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A wider spectrum of spondyloarthopathies
Abstract
As in other diseases of undetermined etiology, the diagnosis of ankylosing spondylitis (AS) and related spondyloarthropathies (SpA) is based on clinical and roentgenographic features. The current criteria for diagnosis of some of these diseases are too restricted, and do not recognize the existence of a much wider disease spectrum. For example, radiographically detected sacroiliitis is extremely frequent in AS, but may not be an obligate manifestation, especially in early or atypical forms of the disease. Arthritis involving the axial skeleton, including the sacroiliac joints, can be present in some patients without evidence of erosive disease roentgenographically. The disease spectrum of Reiter's syndrome has also been broadened considerably, and "incomplete" forms of Reiter's syndrome are observed much more commonly than the classical triad of arthritis, conjunctivitis, and urethritis. The term "B27-associated reactive arthritis" has been used in recent years to refer to SpA following enteric or urogenital infections, and the disease spectrum includes the clinical picture of typical Reiter's syndrome. The clinical spectrum of psoriatic SpA has been better clarified. Some of the less well defined B27-associated clinical syndromes include seronegative oligoarthritis, polyarthritis, or dactylitis ("sausagelike" toes) of the lower extremities, and heel pain caused by calcaneal (and tarsal) periostitis. These and other undifferentiated SpA have been ignored in previous epidemiological studies because of the inadequacy of the existing classification criteria. The European Spondylarthropathy Study Group (ESSG) has completed a study aimed at developing preliminary classification criteria for the whole group of SpA patients, with the specific intention of encompassing patients with undifferentiated SpA.
... Still, some patients cannot be classified into any of the above, and this entity is labeled as undifferentiated pSpA. [6,7,9,10] The nomenclature of undifferentiated pSpA has subsequently changed, and now it is often referred to as pure pSpA [11] or pSpA without an associated illness. There is a paucity of data on pure pSpA from our country. ...
... [17] This could have accounted for higher percentages of sacroiliitis in our series. A detailed comparison of the present study, with the previous two studies from India, [8,10] is given in Table 2. ...
Background
Peripheral spondyloarthritis (pSpA) is usually associated with psoriasis, inflammatory bowel disease, or preceding infection (called reactive arthritis). Pure pSpA is a clinical entity wherein there are enthesitis, dactylitis, or arthritis, without any of the above-associated conditions. We aimed to describe the clinical, laboratory, radiological, and management profile of pure pSpA, among patients with pSpA presenting to the rheumatology outpatient department.
Materials and Methods
In this retrospective, observational study, medical records of all the patients diagnosed as pSpA by a rheumatologist, between January 1, 2016, and December 31, 2018, were included. Among these, thirty patients qualified to be called pure pSpA, and we reported their demographic characteristics (age and sex), clinical features (onset of disease, clinical signs, and symptoms), laboratory parameters (erythrocyte sedimentation rate, hemoglobin, and C-reactive protein), radiological findings, and treatment pattern.
Results
Thirty patients fulfilled the criteria for pure pSpA. The mean age (standard deviation) of the patients at onset was 32 ± 5.8 years. The mean disease duration before diagnosis was 9.7 months. Arthritis, enthesitis, and dactylitis were present in 29 (96.7%), 8 (26.7%), and 9 (30%) patients, respectively. Eighteen (60%) patients had monoarthritis, while 11/30 (36.7%) had oligoarthritis, at presentation. HLA B27 was positive in 24/30 (80%) patients. Seven patients (23.3%) had bilateral sacroiliitis on imaging and two (6.7%) had unilateral sacroiliitis. Twenty patients (66.7%) required conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), while two (6.7%) required biological DMARDs in the form of anti-tumor necrosis factor-alpha inhibitors.
Conclusion
Pure pSpA is a relatively rare clinical disease which presents with either a mono or oligoarthritis and shows good treatment response to csDMARDs.
... By the mid-1980s, it became apparent that radiographic changes in the sacroiliac joints were highly prevalent in AS but not in early or atypical forms of the disease [32]. Later on, it was emphasized that the prevailing definition of AS did not encompass the broader spectrum of the disease [33], and global studies across various racial/ethnic groups have substantiated this perspective [29,[34][35][36]. Improved clinical recognition of "spondylitic disease without radiologic evidence of sacroiliitis" (now referred to as nr-axSpA) [32], which is more commonly found in females, and along with the increased use of MRI since the mid-1990s, has led to reports of the nearly equal prevalence of the extended spectrum of axSpA among both males and females [37][38][39]. ...
Purpose of Review
To commemorate the 50th anniversary of the groundbreaking discovery of a remarkably strong association between HLA-B*27 and ankylosing spondylitis (AS).
Recent Findings
In addition to HLA-B*27, more than 116 other recognized genetic risk variants have been identified, while epigenetic factors largely remain unexplored in this context. Among patients with AS who carry the HLA-B*27 gene, clonally expanded CD8 + T cells can be found in their bloodstream and within inflamed tissues. Moreover, the α and β chain motifs of these T-cell receptors demonstrate a distinct affinity for certain self- and microbial-derived peptides, leading to an autoimmune response that ultimately results in the onset of the disease. These distinctive peptide-binding and presentation characteristics are a hallmark of the disease-associated HLA-B*27:05 subtype but are absent in HLA-B*27:09, a subtype not associated with the disease, differing by only a single amino acid. This discovery represents a significant advancement in unraveling the 50-year-old puzzle of how HLA-B*27 contributes to the development of AS.
Summary
These findings will significantly accelerate the process of identifying peptides, both self- and microbial-derived, that instigate autoimmunity. This, in return, will pave the way for the development of more accurate and effective targeted treatments. Moreover, the discovery of improved biomarkers, in conjunction with the emerging technology of electric field molecular fingerprinting, has the potential to greatly bolster early diagnosis capabilities. A very recently published groundbreak paper underscores the remarkable effectiveness of targeting and eliminating disease-causing T cells in a HLA-B*27 patients with AS. This pivotal advancement not only signifies a paradigm shift but also bolsters the potential for preventing the disease in individuals carrying high-risk genetic variants.
... As an example, it was noted that radiographic changes in the SIJ are extremely frequent in AS but not in early or atypical forms of the disease. 62 In another approach in Germany, early diagnostic criteria were proposed using a combination of the HLA-B27 test with clinical data, ESR and radiological signs, and evaluated in follow-up study of 77 patients with possible AS and controls with other rheumatic diseases. 63 After 10 years, 59% had definite AS according to the NY criteria, 19% had possible or undifferentiated SpA, whereas in 22% of patients other diseases were diagnosed. ...
The human lymphocyte antigen B27 (HLA B27) is a member of the HLA class I family of genes in the major histocompatibility complex whose name goes back to its discovery in studies of transplanted tissue compatibility. Its prevalence in the mid-European population is about 8%. The association of HLA B27 alleles with ankylosing spondylitis (AS), a highly heritable disease, which is part of the spectrum of axial spondyloarthritis (axSpA), was discovered 50 years ago. HLA B27 explains less than 30% of the total genetic load. About 60%–90% of axSpA patients worldwide carry HLA B27. The prevalence of the disease is linked to the frequency of HLA B27 in the population which implies that there are relevant differences. Among the roughly 200 subtypes known there are two which are not disease associated. The function of HLA class I molecules is to present peptides to the immune system to defend the organism against microbes targeted by CD8+T cells. This is much supported by the role of the endoplasmic reticulum aminopeptidase 1 (ERAP 1) in AS, an enzyme that is responsible for the intracellular trimming of peptides, since polymorphisms of this gene are only associated with HLA-B27+ disease. The arthritogenic peptide hypothesis trying to explain the pathogenesis of AS is based on that very immune function assuming that also self peptides can be presented. HLA-B27 also plays an important role in classification, diagnosis and severitiy of axSpA.
... 81,83,84 Quantitative Sacroiliac Scintigraphy for Periostitis-Induced Sacroiliac Pain Juvenile-onset HLA-B27-associated 'unclassifiable' SpA, especially cases without evidence of enteric or genitourinary symptoms, may have tarsal periostitis as an early clinical manifestation and then show bilateral sacroiliac pain later on. 85 One article has reported improvements of the SI joint after convalesce of the foot periostitis, and concluded that stress events, exercise, and abnormal posture can all increase SI ratios, while corrected posture for a period of time, anti-inflammatory drugs, and rehabilitation programmes can all reduce SI ratios. 86 Periostitis of the lower limbs is a common disorder from sports injuries. ...
Background: Back pain a common cause for hospital visits. Nuclear skeletal scintigraphy, at a high sensitivity, provides a functional imaging for detecting bone diseases. Sacroiliitis is an inflammation of the sacroiliac joint. Bone scan with quantitative sacroiliac scintigraphy (QSS) has been a useful inflammation indicator for sacroiliac joints. However, QSS has been ignored in the rehabilitation practice.
... Ankylosing spondylitis (AS) is characterized by inflammation of the axial skeleton, sacroiliac joints and, to a lesser degree peripheral arthritis and certain extra-articular organs, including the gastrointestinal tract, eyes, skin, and cardiovascular system [1]. AS is genetically associated with single nucleotide polymorphisms (SNPs) in the common p40 subunit of interleukin (IL)-12/23 and IL-23 receptor (IL-23R) SNPs. ...
... Since the 1970s, it has been recognized that spondyloarthritis has a wider spectrum than previously thought. [1][2][3][4] Spondyloarthritis comprises a group of diseases including ankylosing spondylitis, psoriatic arthritis, inflammatory-bowel-disease-related arthritis, reactive arthritis, and undifferentiated spondyloarthritis (an entity that does not fit in any of the other categories). [3,4] In the 1890s, Poncet et al reported the first case of polyarthritis that developed in the presence of active extra-articular tuberculosis with no concomitant evidence of infectious arthritis. ...
Rationale:
Rare cases of reactive arthritis induced by active extra-articular tuberculosis (Poncet disease) have been reported. Complete response to antitubercular treatment and evidence of active extra-articular tuberculosis are the most important clinical features of Poncet disease. We report the case of successfully treated a patient with reactive arthritis induced by active extra-articular tuberculosis with a TNF inhibitor after sufficient antitubercular treatment.
Patient concerns:
A 56-year-old Japanese man was admitted to our department with polyarthralgia, low back pain, and high fever. The results of rheumatoid factor, anti-citrullinated protein antibody, human leukocyte antigen B27, and the assays for the detection of infections (with an exception of T-SPOT.TB) were all negative. Fluoro-deoxy-D-glucose-positron emission tomography with CT (PET/CT) showed moderate uptake in the right cervical, right supraclavicular, mediastinal, and abdominal lymph nodes. As magnetic resonance imaging and power Doppler ultrasonography showed peripheral inflammation (tendinitis, tenosynovitis, ligamentitis, and enthesitis in the limbs).
Diagnosis:
A diagnosis of tuberculous lymphadenitis was eventually established on the basis of lymph node biopsy results. There was no evidence of a bacterial infection including acid-fast bacteria in his joints, and the symptoms of polyarthralgia and low back pain were improved but not completely resolved with NSAID therapy; in addition, a diagnosis of reactive arthritis induced by active extraarticular tuberculosis was made.
Interventions:
The patient experienced persistent peripheral inflammation despite antitubercular treatment for more than nine months and was then successfully treated with a tumor necrosis factor inhibitor (adalimumab 40 mg every 2 weeks).
Outcomes:
Finally, the patient responded to the treatment and has been in remission for over 4 months as of this writing.
Lessons:
In patients who present with symptoms associated with spondyloarthritis, it is important to distinguish between classic reactive arthritis and reactive arthritis induced by extra-articular tuberculosis infection. Introduction of biological agents should be carefully considered in settings where reactive arthritis induced by active extra-articular tuberculosis shows progression to chronicity despite sufficient antitubercular treatment.
... Spondyloarthritis is a group of interrelated diseases, which consist of AS, psoriatic arthritis, arthritis/spondylitis with inflammatory bowel disease and reactive arthritis [16,17]. Based on a physical examination that revealed no evidence of gastrointestinal disorder, eye disease, or skin disease in addition to a negative HLA-B27, these types of arthritis from the differential diagnosis of spondyloarthritis were excluded. ...
Introduction:
Stress fracture is generally a result of cumulative and repetitive stress in athletes, which accelerates the normal remodeling process of bones, and the most frequently involved areas are the tibia and metatarsal bones. Therefore, stress fractures of the midshaft of the clavicle are very rare.
Presentation of case:
A 58-year-old female was admitted to our hospital because of pain in the middle of the right clavicle. Based on laboratory and radiographic inspection, it was concluded that the stress fracture of the midshaft of the clavicle in this case was caused by sternocostoclavicular hyperostosis (SCCH). Because the clavicular fracture had no displacement or callus formation, conservative treatment with a clavicle band was undertaken. Shoulder function at the final follow-up visit was satisfactory.
Discussion:
SCCH is a rare chronic inflammatory disorder of the axial skeleton and ossifying diathesis associated with a predominantly osteogenic response. Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome and ankylosing spondylitis (AS) should be considered in the differential diagnosis of SCCH. If a patient with this type of fracture has no history of traumatic injury or sports activity, the differential diagnosis might be very difficult.
Conclusion:
We report the case of a female who had a stress fracture of the midshaft of the clavicle associated with SCCH in SAPHO or AS. Although the patient was treated conservatively, and the shoulder function was satisfactory at the final follow-up visit, re-fracture may occur in the future.
... Medicine ® OPEN from 101 to 250 per 100,000 people, with an annual incidence reported at 6.6 out of every 100,000 people.[5]As the prevalence of psoriasis is 2% to 3% and PsA occurs in about one-third of patients with psoriasis, it is a common condition. PsA is a part of group of diseases named spondylartritis (SpA) which shared similar genetic, clinical, and radiologic features.[6]As for the patients over the age of 65, initial symptoms of SpA are rarely seen, whereas elderly-onset rheumatoid arthritis patients were reported in the literature.[7]There ...
Psoriatic arthritis (PsA) is a chronic inflamatory disease characterized with axial and peripheral joints involvement. It rarely affects patients older than 65 years old.
The purpose of this study is to compare and evaluate the demographic, clinical and laboratory features of elderly-onset psoriatic arthritis (EOPsA) and young-onset (YOPsA) patients.
A total of 180 patients diagnosed with PsA according to CASPAR criteria and followed-up in single center were included in this study. The patients with initial symptoms started after age 65 were accepted as EOPsA. Demographic, clinic, and laboratory data and the medications which the patients received were recorded and retrospectively evaluated.
Nineteen (10.5%) of 180 patients were diagnosed as EOPsA, and 161 (89.5%) patients were evaluated as YOPsA. The mean patient age was 42.1years for the YOPsA group and 68.3 years for the elderly onset group. Mean duration of disease was 5.6 years for the early onset group and 1.3 years for the elderly onset group (P = .001). Fourteen (73.3%) of 19 EOPsA patients were female and 5 of them were male. Higher rates of fatique, pain scores, comorbid diseases, and acute phase reactants elevation were detected in EOPsA patients comparing to YOPsA (P = .000, P = .000, P = .001, and P = .001, respectively). YOPsA patients have more dactilitis, nail involvement, elevated PASI scores, and smoking habitus when compared with EOPsA patients (P = .019, P = .03, P = .005, P = .004, respectively). In terms of the treatment options chosen, there was no significant difference in the use of nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids (CS), methotrexate (MTX), and sulfasalazine (SSL), but there was a more frequent use of anti-tumor necrosis factor-alpha in the YOPsA group.
YOPsA and EOPsA patients may presented with different clinical and laboratory features. EOPsA patients are characterized with higher rates of fatigue, pain scores, comorbid diseases, and acute phase reactants and less dactilitis, nail involvement, and anti-TNF-alpha usage.
... Ankylosing spondylitis (AS) is a common inflammatory rheumatic disease with predilection for the sacroiliac joints and axial skeleton. 1 Several lines of evidence implicate interleukin (IL)-17A-secreting T helper (Th)17 cells in AS pathogenesis. Multiple type 17 immune pathway genes have been identified in AS in genome-wide association studies, 2 Th17 cells are increased in frequency in the blood of patients with AS 3 and IL-17A neutralisation has been shown to be an effective therapy in AS. 4 microRNAs (miRs) are non-coding RNA oligonucleotides that are potent post-transcriptional regulators of gene expression, targeting messenger RNAs (mRNA) for degradation upon binding to complementary sequences, predominantly in the 3 0 untranslated region (3 0 UTR) of mRNAs. ...
Objective:
To determine the microRNA (miR) signature in ankylosing spondylitis (AS) T helper (Th)17 cells.
Methods:
Interleukin (IL)-17A-producing CD4+ T cells from patients with AS and healthy controls were FACS-sorted for miR sequencing and qPCR validation. miR-10b function was determined by miR mimic expression followed by cytokine measurement, transcriptome analysis, qPCR and luciferase assays.
Results:
AS Th17 cells exhibited a miR signature characterised by upregulation of miR-155-5p, miR-210-3p and miR-10b. miR-10b has not been described previously in Th17 cells and was selected for further characterisation. miR-10b is transiently induced in in vitro differentiated Th17 cells. Transcriptome, qPCR and luciferase assays suggest that MAP3K7 is targeted by miR-10b. Both miR-10b overexpression and MAP3K7 silencing inhibited production of IL-17A by both total CD4 and differentiating Th17 cells.
Conclusions:
AS Th17 cells have a specific miR signature and upregulate miR-10b in vitro. Our data suggest that miR-10b is upregulated by proinflammatory cytokines and may act as a feedback loop to suppress IL-17A by targeting MAP3K7. miR-10b is a potential therapeutic candidate to suppress pathogenic Th17 cell function in patients with AS.
... Peripheral joints and certain extra-articular organs, including the eyes, skin, and cardiovascular system, are affected to a lesser degree. 1 Peripheral joint involvement is a presenting feature in only 10-20% of patients, and occurs during the disease course in 30-40% of patients. 2,3 Disease activity is higher in patients with peripheral joint disease, when compared with patients where the disease is limited to the axial skeleton. ...
Objectives:
This study aims to detect candidate micro-ribonucleic acids (miRNAs) from microarray within peripheral blood mononuclear cells and synovial fluid mononuclear cells in patients with ankylosing spondylitis (AS).
Patients and methods:
Samples from three AS patients (3 males, mean age 37.3±2.5 years; range 35 to 40 years) and three healthy controls (3 males, mean age 39.0±2.6 years; range 37 to 42 years) were obtained for miRNA microarray. The microarray experiment proceeded only when the quality of total RNAs were considered to have "passed", and their integrity was good by total RNA quality control using Agilent Bioanalyzer 2100. Hierarchical clustering was performed to understand the impact of the storage condition on the miRNA expression profiles. MiScript primer assays were used for semiquantitative determination of the expression of human miRNAs to validate results from miRNA microarray.
Results:
A total of 887 miRNAs were screened by microarray among groups. After normalization of the raw data, we noted that the expression of five miRNAs was significantly lower (fold change ≤0.5 and p≤0.05) and only hsa-miR-424-5p was significantly higher in AS peripheral blood mononuclear cell (fold change ≥2 and p≤0.05). In AS synovial fluid mononuclear cells, we identified that expressions of 16 miRNAs were significantly down regulated whereas only hsa-miR-424-5p was significantly upregulated (fold change ≥2 and p≤0.05). All above-mentioned miRNAs were reevaluated for further validation. Finally, significantly increased hsa-miR-424-5p and decreased hsa-miR-377 were found in synovial fluid mononuclear cells from AS patients compared with healthy controls. Based on target prediction programs and published papers, potential target genes and its pathways were screened.
Conclusion:
miR-424-5p was increased and miR-377 was decreased in synovial fluid mononuclear cells from patients with AS. These two miRs might have functional roles in patients with arthritis via different pathways.
... Ankylosing spondylitis (AS) is characterized by the inflammation of the axial skeleton and peripheral joints, along with extraarticular manifestations such as the eyes, skin, and gastrointestinal tract 1 . The most characteristic feature of AS is ankylosis and fusion of the axial joints, including the sacroiliac (SI) joint. ...
Objective:
We aimed to evaluate the involvement of the symphysis pubis in patients with ankylosing spondylitis (AS), and to assess the correlations between symphysis pubis changes and clinical findings.
Methods:
We retrospectively evaluated a total of 222 male patients with AS who underwent pelvic and cervical/lumbar spine radiography at the Hanyang University Hospital for Rheumatic Diseases from August 2004 to February 2014. Radiographs were examined by 2 experienced radiologists, and radiographic damage was scored as follows: 0 (no damage), 1 (subtle irregularity and/or subchondral sclerosis), 2 (erosion), 3 (partial ankylosis), and 4 (total ankylosis). We evaluated the patients' clinical characteristics and analyzed their correlations with radiographic symphysis pubis changes.
Results:
The mean patient age was 30.5 ± 8.3 years and mean disease duration was 7.1 ± 4.6 years; 105 patients (47.3%) exhibited radiologic damage in the symphysis pubis. Moreover, 75, 28, 0, and 2 patients had scores of 1, 2, 3, and 4, respectively. When comparing the normal (score 0) and abnormal (score 1-4) symphysis pubis groups, the latter had a longer symptom duration (10.1 ± 7.0 vs 7.6 ± 5.8 yrs, p = 0.004) and higher modified Stoke Ankylosing Spondylitis Spine Score (mSASSS; 18.6 ± 17.0 vs. 14.3 ± 13.4, p = 0.038). Moreover, a significant correlation was noted between the radiographic symphysis pubis damage score and mSASSS (r(2) = 0.147, p = 0.029).
Conclusion:
Among male patients with AS, 47.3% exhibited symphysis pubis involvement. Moreover, a correlation was observed between the radiographic symphysis pubis and spine changes.
... The group of spondyloarthritides comprises a number of closely related rheumatic diseases with common clinical features, 1 including ankylosing spondylitis (AS), psoriatic arthritis (PsA), arthritis/ spondylitis related to inflammatory bowel disease and reactive arthritis (ReA). [2][3][4][5][6] In addition to these subtypes, patients with spondyloarthritis (SpA) can also be grouped into two categories based on their predominant clinical presentation: axial and peripheral. 1 2 This division was reflected in the Assessment of Spondyloarthritis International Society (ASAS) classification criteria, which separated axial and peripheral SpA (axSpA and pSpA). 7 8 Imaging is a key component of classification criteria for SpA, primarily due to the lack of specific clinical symptoms as well as varying disease activity over time. ...
A taskforce comprised of an expert group of 21 rheumatologists, radiologists and methodologists from 11 countries developed evidence-based recommendations on the use of imaging in the clinical management of both axial and peripheral spondyloarthritis (SpA). Twelve key questions on the role of imaging in SpA were generated using a process of discussion and consensus. Imaging modalities included conventional radiography, ultrasound, magnetic resonance imaging, computed tomography (CT), positron emission tomography, single photon emission CT, dual-emission x-ray absorptiometry and scintigraphy. Experts applied research evidence obtained from systematic literature reviews using MEDLINE and EMBASE to develop a set of 10 recommendations. The strength of recommendations (SOR) was assessed by taskforce members using a visual analogue scale. A total of 7550 references were identified in the search process, from which 158 studies were included in the systematic review. Ten recommendations were produced using research-based evidence and expert opinion encompassing the role of imaging in making a diagnosis of axial SpA or peripheral SpA, monitoring inflammation and damage, predicting outcome, response to treatment, and detecting spinal fractures and osteoporosis. The SOR for each recommendation was generally very high (range 8.9-9.5). These are the first recommendations which encompass the entire spectrum of SpA and evaluate the full role of all commonly used imaging modalities. We aimed to produce recommendations that are practical and valuable in daily practice for rheumatologists, radiologists and general practitioners.
... The group of spondyloarthritides comprises a number of closely related rheumatic diseases with common clinical features, 1 including ankylosing spondylitis (AS), psoriatic arthritis (PsA), arthritis/ spondylitis related to inflammatory bowel disease and reactive arthritis (ReA). [2][3][4][5][6] In addition to these subtypes, patients with spondyloarthritis (SpA) can also be grouped into two categories based on their predominant clinical presentation: axial and peripheral. 1 2 This division was reflected in the Assessment of Spondyloarthritis International Society (ASAS) classification criteria, which separated axial and peripheral SpA (axSpA and pSpA). 7 8 Imaging is a key component of classification criteria for SpA, primarily due to the lack of specific clinical symptoms as well as varying disease activity over time. ...
A taskforce comprised of an expert group of 21 rheumatologists, radiologists and methodologists from 11 countries developed evidence-based recommendations on the use of imaging in the clinical management of both axial and peripheral spondyloarthritis (SpA). Twelve key questions on the role of imaging in SpA were generated using a process of discussion and consensus. Imaging modalities included conventional radiography, ultrasound, magnetic resonance imaging, computed tomography (CT), positron emission tomography, single photon emission CT, dual-emission x-ray absorptiometry and scintigraphy. Experts applied research evidence obtained from systematic literature reviews using MEDLINE and EMBASE to develop a set of 10 recommendations. The strength of recommendations (SOR) was assessed by taskforce members using a visual analogue scale. A total of 7550 references were identified in the search process, from which 158 studies were included in the systematic review. Ten recommendations were produced using research-based evidence and expert opinion encompassing the role of imaging in making a diagnosis of axial SpA or peripheral SpA, monitoring inflammation and damage, predicting outcome, response to treatment, and detecting spinal fractures and osteoporosis. The SOR for each recommendation was generally very high (range 8.9-9.5). These are the first recommendations which encompass the entire spectrum of SpA and evaluate the full role of all commonly used imaging modalities. We aimed to produce recommendations that are practical and valuable in daily practice for rheumatologists, radiologists and general practitioners.
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... Ankylosing spondylitis (AS) is characterized by inflammation of the axial skeleton, sacroiliac joints, and, to a lesser degree, peripheral joints and certain extra-articular organs, including the eyes, skin, and cardiovascular system (1). The most unique feature in AS is subchondral eburnation and the presence of syndesmophytes, which possibly lead to ankylosis and spinal fusion. ...
The objective of this study was to develop a Korean version of the Assessment of Spondyloarthritis International Society-Health Index/Environmental Factor (ASAS HI/EF) and to evaluate its reliability and validity in Korean patients with axial spondyloarthritis (SpA). A total of 43 patients participated. Translation and cross-cultural adaptation of the ASAS HI/EF was performed according to international standardized guidelines. We also evaluated validity by calculating correlation coefficients between the ASAS-HI/EF score and the clinical parameters. Test-retest reliability was excellent. The correlations among the mean ASAS-HI score and all tools of assessment for SpA were significant. When it came to construct validity, the ASAS HI score was correlated with nocturnal back pain, spinal pain, patients's global assessment score, the Bath ankylosing spondylitis disease activity index (BASDAI), Bath ankylosing spondylitis functional index (BASFI), Bath ankylosing spondylitis metrology index (BASMI) and EuroQoL visual analogue scale (EQ VAS) (r = 0.353, 0.585, 0.598, 0.637, 0.690, 0.430, and -0.534). The ASAS EF score was also correlated with the patient's global assessment's score, BASDAI, BASFI, BASMI, and EQ VAS score (r = 0.375, 0.490, 0.684, 0.485, and -0.554). The Korean version of the ASAS HI/EF can be used in the clinical field to assess and evaluate the state of health of Korean axial SpA patients.
Graphical Abstract
... AS is characterized by inflammation of the axial skeleton, sacroiliac joints and, to a lesser degree, peripheral joints and certain extra-articular organs, including the eyes, skin and cardiovascular system[1]. The most characteristic feature in AS is subchondral eburnation and syndesmophytes , possibly leading to ankylosis and spinal fusion. ...
Objectives:
The aim of this study was to determine whether the presence of peripheral arthritis can affect radiographic structural damage in patients with AS.
Methods:
A total of 915 subjects comprising 363 patients with a history of peripheral arthritis and 552 patients without a history of peripheral arthritis obtained from the Observation Study of the Korean SpA Registry (OSKAR) were analysed looking at the relationship of peripheral arthritis history in a cross-sectional survey as well as the radiographic damage score according to the presence or absence of peripheral arthritis. Radiographs and clinical information were available for 501 subjects (205 peripheral arthritis patients and 296 without peripheral arthritis) at a mean follow-up of 2.7 years. The modified Stoke AS Spinal Score (mSASSS) was examined by two experienced radiologists to validate the results. Reliability was evaluated using the intraclass correlation coefficient for each radiograph.
Results:
The agreement between the two readers regarding the mSASSS was good. On simple comparison there was a significant difference in the mSASSS between patients with a history of peripheral arthritis and those without [mean 14.62 (s.e.m. 0.83) vs 18.78 (0.79), P < 0.001]. The mSASSS change was stratified according to the presence or absence of peripheral arthritis at baseline. After adjusting for multiple comparisons by Bonferroni correction, the patients with peripheral arthritis had less mSASSS change than those without peripheral arthritis [3.08 (s.e.m. 0.61) vs 5.18 (0.47), P = 0.008].
Conclusion:
The presence of peripheral arthritis delays spinal radiographic progression in AS.
... Ankylosing spondylitis usually begins with back pain and stiffness in adolescence and early presentations may antedate back symptoms in some patients [3][4][5][6][7]. It is very rare for ankylosing spondylitis to first begin after 45 years of age, but disease is diagnosed at an older age in many patients, in part because symptoms over the years have been minimal [8][9][10][11]. ...
Introduction:
Ankylosing spondylitis (AS) is an inflammatory rheumatic disease characterized by spine and sacroiliac joint involvement that mainly affects young male subjects. Bone Mineral Density (BMD) loss occurs in AS disease course. Bone loss in AS appears to be multifactorial and perhaps involves different mechanisms at different stages of disease. The disease typically affects young males and is associated with progressive functional impairment, increased work disability and decreased quality of life. Osteoporosis is frequent in AS and there is a close association of bone mineral density, bone metabolism and inflammatory activity. Osteoporosis is frequently associated with AS and BMD decreased predominantly in patients with active disease.
Aims & objectives:
The aim of the present study was to study bone mineral density in cases of Ankylosing Spondylitis (AS) in comparison to age and sex matched controls.
Material and methods:
The present study was conducted on 100 established cases of AS based on modified New York criteria and 150 controls healthy, age, race, socio-economic matched controls patients. The results were statistically analyzed.
Results:
Hundred cases of AS were subjected to undergo BMD by Dual Energy X-ray Absorption (DEXA) scan of different age groups in cases 35.19± 8.23(min age 23- max age 67years) and controls 33.27±5.22(min age 22years - max age 44years) with height observed in cases is 169.67±6-87 and controls 170.99±7.16 with weight varied in cases 65.63±10.27 and controls 70.14±10.67.
Conclusion:
Osteoporosis is a significant complication in ankylosing spondylitis and needs to be monitored and managed at the earliest. Significant osteoporosis can occur even in early disease. Osteoporosis of spine is much more prevalent than femur.BMD spine is still the most important site to define osteoporosis in ankylosing spondylitis. Rise in BMD in LS spine with duration, is not exclusive for subjects with radiologically evident syndesmophytes. Statistically, presence of syndesmophytes did not affect estimation of osteoporosis of spine.
... Ankylosing spondylitis (AS) is a chronic progressive inflammatory disease, involving the sacroiliac joints, axial skeleton and peripheral joints, with certain extra-articular manifestations (1). The overall prevalence is 0.2%-0.8% ...
The aim of the study was to investigate and compare the clinical manifestations between HLA-B27(+) and HLA-B27(-) ankylosing spondylitis (AS) patients in order to obtain knowledge of the impact of HLA-B27 status on AS, and to inform clinical treatment. A nationwide epidemiological investigation was performed from November 2008 to October 2010. The demographic data and clinical characteristics, and the status of HLA-B27 were collected using questionnaires and laboratory assay, respectively. A total of 2144 patients (78.5% males and 78.4% HLA-B27(+) AS patients) participated in this study. The percentages of males, patients with family history, and involvement of lumbar spine, thoracic spine and hip joints, were observed to be significantly higher in the HLA-B27(+) AS patients than in their HLA-B27(-) AS peers.
... As EAP apresentam características que as distinguem, como o envolvimento articular periférico, assimétrico e com predomínio de artrite de grandes articulações, em especial dos membros inferiores, o acometimento das articulações sacroilíacas e da coluna vertebral, especialmente do segmento lombar, a extensão do processo inflamatório às enteses, a negatividade para a pesquisa do fator reumatóide (FR) pelos métodos convencionais, a ausência de nódulos reumatóides subcutâneos, a história familiar de EAP, a associação com o HLA-B27 e a tendência à sobreposição clínica entre as diversas doenças, principalmente no que se refere às manifestações extra-articulares (3) . Entretanto, sabe-se que este espectro é bem maior, incluindo oligoartrite, poliartrite, dactilite, uveítes, além de alterações cutâneo-mucosas, intestinais, genito-urinárias, neurológicas, renais, cardíacas e pulmonares (4)(5)(6) . Em populações em que o HLA-B27 é encontrado com maior freqüência, observa-se a ocorrência de certas manifestações clínicas, laboratoriais e radiográficas das EAP associadas a ele (7)(8)(9)(10)(11) . ...
OBJETIVO: analisar o padrão de doença de pacientes brasileiros com espondiloartropatias (EAP). PACIENTES E MÉTODOS: foram avaliados 156 pacientes por meio de análise descritiva e análise de associação uni e multivariada entre a distribuição das manifestações clínicas, laboratoriais e radiográficas e a presença do HLA-B27. RESULTADOS: as doenças do grupo identificadas foram a espondilite anquilosante - EA (48,10%), a espondiloartropatia indiferenciada (20,51%), a artrite reativa - ARe (15,39%), a artrite psoriásica AP (14,10%) e a artropatia das doenças inflamatórias intestinais (1,92%). O HLA-B27 foi positivo em 53,85% dos pacientes. O HLA-B27 positivo associou-se ao acometimento clínico e/ou radiográfico das articulações sacroilíacas (p=0,007; OR=3,13; IC 95% 1,38 a 7,06), à presença de sacroiliíte radiográfica > grau II bilateral (p=0,05; OR=2,85; IC 95% 1,02 a 8,04) e ao sexo masculino (p=<0,001; OR=3,00; IC 95% 1,83 a 4,92), enquanto indivíduos com o HLA-B27 negativo apresentaram, significativamente, mais balanite como manifestação evolutiva que indivíduos HLA-B27 positivos (p=0,03; OR=0,21; IC 95% 0,05 a 0,88). CONCLUSÃO: as manifestações clínicas, laboratoriais e radiográficas foram semelhantes às descritas em outros trabalhos. O HLA-B27 apresentou-se em baixa freqüência, quando comparado com outras amostras, e ocorreram associações entre este antígeno e o sexo masculino e o envolvimento das articulações sacroilíacas.
Background: Persistent knee synovitis leads to joint discomfort, incapacitating inflammation, and functional limitations. The conventional approach has involved surgical procedures to eliminate the actively inflamed synovial membrane. This study aims to investigate the recurrence-free survival and functional outcome after synovectomy and subsequent radiosynoviorthesis (RSO) in patients with knee synovitis. Methods: Thirty-seven knees diagnosed with pigmented villonodular synovitis (PVNS), rheumatoid arthritis (RA), and peripheral spondyloarthritis underwent synovectomy and subsequent RSO between May 2005 and October 2016. The mean age was 34.9 ± 15.1 years, and the mean follow-up period was 84 ± 36.4 months. Clinical outcomes were assessed using the Oxford Knee Score and the presence of swelling and pain at the last follow-up. Recurrence-free survival denotes the duration from synovectomy to surgical re-synovectomy. Results: In general, twelve knees underwent re-synovectomy after a mean follow-up of 34.8 ± 24.9 months. The recurrence-free survival was 83.8% at two years, 71.3% at five years, and 61.7% at ten years. The subgroup analysis revealed recurrence-free survival at two years in 63.6% of patients with PVNS, 86.7% of those with RA, and 100% of individuals with peripheral spondyloarthritis. Conclusions: This study demonstrates that combined therapy for synovitis is an effective approach, significantly improving clinical outcomes.
The association of the human lymphocyte antigen B27 (HLA-B27) with ankylosing spondylitis (AS), also now called axial spondylarthritis (axSpA), was first described 50 years ago.
This article gives an overview of the available knowledge on the topic.
This is a narrative review based on the experience of the authors.
The HLA-B27 is a member of the HLA class I family of genes of the major histocompatibility complex (MHC). The prevalence of HLA-B27 in the central European population is approximately 8 %, i.e., the vast majority of carriers of HLA-B27+ remain healthy. The frequency of HLA-B27 shows a decline from north to south. The HLA-B27 explains only 30 % of the genetic burden of axSpA. The prevalence of the disease correlates with the frequency of HLA-B27 in the population, i.e., there are geographic differences. Approximately 60–90 % of patients with axSpA worldwide are HLA-B27+. Some 200 subtypes of HLA-B27 can be differentiated using the polymerase chain reaction (PCR). In Thailand and Sardinia two subtypes were found that are not associated with axSpA. The physiological function of HLA class I molecules is the defence of the organism against microbes. Microbial peptides are presented to the immune system, which can be specifically attacked by CD8+ T‑cells. Genetic polymorphisms of the enzyme endoplasmic reticulum aminopeptidase 1 (ERAP1), which breaks down peptides in the endoplasmic reticulum, are associated only with HLA-B27+ diseases.
The pathogenesis of axSpA is unclear but a major hypothesis is that of the arthritogenic peptides. In this it is assumed that potentially pathogenic foreign or autologous peptides can be presented by HLA-B27. If nothing else, HLA-B27 plays an important role in the diagnosis, classification and determination of the severity of axSpA.
Objectives
Systemic-onset juvenile idiopathic arthritis (SJIA) and adult-onset Still’s disease (AOSD) are the same sporadic systemic auto-inflammatory disease. Spondyloarthritis (SpA) is a group of inflammatory non-autoimmune disorders. We report the observations of eight patients with SJIA/AOSD who also presented features of SpA during their disease evolution and estimate the prevalence of SpA in SJIA/AOSD.
Methods
This was a retrospective national survey of the departments of paediatric and adult rheumatology and internal medicine. To be included, SJIA patients had to fulfil the ILAR criteria, AOSD patients the Yamaguchi or Fautrel criteria, and all patients the ASAS classification criteria for axial or peripheral SpA, ESSG criteria for spondyloarthropathy or CASPAR criteria for psoriatic arthritis. The data were collected with a standardized form.
Results
Eight patients (five adults) were identified in one paediatric and two adult departments. In all but one patient, SpA manifestations occurred several years after SJIA/AOSD onset (mean delay 6.2 ± 3.8 years). Two patients had peripheral and three axial SpA, and four later exhibited psoriatic arthritis and one SAPHO syndrome. The prevalence of SpA in an adult cohort of 76 patients with AOSD was 6.58% (95% CI [2.17–14.69]), greater than the prevalence of SpA in the French general population (0.3%, 95%CI [0.17–0.46]). The prevalence of SpA in an SJIA cohort of 30 patients was 10% (95%CI [2.11–26.53]), more than that reported in the general population of industrialized countries, estimated at 0.016% to 0.15%.
Conclusion
Whilst the temporal disassociation between SpA and AOSD in most cases might suggest a coincidental finding, our work raises the possibility of an SpA AOSD spectrum overlap that needs further study.
The spondyloarthritides are a group of common inflammatory rheumatic diseases with predominant involvement of axial and peripheral joints and entheses, together with other characteristic clinical features, including inflammatory back pain, sacroiliitis, peripheral arthritis (mainly in the legs), enthesitis, dactylitis, preceding infection of the urogenital/gastrointestinal tract, psoriatic skin lesions, Crohn-like gut lesions, anterior uveitis, and a family history of spondyloarthritis (SpA). Five subsets can be distinguished on clinical grounds: (1) axial SpA, including ankylosing spondylitis; (2) reactive (spondylo)arthritis/Reiter’s syndrome; (3) psoriatic (spondylo)arthritis; (4) (spondylo)arthritis associated with inflammatory bowel diseases; and (5) undifferentiated peripheral SpA. Prevalence in any population correlates roughly with that of HLA B27, but the relevance of this to pathogenesis is not known. Another more recent approach is to differentiate the SpA on the basis of the predominant clinical manifestation: predominant axial and/or peripheral SpA.
Aim
This study investigated the use of fat fraction (FF) measurements in the sacroiliac (SI) joint to determine radiologic progression in patients with spondyloarthritis (SpA).
Method
A total of 138 patients who underwent pelvic magnetic resonance imaging (MRI) between September 2014 and March 2015 were retrospectively evaluated. The FF based upon fat deposition (%) using fat signaling on T1 and T2 weighted images in the sacroiliac joint was quantified using a 6‐echo variant of the modified Dixon technique. We defined the normal bone marrow as normal FF, bone marrow edema as active inflammatory FF, and fat metaplasia as post‐inflammatory FF.
Results
The mean FF of normal marrow was 52.0% ± 10.4% and 50.5% ± 10.1% in the left and right SI joints, respectively. The mean FF of post‐inflammatory fat deposition was 81.9% ± 9.7% and 82.3% ± 9.6% in the left and right SI joints, respectively. The mean FF of active inflammatory fat deposition was 15.8% ± 5.9% and 13.5% ± 6.7% in the left and right SI joints, respectively. In multiple linear regression, post‐inflammatory FF was found to be significantly associated with radiologic progression, such as symptom duration, SI joint grade, and modified Stoke Ankylosing Spondylitis Spine Score.
Conclusion
Post‐inflammatory FF indicates the chronicity of SpA. Evaluating FF using MRI in the SI joint will help to determine radiologic progression.
This is the protocol for a review and there is no abstract. The objectives are as follows: To assess the benefit and harm of NSAIDs in controlling disease activity, symptoms and radiographic progression in patients with axial SpA.
Résumé
Objectif
Évaluer l’influence des inhibiteurs du facteur de nécrose tumorale (TNF) sur la progression radiographique chez les patients atteints de spondylarthrite ankylosante (SpA).
Méthodes
Au total 610 patients ont été recrutés et répartis dans deux groupes : patients naïfs d’anti-TNF et patients exposés aux anti-TNF. Nous avons ensuite analysé la progression radiographique rachidienne. Des analyses univariées et multivariées ont été réalisées afin d’identifier des facteurs prédictifs de la progression radiographique, évaluée par le Stokes AS Spinal Score modifié (mSASSS). Comme il s’agissait d’une étude observationnelle, les patients n’ont pas été randomisés dans le bras de traitement et les scores de propension ont également été appariés selon l’âge, le sexe et la CRP à l’inclusion. Le modèle d’équation d’estimation généralisée a été appliqué aux échantillons après appariement. Les éventuels facteurs parasites ont été inclus dans le modèle.
Résultats
La concordance entre les deux lecteurs était excellente. Sur les 610 patients atteints de SPA, 341 n’avaient jamais reçu d’anti-TNF. Il n’y avait pas de différence significative de progression radiographique (moyenne ± ET) entre les groupes (4,73 ± 1,01 et 6,14 ± 2,00, p = 0,54), même après ajustement selon les facteurs parasites (âge, sexe, durée de la maladie, tabagisme, concentration de la CRP, prise d’AINS et score mSASSS à l’inclusion). Les scores de propension ont été appariés pour confirmer l’effet des anti-TNF sur la progression radiographique. Même après ajustement en fonction de l’exposition aux anti-TNF, le résultat n’était pas significatif ; l’Odd Ratio (OR) de la progression avec prise d’anti-TNF était de 0,69 (p = 0,41 ; intervalle de confiance [IC] 95 % : 0,29–1,63).
Conclusion
Les données de notre registre indiquent que les anti-TNF sont restés sans effets sur la progression radiographique chez les patients atteints de SPA sur une période de cinq ans.
Systemic slcerosis, scleroderma.
This is a generalized multisystem autoimmune disease characterized by proliferative microcirculatory change leading to fibrosis of skin, lung, heart, kidney, and gastrointestinal tract.
Objective:
To evaluate the influence of tumor necrosis factor (TNF) blocker on the radiographic progression in ankylosing spondylitis (AS) patients.
Methods:
A total of 610 patients were recruited. We stratified two groups (TNF blocker naïve and exposure patients). After then, we analyzed the radiographic spinal progression. Univariable and multivariable analyses were performed to identify predictors associated with radiographic progression, which was assessed by the modified Stokes AS Spinal Score (mSASSS). As this was an observational study, the patients were not randomized to the treatment arm. Therefore, propensity score matching was also done with age, gender, and the baseline CRP. The generalized estimating equation model was performed in the post-matched samples. Potential confounders were included in the model.
Results:
Agreements between the two readers were excellent. Of the 610 patients with AS, 341 patients did not have any exposure to TNF blocker. The radiographic progression (mean±SEM) was not significantly different between groups (4.73±1.01, and 6.14±2.00, P=0.54) in spite of adjusting for confounding factors (age, gender, disease duration, smoking, CRP level, NSAID intake, and baseline mSASSS). Propensity score matching was done to confirm the effect of TNF blockers on radiographic progression. Even after adjusting for the TNF blocker exposure, the result still remained not significant with an OR for progression while taking TNF blocker of 0.69 (P=0.41; 95% CI: 0.29-1.63).
Conclusion:
Our registry data showed that TNF blocker failed to affect the radiographic progression over 5 years in AS patients.
This study was to clarify whether BehCet's disease (BID) could be classified into the spondyloarthropathy (SpA) complex. It was undertaken on 58 patients with BD (I group), 56 patients with SpA (SpA group), and 3 patients who concurrently satisfied the criteria for BID and SpA (BDSpA group). The clinical parameters and known susceptible HLA antigens were compared between BID group and SpA group. In addition, 3 patients in BDSpA group were reviewed. The prevalence of definitive sacroiliitis (SI) in BID group and SpA group was 46.4% and 5.2%, respectively. However, none had a definitive SI in healthy controls. Enthesitis was observed in 3.4% of BID group and in 50% of SpA group. The patterns of eye involvement were different between these two groups. HLA-B27 was negative in all 49 patients of BID group, whereas it was positive in 67.9% of SpA group. The prevalence of HLA-B51 was 51.7% in BID group, and that in SpA group was 21.4%. One patient in BDSpA group was considered to have concurrent BID and ankylosing spondylitis (AS). Another patient was closer to AS, and the third to BD. Conclusively, it seems that BID could not be classified into the SpA complex.
Objective:
To determine the benefits and harms of nonsteroidal antiinflammatory drugs (NSAID) in axial spondyloarthritis (axSpA).
Methods:
Systematic review using Cochrane Collaboration methodology.
Inclusion criteria:
randomized controlled trials (RCT) and quasi-RCT (to June 2014), investigating NSAID versus any control for axSpA, and observational studies of longterm effects (≥ 6 mos) of NSAID on radiographic progression or adverse events. Main outcomes were pain, Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index, Bath Ankylosing Spondylitis Metrology Index, radiographic progression, number of withdrawals because of adverse events, and number of serious adverse events. Risk of bias was assessed.
Results:
Thirty-five RCT, 2 quasi-RCT, and 2 cohort studies were included. Twenty-nine RCT and 2 quasi-RCT (n = 4356) were included in pooled analyses [traditional NSAID vs placebo (n = 5), cyclooxygenase-2 (COX-2) vs placebo (n = 3), COX-2 vs traditional NSAID (n = 4), NSAID vs NSAID (n = 24), naproxen vs other NSAID (n = 3), and low- vs high-dose NSAID (n = 5)]. Compared with placebo, both traditional and COX-2 NSAID were consistently more efficacious at 6 weeks and equally safe after 12 weeks. No significant differences in benefits or harms between the 2 NSAID classes and no important differences in benefits or withdrawals because of adverse events between different NSAID were found, especially if studies with high risk of bias were excluded. Single studies suggest NSAID may retard radiographic progression, especially by continuous rather than on-demand NSAID use.
Conclusion:
High-quality evidence indicates that both traditional and COX-2 NSAID are efficacious for treating axSpA, and harms are not different from placebo in the short term. Various NSAID are equally effective.
Background: Behçet's disease (BD) is a chronic relapsing inflammatory disease that involves various organ systems. Articular involvement was reported to be present in approximately 50% of Korean BD patients. The joint symptoms of BD patients have usually been described as intermittent, self-limiting and non-erosive, and they are mostly monoarticular and oligoarticular arthritis. Objective: The purpose of our investigations was to evaluate the usefulness of bone scintigraphy for detecting the articular involvement of BD. Methods: We reviewed the medical records, laboratory findings and bone scintigraphy findings of 89 patients who were diagnosed with BD from January 2005 to June 2007. Results: Of the 89 BD patients, 14 patients were male and 75 patients were female with a mean age of 43.92+8.49 yr. The most frequently involved site on bone scintigraphy was die wrist (44.9%) with the decreasing order of frequency as follows: me feet (39.3%), the hands (25.8%), the knee (24.7%), the sacroiliac joint (22.4%), the shoulder (18%), the ankle (16.9%), the hip (12.6%), the spine (10%) and the elbow (3%). The pattern of involvement, which was defined as me number of joints showing hot uptake on the bone scintigraphy at one episode of arthropathy, was monoarticular in 5.6%, oligoarticular in 44.9%, polyarticular in 38.2% and there was no uptake in 11.2%. Among 130 joints, 63.1% of the joints showed close correlation between me clinical symptoms and the bone scintigraphy uptake. Conclusion: We suggest mat bone scintigraphy can be a useful tool to determine the presence and site of articular involvement. However, more studies are needed to exclude non-specific bone scintigraphy uptake and to determine the correlation between clinical symptoms and me bone scintigraphy findings.
Spondyloarthropathies are a cluster of Interrelated and overlapping chronic Inflammatory rheumatic diseases that primarily include ankylosing spondylitis, reactive arthritis, and the arthritis associated with psoriasis and inflammatory bowel diseases. The primary pathologic sites are the entheses (the sites of bony insertion of ligaments and tendons); the axial skeleton, including the sacroiliac joints; the limb joints; and some nonarticular structures, such as the gut skin, eye, and aortic valve. Although spondyloarthropathles are not associated with rheumatoid factor, they show a strong association with HLA-1327; however, this association varies markedly among various spondyloarthropathles and among ethnic groups. The most widely used classification criterion, from the European Spondyloarthropathy Study Group, encompasses the currently recognized wider disease spectrum, with a sensitivity and specificity that generally exceed 85%. Spondyloarthropathies occur in genetically predisposed persons and are triggered by environmental factors, but the cellular and molecular mechanisms of Inflammation are not yet fully understood. Chlamyclial and many enterobacterial infections can trigger reactive arthritis, but an infectious trigger for ankylosing spondylitis has not yet been established. HLA-1327 Itself is involved In enhancing genetic susceptibility, but the underlying molecular basis Is still unknown; additional genes include the putative susceptibility genes for Crohn disease, ulcerative colitis, and psoriasis. A specific susceptibility gene for Crohn disease, NOD2, Is located on chromosome 16q12, and one of the candidate genes for psoriasis, PSORS1, has been mapped to a 60-kb fragment on chromosome 6p, which Is telomeric to the HLA-C locus. This paper reviews the efficacy of anti-tumor necrosis factor-a therapy and other therapeutic advances.
Background:
Axial spondyloarthritis (axSpA) comprises ankylosing spondylitis (radiographic axSpA) and non-radiographic (nr-)axSpA and is associated with psoriasis, uveitis and inflammatory bowel disease. Non-steroidal anti-inflammatory drugs (NSAIDs) are recommended as first-line drug treatment.
Objectives:
To determine the benefits and harms of NSAIDs in axSpA.
Search methods:
We searched CENTRAL, MEDLINE and EMBASE to 18 June 2014.
Selection criteria:
Randomised controlled trials (RCTs) or quasi-RCTs of NSAIDs versus placebo or any comparator in adults with axSpA and observational cohort studies studying the long term effect (≥ six months) of NSAIDs on radiographic progression or adverse events (AEs). The main comparions were traditional or COX-2 NSAIDs versus placebo. The major outcomes were pain, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Metrology Index (BASMI), radiographic progression, number of withdrawals due to AEs and number of serious AEs
Data collection and analysis:
Two review authors independently selected trials for inclusion, assessed the risk of bias, extracted data and assessed the quality of evidence for major outcomes using GRADE.
Main results:
We included 39 studies (35 RCTs, two quasi-RCTs and two cohort studies); and 29 RCTs and two quasi-RCTs (n = 4356) in quantitative analyses for the comparisons: traditional NSAIDs versus placebo, cyclo-oxygenase-2 (COX-2) versus placebo, COX-2 versus traditional NSAIDs, NSAIDs versus NSAIDs, naproxen versus other NSAIDs, low versus high dose. Most trials were at unclear risk of selection bias (n = 29), although blinding of participants and personnel was adequate in 24 trials. Twenty-five trials had low risk of attrition bias and 29 trials had low risk of reporting bias. Risk of bias in both cohort studies was high for study participation, and low or unclear for all other criteria. No trials in the meta-analyses assessed patients with nr-axSpA.Traditional NSAIDs were more beneficial than placebo at six weeks. High quality evidence (four trials, N=850) indicates better pain relief with NSAIDs (pain in control group ranged from 57 to 64 on a 100mm visual analogue scale (VAS) and was 16.5 points lower in the NSAID group (95% confidence interval (CI) -20.8 to -12.2), lower scores indicate less pain, NNT 4 (3 to 6)); moderate quality evidence (one trial, n = 190) indicates improved disease activity with NSAIDs (BASDAI in control group was 54.7 on a 100-point scale and was 17.5 points lower in the NSAID group, 95% CI -23.1 to -11.8), lower scores indicate less disease activity, NNT 3 (2 to 4)); and high quality evidence (two trials, n = 356) indicates improved function with NSAIDs (BASFI in control group was 50.0 on a 100-point scale and was 9.1 points lower in the NSAID group (95% CI -13.0 to -5.1), lower scores indicate better functioning, NNT 5 (3 to 8)). High (five trials, n = 1165) and moderate (three trials, n = 671) quality evidence (downgraded due to potential imprecision) indicates that withdrawals due to AEs and number of serious AEs did not differ significantly between placebo (52/1000 and 2/1000) and NSAID (39/1000 and 3/1000) groups after 12 weeks (risk ratio (RR) 0.75, 95% CI 0.46 to 1.21; and RR 1.69, 95% CI 0.36 to 7.97, respectively). BASMI and radiographic progression were not reported.COX-2 NSAIDS were also more efficacious than placebo at six weeks. High quality evidence (two trials, n = 349) indicates better pain relief with COX-2 (pain in control group was 64 points and was 21.7 points lower in the COX-2 group (95% CI -35.9 to -7.4), NNT 3 (2 to 24)); moderate quality evidence (one trial, n = 193) indicates improved disease activity with COX-2 (BASDAI in control groups was 54.7 points and was 22 points lower in the COX-2 group (95% CI -27.4 to -16.6), NNT 2 (1 to 3)); and high quality evidence (two trials, n = 349) showed improved function with COX-2 (BASFI in control group was 50.0 points and was 13.4 points lower in the COX-2 group (95% CI -17.4 to -9.5), NNT 3 (2 to 4)). Low and moderate quality evidence (three trials, n = 669) (downgraded due to potential imprecision and heterogeneity) indicates that withdrawals due to AEs and number of serious AEs did not differ significantly between placebo (11/1000 and 2/1000) and COX-2 (24/1000 and 2/1000) groups after 12 weeks (RR 2.14, 95% CI 0.36 to 12.56; and RR 0.92, 95% CI 0.14 to 6.21, respectively). BASMI and radiographic progression were not reported.There were no significant differences in benefits (pain on VAS: MD -2.62, 95% CI -10.99 to 5.75; three trials, n = 669) or harms (withdrawals due to AEs: RR 1.04, 95% CI 0.60 to 1.82; four trials, n = 995) between NSAID classes. While indomethacin use resulted in significantly more AEs (RR 1.25, 95% CI 1.06 to 1.48; 11 studies, n = 1135), and neurological AEs (RR 2.34, 95% CI 1.32 to 4.14; nine trials, n = 963) than other NSAIDs, these findings were not robust to sensitivity analyses. We found no important differences in harms between naproxen and other NSAIDs (three trials, n = 646), although other NSAIDs appeared more effective for relieving pain (MD 6.80, 95% CI 3.72 to 9.88; two trials, n = 232). We found no clear dose-response effect on benefits or harms (five studies, n = 1136). Single studies suggest NSAIDs may be effective in retarding radiographic progression, especially in certain subgroups of patients, e.g. patients with high CRP, and that this may be best achieved by continuous rather than on-demand use of NSAIDs.
Authors' conclusions:
High to moderate quality evidence indicates that both traditional and COX-2 NSAIDs are efficacious for treating axSpA, and moderate to low quality evidence indicates harms may not differ from placebo in the short term. Various NSAIDs are equally effective. Continuous NSAID use may reduce radiographic spinal progression, but this requires confirmation.
To evaluate the validity of the Korean version of ASAS-HI in patients with spondyloarthritis in Korea.
" Spondyloarthritis" consists of a group of several diseases sharing clinical, radiological and genetic similarities. Ankylosing spondylitis is the main representative of this group and is characterized by a predominant axial involvement. The presence of radiographic sacroiliitis is essential for the diagnosis of ankylosing spondylitis according to the modified New York criteria. Because the occurence of radiographic sacroiliitis takes 8 to 11 years, the diagnosis of spondyloarthritis is often delayed. Magnetic resonance imaging can depict sacroiliac joint inflammation before the appearance of radiographic damage thereby defining the concept of " non-radiographic axial spondylo-arthritis". This entity was defined by the axial spondyloarthritis classification criteria published by the Assessment of SpondyloArthritis international Society (ASAS). Some factors, such as elevated levels of C-reactive protein at baseline, have been identified as predictors of radiographic sacroiliitis progression, leading to a definite diagnosis of ankylosing spondylitis. These two entities show similar clinical expression (clinical features and activity levels), suggesting continuity between the two diseases. Non-radiographic forms most often affect women and patients with recent symptoms, and are therefore considered as a pre-radiographic status. If the use of magnetic resonance imaging is necessary for the identification of non-radiographic axial spondyloarthritis according to the ASAS criteria, the presumptive diagnosis is mainly based on complaints of inflammatory back pain. The presence of other typical clinical features, such as HLA B27 positivity and/or radiographic sacroiliitis increases the diagnostic probability and indicates the need for referral to a specialist.
El síndrome SAPHO (sinovitis, acné, pustulosis, hiperóstosis, osteítis) es un conjunto de manifestaciones dermatoesqueléticas que aparecen reunidas en un paciente a lo largo de su vida. Las manifestaciones de este síndrome muestran presentaciones clínicas típicas y similares a lo largo del tiempo.Proponemos una forma de presentación clínica atípica del síndrome SAPHO: la afectación sintomática de la articulación temporomandibular como signo de una oligoartritis transitoria periférica.El caso clínico es de una paciente que acudió a la consulta de rehabilitación por dolor y tumefacción temporomandibular, cervicalgia, sensación de rigidez y pesadez cervicobraquial además de dolor y tumefacción en articulaciones de ambos carpos. La sintomatología comenzó a resolverse tras iniciar la corticoterapia. En su historia mostraba signos clínicos y gammagráficos compatibles con el síndrome SAPHO.
The spondyloarthritides (or spondyloarthropathies) (SPAs) are chronic, inflammatory, rheumatic diseases of unknown origin, which share certain clinical, epidemiological, and genetic characteristics. They include ankylosing spondylitis, reactive arthritis (also known as the Reiter Syndrome), psoriatic arthritis, enteropathic spondyloarthropathy (ulcerative colitis, Crohn's disease), undifferentiated spondyloarthritis, juvenile spondyloarthritis, and formes frustes such as acute anterior uveitis, spondyloarthritic carditis, and balanitis circinata. In the past, the SPAs were considered variants of rheumatoid arthritis, but it is now clear that they differ from the latter disease in terms of the pattern of articular and extra-articular involvement, their lack of association with seropositivity for rheumatoid factor, and their strong association with sacro-iliac joint bacino= pelvis sacro-iliac joint sacro-iliac joint sacro-iliac joint sacro-iliac joint sacro-iliac joint the class I human leukocyte antigen B27. sacro-iliac joint bacino= pelvis sacro-iliac joint sacro-iliac joint sacro-iliac joint sacro-iliac joint sacro-iliac joint Their general characteristics are axial involvement; enthesitis; peripheral arthritis involving the lower limbs, which is usually asymmetric; dactylitis; extra-articular manifestations involving the skin, eyes, bowel, and genitals. The musculoskeletal manifestations of the SPAs are due to inflammation at the level of the entheses. It is important to distinguish between the numerous clinical SPA variants based on analysis of symptoms, laboratory tests, and instrumental studies. Thanks to a greater understanding of the pathogenesis of the SPAs and the widespread availability of highly sensitive imaging modalities for their diagnosis, it is now possible to identify these diseases early and modify their course with effective therapy. This approach offers benefits to patients in terms of reduced morbidity and mortality and improved quality of life.
The aim of this study was to assess discriminant validity of Ankylosing Spondylitis Disease Activity Score (ASDAS)-C-reactive protein (-CRP) and ASDAS-erythrocyte sedimentation rate (-ESR) and to compare with The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) as clinical tools for the measurement of disease activity in patients with non-radiographic axial spondyloarthritis (nr-axSpA) and ankylosing spondylitis (AS). Also, the cut-off values for ASDAS-CRP in nr-axSpA and AS is revisited. Patients with axSpA were recruited from Erciyes Spondyloarthritis Cohort (ESPAC) and were assessed for disease activity, quality of life and functional measures. The discriminatory ability of ASDAS-CRP and ASDAS-ESR was assessed using standardized mean differences and receiver operating characteristic (ROC) curves analysis. Optimal cut-off values for disease activity scores were calculated. Two hundred and eighty-seven patients with axSpA (nr-axSpA:132, AS:155) were included in this study. Two ASDAS versions and BASDAI had good correlations with patient's and physician's global assessment in both groups. Discriminatory ability of ASDAS-CRP, ASDAS-ESR and BASDAI were similar in patients with nr-axSpA and AS when the patients were assigned into low and high disease activity according to the ASAS partial remission, patient's and physician's global assessment scores (based on the comparison of ROC curves). ASDAS cut-off values are quite similar between groups indicating that ASDAS-CRP works similarly well in nr-axSpA and AS. The performance of ASDAS to discriminate low and high disease activity and cut-off values are quite similar in patients with AS and non-radiographic axial SpA.
Abstract Vitiligo is a very common disease and is suspected to be autoimmune in its pathogenesis. Many autoimmune complications, such as Hashimoto's thyroiditis, are reportedly associated with vitiligo. The pathogenesis of ankylosing spondylitis (AS) is also suspected to be autoimmune, triggered by some infection. We report a 56-year-old man with concurrent vitiligo and AS, and suggest that both diseases could have a common autoimmune background.
The ASAS (Assessment in SpondyloArtrhritis international Society) classification criteria for axial and peripheral spondyloarthritis permit to classify patients with age at disease onset less than 45 years. Nevertheless, these two forms of spondyloarthritis may begin after the age of 45. With the longer duration of the life expectancy, patients with this late-onset form of spondyloarthritis may be more frequently recognized in the near future. A small percentage (ranging from 3.5 to 6 %) of patients with axial SpA, as defined by the modified New York criteria, have onset of their disease after 45 years of age. Relatively more frequent is the late onset form of peripheral spondyloarthritis with the characteristics of undifferentiated spondyloarthritis. Its clinical spectrum is as broad as it is in children and very young adults. Psoriatic arthritis frequently begins over the age of 45 and occasionally after the age of 60. Some old studies had suggested than elderly-onset psoriatic arthritis is more severe than younger-onset disease, but a recent study found no such difference, and further studies are needed.
Seventeen patients with shoulder pain and radiographic involvement of the sternoclavicular or sternocostal joints, or both, are described. Eleven of these patients also had palmoplantar pustulosis. Histological examination of the joints showed chronic and subacute inflammation, increased osteoblastic activity, and cartilage degeneration. Propionibacterium acnes was cultured in tissue samples from seven of the 15 biopsied patients, a finding at variance with those of previous reports. The possibility that sternoclavicular arthro-osteitis is of infectious origin should be the subject of further investigation. Non-steroidal anti-inflammatory drugs (NSAIDs) may provide pain relief, possibly owing to their inhibitory action on osteoblasts. In cases of severely restricted movement or severe pain resection of the medial clavicle may be considered.
Fifty two patients with psoriatic spondyloarthropathy were monitored prospectively over a mean of 57 months (range 30-107). A comprehensive protocol was used to assess clinical and radiological features of disease activity and severity. Serial radiographs showed a significant increase in the number of patients with syndesmophyte formation and sacroiliitis. In contrast, there was no significant increase in the number of patients with inflammatory neck pain or stiffness, back pain or stiffness, cervical spine limitation, or sacroiliac tenderness. Similarly, there were no significant changes in any of the direct or indirect measurements of thoracolumbar spine mobility. The presence of HLA-B27 did not appear to influence disease progression. These results suggest that although patients with psoriatic spondyloarthropathy have radiological progression of their disease, this remains clinically silent and does not compromise spinal mobility.
A 56 year old man with ankylosing spondylitis and discovertebral destruction presented with signs of spinal cord compression that was the result of the soft tissue reaction occurring at the level of the discovertebral destruction. This case emphasises the importance of early recognition, use of appropriate imaging techniques (computed tomographic myelography or magnetic resonance), and operative intervention in the management of this rare complication of ankylosing spondylitis.
The present study was performed on 61 HLA-B27 positive first-degree relatives and 40 HLA-B27 negative relatives of 20 HLA-B27 positive probands with ankylosing spondylitis (AS). Of 24 HLA-B27 positive relatives 45 years or older, 21% had AS and 38% sacroiliitis. The HLA-B27 negative relatives did not have features of either disease. In the population study of 2,957 individuals 45 years or older, we found 5 cases of HLA-B27 positive sacroiliitis (according to the New York criteria) and 3 of these fulfilled the New York criteria for diagnosis of AS. In 2 of these 3 individuals, the diagnosis was made on clinical grounds. The pheno-type frequency of HLA-B27 in this population is 7.8%, or about 230 HLA-B27 positive individuals in this population sample. Since AS was found in only 3 individuals, 1.3% of the HLA-B27 positive individuals in the population at large have AS; therefore, our data show that among individuals 45 years or older, 21% of HLA-B27 positive relatives of HLA-B27 positive AS patients have AS as compared with 1.3% of the HLA-B27 positive individuals in the population at large. Thus, the risk for AS is 16 times greater in the HLA-B27 positive relatives compared with HLA-B27 positive individuals in the population at large. The discriminatory value of the New York criterion of history of pain or the presence of pain at the dorsolumbar junction or in the lumbar spine was analyzed in the population and family studies and was found to be too nonspecific.
Studies by light microscopy on synovium obtained from 11 patients with Reiter's syndrome during the first month of an episode showed proliferation of synovial lining cells, polymorphonuclear neutrophils among the synovial lining cells, increased surface fibrin, and vascular congestion. Biopsy specimens taken later showed vascular congestion and still proliferated synovial lining cells, fewer polymorphonuclear neutrophils in some, and a tendency toward increased infiltration with lymphocytes and plasma cells. Electron microscopy of samples from 8 patients during the first month of disease activity showed occlusion of vessels by platelets in 4, and fibrin or dense granular material in the vessel walls in 4. Five of the patients with arthritis of less than 4 weeks duration had unidentified intracellular and extracellular particles; some of these were highly suggestive of Chlamydia. No such particles were noted in samples from patients with more chronic cases. Using an antibody to Chlamydia trachomatis and the peroxidase-antiperoxidase technique, immunocytochemistry showed reaction product in synovial macrophages in 2 patients with arthritis of less than 4 weeks duration, but not in the 1 patient studied who had more chronic disease. These studies provide support for dramatic synovial vascular injury consistent with that caused by endotoxin and the presence of chlamydial antigen in synovial macrophages, at least in the early phases of synovitis.
We report 2 independently-conducted family studies of HLA-B27 positive probands with ankylosing spondylitis (AS), both of which support the view that the clinical spectrum of AS is broader than ordinarily assumed, and should include individuals who have symptomatic disease but who do not show radiologic evidence of abnormalities of the sacroiliac joints or the spine. In the Cleveland study of 100 relatives of 30 B27 positive AS probands, 9 relatives did not show radiologic abnormalities of the sacroiliac joints or the spine but had symptoms of chronic inflammatory back pain previously reported to be characteristic of AS. These 9 relatives were all subsequently found to possess B27, in contrast with only 27 of 60 asymptomatic relatives (P < 0.01). In the Leiden study of 101 relatives of 20 randomly chosen B27 positive AS probands, 13 of 86 relatives without radiographic evidence of sacroiliitis reported “thoracic pain and stiffness,” as defined in the Rome criteria for AS. Twelve of these 13 symptomatic relatives were B27 positive. In contrast, among the remaining 73 relatives, only 33 were B27 positive (P < 0.01). The occurrence of these characteristic spondylitic symptoms in B27 positive, but not B27 negative, relatives of AS probands suggests that the spectrum of the clinical manifestations of AS may include individuals with symptomatic disease, but without radiographic evidence of abnormalities of the sacroiliac joints or the spine. The relatively large number of females we found in this group suggests that women are more likely to manifest this variety of disease than are men.
Thirty-nine children with a syndrome of seronegative enthesopathy and arthropathy were evaluated. The group included 25 patients with no apparent underlying primary disease and 13 with either ankylosing spondylitis, inflammatory bowel disease, reactive arthritis, or Reiter's syndrome. Significant distinguishing characteristics of the group included male predominance, late age at onset, positive family histories of arthritis, oligoarthropathy, axial skeleton involvement, and the presence of the B27 histocompatibility antigen. This syndrome is distinguishable from other childhood rheumatic disorders, including juvenile rheumatoid arthritis. Its recognition may reliably identify children with the prodromal manifestations of seronegative spondylarthropathies.
The New York and the Rome diagnostic criteria for ankylosing spondylitis (AS) and the clinical history screening test for AS were evaluated in relatives of AS patients and in population control subjects. The New York criterion of pain in the (dorso) lumbar spine lacks specificity, and the chest expansion criterion is too insensitive. The Rome criterion of low back pain for more than 3 months is very useful. Our study showed the clinical history screening test for AS to be moderately sensitive, but it might be better in clinical practice. As a modification of the New York criteria, substitution of the Rome pain criterion for the New York pain criterion is proposed.
The features and clinical course in 38 patients (25 women, 13 men) who had chronic monarthritis of undetermined origin (UCM) were surveyed over a mean followup period of 24.6 months. At the end of the study, the cause was still unknown in 26 patients (65.7%). In 10 patients, symptoms resolved spontaneously. In the remaining 12 patients, a diagnosis became apparent after a mean period of 17.2 months; diagnoses included spondylarthritis (6 patients), rheumatoid arthritis (3 patients), osteoarthritis (1 patient), erosive arthropathy (1 patient), and glomus tumor (1 patient). Patients in whom a diagnosis emerged were more likely to have positive findings on the following studies: rheumatoid factor (2 of 12); HLA—B27 typing (6 of 11); bone scan, positive over the sacroiliac joint or non-index joint(s) (4 of 6); and roentgenograms of the sacroiliac joint (3 of 8). Findings of these same studies were notably negative in the subgroup of patients with UCM that spontaneously resolved.
We conducted HLA–B27 tissue typing assessments on 430 consecutive children whose main symptom at presentation to our clinic was arthritis/arthralgia. Eighty-five of them (20%) had the B27 antigen. Thirty-six of these children were reexamined after a mean followup period of 8.9 years. Although most had definable rheumatic diseases, only 2 met the New York criteria for ankylosing spondylitis (AS). Children with HLA–B27 and arthritis/arthralgia, although at increased risk of developing AS, have diverse diagnostic and clinical outcomes. The AS criteria used to diagnose the disease in adults may not be appropriate for use in children.
When "sausage-like" swelling of the toes occurs in the absence of clinical Reiter's disease or psoriasis, definite classification is hardly possible. Nine patients with isolated "sausage toes" (dactylitis) and minor involvement of other joints are described. The relationship between this syndrome and HLA B27 permits better classification and more rational treatment.
Synovial cells from nine patients with reactive arthritis following Salmonella enteritidis or Salmonella typhimurium infection were examined for salmonella antigens. Extensive bacterial cultures of the synovial fluid were negative. Eight synovial-fluid cell samples stained positively on immunofluorescence with rabbit antisera against heat-killed S enteritidis or S typhimurium or with monoclonal antibodies specific for the causative salmonella lipopolysaccharide (LPS). Synovial tissue from the ninth patient stained positively in the avidin-biotin-peroxidase complex method with the monoclonal antibody. Control samples (synovial-fluid cells from thirteen patients with other rheumatic diseases and synovial tissue from two) were negative. Synovial cells from eight patients and five controls were studied by western blotting with the same monoclonal antibodies. Four of the eight patients but no controls had blots indicating salmonella LPS in the synovial cells. The presence of bacterial LPS in the joint is a common and pathogenetically important feature of reactive arthritis.
Ankylosing spondylitis and related spondyloarthropathies show a remarkable association with a genetic marker--HLA-B27--and also illustrate the relationship between host and environmental factors. HLA-B27 has revitalized the epidemiology of spondyloarthropathies and has helped to broaden the clinical spectrum of these diseases. These and other aspects of descriptive and genetic epidemiology are reviewed.
In a Yupik Eskimo population, the prevalence, incidence and clinical features of rheumatoid arthritis (RA) were similar to those described for the United States population in general. More frequent than RA were seronegative spondyloarthropathic disorders, many of which could not be classified by existing disease criteria. Of the adult patients with spondyloarthropathy only half could be classified as having Reiter's syndrome (RS), ankylosing spondylitis (AS) or psoriatic spondylitis. The remaining patients had many signs and symptoms consistent with spondyloarthropathy, but they either did not meet the diagnostic criteria for any specific disease or had features pathognomonic of more than one. The clinical manifestations of the patients who did not meet standard disease definitions are summarized and compared to those of the patients with RS, AS and psoriatic spondylitis. Because of the many shared features, we believe that these as yet unclassified disease states belong with AS and RS in a single spondyloarthropathic disease spectrum and should be defined and recognized as such.
A case of skin psoriasis and psoriatic monoarthritis triggered by physical trauma is reported. Possible pathogenic mechanisms of this phenomenon are discussed.
The case histories of 13 elderly patients (8 men/5 women) with a relatively acute onset of a severe symmetrical synovitis affecting the flexor digitorum tendon sheaths and wrist joints with pitting edema of the dorsum of both hands are described. All were persistently seronegative for IgM rheumatoid factors and all went into complete remission without relapse. Asymptomatic residual flexion contractures of the fingers and wrists were a constant feature during remission. HLA-B7 was present in 15 of a total 23 reported cases (relative risk = 4.4). This condition, with its excellent prognosis, is differentiated from rheumatoid arthritis and polymyalgia rheumatica.
In reactive arthritis (ReA), including Reiter's syndrome, a close relationship between chronic enteric and genitourinary infections and the clinical features of enthesitis has been described. In contrast, in Lyme arthritis, a distinct clinical entity, chronic infection with the tick-transmitted spirochete Borrelia burgdorferi has been associated with the disease. In a prospective study, 51 patients with ReA were tested for evidence of chlamydial and spirochetal infection. The presence of Chlamydia was determined by culture in 8 patients, and 7 additional patients had markedly elevated antibody titers. In 9 patients, antibodies specific to B burgdorferi were found. Purified peripheral blood T lymphocytes of all 9 patients proliferated specifically to stimulation with macrophages pre-pulsed with B burgdorferi antigens. Compared with other protein antigens, higher numbers of antigen-pulsed macrophages were necessary to activate B burgdorferi-specific T cells. Although antibody titers decreased in response to antibiotic treatment in 8 of 9 patients, second-line therapy with sulfasalazine or methotrexate was required to obtain clinical remission. These data suggest that chronic infection with B burgdorferi can cause ReA. In predisposed individuals, the arthritogenic immune response might be triggered by persisting infectious agents independent of their antigenic specificities.
We studied prospectively the clinical and radiographic features of sacroiliac and spinal involvement in 20 patients with seronegative enthesopathy and arthropathy. This group was compared with 25 patients with a polyarticular onset form of juvenile rheumatoid arthritis (JRA) and 28 with definite ankylosing spondylitis (AS) of juvenile onset. A significant increasing proportion of patients with seronegative enthesopathy and arthropathy developed back complaints and radiographic sacroiliitis fulfilling the diagnostic criteria for AS from the 3rd-5th year of disease (47.1-75.0%) and thereafter (92.3%). Back complaints were rarely seen in JRA and, furthermore, sacroiliitis of the AS type nerve occurring in this group. There were no significant differences between the group with seronegative enthesopathy and arthropathy and juvenile AS, either at onset or through the years. Clinical and radiographic assessment of axial involvement in children at risk should include a careful analysis of symptoms, periodical measurements of the spinal flexion and, starting from the 3rd year, radiographs of the pelvis.
We report a case of a rare association between acne conglobata and ankylosing spondylarthritis B27 negative which occurred in a young man. The pathogenetic relationship of the association is not certain, although some researches suggest that the onset of ankylosing spondylarthritis can result from cutaneous disease. Despite the long evolution of ankylosing spondylitis, it is not severe. Thus, the presence of B35 CREG antigens confirm that locus B antigens different from B27 could be associated with a more favourable prognosis of the disease.
Out of a cohort of 64 patients with seronegative oligoarthritis (SO), 8 patients with HLA-B13, 5 with Bw16 and 3 with HLA-B17 were invited to participate in a 14-year check-up. Thirteen patients showed some features of psoriatic arthritis, including 5 with suspected skin or nail disease, 5 with a family history of psoriasis, 3 with DIP joint affliction, and 2 with aortic valve insufficiency. It is concluded that a quarter of the patients with SO may have hidden psoriatic arthritis.
We describe a 68-year-old woman who had suffered pain, swelling, heat, and redness in the region of both clavicles for the last 2 years. Her erythrocyte sedimentation rate was markedly elevated; tests for rheumatoid factor were negative. At surgical exploration, ankylosis of the sternoclavicular joints, especially on the left side, was found. Biopsy revealed chronic nonspecific inflammation with new bone formation, consistent with the diagnosis of sternocostoclavicular hyperostosis or pustulotic arthroosteitis.
We examined synovial-fluid cells from 15 patients with reactive arthritis after yersinia infection for the presence of yersinia antigens. Extensive bacterial cultures of the synovial fluid were negative. All the samples were studied by immunofluorescence with use of a rabbit antiserum to Yersinia enterocolitica O:3 and a monoclonal antibody to Y. enterocolitica O:3 lipopolysaccharide. Synovial-fluid cells from 41 patients with other rheumatic diseases served as controls. Synovial-fluid cells from 10 patients with reactive arthritis after yersinia infection stained positively on immunofluorescence; rabbit antiserum and the monoclonal antibody yielded similar results. In most patients the percentage of positive cells ranged from 1 to 10 percent, but in one patient nearly all the cells in the sample stained strongly. Most of the positively stained cells were polymorphonuclear leukocytes, but yersinia antigens were also found in mononuclear phagocytes. All the control samples were negative. Synovial-fluid cell deposits from nine patients were also studied by Western blotting with use of the same antibodies. The results were positive in six of the nine cell deposits from patients with reactive arthritis and in none of the 10 cell deposits from control patients with rheumatoid arthritis. We conclude that in patients with reactive arthritis after yersinia infection, microbial antigens can be found in synovial-fluid cells from the affected joints.
Clinical and laboratory findings in 26 children with atypical spondyloarthritis were compared with those of 76 children with juvenile rheumatoid arthritis. The sensitivity, specificity, predictive value, and efficiency for diagnosis were calculated. The following findings (major criteria) were much more common in atypical spondyloarthritis than in juvenile rheumatoid arthritis: (1) spondyloarthritis within the family; (2) enthesopathy; (3) arthritis of digital joints; (4) sacro-iliitis; (5) presence of HLA-B27; (6) frequent recurrence of arthritis and arthralgia. Six additional findings (minor criteria) were significantly more common in atypical spondyloarthritis (SA): (1) disease onset after the age of 10 years; (2) male sex; (3) involvement of the lower extremities; (4) acute iridocyclitis or conjunctivitis; (5) arthritis of the hip joints; (6) manifestation following a history of enteritis. In the presence of 4 major criteria or 3 major and 3 minor criteria, the diagnosis of an atypical SA was established with a sensitivity of 84.6%, a specificity of 100%, and an efficiency of 96.1%.
Discussion a propos de la pathogenie du syndrome de Reiter a partir de la decouverte d'anticorps anti Borrelia Burgdorferi chez 18% des patients atteints d'arthrite reactionnelle ou du syndrome de Reiter, patients demeurant dans une zone d'endemie de la maladie de Lyme
Description des differentes pathologies rhumatismales liees au syndrome d'immunodepression acquise depuis les arthralgies isolees jusqu'aux arthrites septiques en passant par les arthrites reactionnelles, les arthropathies seronegatives, le rhumatisme psoriasique, le syndrome de Sjogren et diverses connectivites. Considerations etiopathogeniques: role des lymphocytes, effets directs ou indirects du virus du SIDA selon les cas. Traitements: place des immunodepresseurs, des antibiotiques et de la zidovudine
We studied 87 Mexican mestizo patients (82 men and 5 women) with definite ankylosing spondylitis (AS) with particular reference to juvenile and adult onset types. HLA-B27 was present in 32 of 38. Forty-seven patients (54.0%) had onset before the age of 16 years and 40 (46.0%) thereafter. By the end of the 1st year of disease, main features included spinal involvement in 44 (50.6%), peripheral arthropathy in 57 (65.5%) and enthesopathy in 41 (47.1%). Frequency of these increased up to 100.0, 79.3 and 64.4%, respectively, through the course of the disease. Peripheral arthritis and/or enthesopathy occurred in 89.4 and 63.1% of juveniles and 37.5 and 27.5% of adults, respectively, while lumbar pain and/or stiffness occurred in 23.4% of the former and 82.5% of the latter during the first year of disease. Additional findings were high erythrocyte sedimentation rate, anemia and hypergammaglobulinemia. Uveitis was the commonest extraarticular manifestation occurring in 20.6%. Our data suggest that the clinical pattern of AS in our patients was influenced by both age at onset and sex distribution of the disease.
Two more cases of B27 associated peripheral arthritis triggered by physical injury are reported. One patient developed arthritis after a minor insult and in the other Reiter's syndrome occurred after the injury. Possibly, trauma causes release of self antigens from the injured joints.
After studying 10 cases, we describe a form of late onset, B27 related disease. The patients were men over 50 with minimal involvement of the axial skeleton, mild oligoarthritis of the lower limbs, paucicellular joint fluids and fibrosis on synovial biopsy. In contrast, they appeared severely ill with erythrocyte sedimentation rates elevated and a large amount of pitting edema. Their response to nonsteroidal antiinflammatory drugs was poor. The disease did not abate for from one to several years. Five patients later presented bilateral sacroiliitis and 4 of these developed ankylosing spondylitis (AS). This clinical presentation of AS may owe its distinctive features to its late onsets.
Studies by light microscopy on synovium obtained from 11 patients with Reiter's syndrome during the first month of an episode showed proliferation of synovial lining cells, polymorphonuclear neutrophils among the synovial lining cells, increased surface fibrin, and vascular congestion. Biopsy specimens taken later showed vascular congestion and still proliferated synovial lining cells, fewer polymorphonuclear neutrophils in some, and a tendency toward increased infiltration with lymphocytes and plasma cells. Electron microscopy of samples from 8 patients during the first month of disease activity showed occlusion of vessels by platelets in 4, and fibrin or dense granular material in the vessel walls in 4. Five of the patients with arthritis of less than 4 weeks duration had unidentified intracellular and extracellular particles; some of these were highly suggestive of Chlamydia. No such particles were noted in samples from patients with more chronic cases. Using an antibody to Chlamydia trachomatis and the peroxidase-antiperoxidase technique, immunocytochemistry showed reaction product in synovial macrophages in 2 patients with arthritis of less than 4 weeks duration, but not in the 1 patient studied who had more chronic disease. These studies provide support for dramatic synovial vascular injury consistent with that caused by endotoxin and the presence of chlamydial antigen in synovial macrophages, at least in the early phases of synovitis.
Reactive inflammatory arthritis is a common sequel to sexually acquired non-gonococcal genital-tract infection. Approximately 50% of cases are associated with Chlamydia trachomatis infection in the genital tract, although conventional cultures of joint material are sterile. Synovium, synovial-fluid cells, or both, from eight patients with sexually acquired reactive arthritis (SARA) and eight with knee effusions associated with other rheumatic diseases were examined by means of a fluorescein-labelled monoclonal antibody to C trachomatis ('Micro Trak'; Syva). Typical chlamydial elementary bodies were seen in joint material from five patients with SARA but in none of the controls. An inclusion-like cluster of elementary bodies was seen in one synovial biopsy sample. All five patients had high titres of serum chlamydial antibody. It is likely that the synovitis of SARA results directly from the presence of chlamydial elementary bodies in the joint.
Two B27 positive patients developed peripheral arthritis immediately after a significant musculoskeletal injury. Unlike previously reported peripheral arthritis precipitated by trauma in B27 positive subjects the arthritis was rapidly destructive.
Forty-three psoriatic patients with spondylitic involvement (19 women and 24 men, mean age 41 years) have been reviewed. Three
different subsets were recognized. The first (PS1,), with predominant involvement of the axial skeleton, occurred in 22 (seven women and 15 men, mean age 39). The second (PS2) and the third (PS3) showed an overlap of spondylitis and peripheral articular disease. In PS2 this consisted of distal interphalangeal (DIP)
arthritis (five women and three men, mean age 41), while in PS3 there was symmetrical polyarthritis (seven women and six men,
mean age 42). Spinal involvement, present in every case, was characterized by unilateral and asymmetrical syndesmophytes,
often nonmarginal and randomly affecting the vertebral column. Sacroiliitis, absent in the PS2 subset, was present in 15 of the PS1, and in two of the PS3 subgroup and was bilateral in six and unilateral in 11. The HLA-B27 antigen, absent in the PS2 subgroup, was found in 12 of the PS1, and in two of the PS3 subset. It was associated with sacroiliitis in 13 cases and with spondylitis without sacroiliitis in only one case. Nail
changes were recorded in 30% of the total cases and showed a strict relationship with the PS2 subset (40%). Extra-articular symptoms, consisting almost exclusively of ocular involvement, occurred in three patients only
(two cases of conjunctivitis and one of acute anterior uveitis). The clinical course of psoriatic spondylitis appeared less
disabling than that of the idiopathic form.
HLA-B27, an immunogenetic marker that is present in 8 percent of the white population around the world, has been found to be an important risk factor for the development of a group of rheumatic disorders, the seronegative spondyloarthropathies. Our objective was to assess the possible role of HLA-B27 and the associated inflammatory disease process in the development of lone aortic regurgitation.
A group of 91 patients with lone aortic regurgitation were studied by HLA typing and clinical and roentgenologic examination.
The HLA-B27-associated inflammatory disease process was found to be the probable underlying cause in 15 to 20 percent of patients with lone aortic regurgitation of different degrees of severity. Furthermore, HLA-B27 was found in 88 percent of the male patients with the combination of aortic regurgitation and severe conduction system abnormalities.
We suggest that this cardiac syndrome should be regarded as an HLA-B27-associated syndrome, sometimes part of ankylosing spondylitis or Reiter's disease, but just as often presenting without obvious rheumatic disease. The marker is thus an important and widely distributed risk factor not only for the development of rheumatic disease but also for acquired aortic regurgitation and sever conduction system abnormalities.
A survey was made of referral patterns and investigative procedures in 125 patients with HLA-B27 related spondarthritic diseases
reviewed in the rheumatology department of a district general hospital. At the time of referral a large proportion of the
patients had already been seen by other hospital departments for the same complaint although in many cases such referrals
did not result in a correct diagnosis. Multiple referrals had often resulted in prolonged diagnostic delay during which time
unnecessary and invasive investigations were performed. The data indicate the need for improved diagnostic awareness of common
rheumatic conditions by all clinicians dealing with musculoskeletal disease.
We reviewed rheumatic diseases in an Inupiat Eskimo population and found a high frequency of seronegative spondyloarthritides. Most cases of juvenile arthritis, which occurred with particularly high incidence in male children (47.4/100,000), appeared to belong in the spondyloarthropathic category. Both Reiter's disease and undifferentiated spondyloarthropathy were common disorders in adults. The prevalence of ankylosing spondylitis (0.2%) was less than expected in a population with a high percentage of HLA-B27 positive individuals. The prevalence rates of rheumatoid arthritis (1.0%), gout (0.3%), and other rheumatic diseases were similar to those of the United States population in general.
A number of conditions have been found to be associated with the HLA-B27 locus including ankylosing spondylitis, psoriatic spondylitis, Reiter's syndrome, juvenile arthritis, and others. An unusual clinical syndrome of "sausage-like" toe, or dactylitis, associated with an oligoarthritis involving the lower extremities has been reported in adults, as has HLA-B27 associated spondyloarthritis and enthesopathy in children. We describe 3 children with dactylitis of the toe who carry HLA-B27. Their course and treatment are presented, and the importance of establishing this diagnostic entity is discussed.
Eighty-eight patients with possible ankylosing spondylitis (AS) were selected for this followup study. They showed normal or at most suspicious radiographic findings of the sacroiliac joints. After 5 years' followup, 24, and after 10 years 32 patients (59% of the 54 finally available, 36% of the 88 original patients) had definite AS. In 12 individuals, AS could be excluded. Of the 10 remaining patients, 6 still had possible, and 4 had undifferentiated spondyloarthropathy. A comparison between HLA-B27 positive and negative patients showed a significantly increased frequency of definite AS or possible and undifferentiated spondyloarthropathy (p less than 0.05) in the group of HLA-B27 positive patients. The development of AS was characterized by a prolonged course: radiological sacroiliitis became evident after at least 9 +/- 6 years, radiological signs of spinal involvement after 11 +/- 6 years mean disease duration. After 18 +/- 6 years 25 (78%) of 32 patients with AS still maintained good or sufficient functional capacity, indicating a good functional prognosis in the great majority of the patients.
The prevalence of complaints of thoracic pain or stiffness in the past 6 months was assessed by examination, HLA typing and sacroiliac radiographs in 420 relatives of 275 B27+ probands with ankylosing spondylitis (AS). AS or sacroiliitis was found in 15 of 420 relatives (3.6%). The gender of the proband did not influence the probability of AS or sacroiliitis among the relatives. In the absence of sacroiliitis, B27+ relatives had chest pain more often (31 of 208, or 14.9%) than B27- relatives (13 of 197, or 6.6%) (p less than 0.01). Chest pain assessed by questionnaire was associated with pain on pressure at the costosternal junctions. The concept of AS as a combination of radiographic sacroiliitis plus clinical signs or symptoms may be too narrow.
We conducted HLA-B27 tissue typing assessments on 430 consecutive children whose main symptom at presentation to our clinic was arthritis/arthralgia. Eighty-five of them (20%) had the B27 antigen. Thirty-six of these children were reexamined after a mean followup period of 8.9 years. Although most had definable rheumatic diseases, only 2 met the New York criteria for ankylosing spondylitis (AS). Children with HLA-B27 and arthritis/arthralgia, although at increased risk of developing AS, have diverse diagnostic and clinical outcomes. The AS criteria used to diagnose the disease in adults may not be appropriate for use in children.
Epidemiologically-based studies have shown that 20-50% of all cases of early arthritis cannot be classified. More recent data came from experiences with an outpatient clinic especially for early arthritis. Of 149 patients with inflammatory rheumatic disease, 39 (26%) were diagnosed as undifferentiated arthritis and 22 (15%) had a probable diagnosis. Therefore, despite diagnostic progress in recent years, only half of all cases can be diagnosed definitely. Follow-up studies of patients with HLA-B27 positive arthritis and undifferentiated spondylarthropathy show the difficulties of early diagnosis and the heterogeneity of disease course and prognosis. Early diagnostic criteria combining the result of the HLA-B27 test with history, symptoms, erythrocyte sedimentation rate and radiological spinal signs can predict or exclude the development of ankylosing spondylitis (AS) at an early stage of the disease in three-quarters of patients, but the diagnosis of AS should not be excluded before 5 to 10 years' observation.
The study of extensive discovertebral destructive lesions in ankylosing spondylitis has been largely limited to isolated case reports or clinicoroentgenologic reviews with little pathologic correlation. In eight specimens of the spine collected from 35 patients with ankylosing spondylitis showing extensive discovetebral destructive lesions, a detailed pathologic study revealed a consistent picture of complete or near-complete destruction of the disc-bone border and the intervertebral disc. The disc was replaced by fibrous tissue and/or fibrocartilage showing moderate to severe fibrinoid necrosis and cystic degeneration. Such changes are characteristic of pseudarthrosis, which may follow either fracture or degeneration of the disc perpetuated by abnormal stress and motion. The reparative process included fibrovascular tissue proliferation from the vertebral bone marrow. Fibrovascular tissue also perforated the vertebral end-plate and intervertebral spaces resulting in massive discovertebral destruction. Pathologic observations strongly implicate mechanical trauma and pseudarthrosis as initiating and perpetuating extensive discovertebral destruction in ankylosing spondylitis.
Of the many rheumatic manifestations of kidney failure treated by longterm dialysis, a destructive spondyloarthropathy has recently been recognized. We performed a survey of our small, relatively short term (3-year average) dialysis population of 45 patients to establish a prevalence figure and establish a data base to assess risk factors. Destructive spondyloarthropathy was seen in 4 of 34 patients receiving hemodialysis and in 2 patients receiving chronic ambulatory peritoneal dialysis (CAPD). Age of the patient (p less than 0.09) and duration of dialysis (p less than 0.05) seem to be associated risk factors. Although it may be coincidental, radiological and biochemical hyperparathyroidism can be clearly dissociated from destructive spondyloarthropathy. The very peculiar quasiconstant, asymptomatic and early cervical localization of destructive spondyloarthropathy suggests a local mechanical factor accentuated by crystal and/or amyloid deposition disease which may become overwhelming as survival is prolonged.
Prevalence and incidence rates for rheumatic diseases were found to be minimal among the Inuit people in the Keewatin District of the Northwest Territories, Canada. Patient identification was achieved by a review of medical records. All identified patients were interviewed and examined by a participating rheumatologist. Among women, the prevalence of rheumatoid arthritis, adjusted for age of the Manitoba population, was 1,822 per 100,000 and was comparable with that observed in other populations; no cases of rheumatoid arthritis in men were confirmed. The age-adjusted prevalence of osteoarthritis, 1,219 per 100,000 in men and 2,144 per 100,000 in women, was apparently low. A moderately high incidence of Reiter's syndrome, 24.9 per 100,000, was found. The findings in children suggested a high frequency of seronegative spondylarthropathies (yearly incidence 60.1 per 100,000), although the adjusted yearly incidence for juvenile rheumatoid arthritis also appeared to be high, 23.6 per 100,000. The frequencies of HLA antigens in patient groups were compared with those found in 19 patients with musculoskeletal complaints but no rheumatic disease. Both HLA-B27 and HLA-DR4 appeared to be common in these controls, 36.8% and 63.2%, respectively. Nevertheless, there was a higher frequency of HLA-B27 in patients with seronegative spondylarthropathies (87%) than in controls (P = 0.001). Because of the small numbers of patients who had rheumatoid arthritis, no associations with HLA were made for this condition. Although the findings suggest differences in the distribution of rheumatic diseases compared with those found in other populations, more complete studies are required to confirm these observations.
Forty-one members in 4 generations of a family were evaluated clinically for ankylosing spondylitis (AS). Thirty-five individuals were HLA typed. The propositus and 4 male siblings demonstrated AS. A sister had sacroiliitis. Three of the affected sibs shared the B27 containing haplotype, but the remaining 3 individuals lacked the B27 but shared the other maternal haplotype. Two other first degree relatives with B27 did not show evidence of either sacroiliitis or AS. Four members of the family had psoriasis, but did not all share a common haplotype. The lack of association of known HLA antigens with disease expression in this family suggests a role for a putative disease susceptibility gene for psoriasis in the development of B27 negative spondylitis and illustrates the difficulty with the diagnosis of B27 negative AS, since when the family was first studied, it presented as a family of "pure" AS and only after several years of followup did the first evidence of psoriasis appear.
A long-term follow-up of 119 patients with the descriptive diagnosis of B27-positive oligoarthritis showed that after a time between months to several years about half of the patients with this condition develop a definite disease of the seronegative spondarthritis group, especially ankylosing spondylitis. Another great part of the patients go into a complete and presumably persistent remission of their arthritis. After a follow-up time of 8 to 12 years, about 10% present a recurrent B27-associated oligoarthritis with some special clinical features. It is to be discussed whether this condition is a separate disease entity or still an abortive form of a well-known disease of the seronegative spondarthritis group.