A case of brucellar septic arthritis of the knee with a prolonged clinical course

Ayaslioglu, Ergin; Ozluk, Ozlem Arican; Kılıç, Dilek; Kaygusuz, Sedat; Kara, Simay; Aydın, Gülümser; Çokça, Fügen; Tekeli, Emin

doi:10.1007/s00296-004-0453-1

Cited by 18 publications

(17 citation statements)

References 9 publications

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“…Here we show that wild-type C57BL/6 mice inoculated via the footpad with 10 3 to 10 6 CFU of live Brucella develop arthritis and musculoskeletal inflammation. Similar to what has been described in human patients with articular brucellosis (14) and what we previously found in IFN-␥ Ϫ/Ϫ mice, footpad-infected mice also developed inflammation of musculoskeletal tissues surrounding the joint. To our knowledge, this is the first description of a wild-type mouse strain developing arthritis and musculoskeletal inflammation when infected with a conventional dose of Brucella.…”

Section: Discussionsupporting

confidence: 69%

“…Inflammation of the joint synovium is prevalent in infected individuals, with polymorphonuclear and mononuclear leukocytes found in and around synovial tissue (13). Brucella-induced arthritis is commonly treated with antibiotics; however, resolution of arthritis is often protracted, and the disease can relapse (8,14). Untreated articular brucellosis can result in synovial rupture or bone destruction, potentially causing permanent disability (12,15,16).…”

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confidence: 99%

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Temporal Role for MyD88 in a Model of Brucella-Induced Arthritis and Musculoskeletal Inflammation

et al. 2017

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Brucella spp. are facultative intracellular Gram-negative bacteria that cause the zoonotic disease brucellosis, one of the most common global zoonoses. Osteomyelitis, arthritis, and musculoskeletal inflammation are common focal complications of brucellosis in humans; however, wild-type (WT) mice infected systemically with conventional doses of Brucella do not develop these complications. Here we report C57BL/6 WT mice infected via the footpad with 10 3 to 10 6 CFU of Brucella spp. display neutrophil and monocyte infiltration of the joint space and surrounding musculoskeletal tissue. Joint inflammation is detectable as early as 1 day postinfection and peaks 1 to 2 weeks later, after which WT mice are able to slowly resolve inflammation. B and T cells were dispensable for the onset of swelling but required for resolution of joint inflammation and infection. At early time points, MyD88 Ϫ/Ϫ mice display decreased joint inflammation, swelling, and proinflammatory cytokine levels relative to WT mice. Subsequently, swelling of MyD88 Ϫ/Ϫ joints surpassed WT joint swelling, and resolution of joint inflammation was prolonged. Joint bacterial loads in MyD88 Ϫ/Ϫ mice were significantly greater than those in WT mice by day 3 postinfection and at all time points thereafter. In addition, MyD88 Ϫ/Ϫ joint inflammatory cytokine levels on day 3 and beyond were similar to WT levels. Collectively these data demonstrate MyD88 signaling mediates early inflammatory responses in the joint but also contributes to subsequent clearance of Brucella and resolution of inflammation. This work also establishes a mouse model for studying Brucellainduced arthritis, musculoskeletal complications, and systemic responses, which will lead to a better understanding of focal complications of brucellosis.KEYWORDS arthritis, osteomyelitis, Brucella, brucellosis, MyD88, musculoskeletal B rucella spp. infect over 500,000 individuals each year, making brucellosis one of the most common global zoonoses (1). The most prevalent species that infect humans are Brucella melitensis, Brucella abortus, and Brucella suis (2). Transmission to humans typically occurs through the consumption of unpasteurized dairy products or via aerosol following contact with contaminated meat products (3, 4). Although vaccination of livestock has reduced disease incidence, no licensed human vaccine is available, and brucellosis has recently been designated a neglected zoonotic disease by the World Health Organization (5, 6). Osteoarticular and musculoskeletal inflammation are the most common focal complications of human brucellosis and occur in 40 to 80% of Brucella-infected patients (7,8). This arthritis is thought to arise from the hematogenous spread of Brucella to the joints, as viable brucellae can be found within the synovial fluid of infected patients (9, 10). Arthritis can manifest as peripheral arthritis, sacroiliitis, and spondylitis, which are most common in children, young adults and older adults, respectively (7,8,11,12). Inflammation of the joint synovium is pre...

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Section: Discussionsupporting

confidence: 69%

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confidence: 99%

Temporal Role for MyD88 in a Model of Brucella-Induced Arthritis and Musculoskeletal Inflammation

et al. 2017

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“…Here, we report for the first time, to our knowledge, that IFN-␥ Ϫ/Ϫ but not WT mice develop osteoarthritis, along with extensive periarticular soft-tissue inflammation following infection with Brucella. Arthritis, as a result of Brucella in humans, is thought to occur via a hematogenous route [16]; however, bacteremia, following experimental infection with B. suis or B. melitensis infection in WT mice, was found by others to be transient [53][54][55]. Although IFN-␥ ϩ/ϩ and IFN-␥ Ϫ/Ϫ mice possessed similar splenic burdens of brucellae at 14, 28, and 42 days postinfection, IFN-␥ Ϫ/Ϫ spleens contained 10 3 -10 4 more brucellae than WT spleens.…”

Section: Discussionmentioning

confidence: 99%

“…Arthritis, as a result of Brucella, is thought to be septic in nature, resulting from hematogenous spreading to the joints and occurring without an obvious predisposition [16]. Whereas brucellar arthritis normally responds to antibiotic treatment, the resolution of inflammation is often prolonged [8,16], and in some instances, the arthritis can progress to osteoarticular destruction [10]. In addition, cases refractive to antibiotic therapy may require arthroscopic debridement and drainage of the joint [12].…”

Section: Introductionmentioning

confidence: 99%

IFN-γ-deficient mice develop IL-1-dependent cutaneous and musculoskeletal inflammation during experimental brucellosis

Skyberg

Thornburg

Kochetkova

et al. 2012

Journal of Leukocyte Biology

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Human brucellosis exhibits diverse pathological manifestations that can affect almost any organ. In particular, osteoarticular complications are the most common focal manifestation of brucellosis and occur in 40-80% of patients. In immunocompetent mice, Brucella replication is generally restricted to the spleen, liver, and to a lesser extent, LNs, thereby limiting their use for study of focal inflammation often found in brucellosis. Here, we report that nasal, oral, or peritoneal infection of IFN-γ(-/-) mice with WT Brucella melitensis or Brucella abortus results in joint and periarticular tissue inflammation. Histological analysis of the affected joints revealed inflammatory infiltrates and debris within the joint space colocalizing with Brucella antigen. Osteoarthritis, necrosis, periarticular soft tissue inflammation, and substantial brucellae burdens were observed. Oral rifampicin was effective in clearing infection and halting further progression of focal inflammation from infected IFN-γ(-/-) mice, although some symptoms and swelling remained. Elevated IL-1 β, but not TNF-α, IL-6, or IL-17, was detected in joint homogenates from infected IFN-γ(-/-) mice. Whereas more susceptible to systemic infection, IL-1R(-/-) mice depleted of IFN-γ were more resistant to focal inflammation than WT mice similarly depleted of IFN-γ. Collectively, these results show IFN-γ(-/-) mice represent a potential model for study of focal inflammation attributed to Brucella infection and will allow evaluation of intervention strategies targeting IL-1, IL-1R, or other inflammatory mediators, with the potential to complement antibiotic-based therapies.

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“…But in some cases, eradication of the microorganism could not be achieved with this regiment. Therefore, in some cases, the treatment for brucellar arthritis may be required more than two antimicrobial agents [15]. Single-agent treatment regimens are not recommended for the osteoarticular involvement of brucellosis because of their high relapse rates [2].…”

Section: Discussionmentioning

confidence: 99%

A case of brucellar monoarthritis and review of the literature

2011

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Brucellosis is a systemic infectious disease, which constitutes a public health problem in Turkey. Brucellosis has a broad spectrum of clinical manifestations. Osteoarthicular manifestations are often seen in brucellosis but most of the brucellar monoarthritis cases are reactive rather than being septic. We report a case of brucellar (septic) monoarthritis of the knee in a 74-year-old cattleman and review of the literature.

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A case of brucellar septic arthritis of the knee with a prolonged clinical course

Cited by 18 publications

References 9 publications

Temporal Role for MyD88 in a Model of Brucella-Induced Arthritis and Musculoskeletal Inflammation

Temporal Role for MyD88 in a Model of Brucella-Induced Arthritis and Musculoskeletal Inflammation

IFN-γ-deficient mice develop IL-1-dependent cutaneous and musculoskeletal inflammation during experimental brucellosis

A case of brucellar monoarthritis and review of the literature

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