690 Annals ofthe Rheumatic Diseases 1992; 51: 690-697

REVIEW Ann Rheum Dis: first published as 10.1136/ard.51.5.690 on 1 May 1992. Downloaded from Fungal arthritis

Marta L Cuellar, Luis H Silveira, Luis R Espinoza

There are 50 000-200 000 species of fungi, but Candida infections, both focal and generalised, only about 100 of these cause infectious diseases have been increasing rapidly in recent years. (mycoses) in humans.' Fungal infections are not These organisms become pathogens when there readily recognised, do not advertise their is an interruption of the normal defence mech- presence in a characteristic fashion, and the anisms of the host by naturally occurring or causative organism is generally not easy to iatrogenic factors.4 Candida species are the most demonstrate in tissue.2 Musculoskeletal infection common fungi associated with opportunistic by fungi was once rare, but its incidence has infections.3 increased in the past few years. Although Septic arthritis caused by candida species is healthy subjects may host fungal diseases, uncommon and its true incidence is unknown.5 various predisposing factors that depress the It can be divided into two clinical syndromes. immune system have been implicated in most The first is an isolated monarthritis caused by patients developing fungal infections or fungal the direct intra-articular inoculation of fungi arthritis, or both.3 Alcoholism, cirrhosis, that inhabit the skin. The second is the develop- diabetes, , cancer, prematurity, ment of a monarthritis or pauciarthritis as a treatment with corticosteroids, cytotoxic drugs, complication of haematogenously disseminated prolonged use of intravenous antibiotics, intra- . venous drug abuse, granulocytopenia, and The first manner of introducing the organism marrow hyperplasia are among the predisposing to the joint is by injection. The common factors. denominator is repeated aspiration, usually with Fungal arthritis usually follows a chronic injection of corticosteroids, of a previously indolent course of several months that leads to damaged knee joint.5 6 This type of arthritis is delays in diagnosis and to inappropriate treat- extremely rare and only eight cases have been ment such as intra-articular and systemic described. The diagnosis is by means of a

steroids. Consequently, it is important to know positive culture or biopsy sample. Synovial fluid http://ard.bmj.com/ the epidemiology and extra-articular manifesta- white blood counts range from 9 to 43 x 109/l tions of fungal disease to be aware of the with a predominance of polymorphonuclear possibility of musculoskeletal infection and to leucocytes. Uncommon species of candida have establish an appropriate treatment. The table been isolated from joints: C guilliermondi twice, gives the main characteristics of fungal arthritis. C parapsilosis four times, and unspecified candida species twice. The onset of this type of the course arthritis is insidious and indolent, on September 25, 2021 by guest. Protected copyright. Candidiasis chronic, and relatively benign. The patients are Candida organisms are normal commensals of afebrile and have normal blood cell counts. humans and are commonly found on diseased Candida may also enter the joint by con- skin, the gastrointestinal tract, expectorated tamination during surgery.7 ' Eleven episodes sputum, the female genital tract, and in urine of of fungal arthritis by candida complicating patients with indwelling Foley catheters.4 Most knee, hip, and shoulder reconstructive arthro- candida infections are of endogenous origin, but plasty have been reported in nine patients. All human to human or animal to human trans- patients had only pain with a limited range of mission is possible, which is a unique property motion and swelling, and there was no evidence among the mycoses affecting humans. There is of systemic disease. The onset of symptoms also evidence that candida infection can be occurred as late as two years after the initial acquired from the hospital environment. surgery with an average interval of 14 months. Department of Medicine, Section ofRheumatology, All peripheral white blood cell counts reported Louisiana State were normal. The white blood cell counts in University Medical Fungal arthritis: demographic and clinical charactenrstics joint fluid ranged from 4 to 15 x 109/1. The Center, New Orleans, LA, USA Worldwide distribution in most instances cultures yielded C albicans in two patients, C Affects neonates, old, or immunocompromised hosts tropicalis in three, C parapsilosis in three, and C M L Cuellar Prevalence is variable, ranging from 0 4 to 20% of disseminated L H Silveira glabrata in one. Treatment requires the removal L R Espinoza More common in men, and may be an occupational hazard of the components with debridement. Joint disease occurs by contiguous or haematogenous spread prosthetic Correspondence to: common cause of Dr Luis R Espinoza, Usually monarthritis or oligoarthritis, with the knee joint most Although infection is the most LSU Medical Center, commonly affected biological failure of joint arthroplasty, fungal Department of Medicine, Systemic disease often absent rare. Section of Rheumatology, Pulmonary and cutaneous disease are the extra-articular infection in this setting remains extremely 1542 Tulane Ave, manifestations most often present Arthritis complicating haematogenously dis- Diagnosis is based on direct visualisation of the organism or New Orleans, synovial fluid and membrane cultures, or both seminated candidiasis occurs in patients with LA 70112, USA. Combined medical (antimycotic) and surgical treatment often factors.5 Patients are sick and the Accepted for publication necessary predisposing 12 December 1991 usually occurs in normal joints. Fungal arthritis 691

Neonates are the first group of patients in Microscopically, thesynoviumshowsa thickened whom haematogenously originated candida membrane with non-specific mononuclear cell arthritis can occur.5 9 The illness is a hospital infiltration. Isolated synovial fluid lymphocytes Ann Rheum Dis: first published as 10.1136/ard.51.5.690 on 1 May 1992. Downloaded from acquired disease of sick children with underly- show greater stimulation to candida antigens ing diseases such as the respiratory distress syn- than peripheral blood lymphocytes, and CD4 drome, and gastrointestinal defects. C albicans, positive T lymphocyte clones with specificity which is responsible for more than 80% of the for candida antigens have been characterised reported cases, and C tropicalis are the species and further propagated in vitro.'8 responsible for this disease. Arthritis is usually The use of amphotericin B, either alone or present with accompanying metaphysial osteo- in combination with joint drainage, is associated myelitis. Bone infection might originate from with clinical and mycological cure in 90% of the infected synovium or via the metaphysial patients.9 Amphotericin B is used intravenously vessels. Polyarthritis occurs in most patients at dosages of 0-3-0-5 mg/kg/day.5 A total dose and the knee is the joint most often affected. of 1-3 g during a period of six to ten weeks is Physical examination shows a febrile child with given, although cures have been obtained with swollen and tender joints. Radiographs show lower doses. Amphotericin B can also be used in joint effusion, dislocation of the joint in some combination with 5-fluorocytosine, which instances, irregularities and punched out lesions seems to have a synergistic interaction with the at the metaphysis, and, less commonly, perio- former. The latter should never be used alone steal reactions. because of the emergence of resistance. 5- Diagnosis is achieved by isolating the organism Fluorocytosine is available only for treatment by culture of the aspirated joint fluid or bone. by mouth and it is given at doses of 150 Treatment against candida is effective and mg/kg/day divided into four doses. Intra- reduced joint function occurs in only a small articular amphotericin B is a useful adjunctive percentage of cases. treatment in infections restricted to the joint Arthritis originated by haematogenous dis- capsule and not disseminated, as in pyarthrosis semination beyond the neonatal period is usually following direct inoculation of candida,6 9 as a complication of disseminated candidiasis in well as in haematogenously spread infections patients with serious underlying disorders or that have not responded well to systemic treat- intravenous drug abusers.5 '° " C albicans is ment.9 Other treatment options include keto- again the causative organism in about 80% of conazole and fluconazole.5 6 19 cases, and C tropicalis is responsible for most of Patients with HIV infection deserve special the remaining cases. Isolated cases of knee consideration because, in spite of the profound arthritis caused by C parapsilosis,'2 C kruset,'3 state of immunodeficiency present, only isolated and C zeylanoides'4 have been reported. cases of septic arthritis have been reported.20 Two distinct clinical presentations can be Among these cases, candida arthritis is rare.

observed: (a) acute onset of constitutional and Arthritis and osteomyelitis have been reported http://ard.bmj.com/ synovial symptoms (about two thirds ofpatients), in the sternoclavicular joint,2' and in the costo- with the aetiological diagnosis established with- sternal and hip joints22 of HIV infected intra- in the first week, and (b) indolent presentation, venous drug abusers. The reported patients had with mild systemic and arthritic symptoms, and clinical features similar to those previously delay in the diagnosis for months or years, described in skeletal infections of intravenous including some cases diagnosed at necropsy. drug abusers not infected with HIV. Cases of

The knee is affected in most cases, though any candida arthritis in other risk groups for HIV on September 25, 2021 by guest. Protected copyright. other.peripheral joint or the spine can also be infection, such as homosexuals, have not yet affected. Most cases are monarticular, but been reported. Consequently, the presence of polyarticular presentation is common (about candida arthritis in HIV infected patients seems 37%). Osteomyelitis is often present (70-85%). '5 to be related to drug abuse more than to HIV The organisms spread to the bone from the infection itself. affected joint, which is different from other Experimentally induced candida arthritis in fungal diseases such as , in rabbits23 and rats24 has some similarities to which osteomyelitis usually precedes arthritis. candida arthritis in humans. Infection of the olecranon'6 and popliteal'7 bursae by C tropicalis has also been reported. Synovial fluid shows polymorphonuclear Coccidioidosis leucocytosis between 7-5 and 151x109/l.9 immitis is a dimorphic that Candida blastospores are rarely seen in Gram inhabits soils of desert zones such as the stains. The diagnosis is achieved by culture of southwestern United States, northern Mexico, synovial fluid or synovial biopsy specimens. and parts of Central and South America.25 26 Synovial effusions and changes consistent with The infection begins after inhalation of the osteomyelitis, without osteopenia, are the usual infectious units, arthrospores. This primary radiographic abnormalities seen. Scanning with pulmonary infection is asymptomatic in 60% of gallium and technetium should be performed cases and in only 1% does dissemination occur when there is pain in the musculoskeletal with extension to meninges, skin, lymph nodes, system in patients predisposed to candida infec- subcutaneous tissue, bones, and joints.27 28 In tions.5 Positive scans will point to the areas addition to the known predisposing factors, requiring a biopsy sample to be taken. The certain ethnic groups such as Filipino and macroscopic appearance of the synovium is of a African Americans appear to be at greater boggy, thickened membrane that resembles a typical 'pannus' in more advanced cases.9 Serological findings are of help in diagnosis 692 Cuellar, Silveira, Espinoza

and prognosis. Serum, pleural, peritoneal, and usually affecting the hands, may also be present. joint fluids can be tested to detect antibodies. may be the only symptom in approxi- Spherule derived antigens (spherulin) are used mately 90% of patients. The interval between Ann Rheum Dis: first published as 10.1136/ard.51.5.690 on 1 May 1992. Downloaded from for complement fixation tests and have great the onset of symptoms and diagnosis ranges sensitivity, but can cross react with other fungi. from four weeks to many years, with a mean of IgM antibodies are of value in acute disease, 4 5 years. Most patients are men, not white, and reaching maximum titres at the third week of with a mean age of 36 years.30 39 4 Synovial illness, and may be the confirmatory test for an fluid is turbid with decreased viscosity. Leuco- early acute coccidioidal infection.33 IgG anti- cyte counts are moderately high and lympho- bodies develop later, but are more persistent cytes predominate. High protein levels and than IgM. There is a correlation between normal blood/synovial glucose ratios are found. complement fixation titres in serum samples Fungal cultures may be negative. Histopatho- and the severity of coccidioidal disease; titres logical findings include villonodular synovitis or greater than 1/16 may indicate disseminated typical pannus formation with non-caseating disease, and titres greater than 1/128 are associ- , and spherules containing coc- ated with bone and joint disease. Negative cidioidal endospores. serological findings with positive histopatho- Radiological changes may include synovial logical findings are rare. Coccidioidal tests are effusion, osteopenia, joint space narrowing, highly sensitive, and in a severely immuno- bony destruction, and in some instances anky- compromised host the potential for serological losis.37 41-43 Technetium-99m and gallium-67 failure is only between 20 and 25%.34 35 A bone scans can detect early osseous and soft positive complement fixation result at any titre tissue lesions with higher sensitivity than plain in synovial fluid supports a diagnosis of coc- films.40 cidioidal arthritis. A positive result in a skin test Amphotericin B (total dosage 1-10 g) remains implies a delayed cutaneous hypersensitivity the most effective treatment for severe infection reaction (with current or previous infection) and with skeletal disease.40 In limited cases with the results are apparent within three days to monarticular disease local amphotericin B has three weeks after the onset of symptoms. A been used.45 Ketoconazole is the drug of second negative skin test does not rule out coccidio- choice.46 47 Open drainage, synovectomy, idomycosis, and it may be positive in up to 80% arthrodesis, and, if all else fails, amputation, of cases of coccidioidal arthritis. should be considered.39 4 Skeletal manifestations associated with coc- cidioidomycosis include a chronic granulo- matous process in bones, joints, and periarticular structures, and a benign and acute articular Blastomycosis, Gilchrist's disease, or North process known as 'valley fever' or 'desert American blastomycosis, is caused by Blasto-

rheumatism'.36 The latter is a hypersensitivity myces dermatitidis, a dimorphic fungus often http://ard.bmj.com/ syndrome that may occur during primary infec- found in the Mississippi and Ohio river valleys, tion in 20% of cases (eight to 15 days after the and in the southeastern United States. Infection onset); accompanying non-specific symptoms also occurs in Canada, Central and South such as fever, general aches, sore throat, and America, and Africa. mild cough, in addition to peripheral eosino- Acute infection begins in the lungs, and in philia, erythema nodosum, and erythema most cases is asymptomatic and recognisable

multiforme, arthralgias, arthritis, and conjunc- only by skin tests. Other cases have symptoms on September 25, 2021 by guest. Protected copyright. tivitis may be seen. Acute arthritis develops in a such as a productive cough with mucoid sputum, third of patients. It is polyarticular, usually pleural pain, and benign pulmonary lesions that migratory, without effusions, and the joints are heal spontaneously. Patients may also have joint tender to pressure and painful on motion. It and muscle pain, pulmonary densities on radio- may affect any joint, but most often the ankles graphs, and budding in the sputum. and knees, and there is a remission after two to When the primary lesion becomes progressive, four weeks without residual damage.37 38 it is clinically similar to tuberculosis, histo- Musculoskeletal manifestations can also be plasmosis, or coccidioidomycosis. Cutaneous, seen during the disseminated form in 10-50% of bone, and joint disease are the main extra- cases.30 Coccidioidal arthritis may be suspected pulmonary manifestations, but widespread when a patient has chronic progressive mon- or infection may extend to any organ.48 49 Cutan- polyarthritis and a history of being in an eous lesions are seen in 80% of extrapulmonary endemic zone. A history of pulmonary disease disease; skeletal infection appears in up to 60% or abnormal chest radiographs, or both, may of cases.5>52 The spine is often affected; the not be apparent. Arthritis may begin in the infection begins in the vertebral body and can early stages as intermittent, painful swelling of extend to the disc; paravertebral or psoas one joint and, later in the course, it may present abscesses may form. Bone disease can be with large effusions, thickened synovium, asymptomatic, or begin acutely with pain, nodular lesions in periarticular skin, and swell- redness, and swelling.5' It may appear with ing with draining sinuses. Joints may be affected localised (dactylitis) or diffuse osteomyelitis or primarily by haematogenous spread or, in most periostitis, or both, and the epiphysial line is cases, by direct extension from adjacent areas of commonly affected.52 Blastomycotic arthritis, bony disease. Weight bearing joints are often which is usually monarticular (the knee is the involved and knees are affected in 50-70% of most often affected, followed by the ankle, cases, but any joint may be affected. Osteo- elbow, wrist, and hand), may occur by spread of myelitis of spine is common, and tenosynovitis, adjacent osteomyelitis or by haematogenous Fungal arthritis 693

dissemination, and without treatment, poly- Arthritis, tenosynovitis, and osteomyelitis are articular extension may develop.53 It may have rare complications of disseminated histo- an abrupt onset (only candida arthritis may have plasmosis. Joint disease is characterised by Ann Rheum Dis: first published as 10.1136/ard.51.5.690 on 1 May 1992. Downloaded from this presentation), with significant pain and monarthritis, with the knees most often affected, swelling, constitutional symptoms and signs and usually associated with underlying im- (fever, weight loss), and synovial fluid with munosuppression, including one reported case pyogenic-like appearance. Patients often have associated with AIDS.'6 Flexor tendon evidence of pulmonary blastomycosis, and, in a sheaths of the wrist have been affected, and high percentage, cutaneous abscesses, ulcer- carpal tunnel syndrome can be the initial ations, or purulent draining sinus tracts are manifestation.67 Radiological changes include found concomitantly. Two radiological patterns cortical subperiosteal thickening, widening of of bone disease may be seen, one focal without a the medullary canal, osteopenia, and epiphysial periosteal reaction in short bones but with a bone destruction.68 Multiple punched out lesions periosteal reaction in long bones, and one are common in H duboisii infection; destructive diffuse, destructive, and expanding form.54 joint lesions, erosions, sclerosis, and joint space The diagnosis of blastomycotic joint infection narrowing can occur.69 70 Diagnosis is based on requires one or more of direct microscopic the detection of the organism in tissues or evidence of the fungus, culture positivity in . Detection of the organism is possible synovial fluid, or culture positive material at in only 70% of cases. Complement fixation any other site. Organisms are readily identified antibodies to histoplasmin and histoplasma in joint fluid.55 yeast antigens become positive at two to three Treatment with amphotericin B results in a weeks and are an important diagnostic test. It resolution of osteomyelitis and arthritis. may produce false positive results in titres of 2-Hydroxystilbamidine and ketoconazole have less than 1/16 in about five to 15% of serum been found to be effective.5 13 56 As loculations samples from patients in endemic areas.7' Com- of purulent fluid are often present, incision and plement fixation titres of 1/32 or greater have drainage, combined with chemotherapy, are diagnostic significance (most instances of false reported to be effective. positives have been reported with radio- immunoassays). The histoplasmin skin test becomes positive two weeks after infection, Histoplasmosis is a deep mycosis caused by does not discriminate between past or present (, infection, is positive only in 50% of cases of found rarely in North or South America, is disseminated disease, and may stimulate anti- caused by H capsulatum var duboissi and has a body formation. For these reasons, the skin test different clinical spectrum affecting skin and is used primarily for epidemiological studies. In bones), a facultative intracellular parasite.57 It is patients with disseminated disease with the

a dimorphic fungus that grows in soil in the musculoskeletal system affected, amphotericin http://ard.bmj.com/ mycelial form and produces . This world- B, with or without surgery, is the treatment of wide disease, found most commonly in temper- choice. Ketoconazole may also be used with ate climates, is heavily endemic in the Ohio and some success. Mississippi river valleys, and is rare in Europe and Australia. Inhaled spores attack cells of the reticuloendothelial system and spread to the

regional lymph nodes, with granulomatous Sporotrichosis is caused by , on September 25, 2021 by guest. Protected copyright. reaction, necrosis, and then calcification. Most a dimorphic fungus with low virulence that is primary infections undergo benign self limited saprophytic in nature, and was first reported by dissemination and are asymptomatic, but heavy Schenck in 1898. De Beurmann et al in 1909 infections and infections in infants and young described gummatous intraosseous lesions.72 It children may produce an acute influenza-like is almost always a lymphocutaneous disease; syndrome during the primary acute stage. The infections usually occur after cutaneous inocu- host may be affected by reinfection, in which lation during outdoor work such as farming. instance acute histoplasmosis or chronic pul- Less often, infection may occur by the inhalation monary and disseminated disease may occur. of spores that produce a chronic granulomatous Disseminated disease occurs in less than 0-1% pneumonitis, especially over an underlying of infections; one third occurs in children and structural abnormality of the lungs.73 Dis- other cases in immunocompromised hosts.58 5 semination is uncommon, but when it occurs, Bones and joints are rarely affected. any organ system including the joints can be The most common rheumatic manifestation affected.7F78 occurs during primary infection in the form of a Manifestations of sporotrichosis include migratery polyarthritic syndrome that may or lymphangitic and fixed cutaneous lesions in may not coexist with other hypersensitivity 75-80% of cases (cutaneous ulcers and nodules reactions such as erythema nodosum or erythema along the course of the lymphatics). Muco- multiforme, or both, pleuritis, and peri- cutaneous, extracutaneous, or disseminated and carditis.60 61 This syndrome is similar to that primary pulmonary disease complete the extent seen in primary coccidioidomycosis. The of clinical involvement.784 Arthritis is usually articular disease is self limited and disappears chronic, mon- or polyarticular, affecting weight without sequelae. The prevalence of erythema bearing joints (the knee most often, but also the nodosum or erythema multiforme associated wrist and small joints of the hands and feet). with primary histoplasmosis is variable, ranging Diagnosis is usually delayed (three to 96 months from 0 to 34%.62 63 from onset of symptoms).8" 85 Laboratory data 694 Cuellar, Silveira, Espinoza

are non-specific; an increased erythrocyte sedi- 19x 10'/1, with a predominance of mononuclear mentation rate is the most common abnormality cells. Radiographic findings consist of synovial found. Synovial fluid may be serosanguinolent effusion and lytic lesions indicative of osteo- Ann Rheum Dis: first published as 10.1136/ard.51.5.690 on 1 May 1992. Downloaded from and inflamed, with low glucose levels. myelitis in contiguous bone.' Histopathological Diagnosis requires synovial fluid or tissue findings include both acute and chronic cultures and is often repeated and prolonged.85 synovitis.60 88 Cryptococci can be shown with Skin tests are not useful, but agglutination and special stains of synovial tissue.60 Diagnosis is immunodiffusion (precipitation) procedures can made by isolation of the organism from biopsy be used in the diagnosis.86 Precipitins can be material or synovial fluid. shown in 70-85% of infected subjects, and latex Combined medical and surgical treatment agglutination in a higher percentage. Higher offers the best results.60 88 The combination of agglutinin titres are seen in patients with intravenous amphotericin B and 5-fluorocytosine articular disease, and decrease with treatment. by mouth, which have shown in vitro synergy Intravenous amphotericin B at doses of more against many cryptococcal strains and an in vivo than 1 g in one course of approximately 12 efficacy in the murine model, provides effective weeks has been shown to be effective in medical treatment.60 sporotrical arthritis, although sometimes more than one course is necessary to eradicate the infection.80 Intra-articular amphotericin B and synovectomy are also effective.87 , a dimorphic fungus, is ubiquitous throughout the world and may occasionally cause human infection, most commonly in the immunosuppressed host.88 It is a saprophyte in Cryptococcus neofonnans is a dimorphic en- residual cavities or mucus plugs, usually in capsulated yeast-like fungus found widely in patients with chronic obstructive pulmonary nature and in most countries of the world in disease. Aspergillus fumigatus is the causative association with pigeon droppings.' 88 Crypto- organism in almost all cases, followed by A. coccosis may be acute, subacute, or chronic, flavus. and presents as a primary pulmonary infection. The musculoskeletal system is rarely affected Haematogenous dissemination causes multiple by aspergillus. Osteomyelitis is the most extrapulmonary sites, including bone and joints, common type of disease. It has been reported to be affected. Dissemination can occur in mainly in vertebrae, disc spaces, and ribs.9294 immunocompromised and competent hosts. The mechanism of infection in children is Cryptococcosis is the next most common fungal contiguous spread from a pulmonary infection pathogen following systemic candidiasis and or from skin, whereas in adults it is haemato- aspergillosis in immunosuppression associated genous dissemination.92 deep mycoses. Aspergillus arthritis is rare, with only five http://ard.bmj.com/ The most common musculoskeletal manifes- cases reported.88 Four of the patients had a tation is osteomyelitis, which may occur in predisposing factor. Nearly all the patients had 5-10% of patients.89 It follows a subacute or osteomyelitis of the adjacent bone. The most chronic course with symptoms occurring several common symptoms were pain, swelling, and weeks to months before diagnosis. All major tenderness of the affected joint, and fever, bones can be affected, and the osseous foci are chills, or malaise. Physical examination showed The usually single but may be multiple.88 9 diffuse tenderness, limitation of motion, and on September 25, 2021 by guest. Protected copyright. patient experiences pain or swelling, or both, in synovial effusions. the affected area. Radiographic features are not Mild to moderate leucocytosis and an increased specific, but osteolytic lesions predominate.60 erythrocyte sedimentation rate are found.88 The The organism can be identified by a biopsy. diagnosis is established by isolation of the Arthritis is a rare manifestation of cryptococ- fungus from the affected tissue or from the cosis, and is usually secondary to extension of synovial fluid. The organism can be seen in adjacent osteomyelitis.88 9' A history of contact histopathological sections of bone and other with pigeons is absent in most patients and tissues. Radiographic findings include diffuse there is no apparent racial or occupational soft tissue swelling and typical changes of association.88 Approximately half of the patients osteomyelitis. Synovial fluid can be clear, have a predisposing factor. The most common turbid, or serosanguineous. presentation is monarthritis, though oligo- Treatment includes a combination of surgical arthritis and polyarthritis can occur. The knee debridement and drainage, and intravenous is the joint most commonly affected, though the amphotericin B."' Successful treatment with elbow, sternoclavicular, sacroiliac, and ankle ketoconazole,95 and itraconazole96 has also been joints can also be affected. Systemic symptoms reported. such as malaise, weight loss, or low grade fever may be found. Physical examination shows variable effusion with occasional synovial thick- ening. The course is usually subacute or chronic, Miscellaneous with a diagnostic interval ranging from two Mycetoma, or 'madura foot', is a chronic, weeks to eight months. There is often no granulomatous, and suppurative infection that evidence of infection in another organ system. follows the integumentary introduction of the Laboratory findings are non-specific. Synovial infectious organism and progresses locally by fluid is described as turbid, purulent, and destruction of contiguous tissue including viscous. The leucocyte count ranges from 0-2 to muscle, fascia, tendon, bone, and joints.97 It Fungal arthritis 695

may be caused by a fungus (maduromycosis or was reported.'06 The prosthesis was removed ), or by actinomyces (actinomyce- and a good response to intra-articular ampho- Ann Rheum Dis: first published as 10.1136/ard.51.5.690 on 1 May 1992. Downloaded from toma). There are multiple fungi that may cause tericin B was observed. eumycetoma, and the prevalent organism varies according to the geographical location. The infection begins with the traumatic introduction of the organism, usually in the legs (70% 1 Kobayashi G S. Fungi. In: Davis B D, Dulbecco R, Eisen affecting the foot) or hands, though other sites H N, Ginsberg H S, eds. . Philadelphia: Lippincott, 1990: 737-65. can be affected. The infected foot evolves into a 2 Ehrlich G E. Fungal arthritis [editorial]. JAMA 1978; 240: swollen, nodular, discoloured, and deformed 563. 3 Espinoza L R, Bergen-Losee L L. Basic pathogenetic extremity with multiple granule draining sinuses. considerations. In: Espinoza L R, Goldenberg D L, Fascia and bone are affected with bone destruc- Amett F C, Alarc6n G S, eds. Infections in the rheumatic diseases. A comprehensive review of microbial relations to tion and evidence of remodelling, and by rheumatic disorders. Orlando: Grune and Stratton, 1988: contiguous spread joints become affected. 125-9. 4 Edwards J E Jr. Candida species. In: Mandell G L, Douglas Secondary bacterial infection with osteomyelitis R G Jr, Bennett J E, eds. Principles and practice of may occur. Diagnosis is by culture of the infectious diseases. New York: Churchill Livingstone, 1990: 1943-58. granules. Radiological findings are non- 5 Karsh J. Candida arthritis. In: Espinoza L R, Goldenberg specific.98 The treatment of choice is complete D L, Arnett F C, Alarcon G S, eds. Infections in the rheumatic diseases. A comprehensive review of microbial surgical excision of the affected tissue. Chemo- relations to rheumatic disorders. Orlando: Grune and therapy with amphotericin B, griseofulvin, Stratton, 1988: 189-97. 6 Katzenstein D. Isolated candida arthritis: report of a case dapsone, ketoconazole, and miconazole are and definition of a distinct clinical syndrome. Arthritis reported to be effective.9'°' A preliminary Rheum 1985; 28: 1421-4. 7 Lambertus M, Thordarson D, Goetz M B. Fungal prosthetic course of broad spectrum antibiotics is recom- arthritis: presentation of two cases and review of the mended for actinomycetoma. literature. Rev Infect Dis 1988; 10: 103843. 8 Levine M, Rehm S J, Wilde A H. Infection with Candida Petriellidium boydii (Allescheria boydii) is a albicans of a total knee arthroplasty. Case report and saprophyte isolated from soil, polluted water, review of the literature. Clin Orthop Rel Res 1988; 226: 235-9. sewage, and other outdoor sites.88 The organism 9 Bayer A S, Guze L B. Fungal arthritis. I. Candida arthritis: may cause a broad spectrum of clinical mani- diagnostic and prognostic implications and therapeutic considerations. Semin Arthritis Rheum 1978; 8: 142-50. festations, but mycetoma (especially in the 10 Dupont B, Drohuet E. Cutaneous, ocular, and osteoarticular USA) accounts for about 99% of all infections. candidiasis in heroin addicts: new clinical and therapeutic aspects in 38 patients. J Infect Dis 1985; 152: 577-91. Sixteen cases of P boydii arthritis have been 11 Podzamczer D. Nolla J M, Juanola X, Gudiol F. Candidal reported, including those caused byScedosporium osteomyelitis and septic arthritis in heroin abusers [letter]. J Rheuonatol 1989; 16: 256-7. apiospermum (asexual expression) of P boydii 12 Smith S M, Lee E Y, Cobbs C J, Eng R H K. Unusual and Scedosporium inflatum.102 103 The infection features of arthritis caused by Candida parapsilosis. Arch Pathol Lab Med 1987; 111: 71-3. is more common in men, in rural areas, and in 13 Nguyen V, Penn R L. infectious arthritis. subjects with a history of previous trauma. Joint A rare complication of neutropenia. Am J Med 1987; 83: 963-5. pain, swelling, and decreased range of motion 14 Bisbe J, Vilardell J, Valls M, Moreno A, Brancos M, http://ard.bmj.com/ are usually present. Systemic symptoms are Andreu J. Transient and candida arthritis due to Candida zeylanoides. Eur J Clin Microbiol 1987; 6: absent. Monarthritis affecting the knee is the 668-9. most common presentation. Oligoarthritis may 15 Resnick D, Niwayama G. Osteomyelitis, septic arthritis, and soft tissue infection: the organisms. In: Resnick D, be seen. Arthritis develops within 10 days to Niwayama G, eds. Diagnosis of bone and joint disorders. one year after the trauma, suggesting that the Philadelphia: Saunders, 1988: 2647-754. 16 Murray H W, Fialk M A, Roberts R B. Candida arthritis. A articular infection occurs by extension from manifestation of disseminated candidiasis. Am J Med

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