Immunohistological examination of open sacroiliac biopsies of patients with ankylosing spondylitis: detection of tumour necrosis factor alpha in two patients with early disease and transforming growth factor beta in three more advanced cases.

OBJECTIVE: To characterise the immunohistological features of sacroiliitis in ankylosing spondylitis (AS) at different disease stages. METHODS: Biopsy samples from sacroiliac joints (SIJs) of five patients with AS, two with early, three with advanced changes and samples from age matched controls from one necropsy SIJ and two iliac bone marrow (BM) biopsies were studied. Paraffin sections were immunostained in triplicate for T cells (CD3, CD8), macrophages (CD68), and the cytokines tumour necrosis factor alpha (TNFalpha), interferon gamma, interleukin (IL) 1beta, IL6, IL10, and transforming growth factor beta1 (TGFbeta1). Stained cells were counted over one entire high power field (x400) per section in BM, cartilage, and other connective tissue (CT). Results are the mean of three sections. RESULTS: CD3+ T cells were numerous in the BM of early AS, and in the CT of one patient with early and one with late AS, with variable proportions of CD8+ T cells. All patients with AS had more CD68+ macrophages than controls in BM and CT; in cartilage, one patient with early and one with late AS had increased CD68+ cells, some being osteoclasts. The patient with very early AS had large numbers of TNFalpha cells in the three tissular areas; for the other patient with early disease they were found only in CT and cartilage. IL6 was seen in 4/4 patients with AS in most areas. Patients with early disease had more T cells, TNFalpha, and IL6, and patients with advanced AS more TGFbeta1. CONCLUSION: The immunohistological findings of a limited sample suggest a role for BM in sacroiliitis, for TNFalpha and IL6 in early, active lesions, and for TGFbeta1 at the time of secondary cartilage and bone proliferation.

Anatomic structures involved in early- and late-stage sacroiliitis in spondylarthritis: a detailed analysis by contrast-enhanced magnetic resonance imaging.

OBJECTIVE: To localize inflammatory and chronic changes to defined areas in the sacroiliac joints in patients with early-stage compared with late-stage spondylarthritis (SpA), using magnetic resonance imaging (MRI). METHODS: Using MRI, 93 patients with SpA and inflammatory back pain who had radiographs of the sacroiliac joints were examined, comprising 31 patients with ankylosing spondylitis (AS) and 62 with other SpA subsets, including 48 with undifferentiated SpA (uSpA). MRI was performed using T1-weighted, T2*-weighted, STIR, and dynamic contrast-enhanced (gadolinium diethylenetriaminepentaacetic acid) sequences. Two readers retrospectively analyzed the images by differentiating 9 areas of the sacroiliac joints: the ventral and caudal joint capsule, cavum, subchondral bone, bone marrow, ligament entheses, and ligaments; the sacral and iliac sides were tabulated separately. RESULTS: By MRI, sacroiliitis was more often bilateral in AS (84%) than in uSpA (48%) (P = 0.01). Inflammatory changes were found in a mean +/- SD 4.7 +/- 2.9 regions/joint, with involvement of 4.5 +/- 3.2 regions in early disease versus 5.2 +/- 2.3 regions in late disease (P not significant [NS]). Involvement of the iliac side of the sacroiliac joints was found to be more frequent than the sacral side in early disease (58% versus 48%; P < 0.01) as compared with that in late disease (58% versus 63%; P NS). The dorsocaudal parts of the synovial joint and the bone marrow were the most frequently inflamed structures in early disease (P < 0.001 for ventral versus dorsal joint capsule). In contrast, involvement of the entheses was more common in advanced disease (early 43% versus late 86%; P < 0.001). Similarly, the ligaments were more frequently involved in the late stages (early 26% versus late 40%; P = 0.06). Both patterns of bone marrow inflammation (focal and diffuse) were observed in equal frequencies in early and late disease (17% and 42% versus 26% and 43%, respectively; P NS). HLA-B27-positive patients (n = 80) had more entheseal involvement than did HLA-B27-negative patients (n = 13) (60% versus 39%; P = 0.05). HLA-B27-negative patients had a shorter disease duration (2.2 years versus 4.4 years; P = 0.05) and were more often female (62%; P = 0.02). When all pathologic changes were assessed, the STIR sequence (performed in 62 patients) was less sensitive than the contrast-enhanced sequences in that it was not able to show all relevant changes in 27% of these patients (n = 17), failing to reveal inflammation of the cavum in 15 patients and of the bone marrow and joint capsule in 1 patient each. CONCLUSION: As visualized by MRI, sacroiliitis in SpA is characterized by involvement of different joint structures. Whereas the iliac and the sacral side of the sacroiliac joints are almost equally affected, the dorsocaudal synovial part of the joint is involved significantly more often than the ventral part, especially in early disease. Sacroiliac enthesitis is not a special feature of early sacroiliac inflammation.

Entheses and enthesitis: a histopathologic review and relevance to spondyloarthritides.

There are two types of entheses: fibrous, by Sharpey's fibers in membranous bone, and fibrocartilaginous, on endochondral bone, with discontinuous cement lines at the interface between insertion and bone. The connection of hyaline cartilage to subchondral bone is a kind of fibrocartilaginous enthesis. Fibrocartilages are structurally, chemically, and biomechanically intermediate between tendon and cartilage. Enthesitis is not the sole pathologic feature of spondyloarthritides. Synovitis and subchondral bone marrow changes outside the ligamentous insertions, and cartilage proliferation, are important too. In the subentheseal bone marrow and in the synovium, CD8+ T cells play a central role. Imaging of early changes is better achieved by ultrasonography and even better by magnetic resonance imaging than by radiography. No single immunologic target can be identified. The G1 domain of aggrecan is the best candidate, but this does not apply to fibrous entheses. In these complex pathologic conditions, no single abnormality can thus far be designated as a unique hallmark.

Histopathologic evidence that sacroiliitis in ankylosing spondylitis is not merely enthesitis.

OBJECTIVE: To systematically study the histopathology of sacroiliitis in ankylosing spondylitis (AS) at 5 different stages of the disease. METHODS: Two independent observers assessed 75 microscopic features in the sacroiliac (SI) joints in 12 cases of AS (5 biopsies, 7 autopsies) and in 22 control cases (all autopsies). RESULTS: In AS, synovitis, pannus formation, myxoid marrow, superficial cartilage destruction, enthesitis, intraarticular fibrous strands, new bone formation, and bony ankylosis were significantly more frequent than in control cases, in which there was more endochondral bone within deep-zone articular cartilage. Cartilaginous fusion occurred in both groups, but much earlier in AS. There was no residual synovium when the joint lumen was totally occluded. Mild but destructive synovitis and myxoid subchondral bone marrow were the earliest changes identified in AS. These lesions destroyed the adjacent articular tissues, a loss that was followed to varying degrees by fibrous scarring, woven bone, and new cartilage. The original cartilages also fused, and chondral fusion was the predominant mode of ankylosis. Both the original and the reparative cartilaginous tissues were replaced by bone. Active enthesitis occurred in 2 advanced and 3 late cases; fibrous scar tissue, presumed to represent previous enthesitis, was observed in all stages except the earliest. Paraarticular bone was at first dense, and later porotic. CONCLUSION: 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.

Arthritis and hidradenitis suppurativa diagnosed in a 48-year-old man.

We report the case of a 48-year-old man who presented with an erosive, seronegative, HLA-B27-negative, peripheral polyarthritis, associated with hidradenitis suppurativa of axillae and buttocks. The pertinent literature is reviewed. This paper is the second devoted to this topic in a radiological journal and the first to document erosion of the posterior aspect of the calcaneus.

Commented glossary for rheumatic spinal diseases, based on pathology.

OBJECTIVES: To redefine and comment on terms on a pathological basis, in order to avoid the confusion due to the use of terms with different meanings, to standardise usage among clinicians, radiologists and pathologists, and to facilitate literature searches. METHODS: Within the Committee of Pathology of the European League against Rheumatism, a study group was set up to analyse the medical literature and common practice concerning the nomenclature of rheumatic spinal diseases. The group tried to amalgamate the main trends in the field, to reconcile etymology, historical background, morphology, and common practice. RESULTS: The group warns against use of the terms 'acquired hyperostosis syndrome', '(von) Bechterew's disease', 'Kümmel's disease', 'pseudospondylolisthesis', 'rheumatoid spondylitis', 'spondylarthropathy' in the sense of spondarthritis, and 'spondylosis'. It recommends intercorporal or interapophyseal rather than intervertebral (osteo) chondrosis, zygapophyseal diverticulum rather than cyst, disc hernia rather than prolapse, spondyloarthritis rather than spondyloarthropathy, marginal rather than anterior spondylitis, and discarthrosis. It proposes 'zygarthrosis' to designate zygapophyseal osteoarthrosis. CONCLUSIONS: Knowledge of the pathological basis of diseases and an understanding of the original definitions given by those who coined new terms make it possible to avoid most of the confusion arising from improper use of spinal terms.

Illustrated glossary for spinal anatomy. With explanations and a French and German translation.

The authors define, explain, and illustrate a number of concepts pertaining to normal spinal anatomy that are of practical use but omitted in standard anatomical sources or are the subject of conflicting views: bony and cartilaginous end-plate, marginal ring, cortex of the vertebral body, isthmus, neurocentral junction, uncus, uncovertebral joint, zygapophyseal joint, annulus fibrosus, shorter and longer perivertebral ligaments, interspinous bursa, mamillo-accessory ligament. A French and German translation of recommended terms is provided as well.

Radiological study of the sacroiliac joints in vertebral ankylosing hyperostosis.

A radiological study of the sacroiliac joints was undertaken in 54 patients (32 males, 22 females) with vertebral ankylosing hyperostosis (VAH) and in 46 control patients (24 males, 22 females) matched for age and sex. The ages ranged from 38 to 90 years. The radiographs were taken in anteroposterior, oblique, and craniocaudal projections. The films were read for cranial, ventral, and caudal capsular ossifications, for ventral and caudal osteophytes, and for bone sclerosis. Cranial and/or ventral capsular ossifications were found in 28 (87.5%) males with VAH and in 4 (16.6%) control males (p less than 0.0005), but only in 2 females with VAH and no control female. Sacroiliac capsular ossifications in males with VaH are frequent from the onset, but complete bridging of the joint is not reached before the sixth decade. Women, either VAH or control, have more sacroiliac osteophytes than men. There were 11 out of 22 control women with osteophytes versus 4 out of 24 men (p less than 0.025). The incidence of osteophytes does not seem to increase with age after 50 years. Our findings support the idea of VAH being a distinct entity and not a major form of osteophytosis.

Some pathological features of ankylosing spondylitis as revealed by microradiography and tetracycline labelling.

Five spine specimens obtained at autopsy and five biopsies of sacroiliac joints from subjects with ankylosing spondylitis were submitted to microradiography and to fluorescence microscopy for detection of tetracycline. Decalcified histological sections were also prepared. Microradiography provides a link between the clinical X-ray picture and the classical decalcified section; it enables calcified cartilage, and hence the early stage of most syndesmophytes to be recognised more easily and accurately; It revealed a peculiar calcification of elastic fibers of the ligamentum flavum. Tetracycline labels showed that: in an early case of sacro-iliac arthritis, calcification of the articular cartilage might partly explain the desification of the X-ray picture; syndesmophytes were thickening at both their superficial and deep faces; thickening, lengthening and internal remodelling of the intervertebral bridges occurred together; and calcium was deposited at the end-plates as well.

Craniocaudal axial view of the sacroiliac joint.

A technique that provides a craniocaudal axial view of the sacroiliac joint is described. This technique gives information about the ventral aspect of the sacroiliac joint, particularly at the level of the pelvic brim. It can demonstrate extraarticular ventral ankylosis of the joint, which is not visible or only suspected on anteroposterior films. In osteitis condensans ilii, it shows the thickness of the involved iliac bone. It is very useful for the accurate localization of paraarticular changes.

Histocompatibility antigens in vertebral ankylosing hyperostosis.

All known A, B, and C HLA antigens were determined in 50 white patients with vertebral ankylosing hyperostosis. A statistically significant decrease was found for the A9 and A11 specificities. Only three (6%) of the patients possessed the B27 antigen, a frequency which is not different from that of a control population. B27 therefore does not seem to be linked to abundant new bone formation.