Bone turnover biomarkers, disease activity, and MRI changes of sacroiliac joints in patients with spondyloarthritis.

The lack of valid biomarkers in patients with spondyloarthritis (SpA) requires searching for additional options to increase sacroiliac joint (SIJ) evaluation effectiveness. We assessed the serum levels of bone turnover markers and their relationships with active and chronic changes in SIJs using magnetic resonance imaging (MRI), indices, and laboratory parameters of disease activity in SpA patients. 102 patients with SpA and 15 healthy subjects were included. Testing of serum levels of transforming growth factor-beta (TGF-ß1), Wnt3, sclerostin, and Dickkopf-1 (Dkk-1) was conducted. Active inflammatory lesions in SIJs were evaluated using Spondyloarthritis Research Consortium of Canada (SPARCC) MRI SIJ score, and chronic changes using the Danish scoring method. Bath Ankylosing Spondylitis Disease Activity Index, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), Ankylosing Spondylitis Disease Activity Scores with CRP, and ESR were used to assess disease activity. Serum levels of Dkk-1, TGF-ß1, and sclerostin were significantly lower in SpA patients compared to healthy controls. The serum levels of Dkk-1 positively correlated with CRP. Dkk-1 had a significant negative correlation with Danish score. The sclerostin serum level had a weak negative correlation with the active inflammatory MRI SIJ lesions. There were positive correlations between TGF-ß1 and sclerostin with Dkk-1, and negative correlation between Wnt3 and sclerostin. Dkk-1 positively correlated with CRP and negatively with chronic SIJ changes by Danish score. Sclerostin negatively correlated with the active SIJ lesions by SPARCC. This suggests that Dkk-1 and sclerostin are the most promising candidates to reveal inflammation and bone turnover in patients with SpA.

Noncoding RNAs Involved in the Pathogenesis of Ankylosing Spondylitis.

Ankylosing spondylitis (AS) is a form of arthritis that can lead to fusion of vertebrae and sacroiliac joints following syndesmophyte formation. The etiology of this painful disease remains poorly defined due to its complex genetic background. There are no commonly accepted methods for early diagnosis of AS, nor are there any effective or efficient clinical treatments. Several noncoding RNAs (ncRNAs) have been linked to AS pathogenesis and inflammation via selective binding of their downstream targets. However, major gaps in knowledge remain to be filled before such findings can be translated into clinical treatments for AS. In this review, we outline recent findings that demonstrate essential roles of ncRNAs in AS mediated via multiple signaling pathways such as the Wnt, transforming growth factor-ß/bone morphogenetic protein, inflammatory, T-cell prosurvival, and nuclear factor-κB pathways. The summary of these findings provides insight into the molecular mechanisms by which ncRNAs can be targeted for AS diagnosis and the development of therapeutic drugs against a variety of autoimmune diseases.

An unexpected cause of sacroiliitis in a patient with gout and chronic psoriasis with inflammatory arthritis: a case report.

BACKGROUND: Inflammatory back pain is a condition characterized by inflammation of the sacroiliac joints and lower spine. It is frequently seen in patients with spondyloarthropathies like ankylosing spondylitis, psoriatic arthritis, enteropathic arthritis and reactive arthritis. Inflammatory back pain can be caused by many other conditions like infection and crystal deposition such as gout. In this case, it is difficult to specifically identify gout as a cause by ordinary imaging like magnetic resonance imaging (MRI) or ultrasound. CASE PRESENTATION: This case report describes a young man with severe psoriasis, presumptive psoriatic spondyloarthropathy and chronic extensive tophaceous gout which was difficult to treat because of non-compliance with medications and lifestyle. He presented with inflammatory type low back and buttocks pain with raised inflammatory markers. MRI of the lower back and sacroiliac joints showed features of active sacroiliitis. He was subsequently treated with a Tumor Necrosis Factor (TNF) alpha inhibitor for presumed axial psoriatic arthritis and had no significant benefit. Two attempts DECT of the lumbar spine was not executed correctly. CT lumbar spine and SIJs showed L2/3 endplate and left SIJ erosions mostly related to gout. Rasburicase was introduced. The tophi decreased in size peripherally with marginal improvement in back pain. From this study, we want to bring to the attention of physicians that gout can lead to back pain with inflammatory changes on MRI. We also want to address the importance of other imaging modalities if the cause of the back pain is not clear. CONCLUSION: This case is meant to highlight an important but overlooked cause of active sacroililitis and inflammatory type back pain in patients who have gout, and to bring to the attention that plain X-ray, MRI and ultrasound cannot differentiate between inflammatory sacroiliitis caused by seronegative arthritis versus gouty arthritis. CT scan can add more information but DECT is the preferred method for differentiation and identification of axial tophaceous gout.

Monosodium urate crystal deposition associated with the progress of radiographic grade at the sacroiliac joint in axial SpA: a dual-energy CT study.

BACKGROUND: Previous studies have revealed that ankylosing spondylitis (AS), as the progenitor of axial spondyloarthritis (AxSpA), has been characterized by the insidiously progressive nature of sacroiliitis and spondylitis. Dual-energy computed tomography (DECT) has recently been used to analyse the deposition of monosodium urate (MSU) crystals with higher sensitivity and specificity. However, it remains unclear whether the existence of the MSU crystal deposition detected by DECT at the sacroiliac joint in patients with AxSpA also is associated with the existing structural damage. Here, we performed this study to show the DECT MSU crystal deposits in AxSpA patients without coexisting gout and to ascertain the relationship between the MSU crystal deposition and the structural joint damage of sacroiliac joints. METHODS: One hundred and eighty-six AxSpA patients without coexisting gout were recruited. The plain radiographs of the sacroiliac joint were obtained, along with the DECT scans at the pelvis and the clinical variables. All statistics based on the left or right sacroiliac joint damage grading (0-4) were calculated independently. Bivariate analysis and ordinal logistic regression was performed between the clinical features and radiographic grades at the sacroiliac joint. RESULTS: At the pelvis, large quantities of MSU crystal deposition were found in patients with AxSpA. The average MSU crystal volume at the left sacroiliac joint, the right sacroiliac joint, and the pelvis were 0.902 ± 1.345, 1.074 ± 1.878, and 5.272 ± 9.044 cm3, values which were correlated with serum uric acid concentrations (r = 0.727, 0.740, 0.896; p < 0.001). In bivariate analysis, wide clinical variables were associated with the changes in sacroiliac joint damage. Further, the AxSpA duration, BASFI score, and the volume of MSU crystal at both sides of sacroiliac joint were associated with the progress of radiographic grade at the sacroiliac joints in the ordinal logistic models (left AOR = 1.180, 3.800, 1.920; right AOR = 1.190, 3.034, 1.418; p < 0.01). CONCLUSIONS: Large quantities of MSU crystal deposition detected by DECT were found at the pelvis in AxSpA patients without coexisting gout. In addition to AxSpA duration and BASFI score, the MSU crystal deposition at the sacroiliac joint is associated with the progress of radiographic grade at sacroiliac joints in those patients.

The Accessory Sacroiliac Joint Diagnosed With Bone SPECT/CT.

The accessory sacroiliac (SI) joint is not rare and can be one of the causes of lower back pain. We present a case of a 35-year-old woman with chronic lower back pain. Conventional radiography was equivocal, and bone scintigraphy showed a focus of mildly increased uptake in left SI joint region. SPECT/CT revealed increased uptakes in the accessory articulations between both sacral alae and iliac bones, and confirmed the diagnosis of accessory SI joint. This case illustrates the SPECT/CT findings of the accessory SI joint.

Fat Metaplasia on Sacroiliac Joint Magnetic Resonance Imaging at Baseline Is Associated with Spinal Radiographic Progression in Patients with Axial Spondyloarthritis.

OBJECTIVE: To study the relationship between inflammatory and structural lesions in the sacroiliac joints (SIJs) on MRI and spinal progression observed on conventional radiographs in patients with axial spondyloarthritis (axSpA). METHODS: One hundred and ten patients who fulfilled the ASAS axSpA criteria were enrolled. All underwent SIJ MRI at baseline and lumbar spine radiographs at baseline and after 2 years. Inflammatory and structural lesions on SIJ MRI were scored using the SPondyloArthritis Research Consortium of Canada (SPARCC) method. Spinal radiographs were scored using the Stoke AS Spinal Score (SASSS). Multivariate logistic regression analysis was performed to identify predictors of spinal progression. RESULTS: Among the 110 patients, 25 (23%) showed significant radiographic progression (change of SASSS≥2) over 2 years. There was no change in the SASSS over 2 years according to the type of inflammatory lesion. Patients with fat metaplasia or ankyloses on baseline MRI showed a significantly higher SASSS at 2 years than those without (p<0.001). According to univariate logistic regression analysis, age at diagnosis, HLA-B27 positivity, the presence of fat metaplasia, erosion, and ankyloses on SIJ MRI, increased baseline CRP levels, and the presence of syndesmophytes at baseline were associated with spinal progression over 2 years. Multivariate analysis identified syndesmophytes and severe fat metaplasia on baseline SIJ MRI as predictive of spinal radiographic progression (OR, 14.74 and 5.66, respectively). CONCLUSION: Inflammatory lesions in the SIJs on baseline MRI were not associated with spinal radiographic progression. However, fat metaplasia at baseline was significantly associated with spinal progression after 2 years.

Metabolic disturbances identified by SPECT-CT in patients with a clinical diagnosis of sacroiliac joint incompetence.

PURPOSE: To establish the sensitivity and specificity of cross-sectional scintigraphy [single photon emission computed tomography (SPECT)] combined with computed X-ray tomography (CT) in the detection of sacroiliac joint (SIJ) mechanical dysfunction and evaluate reproducibility of reporting. METHODS: Patients with pelvic girdle pain either on the basis of peri-partum SIJ dysfunction or trauma were included. These patients were imaged with bone scintigraphy with hybrid imaging with SPECT/CT. RESULTS: The study group comprised 100 patients (72 females, 28 males). Trauma accounted for 52% and the remainder were patients with peri-partum pain. Average age was 43 years and average length of history was >2 years. The major finding was increased uptake in the upper SIJ and posterior soft-tissues/ligaments. Hybrid imaging had a sensitivity of 95% and specificity of 99%. Positive predictive value was 99% and negative predictive value 94%. Power of the test was 1.0. Reproducibility of the test was good with kappa values of 0.85. CONCLUSION: Hybrid imaging with SPECT/CT reproducibly demonstrates metabolic alterations around the SIJ in patients with SIJ dysfunction, which we have termed SIJ incompetence. The condition is more common than previously recognised and frequently occurs after trauma, which has not been reported previously.

18F-fluoride PET/CT for detection of sacroiliitis in ankylosing spondylitis.

PURPOSE: The aim of this study was to evaluate the performance of (18)F-fluoride-PET/CT (PET/CT) for the diagnosis of sacroiliac joint (SIJ) arthritis in patients with active ankylosing spondylitis (AS). METHODS: Included in the study were 15 patients with AS according to the modified New York criteria (AS group) and with active disease and 13 patients with mechanical low back pain (MLBP; control group) who were investigated with whole-body (18)F-fluoride PET/CT. The ratio of the uptake in the SIJ and that in the sacrum (SIJ/S) was calculated for every joint. RESULTS: The mean SIJ/S ratio of 30 quantified joints in the AS group was 1.66 (range 1.10-3.07) with PET/CT, and the mean SIJ/S ratio of 26 quantified joints in the MLBP group was 1.12 (range 0.71-1.52). The area under the receiver operating characteristic curve for SIJ arthritis was 0.84. With plain radiography as a the gold standard and taking an SIJ/S ratio of >1.3 as the threshold, the sensitivity, specificity and accuracy on a per patient basis were 80%, 77% and 79%, respectively. On a per SIJ basis, the greatest sensitivity (94%) was found in grade 3 sacroiliitis (n = 16). CONCLUSION: Our results suggest that quantitative (18)F-fluoride PET/CT may play a role in the diagnosis of sacroiliitis in active AS and is an alternative to conventional bone scintigraphy in times of molybdenum shortage.

Computed tomography guided intra-articular injection of etanercept in the sacroiliac joint is an effective mode of treatment of ankylosing spondylitis.

OBJECTIVES: To determine the pathological features of sacroiliitis and the expression of cytokines in joint biopsy samples in patients with ankylosing spondylitis (AS) and to investigate the variance in single photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI) scans, and the response to intra-articular injection of anti-tumour necrosis factor (TNF) therapy. METHODS: Sixteen patients with AS were given CT-guided intra-articular injections of etanercept at 0, 4, and 8 weeks (25 mg per dose). Pathological features of sacroiliitis were observed with light microscopy and immunohistochemistry. Expression of cytokines in joint biopsy samples was estimated by reverse transcription polymerase chain reaction (RT-PCR). Imageological changes in sacroiliitis were observed by SPECT/CT and MRI. All patients were followed up clinically. RESULTS: In all 16 patients who received intra-articular etanercept, sacroiliac joint (SIJ) region of interest (ROI) mean values determined by SPECT improved significantly after 8 weeks (p < 0.05). Bone marrow hydropsia and fatty deposition detected on MRI were relieved significantly after 8 weeks (p < 0.05). In eight patients the expression of TNFalpha and transforming growth factor (TGF)-beta mRNA in joint tissue decreased significantly after 8 weeks (p < 0.05). The frequency of synovitis, enthesitis, chondritis, subchondral bony plate destruction, and bone marrow inflammation decreased significantly, along with the inflammatory cell index (p < 0.05). Participants showed significant clinical improvement after 8 and 12 weeks (p < 0.001) in the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score but no significant difference in spondylitis and periphery arthritis (p > 0.05). This mode of treatment had no notable adverse events. CONCLUSIONS: This study has shown that intra-articular injection of etanercept in SIJ can improve joint function. It has a satisfactory safety profile and is cost-effective. This mode of treatment is most beneficial in local arthropathy of recent onset.

Possible nociceptive structures in the sacroiliac joint cartilage: An immunohistochemical study.

The sacroiliac joint (SI joint) is a known source of low back pain. In the absence of validated physical signs and imaging studies, the diagnosis of SI joint pain can be secured by positive response to SI joint intra-articular infiltration with local anesthetics. The current anatomical and histological knowledge concerning intra-articular structures of the sacroiliac joint is insufficient to explain the efficacy of this infiltration. Consequently, this study was undertaken to detect the intra-articular presence of substance P and calcitonin gene-related peptide (CGRP) positive nerve fibers, providing indirect evidence of nociceptive innervation of the SI joint. Free-floating sections, obtained from iliac and sacral cartilage and subchondral bone of the SI joint and adjacent ligamentous tissue, of 10 human cadavers were studied immunohistochemically. Tissue of nine human cadavers showed the presence of substance P and CGRP immunoreactivity in the superficial layer of sacral and iliac cartilage, and the surrounding ligamentous structures. Subchondral bone reacted weakly to the antisera used. These findings support the view that the SI joint may be capable of intra-articular nociception and may explain the positive response to the intra-articular deposition of local anesthetic.

Nociceptive nerve fibers in the sacroiliac joint in humans.

BACKGROUND AND OBJECTIVES: A positive response to sacroiliac joint intra-articular infiltration with local anesthetics is used to confirm sacroiliac joint pain. However, current anatomical and histological knowledge concerning the anatomy of pain perception within the sacroiliac joint intra- and peri-articular structures is insufficient to explain the efficacy of this infiltration, because of the use of unspecific histochemical visualization techniques. METHODS: In this study, immunohistochemistry for calcitonin gene-related peptide (CGRP) and substance P was used to trace nociceptive fibers and receptors in the anterior and interosseous sacroiliac ligaments obtained from 5 human cadavers without history of sacroiliac joint pain. RESULTS: Microscopic analysis of stained slides showed presence of CGRP and substance P immunoreactive fibers. Thick, wavy, formed bundles were observed in dense and loose connective tissue, whereas single, beaded nerve fibers, occasionally ramified, were observed more frequently in the dense connective tissue and next to blood vessels. Based on their morphologic features, these immunoreactive structures were classified as receptors type IV. Additionally, receptors type II were found in anterior and interosseous ligaments, which contained CGRP or substance P immunoreactive free nerve endings. CONCLUSIONS: We conclude that the presence of CGRP and substance P immunoreactive fibers in the normal anterior capsular ligament and interosseous ligament provides a morphological and physiological base for pain signals originating from these ligaments. Therefore, diagnostic infiltration techniques for sacroiliac joint pain should consider extra- as well as intra-articular approaches.

Sacroiliitis and polyneuropathy during isotretinoin treatment.

Isotretinoin, a medication for acne, has been reported to cause a variety of side effects on the musculoskeletal system. We present a case of sacroiliitis (a relatively uncommon feature) and sensorimotor demyelinating polyneuropathy, which has been reported previously in only a few cases during isotretinoin therapy. Clinical symptoms were improved after the withdrawal of isotretinoin and the follow-up electrophysiological study performed 2 years after the initial diagnosis of polyneuropathy showed mild improvement. Dermatologists are advised to be alert to symptoms of polyneuropathy and sacroiliitis during treatment with isotretinoin.

Adalimumab significantly reduces both spinal and sacroiliac joint inflammation in patients with ankylosing spondylitis: a multicenter, randomized, double-blind, placebo-controlled study.

OBJECTIVE: To compare the efficacy of adalimumab versus placebo in reducing spinal and sacroiliac (SI) joint inflammation, by magnetic resonance imaging (MRI) in patients with active ankylosing spondylitis (AS). METHODS: This was a randomized, multicenter, double-blind, placebo-controlled study. Patients (n = 82) received 40 mg adalimumab or placebo every other week during an initial 24-week double-blind period. MRIs of both the spine and SI joints were obtained at baseline, week 12, and week 52. Spinal and SI joint inflammation were measured using the Spondyloarthritis Research Consortium of Canada (SPARCC) MRI index. RESULTS: The spine SPARCC score in placebo-treated patients increased by a mean of 9.4% from baseline, compared with a mean decrease of 53.6% in adalimumab-treated patients (P < 0.001); the SI joint SPARCC score decreased by a mean of 12.7% from baseline in placebo-treated patients and by 52.9% in adalimumab-treated patients (P = 0.017). The response in adalimumab-treated patients was maintained at week 52. Placebo-treated patients were switched to open-label adalimumab treatment at week 24 and experienced similar reductions in spinal and SI joint inflammation by week 52. Similar large reductions in the spine and SI joint SPARCC scores were noted, even in patients who failed to meet the ASsessment in Ankylosing Spondylitis (International Working Group) criteria (nonresponders) at 12 weeks. In adalimumab-treated patients, a reduced C-reactive protein concentration at week 12 was significantly associated with improvement in the spine SPARCC score (P = 0.018). CONCLUSION: Adalimumab significantly reduced both spinal and SI joint inflammation in patients with active AS after 12 weeks of treatment, and these improvements were maintained for up to 52 weeks.

The histopathology of spondyloarthropathy.

An extensive histopathological analysis of diseased tissues and organs is a crucial step in our understanding of how specific molecular and cellular events described in vitro or in animal models might by relevant to the clinical presentation of a specific disease in humans. Although in spondyloarthropathy (SpA) such an approach is hampered by the fact that some target tissues are not readily accessible for biopsy sampling (the sacroiliac joint, the axial skeleton, the enthesis, and the eye), numerous histological studies of the synovial membrane of the peripheral joint, the gut, and the skin have contributed to new insights into the cellular and molecular base of SpA. Firstly, the peripheral synovitis is characterized by an extensive hypervascularity and the presence of specific macrophage and T cell subsets. Secondly, the fact that the same subsets of macrophages and T cells can be identified in the gut mucosa, even before histological inflammation is present, point to a role for early immune alterations of the gut in the development of the disease. Thirdly, macrophages and macrophage-derived cytokines such as the pro-inflammatory TNFalpha and the anti-inflammatory IL-10 appear to be crucial mediators of the tissue inflammation. Therefore, neovascularization, recirculation of inflammatory cells between gut and synovium, and macrophage-derived cytokines are all potential targets for immunotherapy. As a proof of concept, anti-TNFalpha treatment has been demonstrated to have an impressive clinical effect as well as a major impact on the histological tissue inflammation. Further research should benefit from the combination of classical histopathology with newer molecular techniques (genomics, proteomics) to unravel the molecular and cellular base of the different disease presentations and should aim to translate these basic findings into clinical applications such as histopathological differential diagnosis and follow-up of targeted therapies.

Histologic analysis of neural elements in the human sacroiliac joint.

STUDY DESIGN: The posterior ligament of the human sacroiliac joint was examined for nerves and nerve endings using histologic and immunohistochemical techniques. OBJECTIVE: To identify nerve fibers and mechanoreceptors in the posterior ligament. SUMMARY OF BACKGROUND DATA: According to the findings of previous studies, the human sacroiliac joint receives myelinated and unmyelinated axons that presumably conduct pain and proprioceptive impulses derived from mechanoreceptors and free nerve endings in the human sacroiliac joint. METHODS: Tissue obtained from six patients was stained with gold chloride and that obtained from six additional patients was stained using antibodies specific for substance P and protein gene product 9.5. RESULTS: The staining of joint tissue using the gold chloride technique showed myelinated and unmyelinated nerve fibers, two morphotypes of paciniform encapsulated mechanoreceptors, and a single nonpaciniform mechanoreceptor. Analysis using immunohistochemical staining for protein gene product 9.5 did not unequivocally show axons, nerve fascicles, or mechanoreceptors. Similarly, analysis based on immunohistochemical staining for substance P, one of several neurotransmitters known to signal pain from the periphery, showed reactive elements that may have been nerves, but because of background staining, could not be positively identified as such. CONCLUSIONS: The presence of nerve fibers and mechanoreceptors in the sacroiliac ligament demonstrates that the central nervous system receives information, certainly proprioceptive, and possibly pain from the sacroiliac joint. Although it is not known how the central nervous system uses such information, it seems reasonable to speculate that the proprioceptive information is used to optimize upper body balance at this joint. In addition, because the staining techniques used generally to show nerves and nerve elements in periarticular connective tissue are nonspecific, the distinction between neural and nonneural should be made on the basis of both morphologic and staining characteristics.

Age-related changes in the articular cartilage of human sacroiliac joint.

Iliac and sacral articular cartilage of 25 human sacroiliac joints (1-93 years) are examined by light microscopy and immunohistochemistry in order to gain further insight into the nature and progress of degenerative changes appearing during aging. These changes can already be seen in younger adults as compared to cartilage degeneration known in other diarthrodial joints. Structural differences between sacral and iliac cartilage can already be observed in the infant: the sacral auricular facet is covered with a hyaline articular cartilage, reaching 4 mm in thickness in the adult and staining intensely blue with alcian blue at pH1. Iliac cartilage of the newborn is composed of a dense fibrillar network of thick collagen bundles, crossing each other at approximately right angles. A faint staining with alcian blue suggests a low content of acidic glycosaminoglycans. In the adult, iliac cartilage becomes hyaline and its maximal thickness reaches 1-2 mm. Both articular facets exhibit morphological changes during aging that are more pronounced in the iliac cartilage and resemble osteoarthritic degeneration; the staining pattern of the extracellular matrix becomes inhomogenous, chondrocytes are arranged in clusters and the articular surface develops superficial irregularities and fissures. Sometimes fibrous tissue fills up these defects. Nevertheless, large areas of iliac cartilage remain hyaline in nature. Sacral articular cartilage often remains largely unaltered until old age. The sacral subchondral bone plate is usually thin and shows spongiosa trabeculae inserted at right angles, suggesting a perpendicular load on the articular facet. Iliac subchondral spongiosa shows no definite alignment and joins the thickened subchondral bone plate in an oblique direction. The iliac cartilage therefore seems to be stressed predominantly by shearing forces, arising from the changing monopodal support of the pelvis during locomotion. The subchondral bone plate on both the iliac and sacral auricular facet is penetrated by blood vessels that come into close contact with the overlying articular cartilage. These vessels may contribute to the high incidence of rheumatoid and inflammatory diseases in the human sacroiliac joint. Immunolabelling with an antibody against type II collagen reveals a diminished immunoreactivity in the upper half of adult sacral cartilage and only a faint and irregular labelling in the iliac cartilage. Type I collagen can be detected in a superficial layer on the sacral articular surface and around chondrocyte clusters in iliac cartilage, as in dedifferentiating chondrocytes during the development of osteoarthritis.

Use of immunohistologic and in situ hybridization techniques in the examination of sacroiliac joint biopsy specimens from patients with ankylosing spondylitis.

OBJECTIVE: To investigate mechanisms involved in inflammation and new bone formation in the sacroiliac (SI) joints of patients with ankylosing spondylitis (AS). PATIENTS AND METHODS: Computed tomography-assisted biopsy of the SI joint was performed in 5 patients with AS with a mean disease duration of 4.5 years and radiographic stage 2-3 disease. Immunohistologic studies were performed with the alkaline phosphatase-anti-alkaline phosphatase technique, and cytokine messenger RNA (mRNA) was detected by in situ hybridization. RESULTS: Dense cellular infiltrates with varying amounts of CD3+ cells (mean +/- SD 53.3 +/- 24.1%), CD4+ cells (29.7 +/- 17.6%), CD8+ cells (15.8 +/- 11.4%), CD14+ cells (23.6 +/- 16.9%), CD45RO+ cells (48.4 +/- 23.6%), and CD45RA+ cells (4.5 +/- 2.9%) were found in the synovial portion of the SI joints of all 5 patients. In these infiltrates a high amount of tumor necrosis factor alpha (TNF alpha) mRNA and, near the site of new bone formation, a lower amount of transforming growth factor beta (TGF beta) mRNA, were detected, while no message for interleukin-1 was found in the 3 patients examined by this technique. CONCLUSION: The presence of T cells and macrophages was demonstrated in cellular infiltrates in the SI joints of 5 patients with active AS. The finding of abundant TNF alpha message in these joints could have implications regarding potential immunotherapeutic approaches to this disease. TGF beta might be involved in new bone formation in AS.

A combined method for quantitative pertechnetate scintigraphy in the diagnosis of sacroiliitis. A controlled study.

A simplified scintigraphic technique for the assessment of sacroiliitis is described. It is based on the fact that an inflamed joint shows increased perfusion activity after administration of sodium pertechnetate. The sacroiliac joints are located by injection of a small amount of bone-seeking activity. Thereafter the pertechnetate activity is injected and the bone-seeking activity subtracted. The perfusion (pertechnetate) activity of the sacro-iliac joints is related to the activity of the large vessels of the thigh. Normal values have been established based on a study of 39 healthy controls. The method has been applied to 2 groups of patients with clinical sacroiliitis, one with and one without radiographical signs of sacroiliitis. The patients with radiographically verified sacroiliitis showed significantly higher values than the controls. The technique offers a high specificity and a high positive predictive value.

Gas in spinal articulations.

The purpose of this review is to illustrate, some for the first time, a variety of gas collections in lumbar facet joints and intervertebral discs and in the sacroiliac joint.