Data regarding demographic characteristics, clinical and radiological features, inflammatory biomarkers, microbiology, management, and outcome of patients were collected and analyzed with descriptive statistics using Instat GraphPad GraphPad Software, San Diego, CA.
Continuous variables were summarized using median and range, whereas categorical variables were summarized using frequencies and percentages. Differences in proportions were analyzed by Fisher's exact test. Patients included in this study consisted of nonprosthetic Candida arthritis cases as published in the English literature within the study period from to The first case of Candida arthritis was reported in [ 71 ].
Since this initial report through , a total of published cases [ 7 — ] of Candida arthritis fulfilled predefined criteria for evaluability. Thus, evaluable cases were entered into the database. The majority of patients was not neutropenic nor was receiving corticosteroids or other pharmacological immunosuppression. Other conditions included central venous catheters, prior broad-spectrum antibiotics or antifungal agents, total parenteral nutrition, critical illness, use of illicit intravenous drugs or alcohol abuse, diabetes mellitus, hemodialysis, chronic pulmonary disease, and hypogammaglobulinemia.
This specimen is bone tissue 3 , or bone and cartilage 1 , bone marrow 1 , adjacent abscess 1 , cartilage 1 , thrombus 1 , tendon 1 , disc 1 , or operative samples 1. For the synovial fluid, there was leukocytosis with predominance of neutrophils. Median duration of therapy was 64 days range, 14— days.
There were no other significant differences in features of Candida arthritis between pediatric and adult populations. Candida albicans , C tropicalis , and C parapsilosis were the most common causes of Candida arthritis.
The most common radiological abnormalities in Candida arthritis were bone destruction and joint effusion. An early diagnosis of Candida arthritis is important to prevent joint destruction, preserve function, and determine length of therapy.
Understanding the host factors, clinical manifestations, inflammatory markers, diagnostic imaging, and microbiology are essential to achieving those objectives. The age range, gender distribution, and underlying host factors of Candida arthritis reflect those of candidemia and deeply invasive candidiasis. Candida arthritis needs to be included within the differential diagnosis of osteoarticular symptoms in patients with underlying immunosuppression, including those with hematological malignancies, SOT, HSCT, and corticosteroid therapy.
Likewise, surgery and trauma, particularly in patients receiving broad-spectrum antibiotics and with implanted central venous catheters, constitute other clinical settings in which Candida arthritis may emerge. Candida arthritis may appear as a late manifestation of disseminated candidiasis. Kim et al [ 12 ] reported development of Candida arthritis 2 weeks after a chemotherapy-induced granulocytopenic period in the absence of any invasive manipulation.
Joint swelling or arthralgia after recovery from neutropenia in febrile patients should raise clinical suspicion of fungal arthritis [ 4 , 81 ]. The apparent pathogenesis of most cases of Candida arthritis is that of hematogenous dissemination to the joint. The mammalian synovium is extremely vascular and contains no limiting basement membrane, promoting easy access of blood contents to the synovial space.
Therefore, hematogenous seeding of Candida may affect normal joints [ ]. Although the exact pathogenesis of Candida arthritis remains to be further elucidated, the portal of entry may originate via contamination of central vascular catheters or from altered gastrointestinal microbial flora in the host with subsequent mucosal translocation and hematogenous dissemination [ 4 , 24 , 43 ].
Although infection of a joint is also possible via direct inoculation surgery or intra-articular infection , hematogenous dissemination appears to be the most common mechanism of infection. Hematogenous dissemination was significantly more common as a mechanism of Candida arthritis in children than in adults.
This difference may be understood from the observation that all pediatric patients with Candida arthritis were neonates, infants, and toddlers. These populations are particularly vulnerable to the osteoarticular complications of candidemia, including Candida arthritis. The lack of closure of the epiphyseal plate in neonates, infants, and toddlers allows hematogenously disseminated organisms to extend into the joint space either directly through the articular cartilage or through the bony cortex of the joint capsule and then into the synovial space.
Adults are more likely to have underlying surgical- and trauma-related portals of direct infection, hence accounting for these differences in pediatrics.
Because this study found that Candida arthritis arises in most patients with known invasive candidiasis or at the time of diagnosis of candidemia, an evaluation of musculoskeletal symptoms in overall assessment may reveal localization to 1 or more joints. However, because Candida arthritis also may arise de novo in more than one fourth of patients, one needs to have a high index of reaching this diagnosis in patients with the aforementioned host factors as the first manifestation of disseminated disease.
The clinical manifestations of Candida arthritis of pain, tenderness, and edema are common and should prompt an assessment for septic arthritis with Candida joint infection high in the differential diagnosis in the setting of a susceptible host with or without other evidence of invasive candidiasis. The knee, hip, and shoulder are the most frequently infected sites. The radiological features of bone destruction and joint effusion attest to the virulent nature of Candida arthritis but are not specific.
Because the clinical manifestations and inflammatory markers are not specific for Candida arthritis, arthrocentesis or arthroscopy is warranted for the definitive diagnosis. Given the paucity of fever and specific laboratory findings or radiographic features, diagnosis of fungal osteoarticular infections may be delayed in most cases [ — ].
The differential diagnosis includes bacterial septic arthritis and crystalline arthritis. Although arthrocentesis is readily performed in the knee, the procedure is more challenging in the hip and shoulder. Synovial fluid analysis in Candida arthritis is characterized by acute inflammatory response with a predominance of neutrophils; however, this is not specific. By comparison, recovery of Candida spp provides a definitive diagnosis.
It is noteworthy that Candida spp are seldom laboratory contaminants from normally sterile synovial fluid. That C albicans and C tropicalis constituted the 2 most common organisms causing septic arthritis is consistent with their being the most virulent causes of hematogenous disseminated candidiasis [ 24 , ]. The paucity of cases of C glabrata arthritis, despite its constituting as much as one fourth of cases of candidemia, suggests that this organism may not have the necessary virulence factors needed to establish infection within synovial tissue.
Possible virulence factors, such as adhesion molecules, cell wall hydrophobicity, as well as extracellular proteases and phospholipases differ in their properties and expression among Candida spp [ ]. The objectives of treatment of Candida arthritis are to relieve symptoms, eradicate infection, prevent joint injury, and restore function. Unfortunately, there is no evidence-based standard treatment regimen for patients with fungal osteoarticular infections of native joints due to the heterogeneous spectrum of diseases and the relatively low frequency of this disease.
Current guidelines recommend initial antifungal therapy with amphotericin B or fluconazole combined with surgical debridement [ ]. Ambulatory antifungal therapy may be achieved with orally administered fluconazole. Medical therapy of Candida arthritis in this study most commonly began with amphotericin with or without combinations, such as flucytosine or fluconazole.
Echinocandins were used as part of combination therapy in 6 patients but not used as monotherapy. However, given the activity of echinocandins on Candida biofilms [ — ], primary therapy with an echinocandin is a rational approach for initial medical management of Candida arthritis.
Surgery may also be an important adjunct to medical management of Candida arthritis. Because synovial fluid analysis and radiological features of Candida arthritis reveal this infection to be a suppurative destructive process, the surgical procedures used included irrigation, drainage, and debridement.
Although there was no significant difference in therapeutic response between those who received combined medical plus surgical therapy versus medical therapy alone, there were more deaths and disseminated candidiasis in the latter. These differences may be due to a lack of source control or more immunocompromised host. That the overall responses were similar between the 2 groups does not necessarily justify medical therapy alone for all patients.
We hypothesize that there are some patients who will benefit from antifungal therapy plus adjunctive surgical intervention, whereas others may respond to medical therapy alone. The data warrant that each patient with Candida arthritis be assessed individually for combination medical-surgical therapy versus medical therapy alone. We suggest that a prospective study may help to further define the factors guiding the decision for surgical intervention in Candida arthritis.
The rationale for medical therapy alone versus combined medical and surgical intervention in individual cases was not apparent in most reports. Although combined medical and surgical intervention is certainly considered a standard of care of septic arthritis, serious comorbidities could preclude surgery in some patients.
That the overall therapeutic response was favorable in those treated with medical therapy alone, these data raise the question of whether there is a subset of patients who may be candidates for medical therapy on an individualized basis. Lack of a favorable response to treatment with antibiotics in a possible septic arthritis, particularly in immunocompromised patients, should raise suspicion of a Candida osteoarticular infection.
Prompt therapy in immunocompromised hosts presenting with acute arthritis should include not only antibacterial but also antifungal agents after diagnostic arthrocentesis. However, all of such patients subsequently responded to a second course of antifungal therapy with or without further surgical intervention, suggesting that duration of therapy as well as adequate debridement and drainage are important for successful outcome. The optimal duration of antifungal therapy remains to be defined with individual considerations of immune impairments, type of joint, and adequacy of debridement.
The report by Miller et al [ ] also suggests that local intraoperative irrigation of an infected joint by amphotericin B may assure further local control. Duration of therapy in this study extended a median period of 2 months. This duration is compatible with the previously reported length of therapy of approximately 3 months reported for Candida osteomyelitis [ ]. That this duration may be decreased by aggressive joint irrigation or arthroscopic debridement is suggested by a recent study by Miller et al [ ], who reported a median duration of approximately 2 months for treatment of Candida osteoarticular infections.
Alternatively, induction therapy with an echinocandin and maintenance therapy with more potent triazoles, such as voriconazole, posaconazole, and isavuconazole, warrants further investigation for also reducing the duration of antifungal therapy.
This study design of Candida arthritis has several limitations. Due to the retrospective nature of the design, not all data points were uniformly obtained and documented. Although the study design is strengthened by the detail afforded in individual case reports, it also may be affected by publication bias, which may lead to the reporting of better outcomes. The lack of a denominator in the study design precludes establishing an estimate of incidence; however, this was not the objective of this study.
Although the comprehensive nature of the study design from the earliest reported case to the present time increases an understanding of the clinical manifestations, it introduces variations in advances of imaging and treatment.
Although a prospective, multicenter, case-controlled observational study would address many of these concerns, such a design for Candida arthritis would require years of data collection. Therefore, the study design used in this review provides for a large number of protocol-selected patients analyzed through a finely detailed database to advance our understanding of this uncommon osteoarticular infection.
In summary, this systematic review provides a comprehensive analysis of the demographic characteristics, host factors, clinical manifestations, inflammatory biomarkers, diagnostic imaging, microbiology, and treatment of cases of Candida arthritis. A high index of clinical and microbiological suspicion of Candida spp in the differential diagnosis of septic arthritis in vulnerable hosts may facilitate the timely diagnosis and rapid initiation of the appropriate therapy.
Financial support. Potential conflicts of interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. National Center for Biotechnology Information , U. Open Forum Infect Dis. Published online Dec Maria N. Gamaletsou , 1, 2, 3 Blandine Rammaert , 4, 5 Marimelle A. Bueno , 1 Nikolaos V. Sipsas , 2, 3 Brad Moriyama , 6 Dimitrios P.
Taj-Aldeen , 10 Andy O. Walsh 1, 3, 11 , for the International Osteoarticular Mycoses Consortium. Marimelle A.
Nikolaos V. Dimitrios P. Saad J. Andy O. Thomas J. Author information Article notes Copyright and License information Disclaimer. Candida parapsilosis was cultured in his synovial fluid and identified by sequencing of its Internal Transcribed Spacer ITS gene. Here we present the radiological characteristics, arthroscopic pictures, and synovium pathology of this patient. Also, blood test and chemical analysis of his synovial fluid were listed as well as the ITS sequence of this Candida species identified.
His symptoms resolved and no relapse was observed on the last follow-up. Additionally, a brief but comprehensive review of C. With the detailed clinical information reported in this case and our literature review, we hope they would add to our knowledge of C.
Peer Review reports. Candida arthritis is extremely rare and also represents a major challenge of diagnosis and treatment because the clinical manifestations, laboratory and radiologic findings are not specific and not well defined [ 1 , 2 ].
Among Candida species, Candida albicans contributes the highest incidence of cases with Candida arthritis [ 3 ]. Whereas, the reports of C. In this study, we reported a rare case of fungal arthritis due to C. Furthermore, we conducted a systematic review of C. A year-old man was admitted to our hospital because of recurrent pain and impaired range of motion ROM of his right knee for over a year. His medical history included type 2 diabetes and hypertension which were poorly controlled.
He told us his knee was mild painful and swollen at the first place about one year ago without any injury. His symptoms became better after these treatments. Approximately 5—6 times of aspirations and corticosteroid injections were given to him, but the time-period of pain-release became shorter and shorter. On admission, he was afebrile, T His right knee joint was obviously swelling. Joint line tenderness was present, and floating patella test was positive. Anterior drawer test, Lachman test and McMurray test were negative.
Radiographs of both knees exhibited the formation of osteophytes and narrowing of joint space on the medial compartments which indicated osteoarthritis Fig. MRI T2-weighted and SPAIR sequences demonstrated subchondral bone marrow edema in the lateral femoral condyle, and the presence of soft-tissue abnormalities, including capsulitis, extensive synovial hyperplasia, capsular fluid collection, and periarticular muscle edema Fig.
A year-old man with fungal arthritis of the right knee due to Candida parapsilosis. The patient then underwent thorough arthroscopic debridement and partial meniscectomy of his right knee. Inflammatory synovium was observed under the arthroscopy Fig. Meanwhile, his thick, yellow and turbid synovial fluid was harvested. The Gram stain and acid-fast stain of the fluid demonstrated no bacteria or tuberculosis.
Representative isolates of Candida were cultured in the Sabouraud dextrose agar medium Fig. The sequence of ITS gene amplified from this isolate was listed in Additional file 1. Notably, the budding cells and pseudohyphae were also observed in the synovial tissue by periodic acid-schiff PAS staining Fig.
Susceptibility test was performed and yielded susceptibilities to 5-flurocytosine, amphotericin B, fluconazole, itraconazole, and voriconazole. On one-year follow-up, the patient remained in a clinically stable condition and the last culture of joint fluid was negative for C.
In the present study, the patient manifested with a mild chronic knee arthritis characterized by recurrent pain and swelling, leading to a diagnostic delay that lasted for almost one year.
Fortunately, mycologic investigation was performed in his first visit to our hospital and C. Previously, many lines of evidence have indicated that most patients with fungal infection are immunosuppressed with predisposing factors, including systemic disease, recent surgery, chemotherapy, long-term antibiotics use, corticosteroid therapy and insertion of central venous catheters [ 5 , 6 ].
In the current case, the patient had poorly controlled blood glucose and several events of corticosteroid injection of his knee which might cause global and local impairment of immunity. Owing to these risk factors, the possibility of fungal infection should be taken into consideration. From to there were not more than 20 cases of C. In this study, we collected 16 available cases including one case from the current report which the final diagnoses were made by the mycological culture and exhibited in Table 1 [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ].
The data suggested that local pain and swelling were the most common clinical manifestations of C. Since the symptoms are always mild and unspecific, the diagnosis can often be delayed. For the patients with recurrent infection and underlying immunosuppression, clinicians should raise the suspicion of fungal infection. Moreover, our review showed that C. Knee was the most frequently infected site, which was similar to the previous studies on Candida arthritis [ 3 , 20 ], and almost all cases were monoarticular infection except one.
When this happens, Candida can infect bones and joints, causing pain, stiffness and swelling. The best way to treat candidiasis and prevent recurring infections is to address the underlying cause. The following foods have been shown to help fight Candida infections :. You can find some of these, such as coconut oil , aloe vera gel , kombucha , probiotic supplements , and xylitol online. Candida glabrata is a common type of yeast that lives naturally in and on your body.
This article looks at when C. Oral thrush is an infection caused by the Candida albicans fungus. Esophageal thrush is a yeast infection of the throat.
If left untreated, it can be a severe condition. Fungi in the family Candida cause esophageal…. Only your doctor can diagnose a yeast infection. But, if you're not able to see a doctor, a vaginal pH test may be able to give you some insight. An anal yeast infection is often characterized by persistent and intense anal itching. Learn more about causes and treatment here. Health Conditions Discover Plan Connect.
Share on Pinterest. Oral Thrush. Tiredness and Fatigue. Clin Infect Dis ; Because of the persistency of the arthritis, despite conventional medical and interventional treatment for inflammatory arthritis, the synovial fluid is examined closely and repeatedly. Correct diagnosis is established through the isolation of C.
Candida arthritis is treated with joint debridement and antifungal medications. Prolonged systemic antifungals such as amphotericin, fluconazole, ketoconazole, and 5-flourocytosine 5FC have been used in the treatment of Candida arthritis. Of these antifungals, amphotericin and 5FC can also be administered intra-articularly as an adjunctive treatment.
Amphotericin has been used in most of cases, with encouraging results 6 6. It has been recommended that the duration of medication-based therapy should be at least 6 weeks for Candida arthritis, despite the availability of little data 2 2. In conclusion, in cases of arthritis that are resistant to treatment and prolonged, Candida arthritis should be considered, particularly for patients who have underlying risk factors.
Early diagnosis and therapy are essential to prevent the establishment of joint deformity. Abrir menu Brasil. Revista da Sociedade Brasileira de Medicina Tropical. Abrir menu. About the authors. Abstract Candida arthritis is an unusual manifestation that usually affects the knees.
Keywords: Candida; Arthritis; Spondyloarthropathy. References 1 Springer J, Chatterjee S. Rare case of septic arthritis caused by Candida krusei : case report and literature review. Septic arthritis and osteomyelitis of the hip by Candida albicans J Rheumatol ; We have not received any financial support. Publication Dates Publication in this collection Nov-Dec
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