Hereditary and exogenous etiological factors in ankylosing spondylitis. Ankylosing spondylitis in two sets of monozygotic twins.
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[Cardiac involvement in ankylosing spondylitis].
Ankylosing spondylitis is a rheumatic disease that affects the axial skeleton and has predilection for young men. Of its extraarticular manifestations, the cardiac involvement, reported up to 48%, has been pointed out in recent years. It seems to exist a racial variation in the features of the spondylitis and since most of the studies have been performed in northern countries therefore it appears inadequate to extrapolate the conclusions of such studies to our society. We studied 23 patients with definitive diagnosis of ankylosing spondylitis. All of them had a complete physical examination, electrocardiography and X-ray of the chest; eight patients underwent a Holter study of 24 hours and seven patients were examined by echocardiography. The mean age of the group was 36 years; there were 21 men and two women. The mean duration of the rheumatic disease was 11.5 years. In only 4 (17.4%) of the patients we found cardiac involvement that would not be related to another etiology. By the clinic examination we found two patients with isolated aortic insufficiency; one case had a right bundle branch block. The Holter study did not show modifications, except in the one with isolated aortic insufficiency and right bundle branch block, in whom this block became of variable degree. The echocardiographic study showed the mentioned aortic valvular lesions and did reveal the same lesion in another patient in which the other studies were normal. It is emphasized that it is adequate to search for signs of ankylosing spondylitis in every patient with isolated aortic insufficiency or/and conduction disturbances of unknown etiology and also to performe cardiac careful in each patient with ankylosing spondylitis examination.
Aortic Valve Insufficiency↗
Orthopaedic management of ankylosing spondylitis.
Ankylosing spondylitis is an inflammatory disease of unknown etiology that affects an estimated 350,000 persons in the United States and 600,000 in Europe, primarily Caucasian males in the second through fourth decades of life. Worldwide, the prevalence is 0.9%. Genetic linkage to HLA-B27 has been established. Ankylosing spondylitis primarily affects the axial skeleton and is characterized by inflammation and fusion of the sacroiliac joints, spine, and hips. The resultant deformity leads to severe functional impairment in approximately 30% of patients. Orthopaedic management primarily involves correction of hip deformity through total hip arthroplasty and, less frequently, correction of spinal deformity with spine osteotomy. Closing wedge osteotomies have the lowest incidence of complications. Whether patients with ankylosing spondylitis are at increased risk for heterotopic ossification remains controversial, but comparison with age- and sex-matched counterparts suggests no dramatically higher risk. Because of the high rate of missed fractures and complications after minor trauma in patients with ankylosing spondylitis, plain radiographs are usually not sufficient for evaluation. Thorough patient assessment should include a comprehensive history, physical examination, and laboratory studies.
Anti-Inflammatory Agents, Non-Steroidal↗
Alterations in cardiac diastolic function in patients with ankylosing spondylitis.
Ankylosing spondylitis is associated with a decreased survival that appears attributable to cardiovascular causes. To determine whether alterations in systolic or diastolic cardiac function precede overt cardiac disease, 20 ankylosing spondylitis patients without clinical evidence of cardiovascular disease and 25 healthy age and gender matched controls were studied by cross-sectional and Doppler echocardiography. Systolic function was assessed by wall motion analysis and ejection velocities. Diastolic function was measured by the peak velocity of early ventricular inflow, peak velocity in late diastole during atrial systole, the ratio of these velocities and the diastolic filling time. Atrial, ventricular and aortic dimensions were similar in patients and controls. Ejection indexes and systolic wall motion were normal in both groups. Diastolic function differed in patients as evidenced by a shorter diastolic filling period [405 +/- 68 ms vs 548 +/- 136 ms, p = 0.0001], a reduced velocity of early mitral inflow [0.55 +/- 0.09 m/s vs 0.63 +/- 0.11 m/s (p = 0.005)], and lower ratios of early/late inflow velocities [1.21 +/- 0.33 vs 1.60 +/- 0.35 (p = 0.0005) for mitral and 1.36 +/- 0.34 vs 1.71 +/- 0.42 (p = 0.016) for tricuspid]. These changes are consistent with impaired ventricular relaxation in some patients with ankylosing spondylitis.
Adult↗
[The role of biologic agents in the therapy of ankylosing spondylitis].
Ankylosing spondylitis is a chronic, inflammatory rheumatic disease which etiology and pathogenesis are not yet fully understood. The inflammation involves the spine and also the peripheral joints might be affected in some cases resulting in a progressive ankylosis, restricted mobility, significant disability, loss of productivity and decreased quality of life. Gene technology based new drugs of the past decade, the biologic agents, offer an alternative opportunity for the treatment of ankylosing spondylitis in comparison with the previous drugs with doubtful efficiency. In Hungary infliximab and etanercept has been registered for ankylosing spondylitis. The aim of this study was to evaluate the efficacy of infliximab and etanercept by the available randomised controlled trials. A systematic search of the literature was performed from 01. 01. 2000 to 08. 31. 2005. and the relevant publications were analysed following the concepts of evidence based medicine. 7 double blind, randomised, placebo controlled trials were identified, three for infliximab (n = 389) and four for etanercept (n = 431). Although the inclusion criteria, the duration of the trials and the primary endpoints were different, the results confirm that both drugs significantly decrease symptoms and disease activity, and this effect is sustained during the therapy, nevertheless half of the patients did not achieve the standardised criteria of 50% decrease in disease activity. Both agents are well tolerated by patients. The outcomes of long-term therapy are reassuring by open extension studies of three years. Guidelines for biologic therapy has been developed in Hungary determining the target patient group, the conditions of the therapy and also an arthritis centre network has been established. Though individual admission is feasible, biologic drugs are not under reimbursement in Hungary. High drug costs makes the implementation of this new therapeutic opportunity difficult in the daily medical practice.
Antibodies, Monoclonal↗
Transverse myelitis in a patient with long-standing ankylosing spondylitis.
Ankylosing spondylitis is reported to involve not only the joints but other organs as well. Among these extra-articular involvements, uncommon complications associated with nervous system such as single root lesions, compression of the myelum and cauda equina syndrome have also been documented. Here we present a patient with long-standing ankylosing spondylitis who developed spastic paraparesis. Extensive study to find the cause of a spastic paraparesis failed and therefore led to the conclusion that this patient was suffering from transverse myelitis. Similar reports in the past have been attributed to an association with multiple sclerosis; however, we suggest that the findings support the diagnosis of a rare complication of ankylosing spondylitis with an unknown etiology.
Adult↗
[New pathogenetic aspects of ankylosing spondylitis].
Ankylosing spondylitis is one of the oldest diseases in humans; however, it is still one of the most fascinating and mysterious in human pathology. The unusual combination of both fundamental pathological processes: inflammation and ossification (which are mostly independent in respect to time and place) is unique. Until 1973, ankylosing spondylitis did not attract much immunological research. After the detection of an association between HLA B27 and the disease, clinical and immunological research was stimulated. It was supposed that HLA B27 may be a pathogenic factor. Meanwhile, it has become well known that HLA B27 itself is not required for development of the disease; however, discovery of immunological cross-reactivity between HLA B27 and some Klebsiella antigens inspired pathogenic considerations. It is discussed that the structural similarities between enteric bacteria and HLA B27 induce autoantibodies, or that HLA B27 plays a role in antigen recognition. Possibly, HLA B27 may also act as a receptor for infectious agents and their products. Fascinating, but controversely discussed is the hypothesis that bacterial products modify the B27 molecule and, in this way, trigger the disease. All present theories about pathogenesis of ankylosing spondylitis are unsatisfactory, because many important questions cannot be answered. There are no explanations for the unusual affinity of possible pathogenic immune reactions to the spine and other organs, the induction of ossification, the merging of cartilage, or the development of sacroilitis. Especially, we do not know the important bridge (if one exists) between inflammation and ossification. The typical ossification of the spine is of dramatic consequence for the patient in respect to function and mobility.(ABSTRACT TRUNCATED AT 250 WORDS)
Autoantibodies↗
Efficacy of diclofenac in ankylosing spondylitis.
Ankylosing spondylitis is a systemic rheumatic disorder characterized by inflammation of the spine, sacroiliac, and large peripheral joints. Effective management demands both immediate and long-term objectives. The physician must first relieve joint inflammation and discomfort with nonsteroidal anti-inflammatory drugs, then begin long-range planning with daily exercise and other supportive measures to prevent, delay, or correct deformity. Diclofenac sodium, a nonsteroidal anti-inflammatory drug that is used worldwide in ankylosing spondylitis, has not yet been marketed in the United States. This article highlights two American studies with diclofenac: (1) a short-term, double-blind comparison with indomethacin, and (2) a 38-week extension with diclofenac for long-term efficacy and safety data. The results of these trials demonstrate diclofenac to be effective and safe for both short- and long-term treatment. When compared with indomethacin, a standard reference drug in trials of ankylosing spondylitis, diclofenac was comparable in efficacy but had a more favorable side-effect profile.
Adult↗
Double spinal cord injury in a patient with ankylosing spondylitis.
Ankylosing spondylitis patients are more prone to spinal fractures and these fractures commonly result in mobile nonunion. We report a patient with a 30-year history of ankylosing spondylitis who sustained double spinal cord injuries following minor trauma. The first injury occurred at the lumbar level due to pseudoarthrosis of an old fracture, and the second at the thoracic level following cardiopulmonary arrest and an episode of hypotension. The possible mechanisms of the injuries are discussed and maintaining normal blood pressure in these patients is emphasized.
Aged↗
[Current views on the pathogenesis and therapy of ankylosing spondylitis].
Ankylosing spondylitis is a frequent and disabling inflammatory chronic disease, that affects mainly young men. In this paper the authors reviewed the pathogenetic mechanism and pharmacological and physical treatment. Nowadays the pathogenesis of ankylosing spondylitis is considered similar to that of reactive arthritis. The management of each patient should take into account the different aspects of the disease; therefore it should be individually designed.
Adult↗
Apophyseal arthritis limits lumbar motion in patients with ankylosing spondylitis.
Ankylosing spondylitis patients who develop progressive spinal flexion may assume this posture to alleviate the pain of apophyseal arthritis. To examine this relationship, we scored injury to L4-L5 and L5-S1 apophyseal joints, as assessed by computed tomography, in 10 men with early ankylosing spondylitis. Both by the modified Schober test and by radiography of the lateral spine, impaired spinal motion correlated highly with evidence of apophyseal injury.
Adolescent↗
Radiologic changes of cervical spine in ankylosing spondylitis.
Ankylosing spondylitis (AS) is characterised by its effects on the axial skeleton. The cervical spine is also vulnerable to the disease process. Our aim was to determine the frequency of radiologic changes to the cervical spine and their correlation with clinical variables. We also used the Bath Ankylosing Spondylitis Radiology Index (BASRI) system, which is one of the reliable scoring systems of radiography, to score the global radiologic changes to the cervical and lumbar spine and the hip joints in our AS cohort. There were 181 patients with anteroposterior and lateral full-flexion views on radiography of the cervical spine here included in the study. A radiologist examined the radiologic changes to all anatomical compartments of the cervical spine in detail and graded them according to the BASRI system. We used the clinical and demographic data of our AS cohort to determine their relation to the radiographic changes. Eighty-eight patients (48.6%) showed radiological changes to the cervical spine; to the discovertebral joint 35.9%; the apophyseal joint 26.0%; atlantoaxial articulation 22.1% (atlantoaxial subluxation 13.8%); the costovertebral joint 18.2%; and to the posterior ligamentous attachment 11.6%. Using the BASRI system, 73 patients (40.3%) showed radiologic changes to the cervical spine and were graded as score 1 (1.7%), 2 (22.7%), 3 (6.6%) or 4 (9.4%). Among those graded as normal by the BASRI system, 17 showed some changes the cervical spine, such as atlantoaxial joint subluxation or narrowing, and severe osteoporosis with no other radiographic changes. Current age, disease duration, inflammatory back pain and cervical symptoms were associated with the radiographic changes to the cervical spine. The BASRI-cervical spine score correlated with the BASRI-lumbar spine and hip joint score, sacroiliitis, disease duration, and duration of inflammatory back pain and cervical symptoms. Our data suggest that radiographic changes to the cervical spine are frequent in AS, and can be predicted in the patients with old age, long duration of disease and inflammatory back pain, and cervical symptoms. Also, the BASRI scoring system showed similar results as a detailed assessment of the cervical spine in our study.
Adolescent↗
[Anti-TNF alfa therapy in ankylosing spondylitis].
Ankylosing spondylitis (AS) is an inflammatory chronic disease that affects young males and in more than 90% of cases is associated with HLA B27 antigen. Therapeutic options for those patients with spondyloarthropathies have been limited during the last decades. Infliximab and etanercept are both approved for the treatment of patients with active disease that does not respond to conventional therapies. Anti-TNF therapy is very effective in AS, and eventually can be more effective than in rheumatoid arthritis. In 2003 Assessments in Ankylosing Spondylitis Group (ASAS) published international recommendations about the use of these agents in AS, which can be used as guidance in taking decisions and elaborating guidelines. To define their utilization it is necessary more studies about efficacy, toxicity and about ways of use.
Anti-Inflammatory Agents, Non-Steroidal↗
Genetic susceptibility to ankylosing spondylitis.
Ankylosing spondylitis is a highly heritable, common rheumatic condition, primarily affecting the axial skeleton. The association with HLA-B27 has been demonstrated worldwide, and evidence for a role of HLA-B27 in disease comes from linkage and association studies in humans, and transgenic animal models. However, twin studies indicate that HLA-B27 contributes only 16% of the total genetic risk for disease. Furthermore, there is compelling evidence that non-B27 genes, both within and outwith the major histocompatability complex, are involved in disease aetiology. In this post-genomic era we have the tools to help elicit the genetic basis of disease. This review describes methods for genetic investigation of ankylosing spondylitis, and summarises the status of current research in this exciting area.
Animals↗
HLA-B27-restricted CD8 T cells derived from synovial fluids of patients with reactive arthritis and ankylosing spondylitis.
Ankylosing spondylitis and seronegative spondylarthropathies such as Reiter's syndrome and reactive arthritis are strongly associated with HLA-B27. However, the mechanisms by which HLA-B27 is involved in disease susceptibility and pathogenesis are unknown. If the disease association is a consequence of HLA-B27's physiological function in antigen presentation, the disease should be mediated by cytotoxic T lymphocytes (CTLs) that recognise bacterial or self peptides presented by HLA-B27. Proof of this arthritogenic peptide model requires isolation of B27-restricted CD8 T cells from arthritic joints of patients with spondylarthropathies. An important question is whether "arthritogenic" bacteria such as yersinia or salmonella can generate HLA-B27-restricted bacteria-specific CTLs. We describe such HLA-B27-restricted CTLs. We tested a panel of 354 alpha beta-TCR CD8 T lymphocyte clones (TLCs) that had been derived from the synovial fluid of 4 patients with reactive arthritis and 2 patients with ankylosing spondylitis. In 1 patient with yersinia-induced arthritis, 2 TLCs were identified that killed specifically yersinia-infected B27 target cells. In another patient with salmonella-induced arthritis, 1 B27-restricted CD8 TLC that recognised both salmonella and yersinia was identified. In 5 of the 6 patients autoreactive CTLs were found, 5 of which showed B27-restricted killing of uninfected cell lines. B27-restricted CTLs with specificity for arthritogenic bacteria or autoantigens provide a missing link in the pathogenesis of the HLA-B27-associated spondylarthropathies.
Adult↗
Relevance of residue 116 of HLA-B27 in determining susceptibility to ankylosing spondylitis.
Ankylosing spondylitis (AS) is an autoimmune disorder strongly associated with HLA-B27. A direct role of B27 molecules in the disease pathogenesis has been postulated, possibly by presenting to T cells an as-yet unidentified arthritogenic peptide that triggers the autoimmune response. There are nine HLA-B27 alleles differing from each other at one or more amino acid positions. It is important, for the identification of the arthritogenic peptide, to define which alleles, and therefore which polymorphic positions, predispose to the disease. Here, we report that HLA-B*2709 is not associated with AS, as it was not found in patients. HLA-B*2709 differs from the most frequent and disease-associated HLA-B*2705 allele for a single substitution (His vs. Asp) at position 116. Amino acid 116 is located at the bottom of the groove where the antigenic peptide sits, and it has been proven to influence the peptide-binding specificity of HLA class I molecules. The most likely interpretation of these data is that the differences in charge and size that accompany the His-to-Asp substitution exclude the acceptance of the arthritogenic peptide.
Alleles↗
Cloning and sequencing of the gene that codes for the Klebsiella pneumoniae GroEL-like protein associated with ankylosing spondylitis.
Ankylosing spondylitis (AS) is a chronic inflammatory disease of the sacroiliac joints and vertebral column of unknown aetiology, but strongly related to the presence of the HLA-B27 antigen. The participation of bacterial infections as triggering factors have also been suggested. We have associated the 60 kDa heat shock protein of Klebsiella pneumoniae (HSP60Kp) with AS since we have previously demonstrated that most of the patients have IgG antibodies and active T cells that recognize preferentially this protein, but we have not yet identified the epitopes involved in the recognition. In order to know the amino acid sequence of HSP60Kp, and to be able to analyse in the future the relevant epitopes; we amplified by PCR and cloned the gene coding for this protein into the SmaI site of pUC19. The nucleotide sequence of the gene was obtained by the Sanger method using both manual and automatic techniques. Amino acid sequence of the HSP60Kp was deduced by translating the nucleotide sequence of the gene. The antigenic analysis of this sequence was compared to the antigenic analysis of the reported sequences of Escherichia coli GroEL and Yersinia enterocolitica HSP60. Using a software to predict HLA class I motifs, the nonapeptide (KRGIDKAVL) residues 117-125 of HSP60Kp showed a much higher affinity for HLA-B27 than the similar nonapeptide of E. coli GroEL and Y. enterocolitica HSP60. The only difference between the three peptides was in position nine. This finding could explain the association of AS only with the HSP60 of Klebsiella pneumoniae. On the other hand, hydrophilicity analysis, which indicates B cell epitopes, showed three similar strongly antigenic regions in the three proteins.
Amino Acid Sequence↗
[Diagnosis and early diagnosis of ankylosing spondylitis].
Ankylosing spondylitis (AS) is often diagnosed not before 5-10 years after onset of clinical symptoms. The main reason for this delay is the late appearance of unequivocal radiographic sacroiliitis which is a prerequisite for making the diagnosis. It is important to realize that both the early stage without radiographic sacroiliitis and the late stage with radiographic sacroiliitis are part of the same disease and, therefore, should be considered as a disease continuum. The term axial spondyloarthritis (SpA) appears appropriate to describe this disease continuum. Diagnosing axial SpA without radiographic sacroiliitis, however, is difficult and associated with diagnostic uncertainties since there are no diagnostic criteria available. Considering all SpA features which are relevant for the diagnosis of axial SpA (with and without radiographic sacroiliitis), we have recently proposed a diagnostic algorithm based on calculations using Bayes' theorem to be applied in individual patients. This diagnostic algorithm enables the physician to diagnose or to exclude axial SpA with a high degree of confidence. An early and reliable diagnosis is relevant to both the patient and the physician since an early diagnosis allows the best therapy to be introduced and consequently maintained.
Algorithms↗