of 9,100/mm3, a hematocrit value of 34 per cent and a platelet count of 252,000/mm3; urinalysis showed microscopic hematuria; fasting blood sugar, blood urea nitrogen, calcium and uric acid levels were within normal limits. Serologic tests (VDRL and FTA) for syphilis were reactive. Chest films showed cardiomegsly, and an electrocardiogram revealed sinus tachycardia with left bundle branch block. Hyperthyroidism was confirmed with a serum thyroxine (T4) value of 26.6 kg per cent, and the patient received radioactive iodine, propylthiouracil and digitalis therapy. Cerebrospinal fluid VDRL was nonreactive, and benzathine penicillin therapy was given for latent syphilis. Bone marrow iron stores were absent, a barium enema and a roentgenographic series of the gastrointestinal tract were negative, and oral iron therapy was given. Urine culture was sterile. An intravenous pyelogram showed left ureterovesical junction obstruction, and a biopsy specimen of the bladder wall revealed papillary carcinoma. Bone and liver scans were normal. On the 17th hospital day, the patient underwent bilateral ureteral catheterization for selective cytology specimens; one day later he had a fever with a temperature of 40°C. Urine sediment showed many white blood cells and gramnegative rods, and intravenous ampicillin therapy was instituted. The following day the patient’s condition deteriorated with leukopenia, oliguria and hypotension. A Foley urinary catheter and a central venous line were inserted and parenteral gentamicin was given. Multiple cultures of the blood and urine for bacteria were negative. Over the next several days the patient’s condition improved clinically, and he was afebrile by the 23rd day. On the 26th hospital day, two cultures of blood drawn from peripheral veins on the 21st and 23rd days were reported positive for C. tropicalis. Cultures of blood and urine obtained on the 22nd day were negative. At the time candidemia was reported, blood for two more cultures was obtained, antibiotic therapy was discontinued and the central venous catheter was removed. Both blood cultures were positive for C. tropicalis; culture of material from the intravenous catheter tip was negative. Urine sediment on the 28th day showed pseudohyphae, and culture was positive for C. tropicalis. Stool and throat cultures for fungus were negative. During this period, the patient remained afebrile and

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showed progressive improvement. Seven blood cultures obtained over the next two weeks were negative. Urine cultures became negative for C. tropicalis three days after removal of the indwelling urinary catheter. Serum immunodiffusion and latex agglutination tests for Candida were negative and 1:32, respectively [23] l. On the 44th hospital day, two and a half weeks after the fungemia, the patient complained of pain in the right shoulder; the joint was tender and swollen with an effusion. There was no warmth or redness and no other joints were affected; the patient was afebrile and had no leukocytosis. Thirty cubic centimeters of cloudy, yellow synovial fluid were aspirated. The white blood cell count was 55,000/mm3 with 92 per cent polymorphonuclear leukocytes, the red blood cell count was 1,067/mm3, protein 3.7 g/100 ml and glucose 91 mg/iOO ml. Smears were negative and crystals were not seen. Culture of the fluid, however, yielded C. tropicalis. Multiple cultures of blood and urine obtained at this time were negative. The shoulder effusion reaccumulated three days later and repeat aspiration showed a white blood cell count of 151,000/ mm3 (93 per cent polymorphonuclear leukocytes), protein 4.1 g/ 100 ml, glucose 42 mg/ 100 ml, and C tropicalis was again isolated. On the 50th day an asymptomatic left olecranon bursal effusion was noted and aspiration (15 cc) revealed cloudy, yellow fluid with a white blood cell count of 1 1,000/mm3 (92 per cent polymorphonuclear leukocytes), a red blood cell count of 9,600/mm3, protein 2.5 g/100 ml and glucose 52 mg/lOO ml. Smears of the fluid were negative for organisms, but C. tropicalis was isolated by culture. Urine cultures became positive for C. tropicalis. At this time, the serum immunodiffusion test was positive, and the latex agglutination titer was 1:128. X-ray films of the right shoulder were negative; films of the left elbow showed moderate changes of osteoarthritis. Repeat bone scan revealed increased uptake over the right shoulder and left elbow. Funduscopic examination, chest film and esophagram were within normal limits. Parenteral amphotericin B therapy was instituted, and the dosage was increased incrementally to 1 mg/kg given on alternate days. Joint symptoms and effusions resolved following three additional aspirations and the administration of 91 mg of amphotericin B. The immunodiffusion test remained positive, and the latex agglutination titer was 1: 256. Repeat urine cultures were negative, and the patient was discharged asymptomatic to complete amphotericin B therapy as an outpatient. The minimum inhibitory concentration (MIC) of the organism to amphotericin B was 0.8 pg/ml, and the patient’s serum was inhibitory at a 1:4 dilution one and a half hours after the infusion of 80 mg of amphotericin B. On two separate occasions after the administration of 50 mg of amphotericin B, the patient’s serum and bursal fluid were inhibitory at a dilution of I:8 and 1:2, respectively. Over the subsequent nine weeks a total dose of 1,O11 mg of amphotericin B was given. Four weeks after dis-

“Immunodiffusion and latex agglutination tests were kindly performed by Dr. Leo Kaufman, Fungus Immunology Branch of the Mycology Division, Center for Disease Control.

CANDIDA ARTHRITIS-MURRAY

charge (511 mg of amphotericin B), the painless olecranon bursal effusion recurred and aspiration (15 cc) revealed yellow fluid with a white blood cell count of 3,778/mm3 (54 per cent polymorphonuclear leukocytes) and a glucose of 82 mg/lOO ml. Smears and cultures of the fluid were negative. The immunodiffusion test was weakly positive, and the latex agglutination titer had decreased to 1:64. A modest amount of bursal fluid reaccumulated three weeks later and was aspirated. At the time therapy was concluded, examination of the elbow revealed only bursal thickening. The right shoulder remained unchanged. Repeat immunodiffusion and latex and latex agglutination tests were trace positive and 1:64, respectively. Following completion of amphotericin B therapy, the patient was readmitted, and a hemicystectomy and distal left ureterostomy were performed for stage C epidermoid carcinoma. On the 17th day, culture of reaccumulated bursal fluid grew C. tropicalis. Cultures of blood and urine were sterile. The immunodiffusion test was negative, and the latex agglutination titer had fallen to 1~16. Four weeks later, repeat culture of the bursal fluid was again positive for C. tropicalis. A renograffin study of the bursa revealed no communication with the joint space, and a superficial bursectomy of the left elbow was performed. At surgery, the superficial bursa was replaced by thick fibrous tissue; there was no involvement of the deep bursa. Microscopically, chronic nonspecific inflammation was present, and yeast forms were seen near the surface of the bursal tissue. Granulomatous changes were not seen. The patient was discharged asymptomatic with a blood urea nitrogen level of 19 mg/iOO ml and a hematocrit value of 31.8 per cent. There was no clinical or laboratory evidence of Candida infection over the subsequent five months. Repeat serologic tests for Candida remained unchanged. A correlation of the clinical and serologic data is shown in Table I.

TABLE

Correlation of Clinical and Serologic Data 1231

I

__ __. _____~~___~_ ___-Days after Candidemia 17

Clinical Manifestations of Candidiasis Candiduria (resolved with removal of urinary catheter) Arthritis, bursitis, candiduria Bursitis Bursitis Bursitis Bursitis (Bursectomy) None

26 39 69 95 129 165 218

ET AL.

eradication

of infection

_________~___-_-_

Parenteral Amphotericin B (mg)

Immunodiffusion Test 0

I:32

+

1:128

+ Weakly + Trace + 0

1:256 I:64 I:64 I:16

0

I:16

. 91 511 1,011

Latex Agglutination Titer

..

and prevention

of joint

de-

[26,27,33,34]. Candida Arthritis. Table II summarizes the clinical characteristics of the nine welldocumented cases of Candida joint infection reported in the English literature. Two additional instances of joint involvement have been described without case reports [ 11,121. Significant underlying diseases and factors predishosing to Candida infection were present in all patients. Candida arthritis was diagnosed antemortem in six of nine cases. By clinical course, antemortem mycologic evidence or postmortem examination, disseminated candidiasis was present in six of the patients. Endocarditis (Case 2) transient candidemia (Case 3) and arthritis secondary to direct inoculation (Case 9) were present each in one instance. Although blood cultures were positive in only two cases, hematogeneous spread to the joints was implicated in eight of nine patients, and in each, C. albicans was the infecting species. C. guilliermondii was isolated in the one case associated with direct inoculation (Case 9) at the time of initial synovectomy. The interval from the first positive culture for Candida from any site (i.e., skin, blood, gastrointestinal tract) to the recognition of arthritis was 12 days to seven weeks in five of six antemortem cases. In two patients (Cases 6 and 8), arthritis followed removal of a culture-positive intravenous catheter by 12 days and three weeks. Intravenous catheters, however, may not always be a prerequisite for hematogeneous spread to joints. In Case 5, C. albicans was isolated from a gastric aspirate at three hours of age and in Case 6 the mother had vaginal candidiasis at delivery. Although intravenous lines were subsequently used in both cases, the possibility of infection via oral contamination leading to gastrointestinal and systemic infection cannot be excluded. In two cases, foci of struction

COMMENTS Joint involvement with systemic mycosis is uncommon. Arthritis is associated most frequently with acute primary coccidioidomycosis which appears to represent an allergic manifestation rather than actual joint infection [24]. Less than 20 per cent of the pa-

tients with chronic disseminated coccidioidomycosis have, granulomatous involvement of bones and joints [25,26]. Much less common is septic arthritis associated with North American blastomycosis [27] and systemic sporotrichosis [ 281. Rarely, cryptococcosis [ 291, histoplasmosis [ 30,3 l] and aspergillosis [ 321 may involve joints. Arthritis results from either direct spread from adjacent soft tissue or subchondral osteomyelitic foci or from hematogeneous dissemination with primary synovial infection. The diagnosis is established by culture and histologic examination of tissue obtained at synovial biopsy and less often by culture of synovial fluid [33]. Effective therapy for these fungi usually requires not only amphotericin B and drainage, but also synovectomy for complete

April

1976

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Journal

of Medicine

Volume 60

559

Newsom et

1

Adler et al. [71,1972

Lindstrom, Lindholm [Sl,1973

7

Klein et al. [61,1972

1972

Hughes, Remington [51,

6

5

4

Pruitt et

3

al. [41, 1969

MGH [31, 1968

2

al. [21, 1967

Reference

37.F

3 wk. F

1 da\/,F

25,F

6 wk,F

28.M

2O.F

Hyaline membrane disease Renal transplant

Aspiration pneumonitis

Abdominal surgery; lupus

Malabsorption; sepsis

Lupus, Salmonella endocarditis and arthritis

Cardiac surgery

...

I

cs.

+

+

-

!V. A

CS, IV, A

CS, IV, A

IV, A

CS.fV.A

IV, A

+

..

-

..

+ cut

..

...

+1v, + spinal fluid, + stool, + gastric aspirate + spinal fluid

+ ascites fluid

+ liver,

down site, - stool

. .

+ vagina

+ oral,

. . .

..

Other*

Antimortem ExtraArticular Fungal Cultures Blood” Urine*

Arthritis

Predisposing Factors*

of Candida

Underlying Clisease

Characteristics

Age (yr) and Sex

Clinical

Case No.

TABLE II

Elbows, knee

Knees

Knees

Shoulder

Knee

Hip, knee

Hip

2wk

12days

5wk

. . .

7wk

...

...

Time from Initial Infection* Joint to Involved Arthritis

. .

. .

. .

. .

+

...

...

Smear*

C. albicans

C. albicans

C. albicans

C. albicans

C. albicans

C. albicans

C. albicans

Culture

Joint Fluid

-

IV amphotericin B X 3 (6,5,8 wk); 5-fluorocytosine X 2 (IO, 64 wk); knee synovectomy

IV amphotericin 69.8 mg (4 wk)

5 mg

IV amphotericin 100 mg (IO weeks); IA amphotericin

IV amphotericin B 200 mg; IA amphotericin X 2 (12.5 mg, 5 mg) IV amphotericin B6dmg

None

None

Antifungal Treatments (dose/duration)

Relapse X 3, cured

Cured

Cured

(Died)”

Cured

(Died)

(Died)”

Course

I’

Clinical

Osteomyelitis of humerus, both femurs Fungal pneumonia and fever 2 wk prior to arthritis; distal femur destruction 15 mo after initial infection

.

Disseminated infection with shoulder culture positive at postmortem

Infected mycotic aorticaneurysm at site of prior aortotomy, Candida cultured from hip, spine, multiple organs Candida endocarditis; postmortem cultures of blood, hip, knee positive Presumed transient candidemia

Findings

Comments/ Associated

?

< m -I

e

$ w

2

9

9

z g

CANDIDA ARTHRITIS-MURRAY

ET AL.

intravascular infection were unexpectedly discovered at autopsy; aortic valve endocarditis (Case 2) and a mycotic aneurysm at the site of prior aortotomy (Case 1). Postmortem blood cultures were positive for C. albicans in one of these cases, but in both cases antemortem cultures were negative. The typical clinical presentation of Candida arthritis included joint pain and swelling with tenderness and effusion. In only one case (Case 7) was significant warmth or redness described. Polyarticular involvement was frequent, and there was a predilection for the larger joints of the lower extremities. The knee was most commonly affected (five of nine cases) either singly or with other joints. The hip was involved in three cases, and the elbow and shoulder in one case each. Bilateral knee infection occurred twice. The small joints were not involved. Joint roentgenographic findings at the onset of arthritis revealed soft tissue swelling and effusions. in two cases and metaphysitis with effusion in another (Case 5). After 10 weeks of amphotericin B therapy, follow-up films in this latter case were within normal limits. Spread from adjacent foci of osteomyelitis or soft tissue infection was not apparent in any patient at the onset of arthritis. In one of the four cases in which bony destruction developed, joint infection had been present for 15 months before erosion was noted roentgenographically, illustrating the possible slow destructive nature of Candida infection. This is in contrast to the destructive arthritis not uncommonly seen with joint infection caused by other fungi [34]. The course of untreated experimental Candida arthritis produced in animals by direct inoculation of C. albicans into the knee, however, is one of progression from synovial swelling to abscess and pannus formation, to destruction of cartilage and finally osteoarthritic changes after eight weeks of time

[351Synovial fluid characteristics were briefly described in only two cases and included a white blood cell count of 28,000/mm3 with 86 per cent polymorphonuclear leukocytes in one and 99 per cent polymorphonuclear leukocytes (white blood cell count not recorded) with a glucose level of 89 mg/lOO ml in the other. In the few instances in which the pathologic examination was reported, gross inspection of the infected joint revealed thickened, hyperemic synovia, purulent arthritis and erosion of cartilage. Microscopically, acute and chronic inflammatory cell infiltrates and necrotic eosinophilic material were present. Granulomatous changes were not described. The diagnosis in all cases was confirmed by synovial fluid culture. In addition, yeast forms were seen on joint aspirate smear in two of three cases and in the synovium in one case at synovectomy.

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Treatment in the cases diagnosed antemortem has consisted of combinations of joint aspiration, local or systemic antifungal chemotherapy, and synovectomy. Candida arthritis may be strikingly indolent and masquerade as an exacerbation of underlying chronic rheumatoid arthritis as in Case 9. The infection may also be difficult to eradicate as illustrated by the two year relapsing course in Case 7 in which relapse and progression to new joint involvement occurred despite several courses of antifungal therapy. Synovectomy and long-term antifungal therapy were eventually necessary for cure. In Case 9, in which infection was introduced by direct inoculation at the first synovectomy, multiple arthrocenteses and a second synovectomy did not prevent recurrent positive joint fluid cultures over three and a half years. After recognition of the fungal infection and the subsequent isolation of C. guilliermondii from the joint, a third synovectomy and a short course of amphotericin B therapy resulted in resolution of the infection [lo]. Thus, synovectomy may ultimately be necessary to eradicate persistent or progressive infection if one or more courses of antifungal chemotherapy fail. The use of intra-articular amphotericin B in the treatment of fungal arthritis is not uncommon [29,36]. Indeed, one patient with coccidioidal synovitis has been successfully treated with intra-articular therapy alone [37]. Although the clinical experience with Candida arthritis is limited, intra-articular therapy employed in two of the reported cases was considered useful (Cases 3 and 5). It has been proposed, although not documented, that local instillation will avoid the immediate side effects, and the hematopoietic and renal toxicity of amphotericin B [33]. Parenteral amphotericin B was employed in all antemortern cases and in one postmortem case. Total dose and duration of therapy were variable. In two cases (Case 3 and 8) repeat joint cultures were negative after approximately 150 to 200 mg of therapy given over 21 and 11 days, respectively. In one instance (Case 4), however, postmortem cultures of joint fluid were still positive despite the administration of 60 mg of amphotericin B prior to death. 5fluorocytosine (5 FC) was employed in only one instance (Case 7) and was given for a total of 19 months. 5-FC has been effective in the treatment of some Candida infections including osteomyelitis [38-421, but adequacy of joint penetration has not been demonstrated to our knowledge. C. tropicalis Arthrltis and Bursitis as a Manifestation of Disseminated Candidiasis. In our patient candidemia developed in the typical clinical setting of an underlying disease, broad-spectrum antibiotic therapy, and indwelling intravenous and urinary catheters

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[ 11,15,19-21,43-571. Candidemia was transient [ 181, clinically benign and spontaneously resolved upon removal of the intravenous catheter. The appearance of candiduria after transient candidemia is not unusual [ 16,18,58] and does not appear to indicate necessarily systemic disease with renal infection. Candiduria in our patient cleared promptly with removal of the indwelling urinary catheter. For these reasons, antifungal therapy was withheld. The present case is similar to the other reported cases of Candida arthritis in regard to the late development of overt joint infection two to seven weeks after the first positive Candida culture and involvement of a large joint (shoulder). Tenderness and swelling, similar to that in other reported cases of Candida arthritis, were the only manifestations of joint infection. As noted previously, redness and warmth are uncommon in contrast to the usual septic appearance of joints infected by the other systemic mycoses [26-281. Furthermore, fever and leukocytosis were not present in our case. Since the infection by Candida is primarily synovial, early roentgenograms of the joints were unremarkable except for soft tissue swelling with effusion. Synovial fluid findings in previous reports have not been well characterized. The aspirate from our patient’s shoulder was compatible with a septic arthritis with purulent fluid, marked polymorphonuclear leukocytosis, increased protein and, on one occasion, a decreased glucose level. The bursal fluid findings were in general comparable to synovial changes seen with joint infections caused by other fungi [27,28]. Although repeated cultures of joint and bursal fluid were positive, organisms were consistently not seen on gram stain in our patient. The serial changes in serologic tests for Candida in our case correlated well with the clinical course of the infection (Table I). In retrospect, despite the negative immunodiffusion test, the presence of candiduria and a positive latex agglutination titer (1:32), (17 days after clearing of fungemia and seven days prior to the onset of arthritis) was the first sign suggesting deep tissue invasion by Candida [ 231. At the time the joint and bursal infections were clinically apparent and candiduria reappeared, the immunodiffusion test [17,59-611 was positive and the latex agglutination titer had increased fourfold [23]. After five weeks of treatment (multiple aspirations and 511 mg of amphotericin B) and complete resolution of the arthritis, the decline in positivity of both serologic tests suggested appropriate therapy [23,62-661. Although the immunodiffusion test was negative and the latex agglutination titer had decreased to 1:16 one month after completion of amphotericin B therapy, cultures of bursal fluid were still positive for C. tropicalis, pre-

CANDIDA

ARTHRITIS-MURRAY

ET AL.

ly and antigenically) of the bursal infection. Previous experience with fungal infections of bursae has been limited. To our knowledge, except for the present case, mycotic bursal involvement has only been reported in three patients with systemic sporotrichosis [67-691. The olecranon bursa was affected in all three cases and was associated with adjacent articular erosions. Popliteal and synovial cysts have also been involved with systemic S. schenckii infection [67,70]. Two of the three patients with sporotrichial bursa infection had a relapse after ther-

other fungi with 0.75 to 3 g of amphotericin B [2628,331. Since our patient tolerated and responded to parenteral amphotericin B, intra-articular therapy was not used. However, intra-articular amphotericin B as the only mode of therapy may be effective in those cases of focal joint involvement caused by direct inoculation [lo]. In addition to appropriate antimicrobial therapy, adequate drainage, as in bacterial arthritis [72], is required for successful treatment of fungal joint infections. As demonstrated in the present case, the initial procedure of choice is frequent needle aspira-

apy consisting of aspiration, potassium iodide, and parenteral and intrabursal amphotericin B. In one instance, however, treatment with intravenous and prolonged (15 weeks) intrabursal amphotericin B

tion. If aspiration is inadequate or technically difficult, surgical drainage may be necessary. Repeated arthrocenteses not only relieve joint symptoms but also may permit evaluation of the response to therapy

(210 mg and 180 mg, respectively) cured the bursal infection [69]. Bursectomy was not performed in these patients. Although systemic findings were not associated with our patient’s fungal bursitis, bursectomy was chosen because of persistent infection, i.e., repeated fluid reaccumulation, despite the parenteral administration of amphotericin B and multiple needle aspirations. Fungicidal levels of amphotericin B have been documented in the synovial fluid of a patient receiving parenteral therapy for Candida ar-

]721.

sumably

reflecting

the focal

nature

(both anatomical-

thritis [9] ; bursal penetration, however, has not been reported previously. The bursal fluid levels achieved in our patient were sufficient to suppress but not to eradicate the infection, and bursectomy promptly eradicated the residual infection. Thus, bursectomy, a relatively simple procedure which may be per-

CONCLUSION The case we report illustrates several important points. In the absence of prior joint surgery or needle aspiration, a positive synovial fluid culture for Candida should alert the physician to the presence of disseminated candidiasis. Although C. albicans is the most commonly

isolated

Candida

species

from clini-

cal material [5,14,15,19,21,47], the pathogenicity of the less frequently observed C. tropicalis has been well-established [ 19,47,73]. Moreover, neither by clinical course nor postmortem findings can infection with C. tropicalis be differentiated from that due to C. albicans [47]. Clinically benign, transient candidemia is usually

formed under local anesthesia, can be an effective alternative to prolonged local instillation of amphotericin B. Although Lindstrom and Lindholm [8] have suggested that short, apparently effective courses of antifungal therapy may not completely eradicate in-

related to an intravenous catheter [5,16,18,21,52], and in most patients may be managed simply by elimination of iatrogenic predisposing factors

fection, the other patients with Candida arthritis including our own were successfully treated with joint aspirations and parenteral amphotericin 6. Based on limited experience, joint signs and symptoms resolve

note, however, that transient candidemia may be complicated by late manifestations such as arthritis and bursitis, meningitis [75], endocarditis [ 151 and

within one to three weeks after the initiation of amphotericin B therapy. In our patient initial resolution

[ 18,57,74]. If deep tissue infection does not ensue, fungemia should clear promptly in from 48 to 72 hours without specific therapy [ 181. One should

endophthalmitis [76-781. Thus, prolonged observation of all patients with untreated candidemia is nec-

of arthritis appeared to be more closely related to multiple joint aspirations than to the small dose of amphotericin B (91 mg) received at the time he be-

essary for the recognition of disseminated infection. Despite the increasing incidence of systemic candidiasis, joint and periarticular infections remain uncommon. However, recognition of the potential for

came asymptomatic (15 days). Recommendations for the amount and duration of amphotericin B therapy are difficult in light of such limited experience. Although a small dose regimen of amphotericin B has recently been advocated for both focal and disseminated candidiasis [ 711, a total dose of 1 g was selected in our patient because of previous successful experience in treating joint infections caused by

joint and bursal involvement by Candida species is important since combined medical and surgical therapy appear to be effective in eradicating these localized foci of infection and in preventing significant functional impairment. We anticipate that further clinical experience with Candida joint infections will occur and thus appropriate management will be defined.

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REFERENCES 1.

2. 3. 4.

5. 6.

7. 8. 9. 10.

11.

12. 13.

14. 15.

16.

17.

18. 19. 20. 21. 22.

23.

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