Fungal osteomyclitis and arthritis are uncommon diseases, often presenting in an indolent fashion. Alterations of human flora, disruption of mucocutaneous membranes, and impaired immune function may predispose to fungal infection [1-3]. There is frequently a long period between onset of symptoms and diagnosis. Fungal osteomyelitis and arthritis arise as a result of hematogenous dissemination, direct inoculation from an exogenous source, such as trauma, surgery, joint injection, or aspiration [1,4,5], or direct extension from an adjacent focus [4,6]. Most cases of septic arthritis occur following hematogenous spread, owing to the vascularity of synovial tissue [7]. With disseminated infection, organisms traverse the bloodstream by direct spread from the primary site, seeding distant sites. The specific metastatic site likely depends on factors pertaining to the pathogen and host [4]. Much of the current understanding of the pathophysiology of bone and joint infection stems from studies of Staphylococcus aureus [4]. Blood vessel occlusion by bacteria and inflammatory cells results in tissue necrosis. Bacteria adhere to avascular bone and form a glycocalyx. Following infection of the synovial membrane, polymorphonuclear leukocytes release enzymes that destroy the articular surface [7]. Release of cytokines leads to bone lysis, with destruction of bony trabeculae and matrix and inhibition of collagen synthesis. Segments of avascular bone form sequestra; however, this process occurs less commonly in fungal osteomyelitis. In contrast to bacterial osteomyelitis, reactive new bone formation occurs later in the disease process [4]. Fungal osteomyelitis may occur as part of a multisystem process or in isolation. The most common chief complaint is localized pain. Although virtually any joint can be affected, large, weight-bearing joints such as the knees are most commonly involved [4,8,9]. On physical examination, common findings associated with arthritis may be present, including decreased range of motion, tenderness, swelling, erythema, and joint effusion. Chronic infection may lead to cold soft tissue abscesses and sinus tract formation [4]. Diagnosis may be delayed because of slow progression of disease, absence of characteristic laboratory findings, and failure to recognize fungi as potential pathogens. Patients may have other factors that mask physical signs of inflammation. Initial imaging may reveal lytic lesions with little new bone formation. Adjacent osteoporosis and osteomyelitis and cortical erosion may also be seen [4]. The differential diagnosis based on clinical and radiographic findings includes bacterial osteomyelitis, tuberculosis, sarcoidosis, osteogenic sarcoma, Ewing sarcoma, Langerhans cell histiocytosis, and malignant metastasis. The absence of new bone formation or a periosteal reaction may suggest fungal osteomyelitis [4]. Direct examination of potassium hydroxide-treated or Gram stain smears of synovial fluid usually fail to allow visualization of the organism. Synovial fluid leukocyte counts often resemble noninfectious inflammatory arthritis, and routine cultures are frequently nondiagnostic. Synovial fluid protein concentration is usually greater than 3 g/dL, and the glucose concentration varies from low to normal [4]. On pathologic examination, necrotizing granulomas may suggest the presence of a fungal infection, but do not exclude tuberculosis. Aggressive management and bone or synovial biopsy and culture are often necessary to confirm a diagnosis [3,10,11]. Clinical presentation and outcome differ according to the specific fungal pathogen and host factors [4]. This article discusses each fungal pathogen separately, and addresses special populations, namely neonates and intravenous drug abusers.
