Histopathologic evidence that sacroiliitis in ankylosing spondylitis is not merely enthesitis: Systematic study of specimens from patients and control subjects

François, R; Gardner, D. L.; Degrave, Etienne J.; Bywaters, E. G. L.

doi:10.1002/1529-0131(200009)43:9<2011::aid-anr12>3.0.co;2-y

Cited by 192 publications

(118 citation statements)

References 31 publications

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“…The combination of concomitant synovitis, subchondral bone marrow inflammation, and cartilage destruction and regeneration has implicated sacroiliitis in AS as more than simply an extension of the above enthesitis. 43 The sacroiliac joint inflammation in AS has a predilection for the iliac side of the joint, and this may be due to the greater fibrocartilaginous lining and the greater shear stresses experienced on that side. 56 Neovascularization is also common, along with proliferating fibroblasts and molecular upregulation of TNF␣ and TGF␤ transcripts.…”

Section: Neurosurg Focus / Volume 24 / January 2008mentioning

confidence: 99%

The pathogenesis of ankylosing spondylitis

Shamji

Bafaquh²,

Tsai³

2008

FOC

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✓ Ankylosing spondylitis (AS) is a chronic inflammatory disease that can cause significant functional complications by affecting the sacroiliac joints and axial skeleton. Despite a longstanding knowledge about the familial associations of this disease, particularly among patients positive for human leukocyte antigen (HLA)–B27, the fundamental pathogenetic mechanism by which this disease arises in genetically susceptible individuals remains ill defined. Furthermore, the molecular predilection for characteristic articular site involvement remains under ongoing investigation. Current theories about the HLA-B27 association range from the presentation of novel arthritogenic peptides, to abnormal autoimmune stimulation, to anomalous microbial tolerance. The immune effectors of this damage include CD4+, CD8+, and natural killer cells, with marked heterogeneity at different sites. Biomechanical stresses may trigger this disease by exposing the body to previously immune-sequestered autoantigens or by providing a route for bacterial seeding. Environmental triggers such as infection have not been definitively established but may represent a primary pathogenic step in a molecular-mimicry process. In this article, the authors review the current literature on the origin and pathophysiology of AS, focusing on genetic and molecular associations, consequent pathomechanisms, and associated triggers. An improved understanding of the sequence of molecular events that predispose and initiate the onset of this disease will allow for more specific and targeted therapy and better avoidance of the significant side effects of systemic immunomodulation.

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Section: Neurosurg Focus / Volume 24 / January 2008mentioning

confidence: 99%

The pathogenesis of ankylosing spondylitis

Shamji

Bafaquh²,

Tsai³

2008

FOC

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“…While François et al (6) described synovitis as an inflammatory lesion, besides the subchondral bone marrow changes and chondroid metaplasia, in the sacroiliac joints of AS patients, Ball (7) reported inflammatory infiltrates at entheseal sites and capsular ossification.…”

mentioning

confidence: 99%

Histomorphologic and Histomorphometric Characteristics of Zygapophyseal Joint Remodeling in Ankylosing Spondylitis

Bleil

Maier

Hempfing

et al. 2014

Arthritis & Rheumatology

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Objective To unravel the mechanisms that control bony ankylosis in ankylosing spondylitis (AS). Methods Histomorphologic and histomorphometric analyses were performed on zygapophyseal joints obtained from 18 patients with AS, 9 patients with osteoarthritis (OA), and 10 cadaver donors without a rheumatic disease (controls). The proteoglycan content of the cartilage was determined by Safranin O staining and the chondrocyte apoptosis according to caspase 3 expression. Results AS joints were categorized into 3 groups according to the morphology of the joint surfaces and joint space: group 1 were joints with an open joint space, group 2 were joints with cartilaginous fusion, and group 3 were joints with bony fusion of the joint surfaces. Progressive loss of the joint space from group 1 joints to group 3 joints suggests that this grouping corresponds to sequential stages of joint remodeling. Cartilage thickness and subchondral bone plate thickness declined from group 1 to group 3 (P < 0.01). Increased chondrocyte apoptosis rates were found in groups 1 and 2 (P < 0.05), while in group 3, a reduction in the proteoglycan content was found (P < 0.001). Bone marrow replacement and invasion of the subchondral bone plate by fibrous tissue was found predominantly in AS joints in group 2. Conclusion Cartilage degeneration, indicated by cartilage thinning, enhanced chondrocyte apoptosis, and proteoglycan loss, and subchondral bone thinning, promoted by invasion of the subchondral bone plate by a fibrous tissue originating from the bone marrow, are hallmarks of joint remodeling in AS.

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“…Histological examinations of biopsy specimens from the SIJs [13 -16] and autopsy preparations [17] have improved our understanding of the pathogenesis of SpA. These specimens, in part also presented in this review article, were acquired in the setting of a research project with approval of the local ethics committee during the course of CT-guided steroid injections in painful patients [16].…”

mentioning

confidence: 99%

“…There is controversy about the term "synovitis" because only sparse amounts of synovial, villus-like tissue are histologically demonstrated between the iliac and sacral cartilage near the anterior and posterior joint capsules with obliteration in the further course of the disease [17].…”

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confidence: 99%

Magnetic Resonance Imaging of Sacroiliitis in Patients with Spondyloarthritis: Correlation with Anatomy and Histology

Hermann

Bollow²

2013

Fortschr Röntgenstr

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Magnetic resonance imaging (MRI) of the sacroiliac joints (SIJs) has become established as a valuable modality for the early diagnosis of sacroiliitis in patients with inconclusive radiographic findings. Positive MRI findings have the same significance as a positive test for HLA-B27. Sacroiliitis is one of the key features of axial spondyloarthritis (SpA) in the classification proposed by the Assessments in Ankylosing Spondylitis (ASAS) group.?Early signs of sacroiliitis include enthesitis of articular fibrocartilage, capsulitis, and osteitis. In more advanced disease, structural (chronic) lesions will be visible, including periarticular fatty deposition, erosions, subchondral sclerosis, and transarticular bone buds and bridges. In this article we describe magnetic resonance (MR) findings and provide histologic biopsy specimens of the respective disease stages. The predominant histologic feature of early and active sacroiliitis is the destruction of cartilage and bone by proliferations consisting of fibroblasts and fibrocytes, T-cells, and macrophages. Advanced sacroiliitis is characterized by new bone formation with enclosed cartilaginous islands and residual cellular infiltrations, which may ultimately lead to complete ankylosis. Knowledge of the morphologic appearance of the sacroiliac joints and their abnormal microscopic and gross anatomy is helpful in correctly interpreting MR findings. Citation Format: ??Hermann KGA, Bollow M. Magnetic Resonance Imaging of Sacroiliitis in Patients with Spondyloarthritis: Correlation with Anatomy and Histology. Fortschr R?ntgenstr 2014; 186: 230???237

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Histopathologic evidence that sacroiliitis in ankylosing spondylitis is not merely enthesitis: Systematic study of specimens from patients and control subjects

Abstract: In the sacroiliitis of AS, two findings predominate: 1) synovitis and subchondral bone marrow changes offer a more rational explanation for widespread joint destruction than does enthesitis; and 2) an unusual form of chondroid metaplasia contributes to ankylosis.

Cited by 192 publications

References 31 publications

The pathogenesis of ankylosing spondylitis

The pathogenesis of ankylosing spondylitis

Histomorphologic and Histomorphometric Characteristics of Zygapophyseal Joint Remodeling in Ankylosing Spondylitis

Magnetic Resonance Imaging of Sacroiliitis in Patients with Spondyloarthritis: Correlation with Anatomy and Histology

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