Immunoglobulin A antibodies to oxidized collagen type II as a potential biomarker for the stratification of spondyloarthritis from rheumatoid arthritis.

OBJECTIVES: The discovery of diseased tissue-specific neoantigens offers the opportunity to develop important disease tissue-specific biomarkers that can help in the prediction, diagnosis, and stratification of diseases. This opportunity is specifically significant for autoimmune diseases where diagnostic biomarkers are not available. Inflammatory autoimmune diseases are commonly associated with local generation of large amounts of reactive oxidants. We have previously identified oxidative post-translationally modified (oxPTM) tissue-specific neoantigens in rheumatoid arthritis (RA) and type 1 diabetes that elicit an immune response. In the current study, we studied the presence and clinical significance of antibodies to oxPTM collagen type II (CII) in patients with spondyloarthritis (SpA). METHOD: Levels of antibodies specific to native CII and oxPTM-CII were assessed by enzyme-linked immunosorbent assay. RESULTS: Immunoglobulin G (IgG) binding to oxPTM-CII was observed in 52%, 83%, and 28% of serum samples from patients with axial spondyloarthritis (axSpA), RA, and psoriatic arthritis (PsA), respectively. Importantly, while strong IgA anti-oxPTM-CII responses were detected in axSpA and PsA patients, with 47% and 84% respective binders, no IgA anti-oxPTM-CII was detected in RA patients. IgA anti-oxPTM-CII reactivity in axSpA patients treated with biologics was higher and more frequent, with 85% binders compared to 9% binders in patients treated with synthetic disease-modifying anti-rheumatic drugs. CONCLUSION: Our data imply that SpA and PsA are associated with the presence of antibodies to oxPTM-CII, suggesting that there may be a humoral component that may distinguish patients with SpA from RA. Our approach could be adapted to other diseases, particularly to inflammatory autoimmune diseases.

Tumor necrosis factor inhibitors are associated with reduced complement activation in spondylarthropathies: An observational study.

BACKGROUND: The complement system is involved in pathogenesis of cardiovascular disease, and might play a role in accelerated atherogenesis in spondylarthropathies (SpA). Hence, we examined complement activation in SpA, and its relationship to antirheumatic treatment, inflammatory and cardiovascular markers. METHODS: From PSARA, a prospective observational study, we examined 51 SpA patients (31 psoriatic arthritis (PsA), and 20 ankylosing spondylitis (AS)), starting tumor necrosis factor (TNF) inhibitor alone (n = 25), combined with methotrexate (MTX) (n = 10), or MTX monotherapy (n = 16). Complement activation was determined by the soluble terminal complement complex (sC5b-9), inflammation by erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), and endothelial function by finger plethysmography (Endopat) at baseline, after 6 weeks and 6 months of treatment. RESULTS: SpA patients had sC5b-9 levels at (PsA) or above (AS) the upper limit of the estimated reference range. Median sC5b-9 levels decreased significantly from baseline to 6 weeks, with no significant difference between the AS and PsA group. Notably, a significant reduction in sC5b-9 was observed after administration of TNF inhibitor ± MTX, whereas no significant changes were observed in patients treated with MTX alone. Between 6 weeks and 6 months, sC5b-9 remained stable across all subgroups. Reduction in sC5b-9 was independently related to decreased ESR and CRP, and to increased high density cholesterol and total cholesterol. Reduction in sC5b-9 from baseline to 6 weeks was associated with improved EF in age and gender adjusted analyses. CONCLUSION: TNF-inhibition, but not MTX monotherapy, led to rapid and sustained reduction of complement activation in SpA. Thus, the observed decrease in cardiovascular morbidity in patients treated with TNF-inhibitors might be partly due to its beneficial effect on complement. TRIAL REGISTRATION: Clinical Trials (NCT00902005), retrospectively registered on the 14th of May 2009.

[Methods of efficacy assessment of the knee joint radiosynoviorthesis- personal experience].

OBJECTIVE: Introduction: Radiosynoviorthesis (RS) is local method of treatment of remittent joint effusions among patients who obtained general improvement after disease modifying anti-rheumatic drugs therapy but one or a few joints stay resistant to this treatment and intraarticular corticosteroids injections. The aim: The attempt to identification methods of efficacy assessment of the 90yttrium knee joint RS. PATIENTS AND METHODS: Material and methods: The study group consisted of 43 patients with rheumatoid arthritis (RA) and 19 patients with inflammatory spondyloarthropaties (SPA) where 8 patients were treated for ankylosing spondylitis (AS), 4 for psoriatic arthritis (PsA) and 7 due to undifferentiated inflammatory spondyloarthropaties (USPA). The efficacy of RS was measured subjectively by the patient, physically by the physician and with the help of chosen scores (DAS28), questionnaires (HAQ), laboratory parameters [ESR, level of CRP, osteoprotegerin (OPG), serum amyloid A (SAA), hialuronic acid (HA)] and three-phase bone scintigraphy of affected knee joints. RESULTS: Results: In RA patients very good results - no knee effusion were obtained in 25 (58,1%) joints, good results - minimal effusion in 10 (23,3%) knees and lack of improvement in 8 (18,6%) patients. Cumulatively very good and good results were obtained in 35 (81,4%) treated knee joints. In SPA patients very good results were noted in 12 (63,2%), good in 5 (26,3%), lack of improvement in 2 (10,5%) patients. Cumulatively very good and good results were obtained in 17 (89,5%) treated knee joints. We observed favorable profile changes of chosen scores (DAS28), questionnaires (HAQ), laboratory parameters (ESR, CRP, OPG, SAA, HA) and results of three-phase bone scintigraphy of knee joints. CONCLUSION: Conclusions: 90Yttrium RS is effective treatment of recurrent knee joints effusion in patients with RA i SPA. RS despite being local treatment decreases unspecific inflammatory process and systemic disease activity among patients with RA i SPA. The anatomic period of affected knee joints has negative correlation with treatment efficacy. 90Yttrium RS is safe procedure, favourable profile changes of cartilage and bone turn-over markers after therapy indicates protective influence of RS on these structures. The treatment response based on physical examination, subjective patient's evaluation, acute phase laboratory parameter levels and appropriate scores, questionnaires and imaging exams is fast and long-lasting.

Prevalence of thyroid autoantibodies in patients with systematic autoimmune rheumatic diseases. Cross-sectional study

ABSTRACT BACKGROUND: Thyroid autoimmunity is more common in patients with rheumatic diseases than in healthy populations. The degree of association seems subject to influence from patients' geographical location. Here, we aimed to ascertain the prevalence of thyroid autoantibodies in a cohort of patients with systemic rheumatic disease and the degree of association between its presence and inflammatory activity. DESIGN AND SETTING: Cross-sectional observational study in a rheumatology unit. METHODS: 301 patients with systemic lupus erythematosus (SLE), 210 with rheumatoid arthritis (RA), 58 with scleroderma (SSc) and 80 with spondyloarthritis (SpA) were studied regarding thyroid function (TSH and T4), anti-thyroglobulin (TgAb) and anti-thyroperoxidase (TPOab) and compared with 141 healthy controls. Disease activity in patients with rheumatic disease was assessed through appropriate indexes. RESULTS: There were more antithyroid antibodies in SLE patients with hypothyroidism (P = 0.01; odds ratio, OR 2.7; 95% confidence interval, CI: 1.20-6.26) and in those without hypothyroidism (P = 0.06; OR 2.4; 95% CI: 1.28-4.55) than in controls. SSc patients also showed: P = 0.03 both with antithyroid antibodies and hypothyroidism (OR 3.4; 95% CI: 1.06-10.80) and without hypothyroidism (OR 3.1; 95% CI: 1.11-0.13). RA and SpA patients had the same prevalence as controls (P not significant). Presence of autoantibodies with and without hypothyroidism was not associated with the activity or functional indexes evaluated. CONCLUSION: SLE and SSc were associated with higher prevalence of thyroid autoantibodies in patients with and without hypothyroidism, unlike SpA and RA. There was no link between thyroid autoantibody presence and disease activity or functional impairment.

[Acne inversa/hidradenitis suppurativa: A challenge for the future]. / Acne inversa/Hidradenitis suppurativa: Eine Herausforderung für die Zukunft.

Acne inversa (AI)/hidradenitis suppurativa is a chronic recurrent inflammatory dermatosis with signs of a systemic disease. AI is characterized by typical skin alterations in body areas bearing apocrine glands. The care of the AI patients in Germany is still inadequate. This situation might be significantly improved through the following efforts: (i) shortening of the time between the disease onset and the diagnosis/start of therapy; (ii) the in-depth investigation of AI pathogenesis with the aim of identifying innovative therapeutic targets and blood biomarkers; (iii) establishing a method for quantifying the severity of the disease, which takes into account both the clinical assessment and objective laboratory parameters and the self-assessment of the patient (e.g., Dermatology Life Quality Index [DLQI]); (iv) the elaboration of a clear algorithm for the interdisciplinary treatment of patients, which, in addition to the therapy of skin lesions, also includes lifestyle-modification measures and takes into consideration the systemic character of AI. This article describes the current problems of medical care for AI patients and outlines how we can achieve the predetermined goals.

Elevated levels of serum MRP8/14 in ankylosing spondylitis: associated with peripheral arthritis and active disease.

Monocytes of patients with ankylosing spondylitis (AS) have toll-like receptor 4 (TLR4) overexpression on their monocytes. Myeloid-related protein (MRP) 8/14 protein complexes are calcium-binding proteins, which act as endogenous ligands to TLR4. Thus, we studied the levels of MRP8/14 in adult AS patients. MRP8/14 levels were assessed in 99 adult AS patients satisfying Assessments in Ankylosing Spondylitis International Society 2010 criteria and 71 healthy controls by ELISA. Patient disease parameters like patient and physician global assessment, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), swollen and tender joint count, entheseal count by Maastricht enthesitis index, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were also recorded. Levels were reassessed in 23 patients after 2-5 months of treatment with NSAIDs. All values are in median (IQR). The serum MRP8/14 levels in patients [34.1 (17.94-264.58) µg/ml] were significantly higher than in healthy controls [4.94 (IQR 3.01-8.32) µg/ml (p < 0.0001)]. Patients with peripheral arthritis (n = 50) had higher levels than those with pure axial disease (n = 49) [40.63 (IQR 28.41-73.15) µg/ml vs. 23.72 (11.04-61.55) µg/ml; p = 0.012]. Levels of MRP8/14 correlated with AS Disease Activity Score (DAS)-CRP (r = 0.23, 95%CI = 0.038-0.422, p = 0.02) and CRP (r = 0.28, 95%CI = 0.081-0.45, p = 0.01), and the correlation was better in early disease [≤5 years disease duration; r = 0.40, p = 0.007 and r = 0.57, p = <0.0001, respectively]. Baseline levels were higher in treatment responders than in non-responders [51.17 vs. 32.22 µg/ml; p = 0.02]. Change in MRP8/14 levels correlated with change in BASDAI and ASDAS-CRP (r = 0.489, p = 0.018 and r = 0·498, p = 0.016, respectively). MRP8/14 levels may be used as a biomarker for activity, peripheral arthritis, and response to therapy.

Impaired response to treatment with tumour necrosis factor α inhibitors in smokers with axial spondyloarthritis.

OBJECTIVES: To investigate the impact of smoking on the response to treatment with a first tumour necrosis factor inhibitor (TNFi) in patients with axial spondyloarthritis (axSpA) in a real-life cohort. METHODS: Patients fulfilling the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for axSpA in the Swiss Clinical Quality Management Cohort were included in this study. The potential association between smoking status and differential response to TNFi in terms of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Ankylosing Spondylitis Disease Activity Score (ASDAS) was analysed using multiple adjusted longitudinal mixed effect models. Binary response rates at 1 year were assessed with multiple adjusted logistic analyses. RESULTS: A first TNFi was initiated in 698 patients with axSpA with available smoking status and a baseline or follow-up BASDAI assessment, of which 490 (70%) had complete covariate data. In comparison to non-smokers, current smokers demonstrated significantly smaller reductions in BASDAI and ASDAS scores upon treatment with TNFi (0.75 BASDAI units and 0.69 ASDAS units less, p=0.005 and 0.001, respectively) for patients with elevated baseline C-reactive protein (CRP) level. This effect was numerically smaller in patients with normal CRP. The odds for reaching a 50% improvement in BASDAI response or the ASAS criteria for 40% improvement after 1 year were significantly lower in current smokers than in non-smokers (0.54, 95% CI 0.31 to 0.95, p=0.03 and 0.43, 95% CI 0.24 to 0.76, p=0.004, respectively). CONCLUSIONS: Current smoking is associated with an impaired response to TNFi in axSpA.

Destructive Spondyloarthropathy in Patients on Long-Term Peritoneal Dialysis or Hemodialysis.

Destructive spondyloarthropathy (DSA) is the most serious spinal complication of dialysis-related amyloidosis in patients on long-term hemodialysis (HD), but we could not find any information about DSA in patients on peritoneal dialysis (PD) for over 10 years. We retrospectively evaluated factors contributing to DSA in HD and PD patients. Sixty-seven patients on dialysis for 10 to 19 years were compared between a PD group (n = 23) or a HD group (n = 44). In the PD group, nine patients (39%) developed DSA. The mean age of DSA patients was significantly higher than that of non-DSA patients (66.2 ± 10.0 vs. 51.0 ± 12.8 years, P = 0.03). The frequency of cervical spine DSA did not show any difference between the PD and HD groups, but the frequency of lumbar spine DSA showed a significant difference (22% vs. 5%, P = 0.04). The serum beta-2 microglobulin (B2MG) level was significantly higher in PD patients than in HD patients (38.4 mg/L vs. 27.4 mg/L, P = 0.0025). Mechanical stress such as elevation of the intra-abdominal pressure due to infusion of PD fluid (1500 mL to 2000 mL) for over 10 years might contribute to lumbar DSA in patients on long-term PD.

Vasoactive Intestinal Peptide in Early Spondyloarthritis: Low Serum Levels as a Potential Biomarker for Disease Severity.

Spondyloarthritis (SpA) is a family of inflammatory diseases sharing clinical, genetic, and radiological features. While crucial for tailoring early interventions, validated prognostic biomarkers are scarce in SpA. We analyze the correlation between serum levels of vasoactive intestinal peptide (VIP) and disease activity/severity in patients with early chronic inflammatory back pain. The study population comprised 54 patients enrolled in our early chronic inflammatory back pain register. We collected demographic information, clinical data, laboratory data, and imaging findings. VIP levels were measured by enzyme immunoassay in serum samples from 162 visits. The association between independent variables and VIP levels was analyzed using longitudinal multivariate analysis nested by patient and visit. No significant differences were observed in VIP levels between these two groups. Lower levels of VIP were significantly associated with a higher Bath Ankylosing Spondylitis Disease Activity Index (BASFI) score, presence of bone edema in magnetic resonance imaging (MRI) scan, and lower hemoglobin levels. Coexistence of cutaneous psoriasis was independently associated with lower VIP levels, and similar trend was observed for enthesitis. We conclude that SpA patients with low serum VIP levels had worse 2-year disease outcome, suggesting that serum VIP levels could be a valid prognostic biomarker.

Serum soluble bone turnover biomarkers in psoriatic arthritis and psoriatic spondyloarthropathy.

Because psoriatic arthritis (PsA) is an inflammatory disease of joints, serum soluble biomarkers specific for chronic joint and bone inflammation may predict future disease severity and response to therapy, thereby informing stratified medicine approaches. The objectives of our systematic review were to determine whether serum soluble bone and cartilage turnover biomarkers are (1) associated with PsA or psoriatic spondyloarthropathy; and (2) associated with disease activity, disease severity, or clinical phenotype. Ten studies met eligibility criteria. Matrix metalloproteinase (MMP)-3, Dickkopf (DKK)-1, macrophage colony-stimulating factor (M-CSF), crosslinked telopeptide of collagen-1, and tumor necrosis factor-related apoptosis-inducing ligand were associated with PsA, with equivocal results for osteoprotegerin (OPG) and bone alkaline phosphatase (ALP). MMP-3, DKK-1, M-CSF, CPII:C2C (ratio of cartilage degradation vs byproduct formation), and possibly OPG were associated with PsA independently of psoriasis. C1-2C (a neoepitope released when type 2 cartilage is degraded by collagenases) was associated with both tender and swollen joint counts, and bone morphogenetic protein-4 with patient global assessment of disease, pain score, and the Bath Ankylosing Spondylitis Disease Activity Index. Bone ALP was associated with disease activity. M-CSF and receptor activator of nuclear factor-κB ligand were associated with several plain radiographic features. No studies have investigated biomarker associations specifically with axial PsA.

Calprotectin (S100A8/9) as serum biomarker for clinical response in proof-of-concept trials in axial and peripheral spondyloarthritis.

INTRODUCTION: Biomarkers complementing clinical evaluations may help to reduce the length and size of proof-of-concept (PoC) trials aimed to obtain quick "go/no go" decisions in the clinical development of new treatments. We aimed to identify and validate serum biomarkers with a high sensitivity to change upon effective treatment in spondyloarthritis (SpA) PoC trials. METHODS: The candidate biomarkers high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), pentraxin-3 (PTX-3), alpha-2-macroglobulin (alpha-2-MG), matrix metalloproteinase-3 (MMP-3), calprotectin, and vascular endothelial growth factor (VEGF) were determined by enzyme-linked immunosorbent assay (ELISA) in healthy controls (n = 20) and SpA patients before and after 2 weeks of infliximab (n = 18) or placebo (n = 19) treatment in cohort 1. Clinical outcome was evaluated at week 12. Results were validated in ankylosing spondylitis (AS) with infliximab (cohort 2, n = 21) and peripheral SpA with etanercept (cohort 3, n = 20). RESULTS: Serum levels of calprotectin, hs-CRP, PTX-3, VEGF (all P < 0.001) and MMP-3 (P = 0.062), but not IL-6 and alpha-2-MG, were increased in SpA versus healthy controls. Treatment with infliximab, but not placebo, significantly decreased calprotectin (P < 0.001) and hs-CRP (P < 0.001) levels, with a similar trend for MMP-3 (P = 0.063). The standardized response mean (SRM), which reflects the ability to detect changes over time, was high for calprotectin (-1.26), good for hs-CRP (-0.96) and moderate for MMP-3 (-0.52). Calprotectin and hs-CRP, but not MMP-3, were good biomarkers for treatment response in axial and peripheral SpA as evaluated and confirmed in cohort 2 and 3 respectively. CONCLUSIONS: Calprotectin and hs-CRP are good serum biomarkers with high sensitivity to change upon effective treatment at the group level in small-scale, short term PoC trials in SpA.

Involvement of IL-23 in enteropathic arthritis patients with inflammatory bowel disease: preliminary results.

The role of interleukin (IL)-23 in the pathogenesis of inflammatory bowel disease (IBD) remains unclear. The aim of this work was to study the serum level of IL-23 in IBD with and without arthritis and determine its relation to the subsets and clinical features of the disease. Thirty-seven patients with IBD including 11 with arthritis were included in the study with a mean age of 30.86 ± 4.66 years. Twenty healthy subjects served as control. Seronegative spondyloarthropathy was present in 11 (29.73 %) of the IBD patients; Crohn's disease (CD) was present in 23 and 14 had ulcerative colitis (UC). Serum level of IL-23 was measured in all patients and control by ELISA. IL-23 was significantly higher in IBD patients (46.24 ± 27.19 pg/ml) compared to control (24.1 ± 2.31 pg/ml) (p < 0.0001) being higher in CD patients (52.57 ± 32.78 pg/ml) compared to those with UC (35.86 ± 6.41 pg/ml) (p = 0.026). Furthermore, it was significantly higher in those with peripheral and/or axial arthritis (67.73 ± 40.85 pg/ml) compared to patients without (37.15 ± 10.37 pg/ml) (p = 0.03). There was a tendency to a higher level in males (49.15 ± 30.97 pg/ml) compared to females (38.4 ± 9.54 pg/ml). Serum IL-23 is increased in IBD especially those with CD associated with arthritis and sacroiliitis. The IL-23 could be added to the biomarkers of development of arthritis in IBD patients. These results also confirm the findings of previous studies on the critical role played by IL-23 in the pathogenesis of IBD making it an important new therapeutic target for these patients.

Lipid profile and anti-TNF-α use.

The use of anti-TNF-α has been associated with several changes in lipid profile, although some study results are conflicting. The knowledge of this fact is of great importance when one observes at the association between rheumatic diseases and accelerated atherogenesis. The aim of this analysis was search for changes in lipid profile in anti TNF-α users in the population of Southern Brazil and its association with duration of use, indications, patient gender and type of anti-TNF. For this purpose, we studied the profiles of total cholesterol (TC), HDL cholesterol (HDLc), LDL cholesterol (LDLc), atherogenic index (ATI) and triglycerides (TGs) of 58 patients (42 with rheumatoid arthritis and 16 with spondyloarthritis) before and after using this drug for a median of 16.0 months. There were no changes in the levels of TC, HDLc, LDLc and ATI (P = NS). However, there was a significant increase in TG levels (P = 0.03). The median difference between first and second TG measurements was 16 mg/dL and this increase was not associated with gender, time of use, use indication or type of anti TNF-α (P = NS). It was concluded that the use of anti TNF-α is associated with increased values of TG.

Efficacy of radiosynoviorthesis and its impact on chosen inflammatory markers.

Radiosynoviorthesis is used for the local treatment of recurrent joint effusions and leads to synovium necrosis after radionuclide administration. This procedure provides opportunity to full recovery of normal synovium function after local corticosteroids and systemic modifying drugs failure.

Similarities and differences between spondyloarthritis in Asia and other parts of the world.

PURPOSE OF REVIEW: Spondyloarthritis (SpA) is a group of diverse interrelated inflammatory arthritides, which share multiple clinical features as well as common genetic predisposing factors. Ankylosing spondylitis (AS) is regarded as the most typical subtype. The purpose of this article is to review relevant studies conducted in Asia and other parts of the world, which may open a window to a better understanding of the epidemiology, clinical feature, diagnosis, and management of this condition. RECENT FINDINGS: The prevalence, clinical feature, diagnosis, and therapy of SpA and its correlation with HLA-B27 in Asia are generally similar to other parts of the world. NSAIDs form the cornerstone of the treatment for AS. The new treatment options with tumor necrosis factor (TNF)-α blocking agents seem a breakthrough for patients with SpA refractory to conventional treatment. Recent results showed that thalidomide was an effective, well tolerated, and economic option for refractory AS patients, especially in maintaining disease remission after etanercept or infliximab treatment was discontinued. SUMMARY: The similarities between spondyloarthritides in Asia and other parts of the world are major and the differences are minor. Because of the major socioeconomic burden and poor access to expensive means of treatment of SpA in Asia, the rheumatologists and physicians in Asia are working hard to look for effective but cheaper alternatively regimens for refractory SpA patients. Thalidomide may be a potentially effective option for patients who cannot afford biologicals in undeveloped areas.

Prevalence of thyroid autoimmunity in patients with spondyloarthropathies.

OBJECTIVE: To evaluate the prevalence of chronic autoimmune thyroiditis or Hashimoto's thyroiditis (HT) in a group of patients with spondyloarthritis (SpA). METHODS: We evaluated serum levels of thyroid-stimulating hormone, free triiodothyronine, and free thyroxine, and titers of antithyroglobulin and antithyroid peroxidase (anti-TPO) antibodies in 357 consecutive patients with SpA. We also recruited 318 healthy age-matched controls. Ultrasonography of the thyroid gland was performed in all subjects and rheumatic activity was evaluated. RESULTS: Indices of thyroid autoimmunity were significantly more frequent in patients with SpA than in controls (24.09% vs 10.69%, respectively; p < 0.05). In the SpA group, a higher prevalence of HT was found in patients with an active disease than in those with low-moderate disease levels. Also in the SpA group, patients with a disease duration > 2 years had a higher prevalence of HT and anti-TPO antibodies positivity than patients with a disease duration ≤ 2 years. Ultrasonography detected a significantly higher frequency of thyroid nodules and hypoechoic pattern in patients with SpA than in controls. Among patients with SpA, HT and anti-TPO antibodies positivity were significantly more frequent in patients with peripheral involvement (68.6%) than in patients with axial involvement (31.4%; p < 0.05). CONCLUSION: Our study shows a significantly higher prevalence of thyroid autoimmunity in patients with SpA as compared to controls. Thyroiditis occurs more frequently in patients with longer disease duration and active rheumatic disease. We suggest that thyroid function tests be part of the clinical evaluation in patients with SpA.

Enthesitis and related changes in the knees in seronegative spondyloarthropathies and skin psoriasis: magnetic resonance imaging case-control study.

OBJECTIVE: To describe enhanced magnetic resonance imaging (MRI) features and characteristic entheseal changes in the knees in patients with seronegative spondyloarthropathy (SpA). METHODS: The 56 patients included 30 with psoriatic arthritis, 5 with ankylosing spondylitis, 5 with reactive arthritis, 5 with ulcerative colitis (UC), 5 with Crohn's disease, and another 6 with skin psoriasis. Controls were 20 healthy subjects without knee complaints. MRI was performed in all participants, emphasizing entheseal sites. RESULTS: Both knees were studied in 45 (80.3%) patients and one knee in 11 (19.6%). MRI showed evidence of bone marrow edema in 13 (23.2%) patients, cartilaginous erosions in 18 (32.1%), and bone erosions in 9 (16.1%). Enthesitis was found in medial collateral ligaments in 18 (32.1%), lateral collateral ligaments in 8 (14.3%), posterior cruciate ligaments in 3 (5.35%), patellar tendon in 18 (32.1%), biceps femoris insertion in 3 (5.35%), medial patellofemoral ligaments (MPFL) in 5 (8.9%), and lateral patellofemoral ligament in 1 patient (1.8%). In the UC and Crohn's patients (n = 10), 2 had bone erosions and 5 had enthesitis. In the skin psoriasis group (n = 6), one had bone marrow edema; enthesitis was detected in 5 at the patellar tendon insertion and in one in the MPFL. Entheseal-related changes were absent in the controls. CONCLUSION: This is the first study showing entheseal-related changes in the knees in patients with inflammatory bowel disease or skin psoriasis without clinical arthritis. Enthesitis of the knee on MRI may be an early finding in SpA.

Cervical spine osteolysis in a case of undifferentiated spondyloarthropathy with features mimicking neoplasm or infection.

STUDY DESIGN: Case Report. OBJECTIVE: To present a case of undifferentiated spondyloarthropathy with sternocostoclavicular arthro-osteitis and osteolyis of cervical body requiring surgical reconstruction of the spine and describing the findings which resembled multiple metastases or infection. SUMMARY OF BACKGROUND DATA: Sternocostoclavicular arthro-osteitis is not infrequent in Japan. It has been reported in patients with seronegative spondyloarthropathies as psoriatic arthropathy or its variant, palmoplantar pustulosis. Cervical spine involvement in the seronegative spondyloarthropathy is usually in the form of syndesmophytes, subluxations, or facet erosions/ fusions. To the best of our knowledge, this is the first report on severe osteolytic cervical spondylitis associating anterior chest wall disease, to the extent that surgical reconstruction is needed. METHODS: A 64 year-old woman presented with neck pain. Cervical spine imaging revealed osteolysis and crumbling of C5 vertebral body. Computed tomography of the thorax showed multiple erosions of the anterior chest wall. Multiple hot spots were detected by bone scan. Biopsies were obtained to exclude neoplasm and infection. Surgical reconstruction via combined anterior-posterior approach was performed to achieve solid spine arthrodesis. RESULTS: Neoplasm and infection were excluded. Careful reassessment alerted to the diagnosis of undifferentiated spondyloarthropathy. Solid arthrodesis and pain relief could be obtained by surgery together with medical control of the disease.

Effect of methotrexate and anti-TNF on Epstein-Barr virus T-cell response and viral load in patients with rheumatoid arthritis or spondylarthropathies.

INTRODUCTION: There is a suspicion of increased risk of Epstein-Barr virus (EBV)-associated lymphoproliferations in patients with inflammatory arthritides receiving immunosuppressive drugs. We investigated the EBV load and EBV-specific T-cell response in patients treated with methotrexate (MTX) or anti-TNF therapy. METHODS: Data for patients with rheumatoid arthritis (RA) (n = 58) or spondylarthropathy (SpA) (n = 28) were analyzed at baseline in comparison with controls (n = 22) and after 3 months of MTX or anti-TNF therapy for EBV load and EBV-specific IFNgamma-producing T cells in response to EBV latent-cycle and lytic-cycle peptides. RESULTS: The EBV load and the number of IFNgamma-producing T-cells after peptide stimulation were not significantly different between groups at baseline (P = 0.61 and P = 0.89, respectively). The EBV load was not significantly modified by treatment, for RA with MTX (P = 0.74) or anti-TNF therapy (P = 0.94) or for SpA with anti-TNF therapy (P = 1.00). The number of EBV-specific T cells was not significantly modified by treatment, for RA with MTX (P = 0.58) or anti-TNF drugs (P = 0.19) or for SpA with anti-TNF therapy (P = 0.39). For all patients, the EBV load and EBV-specific T cells were significantly correlated (P = 0.017; R = 0.21). For most patients, short-term exposure (3 months) to MTX or anti-TNF did not alter the EBV load or EBV-specific T-cell response but two patients had discordant evolution. CONCLUSIONS: These data are reassuring and suggest there is no short-term defect in EBV-immune surveillance in patients receiving MTX or anti-TNF drugs. However, in these patients, long term follow-up of EBV-specific T-cell response is necessary and the role of non-EBV-related mechanisms of lymphomagenesis is not excluded.

Serum and synovial fluid levels of p40 IL12/23 in spondyloarthropathy patients.

IL-23 is the main inductor in Th17 polarization of naive T cells, inducing IL-17 production. IL-17 has been demonstrated to be elevated in ankylosing spondylitis (AS). The p40 subunit is common to IL-12 and IL-23. We assessed serum and synovial levels of p40 IL12/23 in spondyloarthropathy (SpA) patients and the evolution under anti-TNF. SpA patients fulfilling ESSG criteria were included. Healthy volunteers served as controls. P40 IL12/23 was assessed using Human Quantikine ELISA (R&D Systems), and at the same time, BASDAI, ESR, CRP, IL-17, MMP-3. Patients treated with anti-TNF were evaluated again after 10 weeks of treatment. Statistical analysis used Mann Whitney and correlation tests. Twenty-seven SpA outpatients (20 men), mean age 40.3 years, mean disease duration 10.5 years, HLA B27 positive n = 21, peripheral arthritis n = 8, mean BASDAI 45.7, mean CRP 30.7 mg/l, and 24 controls (12 men), mean age 50.4 years, were included. There is no statistical difference in serum levels of p40IL12/23 between patients (mean 77.8 pg/ml) and controls (103 pg/ml) and between patients with axial and peripheral involvement. Levels were higher in HLA B-27 negative patients (p = 0.02). No statistical correlation was found between p40 IL12/40 serum levels and each of BASDAI, ESR, CRP, serum levels of IL 17, MMP 3. Fourteen AS patients were treated with TNF blockers. Whereas significant reduction in BASDAI, ESR, and CRP were obvious after treatment, there was no significant change in serum level of p40 IL12/23. Mean levels of synovial p40 IL12/23 were higher in SpA patients (n = 6; mean 536 pg/ml) compared to osteoarthritis patients (n = 3; 133 pg/ml) and compared with paired serum SpA levels. These results suggest that serum levels of p40 IL-12/23 may not be considered as a biologic tool of disease activity assessment in SpA patients.