RHEUMATOID (MARIE-STRUMPELL) SPONDYLITIS,Technique of Examination and Importance of the Costal Joints

Rheumatoid spondylitis in the early prodromal stage may present a complex and obscure clinical picture making diagnosis difficult. It is in this early stage that roentgen examination of the small joints of the spine will often aid in or lead to the correct diagnosis of the disease in which the classical clinical symptoms and roentenographic findings in the sacroiliac fissure have not appeared and may never appear. The changes in these small joints, particularly in the costovertebral and costotransverse joints, are less obvious and require experienced and careful interpretation, but it is to these that the roentgenologist must direct his attention if he is to be of assistance in early diagnosis. A technical procedure for this examination is presented, along with a discussion of the clinical importance of changes at this site.Demonstration of involvement of the sacroiliac joints is of diagnostic importance, but this finding is no more necessary to the diagnosis of rheumatoid spondylitis than is involvement of any other single joint of the spine. Insistence on sacroiliac involvement will often result in missed diagnosis, and has led in part to erroneous conclusions as to sex incidence of the disease.     

强直性脊柱炎生物治疗的现状及新进展

强直性脊柱炎是一种以脊柱病变为主的慢性痫,累及骶髂关节,引起脊柱强直和纤维化,造成不同程度的眼、肺、肌肉、骨骼病变,属自身免疫性疾病。强直性脊柱炎的致病机制仍未完全明了,但在治疗方面,生物治疗策略取得了可喜的新经验,生物药物展现出良好的应用前景。,     

Progress in spondylarthritis. Spondyloarthritis: lessons from imaging

The advent of magnetic resonance imaging (MRI) and advanced sonographic techniques has led to a resurgence of interest in the role of imaging in the evaluation and management of spondyloarthritis. Radiography remains the cornerstone of diagnosis although MRI is more sensitive in early stages of the disease. Inflammatory changes in the sacroiliac joints and spine can now be reliably quantified and can also predict the subsequent development of radiographic changes in the corresponding locations. MRI-based scoring systems for inflammation are highly responsive, facilitating proof-of-concept studies of new therapies for spondyloarthritis. Assessment of chronic changes is much less reliable using MRI, while assessment using radiography lacks sensitivity to change. Assessment of disease modification therefore remains a principle challenge in the development of new therapies for ankylosing spondylitis. Ultrasound may be the preferred approach to the assessment of peripheral inflammation, especially enthesitis. Scintigraphy and computed tomography offer few advantages over MRI.     

Correlation of histopathological findings and magnetic resonance imaging in the spine of patients with ankylosing spondylitis

Ankylosing spondylitis (AS) is a chronic inflammatory disease which affects primarily the sacroiliac joints and the spine. In patients with active disease, magnetic resonance imaging (MRI) of the spine shows areas of bone marrow edema, the histopathological equivalent of which is unknown. In this study we correlate inflammation in the spine of patients with AS as revealed by histological examination with bone marrow edema as detected by MRI. We have compared the histopathological findings of zygapophyseal joints from 8 patients with AS (age: 30 to 64, disease duration 7 to 33 years) undergoing spinal surgery with findings in MRI. For histopathological analysis, we quantified infiltrates of CD3+, CD4+ and CD8+ T cells as well as CD20+ B cells immunohistochemically. Bone marrow edema was evaluated in hematoxylin and eosin stained sections and quantified as the percentage of the bone marrow area involved. All patients with AS showed interstitial mononuclear cell infiltrates and various degrees of bone marrow edema (range from 10% to 60%) in histopathological analysis. However, in only three of eight patients histopathological inflammation and edema in the zygapophyseal joints correlated with bone marrow edema in zygapophyseal joints of the lumbar spine as detected by MRI. Interestingly, two of these patients showed the highest histological score for bone marrow edema (60%). This first study correlating histopathological changes in the spine of patients with AS with findings in MRI scans suggests that a substantial degree of bone marrow inflammation and edema is necessary to be detected by MRI.     

多层CT 诊断强直性脊柱炎骶髂关节病变的价值

目的:评价多层CT诊断强直性脊柱炎骶髂关节病变的价值。方法:对32例患者行骶髂关节16层螺旋CT扫描,患者取仰卧位,采用各向同性的扫描,原始采集层厚0.75mm,矩阵512×512,层厚3mm,在工作站进行三维骨成像处理,包括多平面重建、最大强度投影和容积再现。结果:23例表现为不同程度关节面模糊、破坏,表现为软骨下骨质虫蚀状改变,11例发现皮质下小囊状透亮区。按CT表现分级,11例属于I级,8例属于Ⅱ级,8例属于Ⅲ级,5例属于IV级。结论:多层CT在强直性脊柱炎骶髂关节病变的鉴别诊断与分级中有较大价值,应作为临床可疑患者的优选检查。     

RHEUMATOID ARTHRITIS—Diagnosis in Peripheral Joint Affliction

The diagnosis of rheumatoid arthritis in a typical case depends upon a history of pain and swelling of various joints throughout the body. In the first stages the disease usually involves only the small joints of the hands and feet, but sooner or later it spreads to the larger joints. This may be accompanied by fibrosis of one or more joints, causing disability ranging from disuse of one joint up to total incapacity. Diagnosis in early or atypical cases is often impossible until the patient has been under observation a long time. It is important that diagnosis be made as early as possible, in order that appropriate therapy may be started and ankylosis and disability of the joints prevented.Since laboratory procedures and roentgen films do not show early changes, emphasis is placed on the history and physical examination for diagnosis.     

Rheumatoid arthritis; diagnosis in peripheral joint affliction

The diagnosis of rheumatoid arthritis in a typical case depends upon a history of pain and swelling of various joints throughout the body. In the first stages the disease usually involves only the small joints of the hands and feet, but sooner or later it spreads to the larger joints. This may be accompanied by fibrosis of one or more joints, causing disability ranging from disuse of one joint up to total incapacity. Diagnosis in early or atypical cases is often impossible until the patient has been under observation a long time. It is important that diagnosis be made as early as possible, in order that appropriate therapy may be started and ankylosis and disability of the joints prevented. Since laboratory procedures and roentgen films do not show early changes, emphasis is placed on the history and physical examination for diagnosis.     

LncRNA MEG3 inhibits the inflammatory response of ankylosing spondylitis by targeting miR-146a

Molecular and Cellular Biochemistry - Ankylosing spondylitis (AS) is a progressive systemic disease characterized by chronic inflammation response of the sacroiliac joint and spine. Long non-coding...     

Association Study of Polymorphisms rs4552569 and rs17095830 and the Risk of Ankylosing Spondylitis in a Taiwanese Population

Ankylosing spondylitis (AS) is a chronic inflammation of the sacroiliac joints, spine and peripheral joints. However, the development of anklosing spondylitis is unclear. Human leukocyte antigens HLA-B27 and ERAP1 have been widely reported to be associated with AS susceptibility. A recent genome-wide association study (GWAS) showed that two new susceptibility loci between EDIL3 and HAPLN1 at 5q14.3 (rs4552569) and within ANO6 at 12q12 (rs17095830) contribute to the risk of AS in Han Chinese. In this study, we enrolled 475 AS patients and 475 healthy subjects to assess whether these genetic variations contribute to the susceptibility and the severity of AS in the Taiwanese population. The correlation between genetic polymorphisms, AS activity indexes, (namely, BASDAI, BASFI and BAS-G) and AS complications (uveitis and inflammatory bowel disease) were tested using the markers, rs4552569 and rs17095830. Although no association between rs4552569/rs17095830 genetic polymorphisms and AS susceptibility/severity was found, a significant association between rs17095830 and inflammatory bowel disease was observed in a Taiwanese population.     

Aberrant axial mineralization precedes spinal ankylosis: a molecular imaging study in ank/ank mice

Introduction

The diagnosis of ankylosing spondylitis is made from a combination of clinical features and the presence of radiographic evidence that may be detected only after many years of inflammatory back pain. It is not uncommon to have a diagnosis confirmed 5 to 10 years after the initial onset of symptoms. Development of a more-sensitive molecular imaging technology to detect structural changes in the joints would lead to earlier diagnosis and quantitative tracking of ankylosis progression. Progressive ankylosis (ank/ank) mice have a loss of function in the Ank gene, which codes for a regulator of PPi transport. In this study, we used these ank/ank mutant mice to assess a noninvasive, quantitative measure of joint ankylosis with near-infrared (NIR) molecular imaging in vivo.

Methods

Three age groups (8, 12, and 18 weeks) of ank/ank (15 mice) and wild-type littermates (12 +/+ mice) were assessed histologically and radiographically. Before imaging, OsteoSense 750 (bisphosphonate pamidronate) was injected i.v. Whole-body images were analyzed by using the multispectral Maestro imaging system.

Results

OsteoSense 750 signals in the paw joints were higher in ank/ank mice in all three age groups compared with controls. In the spine, significantly higher OsteoSense 750 signals were detected early, in 8-week-old ank/ank mice compared with controls, although minimal radiographic differences were noted at this time point. The molecular imaging changes in the ank/ank spine (8 weeks) were supported by histologic changes, including calcium apatite crystals at the edge of the vertebral bodies and new syndesmophyte formation.

Conclusions

Changes in joint pathology of ank/ank mice, as evaluated by histologic and radiographic means, are qualitative, but only semiquantitative. In contrast, molecular imaging provides a quantitative assessment. Ankylosis in ank/ank mice developed simultaneously in distal and axial joints, contrary to the previous notion that it is a centripetal process. NIR imaging might be feasible for early disease diagnosis and for monitoring disease progression in ankylosing spondylitis.     

Paleoepidemiology of a central California prehistoric population from Ca-Ala-329: II. Degenerative disease

Degenerative lesions are scored and frequencies of involvement are computed for a skeletal collection from Ca-Ala-329, a prehistoric site on the southeastern side of San Francisco Bay, dating from 500 A.D. up to European contact. A large earthmound site, excavations conducted there by San Jose State University retrieved close to 300 burials. For this epidemiological analysis, reasonably complete and aged skeletons representing 77 adult females and 90 adult males are available. Degenerative changes are scored macroscopically in an ordinal fashion for the large fibro-cartilagenous joints between adjacent vertebral bodies (vertebral osteophytosis) as well as the small apophyseal articulations of the spine. In addition, in the peripheral skeleton degenerative changes are scored in the temporo-mandibular, shoulder, elbow, hip, and knee joints as well as the small articulations of the hands and feet. The most common degenerative changes in the spine are seen between the vertebral bodies of the lower lumbar region. In the peripheral skeleton the highest involvement of degenerative disease is seen in the hands and feet. Compared to other relevant osteological samples, this group of hunting-gathering California Indians shows more degenerative changes than settled agriculturists (from Pecos Pueblo, New Mexico) but substantially less frequent involvement than in arctic hunters (Alaskan Eskimos).     

Osteoimmunology and osteoporosis

The concept of osteoimmunology is based on growing insight into the links between the immune system and bone at the anatomical, vascular, cellular, and molecular levels. In both rheumatoid arthritis (RA) and ankylosing spondylitis (AS), bone is a target of inflammation. Activated immune cells at sites of inflammation produce a wide spectrum of cytokines in favor of increased bone resorption in RA and AS, resulting in bone erosions, osteitis, and peri-inflammatory and systemic bone loss. Peri-inflammatory bone formation is impaired in RA, resulting in non-healing of erosions, and this allows a local vicious circle of inflammation between synovitis, osteitis, and local bone loss. In contrast, peri-inflammatory bone formation is increased in AS, resulting in healing of erosions, ossifying enthesitis, and potential ankylosis of sacroiliac joints and intervertebral connections, and this changes the biomechanical competence of the spine. These changes in bone remodeling and structure contribute to the increased risk of vertebral fractures (in RA and AS) and non-vertebral fractures (in RA), and this risk is related to severity of disease and is independent of and superimposed on background fracture risk. Identifying patients who have RA and AS and are at high fracture risk and considering fracture prevention are, therefore, advocated in guidelines. Local peri-inflammatory bone loss and osteitis occur early and precede and predict erosive bone destruction in RA and AS and syndesmophytes in AS, which can occur despite clinically detectable inflammation (the so-called 'disconnection'). With the availability of new techniques to evaluate peri-inflammatory bone loss, osteitis, and erosions, peri-inflammatory bone changes are an exciting field for further research in the context of osteoimmunology.     

Psoriatic arthritis: recent progress in pathophysiology and drug development

Psoriatic arthritis (PsA) is the second most common inflammatory arthropathy, after rheumatoid arthritis diagnosis, in early arthritis clinics. Most patients have established psoriasis, often for years, prior to the onset of joint pain and swelling; in addition, associated features of nail disease, dactylitis, enthesitis, spondylitis or uveitis may be present. Psoriasis may not be immediately apparent, as small or patchy lesions may occur in the scalp or perineum. PsA presents as a symmetrical polyarthritis, similar to rheumatoid arthritis, or an asymmetrical oligoarthritis with a predilection for the distal interphalangeal joints. Spinal involvement is similar, although not identical, to ankylosing spondylitis. Joint damage occurs early; up to 50% of PsA patients have an 11% annual erosion rate in the first 2 years of disease duration, suggesting it is not a benign condition. There have been significant advances in our understanding of PsA pathogenesis in recent years, in the areas of genetics and molecular biology, implicating both the innate and the adaptive immune systems. This has lead to the introduction of evidence-based targeted therapy, primarily with tumour necrosis factor inhibitor (TNFi) agents. Therapy with disease-modifying anti-rheumatic drugs, such as methotrexate and leflunomide, remains the first-choice therapeutic intervention, even though there are few randomised controlled trials with these agents. In contrast, a number of successful studies of TNFi agents demonstrate excellent efficacy, in combination with methotrexate, and several novel agents are currently in development for the treatment of PsA.     

Spondyloarthritides: evolving therapies

TNF blockade therapy has substantially advanced the treatment of peripheral spondyloarthritides but revolutionised the treatment of severe ankylosing spondylitis. The capacity of biologic treatment to improve dramatically symptoms and quality of life in patients with spinal disease is undoubted, although important questions remain. Notable amongst these are concerns about skeletal disease modification and the true balance between costs and effectiveness. Guidelines for the biologic treatment of ankylosing spondylitis and psoriatic arthritis have been introduced in North America and Europe with considerable consensus. However, the absence of clear criteria for the diagnosis of early disease leaves the issue of biologic treatment of ankylosing spondylitis at the pre-radiographic stage unresolved. Newer biologic agents are entering the field, although superiority over TNF blockers will be difficult to demonstrate.     

Genetic Polymorphisms of Stromal Interaction Molecule 1 Associated with the Erythrocyte Sedimentation Rate and C-Reactive Protein in HLA-B27 Positive Ankylosing Spondylitis Patients

Ankylosing spondylitis (AS) is a chronic inflammation of the sacroiliac joints, spine and peripheral joints. The development of ankylosing spondylitis is still unclear. Genetics factors such as human leukocyte antigen HLA-B27 and ERAP1 have been widely reported to associate to AS susceptibility. In this study, we enrolled 361 AS patients and selected four tagging single nucleotides polymorphisms (tSNPs) at STIM1 gene. The correlation between STIM1 genetic polymorphisms and AS activity index (BASDAI, BASFI, BAS-G) as well as laboratory parameters of inflammation (erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)) were tested. Our results indicated that HLA-B27 positive AS patients who are carrying the minor allele homozygous G/G genotype of SNP rs3750996 significantly associated with a higher level of ESR in serum. Furthermore, rs3750996/rs3750994 pairwise allele analysis indicated that G-C haplotypes also significantly correlated with higher level of ESR as well as CRP. These findings provide a better understanding of STIM1 genetic contribution to the pathogenesis of AS.     

TRP channels in gastric cancer: New hopes and clinical perspectives

Gastric cancer is a multifactorial disease associated with a combination of and environmental factors. Each year, one million new gastric cancer cases are diagnosed worldwide and two-thirds end up losing the battle with this devastating disease. Currently, surgery represents the only effective treatment option for patients with early stage tumors. However, the asymptomatic phenotype of this disease during the early stages poses as a significant limiting factor to diagnosis and often renders treatments ineffective. To address these issues, scientists are focusing on personalized medicine and discovering new ways to treat cancer patients. Emerging therapeutic options include the transient receptor potential (TRP) channels. Since their discovery, TRP channels have been shown to contribute significantly to the pathophysiology of various cancers, including gastric cancer. This review will summarize the current knowledge about gastric cancer and provide a synopsis of recent advancements on the role and involvement of TRP channels in gastric cancer as well as a discussion of the benefits of targeting TPR channel in the clinical management of gastric cancer.     

Erosive arthritis and spondyloarthropathy in Old World primates.

Presence of spine and sacroiliac involvement and the nature and distribution of the erosive lesions allow definitive diagnosis of spondyloarthropathy. Thus, spondyloarthropathy was identified in Theropithecus, Papio, Cercopithecus, Macaca, Colobus, Presbytis, and Hylobates. Only monarticular erosive disease was present in prosimians, precluding a diagnosis of spondyloarthropathy for that group. The distribution of erosive disease and axial joint involvement in 1,349 non-prosimian Old World primates is quite characteristic of that noted in human psoriatic arthritis. While Reiter's syndrome must also be considered, the histologic appearance of skin lesions in Macaca is characteristic of psoriasis. Evidence of spondyloarthropathy abounds in the literature of primate skeletal disease. Environmentally based contagions may be important in the pathophysiology of spondyloarthropathy. The wide geographic distribution of the phenomena in monkeys suggests a "panendemic," with limited individual susceptibility (compared to that noted in gorillas and chimpanzees). Identical occurrence of erosive arthritis/spondyloarthropathy in free-ranging and artificially restrained animals suggests that spondyloarthropathy can validly be studied in artificially restrained populations. This perspective should allow application of human therapeutic approaches to and perhaps improve the quality of life for artificially restrained, afflicted individuals.     

Radiodiagnosis of pelvic injuries

The paper deals with an algorithm for the radiodiagnosis of pelvic injuries. The examination of victims with pelvic injuries allows one to state that multislice spiral computed tomography (MSCT) can define the type of pelvic ring instability and the nature of fragment displacement, visualize all types of fractures of pelvic bones and cotyloid cavity walls, and reveal intrapelvic hematomas, as well as changes in adjacent soft tissues, sacroiliac joints, intrapelvic vessels and organs. MSCT angiography is a technique that can be successfully used at different stages of diagnosis and as the first imaging method or as a pre-examination one if the diagnosis is established and as a control study. The scope and quality of obtained information are generally sufficient to make a decision on treatment policy.