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Objective: To examine the effect of running exercise on behavioral measures of pain and intervertebral disc (IVD) inflammation in the SPARC-null mouse model., Methods: Male and female 8-month old SPARC-null and age-matched control mice received a home cage running wheel or a control, fixed wheel for 6 months. Behavioral assays were performed to assess axial discomfort (grip test) and radiating leg pain (von Frey, acetone tests) and voluntary running was confirmed. Expression of inflammatory mediators (TNF-α, IL-1β, IL-2, IL-10, CCL5, CXCL1, CXCL5, RANKL, M-CSF, and VEGF) in IVDs was determined. Additional inflammatory (IL-1β, IL-1Ra, CXCR1, CXCR2) and macrophage phenotypic markers (ITGAM, CD80, CD86, CD206, Arg1) in IVDs were investigated by qPCR., Results: Voluntary running attenuated behavioral measures of pain in male and female SPARC-null mice. Increases in mediators including IL-1β, CXCL1 and CXCL5 were observed in SPARC-null compared to control IVDs. After 6 months of running, increases in M-CSF and VEGF were observed in male SPARC-null IVDs. In females, pro-inflammatory mediators, including CXCL1 and CXCL5 were downregulated by running in SPARC-null mice. qPCR analysis further confirmed the anti-inflammatory effect of running in female IVDs with increased IL-1Ra mRNA. Running induced upregulation of the macrophage marker ITGAM mRNA in males., Conclusions: Voluntary running reversed behavioral signs of pain in male and female mice and reduced inflammatory mediators in females, but not males. Thus, the therapeutic mechanism of action may be sex-specific., Competing Interests: Declaration of Competing Interest The authors declare no competing financial interests., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: PsA is characterized by enthesitis, synovitis and osseous involvement in the peripheral and axial joints. Few studies have examined axial involvement in PsA using imaging techniques. Here we examined axial involvement in PsA patients using MRI. In addition, we determined the efficacy of 24 week adalimumab treatment in improving the MRI findings of spondylitis and sacroiliitis., Methods: This was a prospective, open-label, single-arm study in patients with PsA. Adalimumab was administered to patients for a total of 24 weeks. MRI examinations were conducted at baseline and at week 24 of adalimumab treatment., Results: Thirty-seven patients with PsA were included in this study. Spondylitis was observed in at least one site of the positive scan in 91% (n = 31) of patients with PsA. The number of arthritic sites in the cervical, thoracic and lumbar regions of the spine was 48, 67 and 53, respectively. All patients had MRI-determined sacroiliitis of grade ≥1 severity while 28 patients (82%) had grade ≥2 sacroiliitis in at least one sacroiliac region. Sacroiliac arthritis was statistically more severe on the right side than on the left side (P < 0.05). In 34 patients with PsA, the thoracic spine was the most common site of spondylitis. In addition, 24 week adalimumab treatment led to an improvement in the mean number of spondylitis sites and the mean grade of sacroiliitis., Conclusion: Treatment with adalimumab for 24 weeks resulted in improvement in spondylitis and sacroiliitis., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

To compare the surgical outcomes of autogenous spinous process with iliac bone graft in managing single segment lumbar pyogenic spondylitis (PS) after posterior debridement and instrumentation. We performed a retrospective study for adult patients with single level lumbar PS. 60 patients with single segment lumbar PS underwent one-stage posterior debridement, autogenous bone graft and instrumentations. The patients were divided into Group A (autogenous iliac bone) and Group B (autogenous spinous process). Preoperative Charlson comorbidity index (CCI) was analyzed to assess the comorbidity. Low back pain was evaluated using the visual analog scale (VAS). Neurological status was assessed with the American Spinal Injury Association (ASIA) scale. Clinical infection index including the C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) was also reviewed. Moreover, fusion and changes of sagittal alignment were investigated radiologically. There was a significantly longer operative time, hospital stay and greater blood loss in group A. The VAS scores improved significantly at each follow-up interval and post-operative VAS score was significantly lower in group B. At the last follow-up, ESR and CRP returned to normal for all patients. There was at least one grade level improvement in ASIA score. No statistical difference in corrected rate, loss of sagittal angle and lumbar lordosis was found between the two groups. There was no significant difference in fusion rate, mean fusion time and complications between the two groups. Compared with iliac bone graft, the autogenous spinous process bone graft can be less invasive and painful for the single segment lumbar PS. One-stage posterior debridement, autogenous spinous process bone graft and instrumentation can provide satisfactory results for appropriate cases.

We report a case of infectious spondylitis in a 52-year-old woman who presented with progressive difficulty in walking. The patient had a 2-month long history of neurological symptoms, which progressed rapidly to paraplegia, following her admission. Imaging studies demonstrated the presence of vertebral lesions as well as additional tissue with inflammatory elements in the spinal canal, which caused a mass effect. In combination with the presence of increased cells and protein in the cerebrospinal fluid (CSF), the differential was steered towards causes of infectious spondylitis, primarily tuberculosis. However, brucellosis was also considered, as it is endemic in our area. Prompt surgical decompression produced biopsy samples, which confirmed the presence of granulomatous inflammation. The patient was started on an empiric regimen covering both for tuberculosis and brucellosis, and gradually regained full mobility in her lower limbs. The differential of infectious spondylitis is discussed, with an emphasis on the differentiation between tuberculosis and brucellosis., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Whole-body vibration (WBV) is associated with back and neck pain in military personnel and civilians. However, the role of vibration frequency and the physiological mechanisms involved in pain symptoms are unknown., Questions/purposes: This study asked the following questions: (1) What is the resonance frequency of the rat spine for WBV along the spinal axis, and how does frequency of WBV alter the extent of spinal compression/extension? (2) Does a single WBV exposure at resonance induce pain that is sustained? (3) Does WBV at resonance alter the protein kinase C epsilon (PKCε) response in the dorsal root ganglia (DRG)? (4) Does WBV at resonance alter expression of calcitonin gene-related peptide (CGRP) in the spinal dorsal horn? (5) Does WBV at resonance alter the spinal neuroimmune responses that regulate pain?, Methods: Resonance of the rat (410 ± 34 g, n = 9) was measured by imposing WBV at frequencies from 3 to 15 Hz. Separate groups (317 ± 20 g, n = 10/treatment) underwent WBV at resonance (8 Hz) or at a nonresonant frequency (15 Hz). Behavioral sensitivity was assessed throughout to measure pain, and PKCε in the DRG was quantified as well as spinal CGRP, glial activation, and cytokine levels at Day 14., Results: Accelerometer-based thoracic transmissibility peaks at 8 Hz (1.86 ± 0.19) and 9 Hz (1.95 ± 0.19, mean difference [MD] 0.290 ± 0.266, p < 0.03), whereas the video-based thoracic transmissibility peaks at 8 Hz (1.90 ± 0.27), 9 Hz (2.07 ± 0.20), and 10 Hz (1.80 ± 0.25, MD 0.359 ± 0.284, p < 0.01). WBV at 8 Hz produces more cervical extension (0.745 ± 0.582 mm, MD 0.242 ± 0.214, p < 0.03) and compression (0.870 ± 0.676 mm, MD 0.326 ± 0.261, p < 0.02) than 15 Hz (extension, 0.503 ± 0.279 mm; compression, 0.544 ± 0.400 mm). Pain is longer lasting (through Day 14) and more robust (p < 0.01) after WBV at the resonant frequency (8 Hz) compared with 15 Hz WBV. PKCε in the nociceptors of the DRG increases according to the severity of WBV with greatest increases after 8 Hz WBV (p < 0.03). However, spinal CGRP, cytokines, and glial activation are only evident after painful WBV at resonance., Conclusions: WBV at resonance produces long-lasting pain and widespread activation of a host of nociceptive and neuroimmune responses as compared with WBV at a nonresonance condition. Based on this work, future investigations into the temporal and regional neuroimmune response to resonant WBV in both genders would be useful., Clinical Relevance: Although WBV is a major issue affecting the military population, there is little insight about its mechanisms of injury and pain. The neuroimmune responses produced by WBV are similar to other pain states, suggesting that pain from WBV may be mediated by similar mechanisms as other neuropathic pain conditions. This mechanistic insight suggests WBV-induced injury and pain may be tempered by antiinflammatory intervention.

Our aim was to determine whether the inflammatory component associated with age-related degenerative changes in the spine can be assessed by (18)F-fluoro-2-deoxy-D-glucose positron emission tomography ((18)F-FDG-PET). Mean and maximum standardize uptake values (SUV(mean) and SUV(max)) of intervertebral discs and spinous processes were measured in 45 patients who had undergone (18)F-FDG-PET for any clinical indication. Correlations between age and FDG-PET indices (SUV(mean) and SUV(max) of intervertebral discs and spinous processes) were determined. Pearson's correlation coefficients between age and intervertebral disc SUV(mean), between age and intervertebral disc SUV(max), and between age and spinous process SUV(mean) were 0.4821, 0.3946, and 0.5017 (P<0.05), indicating moderate positive correlations between these parameters. However, Pearson's correlation coefficient between age and spinous process SUV(max)was 0.7998 (P>0.05), indicating no correlation between these two parameters. In conclusion, intensity of (18)F-FDG uptake in the intervertebral discs and spinous processes generally increases with aging, which is likely to reflect associated inflammatory processes.

Pyogenic spondylitis is a neurological and life threatening condition. It encompasses a broad range of clinical entities, including pyogenic spondylodiscitis, septic discitis, vertebral osteomyelitis, and epidural abscess. The incidence though low appears to be on the rise. The diagnosis is based on clinical, radiological, blood and tissue cultures and histopathological findings. Most of the cases can be treated non-operatively. Surgical treatment is required in 10-20% of patients. Anterior decompression, debridement and fusion are generally recommended and instrumentation is acceptable after good surgical debridement with postoperative antibiotic cover.

Introduction: The purpose of this study is to evaluate the role of magnetic resonance imaging (MRI) in evaluation of tubercular spondylitis and to correlate imaging findings with clinical severity of the disease., Methods: One hundred consecutive patients, who presented with features suggestive of spinal infections, were subjected to MRI examination. T1W and STIR images were obtained followed by T2W and post-contrast T1W images. Various imaging characteristics of spinal infections were noted and correlated with the clinical severity of the disease., Results: Backache was the most common presenting symptom present in 86 %, while paraparesis was the most common sign seen in 62 %. The neurological status of the patients correlated well with MRI findings in the majority of the cases with an overall good correlation obtained in 96 % of cases. The majority of the vertebrae and intervertebral discs affected showed hypointensity or isointensity on T1W images and hyperintensity on T2W images. Epidural/dural disease was present in 74 % while 68 % of patients demonstrated decreased intervertebral disc height. Epidural extension and subligamentous spread was in 74 % and 90 % of patients respectively., Conclusions: MRI plays a vital role in early and accurate diagnosis of spinal infections. It is non-invasive and clearly demonstrates soft tissue anatomy and pathology which makes it superior to X-rays and Computed Tomography (CT). Imaging findings of tubercular spondylitis were also found to have a good correlation with the clinical status of the patients. Hence, it is of much help in the evaluation and assessment of patients presenting with features of spinal infections.

Objectives: To investigate the effectiveness of etanercept on axial manifestations of a group of patients with established psoriatic arthritis (PsA)., Methods: This was a multicentre observational study. PsA was classified based on the CASPAR criteria. Inclusion criteria were refractory PsA with axial manifestations and suitability for anti TNF-α therapy. Effectiveness was defined according to the ASAS response criteria (BASDAI: 50% relative or absolute change of 20mm and expert opinion in favour of continuation), and on the improvements of BASFI, anthropometric measures, PASI, ESR and CRP at 12 months. PASI 50 and 75 were also assessed, as well as the ACR20 and ACR50 response criteria for patients with peripheral arthritis. Comparisons between baseline and after 12-month treatment were done using the Wilcoxon signed rank test for the end-points considered., Results: The study included 32 patients (25/7 M/F; median age 51yrs; 25th-75th percentiles: 34.5-58.7; median disease duration 14.5 yrs; 25th-75th percentiles: 9.2-17.00). Effectiveness of etanercept was observed in 72% of patients for the BASDAI (p<0.001), in 68% for the BASFI (p<0.001), in 76% for ESR (p<0.001) and in 68% of patients for CRP (p<0.01). The PASI improved in 72% of patients treated (p<0.0001), while PASI 50 and PASI 75 was reached in 81% and 55% of patients, respectively. ACR 20 and 50 was reached in 78 and 56% of patients with peripheral involvement respectively., Conclusions: The present study has shown that etanercept is effective on axial manifestations of established PsA, confirming the positive effects of anti TNF-α therapy on clinical manifestations of the disease.

Background: Shoulder complaints, and especially the outlet-impingement syndrome, are a common condition. Among other things, poor posture has been discussed as a cause. A correlation between impingement syndrome and restricted mobility of the thoracic spine (T) has been described earlier, but there has been no motion analysis of the thoracic spine to show these correlations. In the present prospective study, we intended to find out whether there is a significant difference in the thoracic sagittal range of motion (ROM) between patients with a shoulder outlet impingement syndrome and a group of patients who had no shoulder pathology. Secondly, we wanted to clarify whether Ott's sign correlates with ultrasound topometric measurements., Methods: Two sex- and age-matched groups (2 x n = 39) underwent a clinical and an ultrasound topometric examination. The postures examined were sitting up straight, sitting in maximal flexion and sitting in maximal extension. The disabilities of the arm, shoulder and hand (DASH) score (obtained by means of a self-assessment questionnaire) and the Constant score were calculated. Lengthening and shortening of the dorsal projections of the spine in functional positions was measured by tape with Ott's sign., Results: On examination of the thoracic kyphosis in the erect seated posture there were no significant differences between the two groups (p = 0.66). With ultrasound topometric measurement it was possible to show a significantly restricted segmental mobility of the thoracic spine in the study group compared with the control group (p = 0.01). An in-depth look at the mobility of the subsegments T1-4, T5-8 and T9-12 revealed that differences between the groups in the mobility in the lower two sections of the thoracic spine were significant (T5-8: p = 0.03; T9-12: p = 0.02). The study group had an average Constant score of 35.1 points and the control group, 85.5 (p < 0.001). On the DASH score the patient group reached 34.2 points and the control group, 1.4 (p < 0.001). The results of Ott's sign differed significantly between the two collectives (p = 0.0018), but showed a weak correlation with the ultrasound topometric measurements (study group flexion/extension: r = 0.36/0.43, control group flexion/extension: r = 0.29/0.26)., Conclusion: The mobility of the thoracic spine should receive more attention in the diagnosis and therapy of patients with shoulder outlet impingement syndrome.

According to recent systematic reviews, Modic changes are associated with low-back pain. However, their pathophysiology remains largely unknown. A previous study of Northern Finnish males implicated that IL1A and MMP3 polymorphisms play a role in type II Modic changes. The purpose of the current study was to examine the association of IL1 cluster polymorphisms with Modic changes amongst middle-aged men in Southern Finland. The final study sample consisted of 108 men from three different occupations, who underwent magnetic resonance imaging (MRI) with a 0.1 T-scanner. Six single nucleotide polymorphisms (SNP) in the IL1 gene cluster (IL1A c.1-889C>T; IL1B c.3954C>T; IL1RN c.1812G>A; IL1RN c.1887G>C; IL1RN c.11100T>C; IL1RN c.1506G>A) were genotyped with the SNP-TRAP method or by allele-specific primer extension on modified microarray. In all, 45 subjects had Modic changes at one or more disc levels. The presence of the minor allele of IL1A (c.1-889C>T) was associated with these changes (any Modic change p = 0.031, type II changes p = 0.036). The carriers of the T-allele had a 2.5-fold risk of Modic change and the association was independent of the other IL1 gene cluster loci studied. In addition, a minor haplotype, with a frequency of 7.5% in the study population, including the minor alleles of IL1A c.1-889C>T, IL1RN c.1812G>A, and IL1RN c.1506G>A, was significantly associated with Modic changes. This observation is in accordance with the previous finding from a different geographical area, and thus confirms the importance of the IL1A gene in the pathophysiology of Modic changes.

We implemented an experimental model of asymmetrical compression loading of the vertebral end plate (VEP) in vivo. The macroscopic permeability of the VEP was measured. We hypothesized that static asymmetrical loading on vertebrae altered the macroscopic permeability of the VEP. In scoliosis, solute transport to and from the disc is dramatically decreased especially at the apical intervertebral disc. The decrease in permeability could be induced by mechanical stress. Nine skeletally immature pigs were instrumented with left pedicle screws and compression rod at the T5/T6 and L1/L2 levels. After 3 months, three cylindrical specimens of the VEP were obtained from each of the tethered levels. A previously validated method for measuring permeability, based on the relaxation pressure due to a transient-flow rate was used. A pistoning device generated a fluid flow that fully saturated the cylindrical specimen. The decrease in upstream pressure was measured using a pressure transducer, which allowed the macroscopic permeability to be derived. A microscopic study completed the approach. Overall macroscopic permeability was lower for the tethered VEPs than for the VEPs of the control group, respectively -47% for flow-in (p = 0.0001) and -46% for flow-out (p = 0.0001). In the tethered group, macroscopic permeability of the specimens from the tethered side was lower than macroscopic permeability of those from the non-tethered side, -39% for flow-out (p = 0.024) and -47% for flow-in (p = 0.13). In the control group, the macroscopic permeability was greater in the center of the VEP than in its lateral parts for flow-out (p = 0.004). Macroscopic permeability of the center of the VEPs was greater for flow-out than for flow-in (p = 0.02). There was no significant difference between thoracic and lumbar. This study demonstrated that compression loading applied to a growing spine results in decreased permeability of the VEP. This result could be explained by local remodeling, such as calcification of the cartilage end plate or sclerosis of the underlying bone.

Objective: To investigate the risk of radiographic knee osteoarthritis (OA) and lumbar spondylosis associated with occupational activity in elderly Japanese subjects using the large-scale population-based cohort of the Research on Osteoarthritis Against Disability (ROAD) study., Methods: From the baseline survey of the ROAD study, 1,471 participants age > or =50 years (531 men and 940 women) living in mountainous and seacoast communities were analyzed. Information collected included a lifetime occupational history and details of specific work place physical activities. Radiographic severity at the knee and lumbar spine was determined by the Kellgren/Lawrence (K/L) grading system., Results: The prevalence of K/L grade > or =2 knee OA and lumbar spondylosis among agricultural, forestry, and fishery workers was significantly higher than among clerical workers and technical experts in the overall population. For occupational activities, sitting on a chair had a significant inverse association with K/L grade > or =2 knee OA and lumbar spondylosis. Standing, walking, climbing, and heavy lifting were associated with K/L grade > or =2 knee OA, but were not associated with K/L grade > or =2 lumbar spondylosis. Kneeling and squatting were associated with K/L grade > or =3 knee OA., Conclusion: This cross-sectional study using a population-based cohort suggests that sitting on a chair is a significant protective factor against both radiographic knee OA and lumbar spondylosis in Japanese subjects. An occupational activity that includes heavy lifting appears to have a greater effect on knee OA than on lumbar spondylosis.

The concept of synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome has been well clarified, after Chamot et al. suggested this peculiar disorder in 1987. The most commonly affected site in SAPHO syndrome is the anterior chest, followed by the spine. However, the clinical course and taxonomic concept of SAPHO spinal lesions are poorly understood. This study was performed to analyze: (1) the detailed clinical course of spinal lesions in SAPHO syndrome, and (2) the relationship between SAPHO syndrome with spinal lesions and seronegative spondyloarthropathy. Thirteen patients with spondylitis in SAPHO syndrome were analyzed. The features of spinal lesions were a chronic onset with a slight inflammatory reaction, and slowly progressing non-marginal syndesmophytes at multi spinal levels, besides the coexistence of specific skin lesions. SAPHO syndrome, especially spinal lesions related to palmoplantar pustulosis, can be recognized as a subtype of seronegative spondyloarthropathy.

This study examines prospectively the randomised, long-term, clinical and radiological results of the treatment of spondylitis patients by ventro-dorsal or ventral spine fusion. Group 1 consisted of 12 patients who (after ventral removal of the focus of infection and autologous bone grafting) were treated by dorsal instrumentation. Group 2 consisted of ten patients who, after similar ventral removal and bone interposition, were stabilised by ventral instrumentation. The patients prospectively underwent clinical and radiological studies. In addition, they were asked to fill in self-assessment questionnaires such as the short-form (SF)-36 health survey, the Oswestry questionnaire, and the visual analog scales (VAS). The postoperative follow-ups were at 6 months, 2 years and 5.4 years. It proved possible to demonstrate clinically that patients with an isolated ventral spondylodesis feel significantly better and experience significantly less pain in the area of spinal fusion than patients with ventro-dorsal fusion 2 and 5.4 years after the operation. Over a number of years a stable fusion can be achieved through either operation. Ventral stabilisation yields more advantages than dorsal instrumentation in the long term. These advantages result in a clinically smoother course after the operation. If, in the individual case, ventral instrumentation is feasible, this method should be used.

Fourteen patients who had cervical spine surgery for cervical spondylotic myelopathy with median-nerve short-latency somatosensory-evoked potentials (SSEP) were followed preoperatively and until six months postoperatively. We evaluated the N18 latency and compared it with the JOA score recovery rate for each period. Seven patients demonstrated improvement in the N18 latency immediately following the operation and showed improvement of upper- as well as lower-extremity function 12 weeks postoperatively. We found a statistically significant correlation between improvement in the SSEP during the early decompression period and a good surgical outcome at 12 weeks postoperatively. We conclude that evaluating the median nerve SSEP is useful for prediction of the prognosis in patients with cervical spondylotic myelopathy treated surgically.

Study Design: Case report describing Burkholderia pickettii spondylitis in a healthy adult., Objectives: To describe this very rare form of spondylitis and to discuss some of the difficulties in the diagnosis of B. pickettii spondylitis., Setting: Department of Orthopaedic Surgery, Nayoro City General Hospital, Japan., Methods: A 48-year-old woman presented with a complaint of severe back pain radiating from the right side of her chest. Plain radiographs of the spine showed osteolytic destruction of the right side of the T10 vertebral body at T10 level, with an involvement of the pedicle. Magnetic resonance image of the spine showed a low signal intensity from the T10 vertebral body on a Tl-weighted image and an increased signal intensity on T2-weighted sequence image. These lesions were enhanced when a contrast medium was used. The patient underwent open biopsy and specimens were collected through the right pedicle., Results: Diagnosis was established on the basis of direct identification of the microorganism. Histological findings were consistent with examination of B. pickettii spondylitis. Chemotherapy (intravenous cefepime and per os minocycline) resulted in complete cure., Conclusion: B. pickettii is widely distributed in aqueous sources in nature and has not previously been considered to be an aggressive pathogen towards humans. This case report will help to improve our understanding of the ecology and virulent pathogenicity of this organism. A biopsy is an essential and reliable method for the early etiologic diagnosis, which will lead to prevent the development of more severe complications such as spinal cord compression.

The spondyloarthropathies include ankylosing spondylitis, reactive arthritis (including Reiter's syndrome), psoriatic arthritis, inflammatory bowel disease-associated spondyloarthropathy, and undifferentiated spondyloarthropathy. These diseases are linked by their association with the HLA-B27 gene and by the presence of enthesitis as the basic pathologic lesion. Additional clinical features include inflammatory back pain, dactylitis, and extra-articular manifestations such as uveitis and skin rash. The history and physical examination are the major diagnostic tools, although radiographic evidence of sacroiliitis is helpful. Therapeutic options include nonsteroidal anti-inflammatory drugs, sulfasalazine, methotrexate, and tumor necrosis factor-alpha inhibitors. Early recognition and appropriate treatment can help to limit disability.

Study Design: A case report., Objectives: To present and discuss some of the difficulties in the diagnosis of brucellar spondylitis., Setting: Ankara University, Ibni Sina Hospital, Turkey., Methods: We report a patient with paraplegia, misdiagnosed as having a malignancy or tuberculosis who actually suffered from brucellar spondylitis. Diagnosis was established by her history and a compatible clinical picture together with a standard tube agglutination (Wright test) titer of > or =1/160 of antibodies for brucellosis. The patient was treated with oral doxycycline, rifampicin, and ciprofloxacin combination., Results: At the end of the treatment, the blood Brucella Wright and anti-human globulin T titer levels decreased. Her lower limb weakness improved. She could walk, and climb stairs with the help of a cane. Urinary retention and fecal incontinence also resolved., Conclusion: Brucellosis is a systemic infection involving the musculoskeletal and nervous systems. Spondylitis frequently occurs in elderly patients. An early diagnosis of brucellar spondylitis can often be difficult. In endemic regions, as in the case of our country, brucellar spondylitis should always be considered in the differential diagnosis of older patients with back pain and constitutional symptoms. An early diagnosis will help to prevent the development of more severe complications such as spinal cord compression.

Objective: Experimental immunity to the G1 domain of the cartilage proteoglycan (PG) aggrecan (AG1) leads to the development of spondylitis as well as polyarthritis in BALB/c mice. The PG versican contains a structurally similar G1 domain (VG1). This study was conducted to determine whether immunity to VG1 would elicit similar pathology in these mice., Methods: Recombinant natively folded VG1 and AG1 were prepared. BALB/c mice received either a series of 5 injections of human VG1 or AG1, or no protein. Polyarthritis was determined clinically, and spondylitis and sacroiliitis histologically. Immunohistochemistry of rat tissues was used to study the localization of versican. Enzyme-linked immunosorbent assays were employed to study humoral immunity to the recombinant proteins as well as to overlapping synthetic peptides covering all these human G1 domains and mouse homologs. Affinity-purified antibodies to human AG1 and VG1 were isolated from sera of hyperimmunized mice. T lymphocyte proliferation assays were performed using recombinant human proteins. T cell lines reactive with specific immunodominant T cell epitopes in human AG1 and VG1 were isolated. Synthetic peptides encoding sequences in these human proteins and in corresponding mouse proteins were used in these analyses. Guanidinium chloride extracts of mouse spines were also used in Western blots to study antibody cross-reactivity., Results: Immunity to recombinant VG1 did not result in clinical polyarthritis. There was, however, clear evidence that VG1, like AG1, could induce spondylitis in the lumbar spine and sacroiliitis. Accumulation of mononuclear cells was observed in spinal ligaments adjacent to the intervertebral disc, in the intervertebral disc, and in the sacroiliac joints, the same sites where versican is localized. In contrast to AG1-immunized mice, in which T cells reactive with human AG1 cross-reacted with mouse AG1, there was no evidence in VG1-immunized mice that T cell immunity to human VG1 was cross-reactive with a mouse synthetic peptide that contained the sequence corresponding to the single immunodominant T cell sequence recognized in human VG1. Antibodies to specific sequences in human VG1 did, however, cross-react with human AG1 and with corresponding peptide sequences in mouse versican and aggrecan and with mouse proteins containing VG1 and AG1, present in mouse spine extracts. Similarly, antibodies to human AG1 cross-reacted with human VG1 and with extracted mouse VG1 and AG1 and synthetic peptides containing mouse sequences that corresponded to the reactive human epitopes in AG1 and VG1., Conclusion: These observations suggest that humoral immunity to human VG1 is involved in the induction of experimental spondylitis and sacroiliitis in BALB/c mice. This humoral immunity is cross-reactive with mouse versican and aggrecan but is not associated with polyarthritis, probably because of the lack of cross-reactive T cell immunity and the absence of detectable versican in articular cartilage limbs. Induction of polyarthritis by bovine or human aggrecan requires the involvement of immunity mediated by T lymphocytes that are cross-reactive to a mouse aggrecan epitope. Together these observations suggest that humoral immunity to versican as well as immunity to aggrecan may be of importance in the development of the spinal pathology characteristic of spondylarthropathies.

The concept of spondyloarthropathy (SpA) gathers together a group of chronic diseases with common clinical, biological, genetic and therapeutic characteristics. The concept forms a distinct entity, different from other rheumatic diseases. The target organs are not only the joint, but also the axial skeleton, the enthesis, the eye, the gut, urogenital tract, the skin and sometimes the heart. The prevalence of this entity in the general population is estimated 1%, equal to the prevalence of rheumatoid arthritis. Genetical predisposition (HLA-B27) is one of the clues to the pathogenesis of the disease. Since reactive arthritis is induced by specific urogenital or enterogenic bacteriae, and since the gut is implicated in different forms of spondyloarthropathies, especially in IBD, it was clear that the gut could play an important role by permitting exogenous factors to enter the body. This hypothesis was the rationale for investigating the gut in the spondyloarthropathies by performing ileocolonoscopies. In the first ileocolonoscopic studies of SpA patients, histological signs of gut inflammation were found in a relatively great number of patients, mostly without any clinical intestinal manifestations. These lesions were not seen in other inflammatory joint diseases. Further ileocolonoscopic studies confirmed the strong relationship between gut and joint inflammation. In patients in whom a second ileocolonoscopy was performed, remission of the joint inflammation was always connected with a disappearance of the gut inflammation, whereas persistence of locomotor inflammation was mostly associated to the persistence of gut inflammation. The hypothesis was proposed that some patients with a spondyloarthropathy had a form of subclinical Crohn's disease in which the locomotor inflammation was the only clinical expression. This hypothesis was confirmed in prospective long-term studies in which the ileocolonoscoped patients were reviewed 2 to 9 years later: about 6% of SpA patients not presenting any sign of Crohn's disease at first investigation but demonstrating gut inflammation on biopsy, developed full-blown Crohn's disease. The discovery of subclinical gut inflammation in the SpA had therapeutic consequences. Sulphasalazine (SASP) has been proven to be an active drug in the treatment of IBD. Since the gut could play a crucial role in SpA, it was logic to use this drug in the treatment of this disease. Multiple open and double-blind studies have proven the effectiveness of this drug in SpA; recent studies concluded that the beneficial effect of the drug in this disease entity is more prominent on the peripheral arthritis than on the axial disease.