Ankylosing spondylitis and spinal cord injury

Ankylosing spondylitis patients are reported to be at greater risk for vertebral fractures and spinal cord injury. We describe the case of a 72-year-old male with a long history of ankylosing spondylitis who sustained a vertebral fracture after minor trauma. The fracture was initially missed on conventional radiographs but was later diagnosed by magnetic resonance imaging after the development of new neurological symptoms. With this case report the authors outline the factors that increase the incidence of vertebral fractures and spinal cord injury in ankylosing spondylitis patients and discuss prevention strategies to avoid this devastating complication of the disease.     

Bone mineral density and vertebral compression fracture rates in ankylosing spondylitis.

OBJECTIVE--To examine the relationship between disease severity and bone density as well as vertebral fracture risk in patients with ankylosing spondylitis (AS). METHODS--Measurements were taken for bone mineral density (BMD) and vertebral fracture rates in 87 patients with AS. BMD was measured at the hip (femoral neck -FN), lumbar spine (L1-L4-LS) and for the whole body using a hologic-QDR-1000/W absorptiometer. An algorithm based on normal female ranges of vertebral heights was used to define a fracture as occurring when two vertebral ratios were each three standard deviations below the calculated mean of the controls. RESULTS--Patients with AS had significantly lower FN-BMD in proportion to disease severity (based on a Schober index) and disease duration. LS-BMD was also reduced in early disease, but in patients with advanced AS it had increased considerably. Nine vertebral fractures (10.3%) were identified which was considerably higher than expected when compared with a fracture of 1.9% in a control population of 1035 females of a similar age range. Patients with AS with fractures were significantly older, more likely to be male, had longer disease duration and more advanced spinal limitation with less mobility. There was no significant reduction in lumbar spine or femoral neck bone density in the fracture group. CONCLUSIONS--Vertebral fractures that result from osteoporosis are a feature of longstanding AS. BMD used as a measure of osteoporosis of the spine in advanced AS is unreliable probably as a result of syndesmophyte formation and does not predict the risk of vertebral fracture. Alternative sites such as the neck of the femur should be used for sequential assessment of BMD in AS.     

Spinal fractures complicating ankylosing spondylitis

The ankylosed osteoporotic spines of patients with long-standing ankylosing spondylitis are prone to fracture. The spinal trauma is of a trivial nature in many patients and the diagnosis may be overlooked, unless neurologic damage occurs. The fractures most commonly occur in the cervical region and may be multiple. Because of spinal osteoporosis and deformity, radiographic visualization of the fracture site may be difficult. Tomography may be helpful in some patients. Management may be conservative or surgical and is complicated by increased instability of the fracture site, spinal osteoporosis, and deformity. Conservative management of cervical fractures is probably best accomplished by halo traction and body cast. Progression of the neurologic deficit is an indication for surgical intervention.     

Clinical aspects, outcome assessment, disease course, and extra-articular features of spondyloarthropathies.

Much has been written over the years regarding the clinical aspects and disease course of the spondyloarthropathies, but publications relating to outcome assessment that attempt to relate measures of process with outcome are few. Extra-articular features of the spondyloarthropathies, eg, uveitis, colitis, and aortitis, are well described, but in the past few years there has been an increasing interest in the incidence of osteoporosis in this group of patients, particularly those with ankylosing spondylitis. In rheumatoid arthritis functional indices have been developed, such as the Health Assessment Questionnaire score, which has been shown to be robust in monitoring response to therapy, but the situation is quite different in a condition such as ankylosing spondylitis. In the last few years a number of functional indices have been developed that are now beginning to be applied to monitor response to treatment in the spondyloarthropathies. The impact of ankylosing spondylitis in women is an area that has been neglected in the past, and a recent review addresses the effects of the disease on the reproductive capacity in women. This overall review of the past year's publications from the clinical aspects of ankylosing spondylitis confirms that clinical research still has much to contribute to this fascinating group of disorders.     

Multiple sclerosis during adalimumab treatment in a case with ankylosing spondylitis

Ankylosing spondylitis is a chronic and progressive inflammatory disease involving the sacroiliac joints with HLA-B27 positivity in 85 % of the patients and radiologically evidence of sacroiliitis. It is associated with several extraarticular manifestations, but neurological complications are rare. Occurrence of multiple sclerosis in patients with ankylosing spondylitis has been reported in limited cases. Adalimumab, a TNF-α antagonist, offers a significant improvement in ankylosing spondylitis and is considered to be less immunogenic and more tolerable than other TNF-α blockers. A case of multiple sclerosis coexisted with HLA-B27 positive ankylosing spondylitis after treated with adalimumab was reported.     

Sex influence on the cardiac complication of ankylosing spondylitis--analysis of 95 cases of ankylosing spondylitis including our case

Ankylosing spondylitis is apparently rare among Japanese and it is known that this disease is commoner in males than in females. The male to female ratio among general ankylosing spondylitis is 4.5:1. The cardiac conduction abnormalities, aortic insufficiency and mitral insufficiency are sometimes associated with this disease. We analysed the influence of sex on the development of these cardiac complications using 95 reported cases of ankylosing spondylitis including our case. Among the ankylosing spondylitis patients who were accompanied with cardiac complication, 99% were male. This frequency is significantly high compared with that found in general ankylosing spondylitis (p less than 0.0001). The cardiac complication associated with this disease seems to be characteristic for males. This sex difference is useful for differential diagnosis from various diseases which accompany these cardiac complications. The mechanism of sex influence on the cardiac complication of ankylosing spondylitis was also discussed.     

Clinical aspects, outcome assessment, and management of ankylosing spondylitis and postenteric reactive arthritis

The cause of ankylosing spondylitis remains unclear. Proof that this disorder is an autoimmune disease attributable to crossreactivity between bacteria and HLA-B27 is still lacking. Differences in endogenous peptide presentation by HLA-B27 subtypes might be relevant in the etiopathogenesis. Fractures of the osteoporotic spine contribute to morbidity. Spinal cord injury may occur. MR imaging enables identifying sacroiliitis earlier than plain radiography. Sweet syndrome has now been described in patients with ankylosing spondylitis and Crohn disease. Progress has been made in the assessment of ankylosing spondylitis. There are now core sets for different settings and validated instruments for functioning and disease activity that will enable demonstrating efficacy of new therapeutic interventions.The debate continues on classification of postinfectious and reactive arthritis. Bacterial antigens may be found in the inflamed joints; occasionally 16S ribosomal RNA is also demonstrated. Antibiotics seem not to be effective in postenteric reactive arthritis.More than 25 years have now elapsed since the association between ankylosing spondylitis and HLA-B27 was first described in 1973. The cause of this disease is still unknown, but a lot of progress has been made regarding the molecular structure of HLA-B27, the spectrum of disease, the clinical and radiographic assessment of ankylosing spondylitis, and its treatment. Recent advances in research on ankylosing spondylitis are reviewed here.     

Increased disease activity is associated with a deteriorated lipid profile in patients with ankylosing spondylitis

BACKGROUND: Cardiovascular mortality is increased in patients with ankylosing spondylitis. A possible explanation might be a more prevalent atherogenic lipid profile in patients with ankylosing spondylitis than in the general population. It has been postulated that inflammation deteriorates the lipid profile, thereby increasing cardiovascular risk. OBJECTIVE: To explore the association between disease activity and lipid profile in patients with ankylosing spondylitis. METHODS: Disease activity parameters for ankylosing spondylitis and lipid levels (total cholesterol, high-density lipoprotein cholesterol (HDLc) and triglycerides) were measured in 45 patients with ankylosing spondylitis for 6 months after starting treatment with leflunomide or placebo. Findings in this treatment group were compared with those in 10 patients with ankylosing spondylitis treated with etanercept. A specialised regression model, adjusting for repeated measurements, age and sex, was used to assess the influence of the disease activity variables on the lipid levels. RESULTS: Multilevel regression analyses showed significant associations between disease activity parameters and lipid levels-for instance, an increase of 30 mm at the end of the first hour in erythrocyte sedimentation rate was associated with a decrease of about 6% in total cholesterol level and a decrease of about 11% in HDLc levels. Similar significant associations were found between other disease activity parameters and lipid levels. CONCLUSION: Increase in disease activity was associated with decreases in lipid levels. The decrease in HDLc levels tended to be almost twice as large as the decrease in total cholesterol levels, resulting in a more atherogenic lipid profile. Hence, effective treatment of disease activity in patients with ankylosing spondylitis may lower the cardiovascular risk by improving the lipid profile.     

Arthritic Manifestations of Inflammatory Bowel Disease

Rheumatologic conditions associated with inflammatory bowel disease may be divided into four clinical categories. First, a unique form of peripheral arthritis occurs in 15-20% of patients with inflammatory bowel disease. The incidence is higher in Crohn's disease than in ulcerative colitis. This is a self-limited, nondeforming, seronegative arthritis that waxes and wanes with bowel flares. It characteristically involves knees and ankles. Persistent erosive monoarthritis is described. Second, spondylitis clinically and radiographically indistinguishable from idiopathic ankylosing spondylitis occurs in 3-6% of patients with inflammatory bowel disease. HLA-B27 positivity occurs in 53-75% of cases, fewer than in idiopathic spondylitis. Third, a bilateral, symmetrical sacroiliitis is seen in 4-18% of patients. This may not progress to clinical spondylitis. The fourth category encompasses rheumatologic complications of inflammatory bowel disease. These include granulomas of bones and joints, granulomatous vasculitis, clubbing, periostitis, amyloidosis, osteoporosis, osteomalacia, septic arthritis, and complications of corticosteroid therapy.     

Ankylosing spondylitis occurring in a patient with Behçet disease after chronic brucellosis infection: A case report and review of the literature

Behçet disease and ankylosing spondylitis are rarely seen together. This report presents a rare case of ankylosing spondylitis occurring in a patient with Behçet disease after chronic brucellosis infection. Infectious agents have long been considered one of the triggers for autoimmune and autoinflammatory diseases. Therefore, rheumatic processes should be kept in mind, especially in treatment-resistant cases.     

"Ankylosing spondylitis" without sacroiliitis in a woman without the HLA B27 antigen.

An elderly woman with otherwise typical ankylosing spondylitis for 45 years lacked radiologic evidence of sacroiliitis and the HLA B27 antigen. The illness was complicated by renal tuberculosis requiring a left nephrectomy 23 years after the onset of low back pain, and 20 years after an episode of severe iritis. After the eradication of the tuberculosis by surgery and chemotherapy, she has continued to have symptomatic spondylitis. The case seems to be an exception to the rule that sacroiliitis is a sine qua non for ankylosing spondylitis. Women with ankylosing spondylitis tend to have milder disease with an apparently lower frequency of roentgenographic changes in sacroiliac joints.     

Upward subluxation of the axis in ankylosing spondylitis. A clinical pathologic report.

Upward subluxation of the axis associated with cord compression and death was noted in a patient with a long history of idiopathic ankylosing spondylitis. Upward subluxation of the axis has been recognized in up to 8 per cent of patients with rheumatoid arthritis but it is an exceedingly rare complication of ankylosing spondylitis. In this patient psoriasis and then psoriatic dactylitis developed 26 years after the onset of his ankylosing spondylitis. It is tempting to speculate that the unusual destruction of the joints around the atlas might be due to an added effect of psoriasis on idiopathic ankylosing spondylitis.     

HLA B27 and the genetics of ankylosing spondylitis.

One hundred and twenty-eight of 145 patients with ankylosing spondylitis (AS) were found to be HLA B27 positive. Five patients had evidence of a sero-negative peripheral arthritis resembling peripheral psoriatic arthritis and 3 of these were B27 negative. One further B27 negative patients had a sister with ankylosing spondylitis and ulcerative colitis and a mother with ulcerative colitis. There was evidence of a somewhat later age of onset of symptoms in B27 negative patients. These findings are interpreted as suggesting some degree of clinical and genetic heterogeneity in ankylosing spondylitis with genes for psoriasis and inflammatory bowel disease being important in some individuals, particularly those who are B27 negative. Twenty-five first-degree relatives with ankylosing spondylitis were all B27 positive. The only instance of disassociation of B27 and spondylitis in a family was where the proband had ulcerative colitis as well as spondylitis. Of 13 B27 positive fathers 3 could be diagnosed as having definite ankylosing spondylitis (23%). These findings are thought to provide evidence against the concept that the gene for ankylosing spondylitis is not B27 but a closely linked gene and favour the occurrence of an environmental event affecting approximately one-fifth of B27 positive males to result in disease.     

Systemic and mucosal antibodies to Klebsiella in patients with ankylosing spondylitis and Crohn''s disease.

Whole gut lavage fluid is a useful source of material for the study of intestinal immunity and inflammation in humans. Systemic and mucosal antibodies to Klebsiella pneumoniae were measured by enzyme linked immunosorbent assay (ELISA) in serum samples and whole gut lavage fluid from 14 patients with ankylosing spondylitis, 14 with Crohn's disease, and 16 immunologically normal controls. As the concentration of IgG in whole gut lavage fluid reflects disease activity in Crohn's disease, this approach was used to detect intestinal inflammation in patients with ankylosing spondylitis who also had disease activity and use of non-steroidal anti-inflammatory drugs (NSAIDs) recorded. Small intestinal permeability to cellobiose and mannitol was also studied. In serum samples, levels of IgA antibody to klebsiella were high in patients with Crohn's disease and in patients with active ankylosing spondylitis, and were significantly correlated with the erythrocyte sedimentation rate in patients with ankylosing spondylitis. Levels of IgG antibody to klebsiella were also high in patients with Crohn's disease. Studies of whole gut lavage fluid showed similar levels of IgA antibody to klebsiella in the three study groups, but levels of whole gut lavage fluid IgM and IgG antibodies to klebsiella were high in patients with Crohn's disease. Levels of IgG in whole gut lavage fluid were high in patients with Crohn's disease but in only one patient with ankylosing spondylitis, though the cellobiose/mannitol permeability ratio was abnormal in eight of 13 patients with ankylosing spondylitis. It is concluded that high levels of serum IgA antibody to klebsiella are not specific to ankylosing spondylitis, and that there is no evidence of an abnormal intestinal IgA antibody response to klebsiella in patients with ankylosing spondylitis.     

First update of the international ASAS consensus statement for the use of anti-TNF agents in patients with ankylosing spondylitis

OBJECTIVE: To update the international recommendations for use of anti-tumour necrosis factor (TNF) agents in the treatment of ankylosing spondylitis. METHODS: The published recommendations on anti-TNF treatment in ankylosing spondylitis formed the basis of the update. A questionnaire was sent to the ASAS (assessment in ankylosing spondylitis) members before the final decisions were agreed upon at an international meeting of the ASAS working group. RESULTS: Only minor changes to the original consensus statement were required. For the initiation of anti-TNF treatment, there should be: a diagnosis of definitive ankylosing spondylitis (normally based on modified New York criteria); active disease for at least four weeks, as defined by a sustained Bath ankylosing spondylitis disease activity index (BASDAI) of > or =4 on a 0-10 scale and expert opinion based on clinical findings; refractory disease, defined by failure of at least two non-steroidal anti-inflammatory drugs during a three month period, failure of intra-articular steroids (if indicated), and failure of sulfasalazine in patients with predominantly peripheral arthritis; and application of the usual precautions and contraindications for biological treatment. For monitoring anti-TNF treatment: both the ASAS core set for clinical practice and the BASDAI should be followed after the initiation of treatment. Discontinuation of anti-TNF treatment in non-responders should be considered after 6-12 weeks. Response is defined by improvement of at least 50% or 2 units (on a 0-10 scale) of the BASDAI. CONCLUSIONS: This updated consensus statement is recommended in guiding clinical practice and as a basis for developing national guidelines. Evaluation and regular update of this consensus statement is subject to further research by the ASAS group.     

Knochendichtemessungen bei entzündlich-rheumatischen Erkrankungen

Bone densitometry should be performed earlier in patients with inflammatory arthritis, since factors such as inflammation and drug therapy, in particular treatment with glucocorticoids, have an important impact on the development of osteoporosis. DXA (Dual energy X-ray Absorptiometry) is considered the gold standard for bone densitometry. According to the German guidelines for osteoporosis, bone densitometry plays a crucial role in the choice of therapy. In patients with rheumatoid arthritis, measurement of peripheral bone (forearm) density in addition to lumbar spine and hip is recommended, since local bone loss is pathognomonic for this disease. DXA measurements of the hand enable the diagnosis of juxtaarticular osteoporosis at an earlier stage; however, this has not yet been established in routine practise. Bone measurement in patients with ankylosing spondylitis can be performed in the lumbar spine and the hip at disease onset. In systemic lupus erythematosus, bone loss is more frequent in patients with high inflammatory activity. Patients with psoriasis arthritis frequently have osteoporosis in the case of a destructive development of the joints.     

Discovertebral (Andersson) lesions in severe ankylosing spondylitis: a study using MRI and conventional radiography

The objective of this study is to investigate the prevalence of Andersson lesions (AL) in ankylosing spondylitis (AS) patients who will start anti-tumor necrosis factor (TNF) treatment. Radiographs and magnetic resonance imaging (MRI) of the spine were performed before therapy with anti-TNF. ALs were defined as discovertebral endplate destructions on MRI, associated with bone marrow edema and fat replacement or sclerosis, a decreased signal on T1, enhancement after contrast administration (gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA)), and increased signal on T2 and short tau inversion recovery (STIR). Additionally, conventional radiography showed a fracture line, irregular endplates, and increased sclerosis of adjacent vertebral bodies. Fifty-six AS patients were included, 68% males, mean age of 43 years, and mean disease duration of 11 years. The mean bath ankylosing spondylitis disease activity index was 6.4, and 24% of all patients had ankylosis. Only one patient showed a discovertebral abnormality with bone marrow edema of more than 50% of the vertebral bodies adjacent to the intervertebral disk of T7/T8 and T9/T10, a hypodense signal area on T1, and a high signal on STIR. Irregular endplates were depicted, and T1 after Gd-DTPA demonstrated high signal intensity around the disk margins. However, no fracture line was visible on conventional radiology, and therefore, this case was not considered to be an AL. No AL was detected in our AS patients, who were candidates for anti-TNF treatment. One patient showed a discovertebral abnormality on MRI, without a fracture line on conventional radiology. The relative small proportion of patients with a long-established disease might explain this finding for, particularly, an ankylosed spine is prone to develop an AL.     

Simultaneous presentation of upper lobe fibrobullous disease and spinal pseudarthrosis in a patient with ankylosing spondylitis.

A 51 year old man with a 20 year history of ankylosing spondylitis and pronounced thoracic gibbus presented with two simultaneous complications of longstanding ankylosing spondylitis, upper lobe fibrobullous disease, and spinal pseudarthrosis. No neurological sequelae developed and treatment was conservative. Both these lesions mimic tuberculosis, and so it is important to determine them accurately to avoid unnecessary antituberculosis treatment. Both of these complications are reported to occur in longstanding ankylosing spondylitis and their simultaneous presentation may be more common than is realised. This case is believed to be the first such report of their association.     

Inflammatory Rheumatic Disorders and Bone

Inflammatory joint diseases such as rheumatoid arthritis, as well as other rheumatic conditions, such as systemic lupus erythematosus (SLE) and ankylosing spondylitis, comprise a heterogeneous group of joint disorders that are all associated with extra-articular side effects, including bone loss and fractures. The concept of osteoimmunology is based on growing insights into the links between the immune system and bone. The pathogenesis of osteoporosis in these patients is multifactorial. We have, more or less as an example, described this extensively for patients with SLE. High disease activity (inflammation) and immobility are common factors that substantially increase fracture risk in these patients, on top of the background fracture risk based on, among other factors, age, body mass index, and gender. Although no fracture reduction has been shown in intervention studies in patients with inflammatory rheumatic diseases, we present treatment options that might be useful for clinicians who are treating these patients.     

Ankylosing spondylitis and bone mineral density—what is the ideal tool for measurement?

Ankylosing spondylitis (AS) is characterised by chronic inflammation and partial ossification, yet vertebral fractures due to osteoporosis, although common, are frequently unrecognised. The aim of this study was to (1) show the frequency of changes in the progress of osteopenia/osteoporosis in AS depending on duration and stage of the disease and (2) assess the ranking of two different methods of bone density measurement in this clinical pattern. We measured bone density in 84 male and female patients with both dual X-ray absorptiometry (DXA) and single energy quantitative computed tomography (SE-QCT). In the initial and advanced stages of the disease, a high decrease in axial bone density could be verified (DXA: osteopenia in 5% and osteoporosis in 9.2%; SE-QCT: osteopenia in 11.8% and osteoporosis in 30.3%). Peripheral bone density decrease as in osteopenia could be proven in 17.6% by DXA measurement. With SE-QCT, a decrease in vertebral trabecular bone density could already be observed in the initial stage and continued steadily during the course of the disease; cortical bone displayed the same trend up to stages of ankylosis. With DXA, valid conclusions are more likely to be expected in less marked ankylosing stages of AS. In stages of advanced ankyloses in the vertebral region (substantial syndesmophytes), priority should be given to SE-QCT, due to the selective measurement of trabecular and cortical bone. The DXA method often yields values that are too high, and the replacement of vertebral trabecular bone by fatty bone marrow is not usually recorded as standard. There may already be an increased risk of bone fracture in AS in osteopenia on DXA along with an osteoporosis already established on SE-QCT.