Candida Arthritis: Analysis of 112 Pediatric and Adult Cases

Background. Candida arthritis is a debilitating form of deeply invasive candidiasis. However, its epidemiology, clinical manifestations, management, and outcome are not well understood. Methods. Cases of Candida arthritis were reviewed from 1967 through 2014. Variables included Candida spp in joint and/or adjacent bone, underlying conditions, clinical manifestations, inflammatory biomarkers, diagnostic imaging, management, and outcome. Results. Among 112 evaluable cases, 62% were males and 36% were pediatric. Median age was 40 years (range, <1–84 years). Most patients (65%) were not pharmacologically immunosuppressed. Polyarticular infection (≥3 joints) occurred in 31% of cases. Clinical manifestations included pain (82%), edema (71%), limited function (39%), and erythema (22%) with knees (75%) and hips (15%) most commonly infected. Median erythrocyte sedimentation rate was 62 mm/hr (10–141) and C reactive protein 26 mg/dL (0.5–95). Synovial fluid median white blood cell count was 27 500/µL (range, 100–220 000/µL) with 90% polymorphonuclear neutrophils (range, 24–98). Adjacent osteomyelitis was present in 30% of cases. Candida albicans constituted 63%, Candida tropicalis 14%, and Candida parapsilosis 11%. Most cases (66%) arose de novo, whereas 34% emerged during antifungal therapy. Osteolysis occurred in 42%, joint-effusion in 31%, and soft tissue extension in 21%. Amphotericin and fluconazole were the most commonly used agents. Surgical interventions included debridement in 25%, irrigation 10%, and drainage 12%. Complete or partial response was achieved in 96% and relapse in 16%. Conclusion. Candida arthritis mainly emerges as a de novo infection in usually non-immunosuppressed patients with hips and knees being most commonly infected. Localizing symptoms are frequent, and the most common etiologic agents are C albicans, C tropicalis, and C parapsilosis. Management of Candida arthritis remains challenging with a clear risk of relapse, despite antifungal therapy.

[1]  D. Kontoyiannis,et al.  Successful treatment of Candida osteoarticular infections with limited duration of antifungal therapy and orthopedic surgical intervention , 2015, Infectious diseases.

[2]  S. Fischer,et al.  Fungal Osteomyelitis and Septic Arthritis , 2014, The Journal of the American Academy of Orthopaedic Surgeons.

[3]  B. Moriyama,et al.  Aspergillus osteomyelitis: epidemiology, clinical manifestations, management, and outcome. , 2014, The Journal of infection.

[4]  J. Gerber,et al.  Candida krusei arthritis in an adolescent with acute myelogenous leukemia. , 2013, The Pediatric infectious disease journal.

[5]  G. Guillerm,et al.  Fungal arthritis of the hip in patient with aplastic anaemia , 2013, BMJ Case Reports.

[6]  T. Walsh,et al.  Species-Specific and Drug-Specific Differences in Susceptibility of Candida Biofilms to Echinocandins: Characterization of Less Common Bloodstream Isolates , 2013, Antimicrobial Agents and Chemotherapy.

[7]  B. Moriyama,et al.  Candida osteomyelitis: analysis of 207 pediatric and adult cases (1970-2011). , 2012, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[8]  M. Suarez‐Almazor,et al.  Rare Case of Septic Arthritis Caused by Candida krusei: Case Report and Literature Review , 2012, The Journal of Rheumatology.

[9]  G. Lee,et al.  Primary Candida guilliermondii Infection of the Knee in a Patient without Predisposing Factors , 2012, Case reports in medicine.

[10]  M. Beer,et al.  Osteoarticular infection by Candida albicans in an infant with cystic fibrosis. , 2011, Journal of medical microbiology.

[11]  Dong Ho Kim,et al.  Candida tropicalis arthritis of the elbow in a patient with Ewing's sarcoma that successfully responded to itraconazole , 2011, Korean journal of pediatrics.

[12]  D. Andes,et al.  Role of Fks1p and Matrix Glucan in Candida albicans Biofilm Resistance to an Echinocandin, Pyrimidine, and Polyene , 2010, Antimicrobial Agents and Chemotherapy.

[13]  Myeung-Su Lee,et al.  Candida Arthritis after Arthroscopic Arthroplasty in a Patient without Predisposing Factors , 2010, The open rheumatology journal.

[14]  Christopher M. Bland,et al.  Micafungin plus Fluconazole in an Infected Knee with Retained Hardware due to Candida albicans , 2009, The Annals of pharmacotherapy.

[15]  J. Sobel,et al.  Clinical practice guidelines for the management of candidiasis: 2009 update by the Infectious Diseases Society of America. , 2009, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[16]  D. Muscolo,et al.  Massive Bone Loss from Fungal Infection after Anterior Cruciate Ligament Arthroscopic Reconstruction , 2009, Clinical orthopaedics and related research.

[17]  E. Reisin,et al.  A rare case of Candida arthritis in a hemodialysis patient. , 2008, The American journal of the medical sciences.

[18]  J. Bariola,et al.  Candida lusitaniae septic arthritis: case report and review of the literature. , 2008, Diagnostic microbiology and infectious disease.

[19]  N. J. Nasser,et al.  Candida parapsilosis septic arthritis in a renal transplant patient. , 2008, Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases.

[20]  B. Ferhanoğlu,et al.  Candida krusei arthritis in a patient with hematologic malignancy: successful treatment with voriconazole. , 2007, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[21]  Z. Khan,et al.  Candida lusitaniae arthritis in an intravenous drug user , 2007, Mycoses.

[22]  Chang-Youh Tsai,et al.  An unusual case of Candida tropicalis and Candida krusei arthritis in a patient with acute myelogenous leukemia before chemotherapy , 2007, Clinical Rheumatology.

[23]  D. Kontoyiannis,et al.  Fungal osteoarticular infections in patients treated at a comprehensive cancer centre: a 10-year retrospective review. , 2006, Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases.

[24]  P. Shao,et al.  Successful treatment of Candida tropicalis arthritis, osteomyelitis and costochondritis with caspofungin and fluconazole in a recipient of bone marrow transplantation. , 2006, Acta paediatrica.

[25]  M. Assal,et al.  Successful treatment of Candida parapsilosis (fluconazole-resistant) osteomyelitis with caspofungin in a HIV patient , 2006, Scandinavian journal of infectious diseases.

[26]  J. Sim,et al.  Candida tropicalis arthritis of the knee in a patient with acute lymphoblastic leukaemia: successful treatment with caspofungin. , 2005, Hong Kong medical journal = Xianggang yi xue za zhi.

[27]  J. Bisbe,et al.  Transient fungemia and Candida arthritis due toCandida zeylanoides , 1987, European Journal of Clinical Microbiology.

[28]  J. M. Romero,et al.  Candida arthritis in an immunocompetent patient without predisposing factors , 2005, Clinical Rheumatology.

[29]  Marisela Silva,et al.  Candida albicans osteomyelitis: case report and literature review. , 2004, International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases.

[30]  F. de Lalla,et al.  Candidal prosthetic hip infection in a patient with previous candidal septic arthritis. , 2004, The Journal of arthroplasty.

[31]  D. Yousefzadeh,et al.  Neonatal and infantile candidal arthritis with or without osteomyelitis: A clinical and radiographical review of 21 cases , 1980, Skeletal Radiology.

[32]  P. Vicari,et al.  Septic arthritis as the first sign of Candida tropicalis fungaemia in an acute lymphoid leukemia patient. , 2003, The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases.

[33]  K. Kawanabe,et al.  Candida septic arthritis of the hip in a young patient without predisposing factors. , 2003, The Journal of bone and joint surgery. British volume.

[34]  B. Turgut,et al.  Candida arthritis in a patient with chronic myelogenous leukemia (CML) in blastic transformation, unresponsive to fluconazole, but treated effectively with liposomal amphotericin B , 2002, Annals of Hematology.

[35]  M. Ghannoum,et al.  Antifungal Susceptibility of Candida Biofilms: Unique Efficacy of Amphotericin B Lipid Formulations and Echinocandins , 2002, Antimicrobial Agents and Chemotherapy.

[36]  M. Hacımustafaoğlu,et al.  Bilateral septic arthritis of the knee joint in three children caused by unusual infectious agents , 2001, Pediatrics international : official journal of the Japan Pediatric Society.

[37]  Y. Ko,et al.  Candida polyarthritis in a renal transplant patient: case report of a patient successfully treated with amphotericin B. , 2000, Transplantation proceedings.

[38]  J. Pleasure,et al.  Candidal arthritis in infants previously treated for systemic candidiasis during the newborn period: report of three cases. , 2000, Pediatric emergency care.

[39]  Weigl Ja Candida arthritis in a premature infant treated successfully with oral fluconazole for six months. , 2000 .

[40]  J. Weigl Candida arthritis in a premature infant treated successfully with oral fluconazole for six months. , 2000, Annals of the Academy of Medicine, Singapore.

[41]  W. Barth,et al.  Candida lambica polyarthritis in a patient with chronic alcoholism. , 1999, The Journal of rheumatology.

[42]  T. Gumbo,et al.  Candida (Torulopsis) glabrata septic arthritis. , 1999, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[43]  L. Palomera,et al.  Successful lipid-complexed amphotericin B treatment of Candida arthritis in a lymphoma patient. , 1999, Revue du rhumatisme.

[44]  G. Verbruggen,et al.  Candida Glabrata Arthritis: Case Report and Review of the Literature of Candida Arthritis , 1999, Clinical Rheumatology.

[45]  D. H. Brooks,et al.  Successful salvage of a primary total knee arthroplasty infected with Candida parapsilosis. , 1998, The Journal of arthroplasty.

[46]  A. Pérez-Gómez,et al.  Role of the new azoles in the treatment of fungal osteoarticular infections. , 1998, Seminars in arthritis and rheumatism.

[47]  M. Hacımustafaoğlu,et al.  Systemic candidiasis with acute Epstein‐Barr virus infection , 1997, Acta paediatrica.

[48]  K. Shirakura,et al.  Candida arthritis after total knee arthroplasty--a case of successful treatment without prosthesis removal. , 1997, Acta orthopaedica Scandinavica.

[49]  J. Meis,et al.  Candida tropicalis arthritis in a patient with acute myeloid leukemia successfully treated with fluconazole: Case report and review of the literature , 1997, Infection.

[50]  E. Roilides,et al.  Multifocal osteoarthritis due toCandida albicans in a neonate: Serum level monitoring of liposomal amphotericin B and literature review , 1997, Infection.

[51]  M. Pfaller,et al.  Candida albicans arthritis one year after successful treatment of fungemia in a healthy infant. , 1996, The Journal of pediatrics.

[52]  J. Iannotti,et al.  Autoimmune arthritis caused by Candida septic arthritis. , 1995, Journal of shoulder and elbow surgery.

[53]  B. Hansen,et al.  Fungal Arthritis: A review , 1995 .

[54]  Jia-yuh Chen,et al.  Neonatal candidiasis associated with meningitis and endophthalmitis , 1994, Acta paediatrica Japonica : Overseas edition.

[55]  A. Olivé,et al.  Candida albicans spondylodiscitis and vertebral osteomyelitis in patients with intravenous heroin drug addiction. Report of 3 new cases. , 1994, The Journal of rheumatology.

[56]  M. Weisse,et al.  Treatment of Candida arthritis with flucytosine and amphotericin B. , 1993, Journal of perinatology : official journal of the California Perinatal Association.

[57]  J. Peña,et al.  Osteoarticular infection in intravenous drug abusers: influence of HIV infection and differences with non drug abusers. , 1993, Annals of the rheumatic diseases.

[58]  J. Andreu,et al.  Candida arthritis in adult patients who are not intravenous drug addicts: report of three cases and review of the literature. , 1993, Seminars in arthritis and rheumatism.

[59]  D. Blaise,et al.  Candida arthritis treated with intra-articular amphotericin B. , 1993, The European journal of medicine.

[60]  J. D. McNeil,et al.  Candida albicans arthritis in a renal allograft recipient with an interaction between cyclosporin and fluconazole. , 1993, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[61]  L. Ryd,et al.  Candida albicans arthritis in a nonimmunocompromised patient. Complication of placebo intraarticular injections. , 1993, Acta orthopaedica Scandinavica.

[62]  M. Grossman,et al.  Disseminated candidiasis, Candida arthritis, and unilateral skin lesions. , 1992, Journal of the American Academy of Dermatology.

[63]  S. Pizarro,et al.  Favorable outcome with ketoconazole in Candida septic arthritis. , 1992, The Journal of rheumatology.

[64]  C. Trautwein,et al.  Candida arthritis: cellular immune responses of synovial fluid and peripheral blood lymphocytes to Candida albicans. , 1991, Annals of the rheumatic diseases.

[65]  R. Mccabe,et al.  Candida albicans septic arthritis and osteomyelitis of the sternoclavicular joint in a patient with human immunodeficiency virus infection. , 1991, The Journal of rheumatology.

[66]  T. O’Meeghan,et al.  Fluconazole concentration in joint fluid during successful treatment of Candida albicans septic arthritis. , 1990, The Journal of antimicrobial chemotherapy.

[67]  R. D. Meyer,et al.  Candidal pyarthrosis in an AIDS patient. , 1990, Scandinavian Journal of Infectious Diseases.

[68]  D. Campen,et al.  Candida septic arthritis in rheumatoid arthritis. , 1990, The Journal of rheumatology.

[69]  M. Lambertus,et al.  Fungal Prostbetic Artbritis: Presentation of Two Cases and Review of the Literature , 1988 .

[70]  J. Rotés-Querol,et al.  Costochondral involvement in systemic candidiasis in heroin addicts: clinical, scintigraphic, and histologic features in 26 patients. , 1988, Arthritis and rheumatism.

[71]  D. Hauglustaine,et al.  Candida parapsilosis in a patient receiving chronic hemodialysis. , 1988, The Journal of rheumatology.

[72]  D. Thordarson,et al.  Fungal prosthetic arthritis: presentation of two cases and review of the literature. , 1988, Reviews of infectious diseases.

[73]  M. Levine,et al.  Infection with Candida albicans of a total knee arthroplasty. Case report and review of the literature. , 1988, Clinical orthopaedics and related research.

[74]  V. Q. Nguyen,et al.  Candida krusei infectious arthritis. A rare complication of neutropenia. , 1987, The American journal of medicine.

[75]  Engelbert Rh,et al.  Unusual features of arthritis caused by Candida parapsilosis. , 1987 .

[76]  P. Collignon Candida osteomyelitis. , 1987, The American journal of medicine.

[77]  R. Eng,et al.  Unusual features of arthritis caused by Candida parapsilosis. , 1987, Archives of pathology & laboratory medicine.

[78]  R. H. George,et al.  Candida albicans arthritis in an infant. , 1986, The Journal of infection.

[79]  P. L. Gambrioli,et al.  Candida arthritis of the knee. Case report. , 1986, Italian journal of orthopaedics and traumatology.

[80]  D. Katzenstein Isolated Candida arthritis: report of a case and definition of a distinct clinical syndrome. , 1985, Arthritis and rheumatism.

[81]  L. Calabrese,et al.  Two unusual strains of Candida arthritis. , 1984, The American journal of the medical sciences.

[82]  B. Duquesnoy,et al.  Ketoconazole for treatment of Candida arthritis. , 1984, The Journal of rheumatology.

[83]  A. Dalton,et al.  Assessment of antifungal therapy in an 800-gram infant with candidal arthritis and osteomyelitis. , 1983, Pediatrics.

[84]  G. Bodey,et al.  Septic arthritis due to Candida species on patients with cancer: report of five cases and review of the literature. , 1982, Reviews of infectious diseases.

[85]  T. Pope Pediatric Candida albicans arthritis: case report of hip involvement with a review of the literature. , 1982, Progress in pediatric surgery.

[86]  G. Jonas,et al.  Candida albicans arthritis in a healthy adult. , 1981, Southern medical journal.

[87]  M. Glauser,et al.  Erosive candida arthritis in a patient with disseminated candidiasis. , 1980, The Journal of rheumatology.

[88]  G. Myers,et al.  Candida meningitis in the newborn. , 1979, Southern medical journal.

[89]  R. Yarchoan,et al.  Isolated Candida parapsilosis arthritis in a heroin addict. , 1979, The Journal of rheumatology.

[90]  O. Khermosh,et al.  Neonatal osteomyelitis caused by Candida tropicalis. Report of two cases and review of the literature. , 1979, The Journal of bone and joint surgery. American volume.

[91]  E. Ginzler,et al.  Candida arthritis secondary to repeated intra-articular corticosteroids. , 1979, New York state journal of medicine.

[92]  A. Bayer,et al.  Fungal arthritis. I. Candida arthritis: diagnostic and prognostic implications and therapeutic considerations. , 1978, Seminars in arthritis and rheumatism.

[93]  D. Musher,et al.  Candida tropicalis arthritis - assessment of amphotericin B therapy. , 1978, The Journal of rheumatology.

[94]  S. Mendoza,et al.  Systemic candidiasis in infants: a case presentation and literature review. , 1977, American journal of diseases of children.

[95]  D. D'alessio,et al.  Flucytosine treatment of Candida arthritis. , 1977, JAMA.

[96]  A. Meberg,et al.  Candida‐septicemia with chorioretinitis, osteomyelitis and arthritis treated with systemic miconazole and intraarticular amphotericin B , 1977, Mykosen.

[97]  E. E. Specht Candida pyarthrosis of the hip and renal homotransplant. Report of a case treated by femoral head and neck resection and 5-fluorocytosine. , 1977, Clinical orthopaedics and related research.

[98]  D. Principe,et al.  DISSEMINATED ARTHRITIS AND OSTEITIS BY CANDIDA ALBICANS IN A TWO MONTH OLD INFANT RECEIVING PARENTERAL NUTRITION , 1977, Acta paediatrica Scandinavica.

[99]  S. Jacobelli,et al.  Candida arthritis associated with positive birefringent crystals without chondrocalcinosis. , 1977, The Journal of rheumatology.

[100]  Y. Lertratanakul,et al.  Arthritis and osteomyelitis due to Candida albicans: a case report. , 1977, The Journal of rheumatology.

[101]  L. Marmor,et al.  Candida arthritis of the knee joint. , 1976, Clinical orthopaedics and related research.

[102]  H. Murray,et al.  Candida arthritis: A manifestation of disseminated candidiasis , 1976 .

[103]  D. Poplack,et al.  Candida arthritis treated with amphotericin B. , 1975, The Journal of pediatrics.

[104]  J. Lloyd-Still,et al.  Candida arthritis. A case report and review of the literature. , 1975, Clinical Orthopaedics and Related Research.

[105]  M. Chapman,et al.  Candida pyarthrosis. Report of a case and results of treatment with 5-fluorocytosine. , 1974, The Journal of bone and joint surgery. American volume.

[106]  R. Soper,et al.  Candida osteomyelitis associated with intravenous alimentation. , 1974, Journal of pediatric surgery.

[107]  H. B. Noble,et al.  Candida osteomyelitis and arthritis from hyperalimentation therapy. Case report. , 1974, The Journal of bone and joint surgery. American volume.

[108]  T. G. Mitchell,et al.  Recovery from disseminated candidiasis in a premature neonate. , 1974, Pediatrics.

[109]  F. Lindström,et al.  Candida albicans arthritis treated with flucytosine. , 1973, Annals of internal medicine.

[110]  F. Noyes,et al.  Acute candida arthritis. Report of a case and use of amphotericin B. , 1973, The Journal of bone and joint surgery. American volume.

[111]  R. Lachman,et al.  Neonatal systemic candidiasis and arthritis. , 1972, Radiology.

[112]  J. Klein,et al.  Neonatal candidiasis, meningitis, and arthritis: observations and a review of the literature. , 1972, The Journal of pediatrics.

[113]  S. Plotkin,et al.  Candidal osteomyelitis and arthritis in a neonate. , 1972, American journal of diseases of children.

[114]  J. Achord,et al.  Glucose-galactose malabsorption complicated by monilial arthritis. , 1969, Pediatrics.

[115]  S. Newsom,et al.  Fatal fungal infection following open-heart surgery. , 1967, British heart journal.