Seronegative Spondyloarthritides Research Articles

Chronic sexually acquired reactive arthritis secondary to Chlamydiatrachomatis

Reactive arthritis is included in the spectrum of seronegative spondyloarthritides, occurring secondary to triggers of genitourinary and gastrointestinal tract infections. We describe two cases of sexually acquired reactive arthritis secondary to genital infection by Chlamydia trachomatis, diagnosed by in-house polymerase chain reaction performed on the first void urine. Both patients were managed with a combined approach of short course antibiotics, immunosuppressive agents, biologicals and surgical intervention.

Safety and Efficacy of Various Doses of Tofacitinib among Patients with Active Seronegative Spondyloarthritides – A Retrospective Observational Study

Introduction: Seronegative spondyloarthritides (SpA) are a family of various joint disorders that classically include ankylosing spondylitis (AS), psoriatic arthritis (PsA), inflammatory bowel disease (IBD) associated arthritis, reactive arthritis (formerly Reiter syndrome; ReA), and undifferentiated SpA. Treatment goals for SpA are reducing symptoms, decreasing complications associated with the disease, and reducing functional limitations. Aim of the study: The purpose of this study is to find efficacy and safety of various doses of Tofacitinib, an oral Janus kinase inhibitor, compared with placebo in different stages of the treatment in patients with active Seronegative Spondyloarthritides. Methods: This retrospective observational study was carried out in the Popular Medical College Hospital, Bangladesh. Total 203 subjects of both sexes, aged more than 18 years were selected during the period of May 2023 to November 2023. In this 6 months study duration, patients received 16 weeks treatment (12-week treatment, 4-week washout) and were under follow up session for 8 weeks. Study patients with active SpA phase II were grouped to receive (N=25, 25, 25, 25, respectively) placebo or Jakloc (Tofacitinib) 5 mg and Jakloc (Tofacitinib) XR 11 mg manufactured by Popular Phermaceuticals PLC and Tofacitinib 2 mg or 10 mg (manufactured by other phermaceuticals) twice daily. Jakloc (Tofacitinib) XR 11 mg was used for adult patients with inadequate response or intolerance to methotrexate (3 patients). The primary efficacy endpoint was Assessment of SpondyloArthritis International Society 20% improvement (ASAS20) response rate at week 12. Secondary endpoints included objective measures of disease activity, patient-reported outcomes and MRI of sacroiliac joints and spine after follow up session for 8 weeks. Safety was monitored. Result: The Emax model analysis of the primary endpoint predicted a Jakloc (Tofacitinib) 10 mg twice daily ASAS20 response rate of 67.4%, which ........

Comprehensive Review Exploring Novel Treatments for Psoriatic Arthritis and Axial Spondyloarthritis from 2016 to 2021

Over the past decade, numerous novel therapies have been approved for use in the seronegative spondyloarthritides, including psoriatic arthritis and axial spondyloarthritis. With large variability seen in the spondyloarthritides with respect to presentation and perhaps pathogenesis, potential therapies continue to be discovered and trialled in the hope of better controlling disease activity. This review details therapies that have emerged for the treatment of psoriatic arthritis and axial spondyloarthritis from 2016 to 2021. We discuss those that have been approved for use in the USA and those that remain under investigation.

CT-P13 subcutaneous infliximab in gastroenterology and rheumatology.

The drug infliximab has been a key milestone in the treatment of inflammatory conditions such as Crohn'sdisease, ulcerative colitis, rheumatoid arthritis and the seronegative spondyloarthritides. Biosimilar drugs followed the originator, further improving access and diversity of therapy choice. Subcutaneous infliximab (CT-P13) holds potential for greater patient flexibility by self administration, reducing travel and hospital attendance for infusion, particularly relevant at a time of pandemic. We highlight the pharmacodynamic and pharmacokinetic basis of the subcutaneous device, clinical trials in rheumatology and gastroenterology and consider the safety and cost implications. Real-world switching data is required to confirm the efficacy data from clinical trials given the reduction in dosing flexibility compared withintravenous therapy.

Adult Inflammatory Arthritides: What the Radiologist Should Know

Developments and improvements in knowledge are rapid and ongoing in both the radiologic and rheumatologic fields. During the past decade, the roles of imaging and the radiologist in the assessment and management of many inflammatory rheumatologic diseases have undergone several changes. To remain effective in patient care, the radiologist needs to be aware of these changes when recommending and interpreting imaging examinations for the referring physician. The goal of contemporary rheumatoid arthritis (RA) management is to redefine RA as a disease that is no longer characterized by erosions, which reflect established or long-standing untreated disease. Most cases of RA are now diagnosed clinically, but imaging increases diagnostic confidence, is superior to clinical examination for the detection of joint inflammation, and plays an important role in patient management. The concept of the seronegative spondyloarthritides has recently been redefined by the Assessment of SpondyloArthritis International Society (ASAS). This new set of ASAS classification criteria divides the spectrum of spondyloarthritis on the basis of predominantly axial skeletal clinical manifestations or predominantly peripheral skeletal clinical manifestations. For axial spondyloarthritis, magnetic resonance imaging and radiography play crucial roles for classification and diagnosis. For both peripheral spondyloarthritis and psoriatic arthritis, the radiologist can provide important information that influences classification and diagnosis, including documenting radiologic evidence of juxta-articular new bone formation, diagnosing sacroiliitis, or delineating the presence and extent of enthesitis and dactylitis. The radiologist's familiarity with recent classification criteria, in addition to the traditional diagnostic characteristics of the individual inflammatory arthritides, maximizes the productive interface between the radiologist and the rheumatologist. ©RSNA, 2016.

HLA-B27-associated uveitis: From pathogenesis to therapy

Uveitis is the inflammation of the uvea, which generally occurs in young people and may be accompanied by serious complications leading to disability. The review analyzes the data of Russian and foreign investigations on the pathogenesis of HLA-B27-associated uveitis occurring in different diseases from a group of seronegative spondyloarthritides (SpA) and also discusses current therapeutic approaches in this disease. Since the late 20th century, there has been rapid progress in studying the pathogenesis of HLA-B27-associated uveitis and in identifying the genetic factors predisposing to this pathology. Investigations of HLA-B27 antigen and its alleles are being continued. Tumor necrosis factor-α (TNF-α), the higher levels of which in blood, synovial fluid, and ocular fluid in rheumatic diseases has been proven in many works of both foreign and Russian scientists, is most studied among the inflammatory mediators. Due to the key role of this cytokine in the development of inflammation, drugs inhibiting TNF-α activity have been designed and successfully used in the past decade, which results in partial and occasionally stable remission.

How to investigate: Chronic pain.

Chronic pain is defined as an unpleasant sensory and emotional experience persisting longer than the normal process of healing, usually longer than 3 months. About a fifth of the world's population is believed to suffer from chronic pain. In Europe, chronic pain accounts for nearly 500m lost working days, and it costs the European economy >€34 billion (£28 billion) every year. Establishing a reliable diagnosis is the primary challenge in evaluating a patient with chronic pain. Common diagnoses not to miss include seronegative spondyloarthritides, endocrine abnormalities including severe vitamin D deficiency and polymyalgia rheumatica. Once important or treatable diagnoses have been ruled out, the history can be used as a tool to establish a therapeutic plan for shared decision-making using the biopsychosocial model. Onward referral to pain clinics can be helpful for more involved patient management, but often good outcomes are achieved with the support of primary care.

Seronegative arthritis

The inflammatory arthritides are often divided into those that are ‘seropositive’ and those that are ‘seronegative’. The former test positive with blood tests that look for two proteins: rheumatoid factor; and anti-cyclic citrullinated peptide antibody. However, although seropositivity is part of the diagnostic criteria for rheumatoid arthritis (RA), seronegativity does not exclude the diagnosis, but rather suggests a more benign disease. The term ‘seronegative arthritis’ has evolved from a term used to describe variants of RA, to the present understanding of a spectrum of ‘seronegative spondyloarthritides’ (defined as inflammation within the axial skeleton and vertebral column). These are a closely linked group of conditions with common serological, genetic, clinical and radiological features. These include: ankylosing spondylitis; juvenile ankylosing spondylitis; psoriatic arthritis; reactive arthritis; enteropathic arthritis; undifferentiated spondyloarthritis; and seronegative enthesopathic arthritis syndrome. This article will outline the diagnosis and management of seronegative arthritis.

OP0191-PC Prevalence of inflammatory back pain in a UK primary care population

BackgroundIt is accepted that seronegative spondyloarthritides such as Ankylosing Spondylitis (AS) are frequently misdiagnosed or diagnosed late in the disease course; early diagnosis and subsequent treatment improves patient symptoms and...

Celiac disease arthropathy and autoimmunity study

To evaluate presence of sero-negative spondyloarthritis (SpA) in celiac disease (CD) patients, and whether compliance with a gluten free diet (GFD) improved arthritis manifestations in these patients. We undertook a prospective, questionnaire based, cross-sectional cohort study to evaluate the presence or absence of SpA simultaneously in both CD and non-CD cohorts. 356/590 (60.3%) patients with CD participated in this study. 99% had diagnosis confirmed by a diagnostic test (79% small bowel biopsy, 19.8% blood test, 3.9% stool test). Approximately 131 (37%) cases of arthritis were reported in CD patients. Of the 6/356 CD patients with seronegative spondyloarthritides, four had sacroiliitis, two ankylosing spondylitis, and one psoriatic arthritis, compared to one ankylosing spondylitis and five psoriatic arthritis in non-CD. Osteoarthritis (89 vs 59, P = 0.93) was the most common diagnosis reported by respondents. More CD patients with diarrhea (94%) and anemia (81%) improved on GFD, compared to arthritis symptoms (30%). Autoimmune thyroiditis (10.6% vs 0.4%), insulin dependent diabetes mellitus (IDDM) (2.2% vs 1.7%), systemic Lupus erythematosus (SLE) (1.1% vs 0), and psoriasis (12.9% vs 5.5%) occurred more frequently in CD patients. The prevalence of Crohn's disease, ulcerative colitis, Sjogren's syndrome, primary biliary cirrhosis, and primary sclerosing cholangitis was around 1% each. Univariate Logistic regression analysis showed ≤ high school education (odds ratio [OR] 2.01, P < 0.003), age ≥ 60 years (OR 4.13, P < 0.001), and osteoporosis (OR 2.78, P < 0.001) to be significantly associated with report of arthritis in CD patients. We did not find a high rate of SpA in CD patients. In contrast, increased rates of autoimmune thyroiditis, SLE, IDDM, and psoriasis were seen in CD.

Effects of TNF antagonists on immune and neuroendocrine system

In the article, the literature on the effects of TNFα-antagonists (etanercept, infliximab and adalimumab) on the immune system is reviewed. These biologic agents are employed in chronic inflammatory diseases such as rheumatoid arthritis, seronegative spondyloarthritides, as well as psoriasis and Crohn's disease. The differences of these drugs, testified by the different effects on the immune response, are discussed. These molecules exert their effect through cytokine inhibition, but they present striking differences since they can modulate macrophage activity, T cells apoptosis, leukocyte migration, and angiogenesis to a different degree. Some studies showed that these agents also affect the hypothalamo-pituitary-adrenal axis. The potential immunogenicity of these biologic agents is also discussed.

Anterior chest wall examination reviewed

Anterior chest wall involvement is not infrequently observed within inflammatory arthropaties, particularly if one considers seronegative spondyloarthritides and SAPHO syndrome. Physical examination is unreliable and conventional X-rays analysis is an unsatisfactory tool during diagnostic work-up of this region. Scintigraphic techniques yield informations both on the activity and on the anatomical extent of the disease while computerized tomography visualize the elementary lesions, such as erosions, which characterize the process. Moreover, when available, magnetic resonance imaging couple the ability to finely visualize such lesions with the possibility to show early alterations and to characterize the "activity" of the disease, presenting itself as a powerful tool both for diagnosis and follow-up. This review briefly shows the applications of imaging techniques for the evaluation of the anterior chest wall focusing on what has been done in the SAPHO syndrome which can be considered prototypical for this regional involvement since it is the osteo-articular target mainly affected by the disease.

Imaging the spine in arthritis—a pictorial review

Spinal involvement is frequent in rheumatoid arthritis (RA) and seronegative spondyloarthritides (SpA), and its diagnosis is important. Thus, MRI and CT are increasingly used, although radiography is the recommended initial examination. The purpose of this review is to present the typical radiographic features of spinal changes in RA and SpA in addition to the advantages of MRI and CT, respectively. RA changes are usually located in the cervical spine and can result in serious joint instability. Subluxation is diagnosed by radiography, but supplementary MRI and/or CT is always indicated to visualise the spinal cord and canal in patients with vertical subluxation, neck pain and/or neurological symptoms. SpA may involve all parts of the spine. Ankylosing spondylitis is the most frequent form of SpA and has rather characteristic radiographic features. In early stages it is characterised by vertebral squaring and condensation of vertebral corners, in later stages by slim ossifications between vertebral bodies, vertebral fusion, arthritis/ankylosis of apophyseal joints and ligamentous ossification causing spinal stiffness. The imaging features of the other forms of SpA can vary, but voluminous paravertebral ossifications often occur in psoriatic SpA. MRI can detect signs of active inflammation as well as chronic structural changes; CT is valuable for detecting fracture.

Imaging of seronegative spondyloarthritis

Magnetic resonance imaging (MRI) and ultrasonography (US) are useful adjuncts in the diagnosis of seronegative spondyloarthritides (SpA); a group of diseases that present early at a stage when radiographic assessment is invariably normal. This chapter will review how MRI and US can be used in the evaluation of early SpA. The diffuse osteitis/enthesitis on MRI may serve as a diagnostic hallmark for SpA spinal disease, but needs confirmatory studies for comparison with other spinal pathologies. MRI is the modality of choice for monitoring axial disease in anti-tumour necrosis factor (TNF) therapy responses in the research environment, but it is not yet certain whether this will be relevant in clinical practice. Anti-TNF therapy may be associated with regression of MRI-determined osteitis, but retardation of associated bony fusion is debatable. MRI and US are still undergoing evaluation for the diagnosis of enthesitis of the appendicular skeleton; US, in particular, shows promise at these sites.

Magnetic resonance imaging of sacroiliac joints in patients with seronegative spondyloarthritides

Objective. To study diagnostic possibilities of magnetic resonance imaging (MRI) of sacroiliac joints (SIJ) in pts with seronegative spondyloarthritides (SS). Material and methods. MRI and radiological examination was performed in 15 pts: 10 with ankylosing spondylitis (AS) and 5 with undifferentiated SS. MRI was done with Magnetom Symphony apparatus (Siemens, Germany) with magnetic-field strength 1,5 tesla. Tl, T2 and T2-FS weighted were used. Tl-FS weighted performed in 3-4 minutes after intravenous infusion of gadolinium were additionally used in 5 pts. Inflammatory and structural (erosions, subchondral sclerosis) MRI changes of SIJ were studied. Inflammatory changes of SIJ were analyzed in subchondral bone, bone marrow, joint capsule, joint cavity, interosseous ligaments. SS activity was assessed with BASDAI. Results. Median age of pts was 24 years, median SS duration — 3 years. HLA-B27 was revealed in 13 from 15 pts. All pts had radiological signs of sacroiliitis: 13 - bilateral (12 - II or III stage and 1 — I and III stage according to Kellgren), 2 — unilateral (II stage). So radiological signs of inflammation were revealed in 28 from 30 examined SIJ. MRI signs of sacroiliitis were present in the same 28 SIJ. Subchondral edema of sacrum and/or huckle-bone was revealed in 23 SIJ of 13 pts, bone marrow edema — in 20 SIJ of 13 pts, joint cavity edema - in 21 SIJ of 14 pts, capsule edema — in 12 SIJ of 8 pts, interosseous ligaments inflammation signs — in 3 SIJ of 2 pts. Inflammatory changes of all 5 examined anatomic structures were present in 1, 4 — in 9, 3 — in 13 SIJ. In 1 SIJ inflammation was localized in capsule only. Structural changes were revealed in 22 (73%) SIJ of 14 pts. Structural MRI changes of SIJ at II radiological stage of sacroiliitis were noted in 67% and at III stage — in 83%. Combination of inflammatory and structural changes was present in 22 from 30 SIJ (73%). Frequency of such combination was similar at different radiological stages of sacroiliitis. Isolated inflammatory signs without structural changes were present in 3 SIJ of 3 pts. Gadolinium administration allowed to reveal 5 additional edema zones in SIJ region of 4 from 5 pts. Inflammatory changes of SIJ were revealed with similar frequency in presence (81%) or absence (88%) of pain in this region. Pts with high (BASDAI>40) or not high (BASDAK40) general activity of the disease had about the same mean number of SIJ inflammatory changes (7,6 and 7,8 respectively). Conclusion. MRI is highly sensitive method for revealing SIJ changes in pts with SS. Inflammatory MRI changes were present in all joints with radiological changes irrespectively from radiological stage.

Pharmacological management of undifferentiated spondyloarthropathies

Among undifferentiated spondyloarthropathies (uSpA) are included incomplete forms or early phases of definite seronegative spondyloarthritides and cases of spondyloarthritides that remain undifferentiated. The treatment of all spondyloarthritides is more conditioned by the disease localisation, number of involved districts and severity of inflammation rather than by the subtype of the spondyloarthritides itself. Specific studies focused on the pharmacological approach to uSpA are scarce. As a consequence, many drugs are used on the basis of the experiences that have been gained in the treatment of other spondyloarthritides. At present, non-steroidal anti-inflammatory drugs/COX-2 inhibitors and disease-modifying antirheumatic drugs are the main therapeutic agents for the involvement of peripheral joints in uSpA. In those cases in which severe symptoms persist despite these treatments or when there is a severe axial involvement, antitumour necrosis factor agents represent an effective choice. In these patients, antitumour necrosis factor treatment raises the important possibility of blocking a shift from uSpA to differentiated severe forms of spondyloarthritides such as ankylosing spondylitis. Local administration of corticosteroids is useful when a small number of joints are involved, as is also the case for the extra-articular localisations of soft tissues.

Parvovirus B19 infections serological diagnostics in rheumatic diseases

Objective. To study contamination with parvovirus B19 of a group of patients with rheumatic diseases (RD). Methods. 77 pts with RD (mean age 42,5 years, 79% female) admitted to Institute of Rheumatology of RAMS were examined. 34 of them had rheumatoid arthritis (RA), 11 - systemic lupus erythematosus (SLE) and Sjogren's disease (SD), 15 with osteoarthritis (OA) and seronegative spondyloarthritides (SS) and 17 with early (before a year) undifferentiated arthritis (EUA). Quantitative determination of IgM and IgG serum antibodies to parvovirus BI9 was performed by I FA with IBL kits (Hamburg, Germany). Results. Anti-B19 IgG antibodies were found in 52% of pts, IgM antibodies - only in one case. Mean antibodies values in pts with RD of disease duration less then 6 months were significantly higher then in pts with longer disease duration (21,5+36 U/ml and 8,4+14.7 U/ml respectively, p<0,05). Anti-B 19 antibodies were present in 62% of pts with RA, 53% of pts with EUA, 45% of pts with SD, 33% of pts with OA and SS. High levels of antibodies (4-10 times higher positivity threshold) were revealed in 13 pts with different RD with short duration of joint syndrome (6,3±7,6 months) and fever at presentation. A case of B19 parvovirus infection in a boy of 3 years age accompanied by symptoms of Still's disease is described.

MR imaging in seronegative spondyloarthritis

In twenty-five patients with a clinical diagnosis of suspected sacroiliitis conventional radiography, CT and MRI were performed. In ten patients no abnormalities were demonstrated. In thirteen cases CT and MRI revealed sacroiliitis. In two patients with normal plain films and CT para- and intraarticular changes of signal intensity suggested suspicious sacroiliitis. MRI can be considered as an important imaging modality for early diagnosis of sacroiliitis. In eighteen patients with a firm diagnosis of ankylosing spondylitis and plain films of the thoracolumbar junction suggesting destructive Romanus and Anderson inflammatory lesions MRI was done. Two distinct groups of inflammatory changes were found. In ten patients MRI findings compatible with active inflammatory enthesitis were revealed at the disco-vertebral junction. In eight cases focal and linear changes of signal intensity within the intervertebral disks suggested an active inflammation. Using MRI the spectrum of inflammatory changes in sero-negative spondylitis can be presented. In sixteen patients with definite clinical diagnosis (psoriatic arthritis--thirteen cases and Reiter's syndrome--three cases) plain films and MRI of small hand joints were performed. The patients fell into two distinct groups. In the first MRI findings could not be differentiated from those seen in rheumatoid arthritis. In nine cases the distribution and extent of soft tissue findings were different, similar to changes seen in enthesitis. Therefore, on the basis of MRI findings in small peripheral joints easier differential diagnosis between sero-negative spondyloarthritides and rheumatoid arthritis is possible. In five patients with a diagnosis of Reiter's syndrome having clinical signs of enthesitis plain films and MRI of calcaneus were done. MRI revealed findings compatible with active inflammation which resembled those seen at the attachment of the annulus fibrosus and collateral ligaments of the small hand joints.

Formula omitted] T cells and their subpopulations in blood and synovial fluid from rheumatoid arthritis and spondyloarthritis

T cell receptor (TCR) γ δ bearing lymphocytes in peripheral blood and synovial fluid from rheumatoid arthritis (RA) and seronegative spondyloarthritides (SSA) were evaluated by means of double label immunofluorescence and cytofluorographic analysis. Three monoclonal antibodies (MAb) were used. TCR δ-1 against a common δ chain epitope, BB3 directed against the T cell subset whose TCR is encoded by the Vδ2 gene, and A13 directed against the Vδ1 subset. Peripheral blood Tγδ cells were significantly reduced compared to normal control blood in RA patients who had joint effusion but not in other RA patients. The decrease of Tγδ in the RA PB was mainly confined to the A13+ subset. In RA synovial fluid (RA SF) Tγδ cells were significantly increased compared to paired but not normal peripheral blood, the most significant being the increase of A13+ cells. In contrast, in patients with SSA, no change in Tγδ cells was observed on PB or SF. These data suggest that in RA, but not SSA, Tγδ cells migrate from PB to inflamed synovium and thus may be involved in the pathogenesis of RA.

Pedal manifestations of the seronegative spondyloarthritides. Part IV: Enteropathic arthropathy of Crohn's disease.

Pedal manifestations of the seronegative spondyloarthritides. Part IV: Enteropathic arthropathy of Crohn's disease.