Demyelination during anti-TNFα therapy for ankylosing spondylitis

A 34-year-old ankylosing spondylitis (AS) patient on etanercept for 30 months presented to neurologists with paresthesia of his hands and feet. Magnetic resonance imaging (MRI) scans showed multifocal hyperintense lesions. Symptoms did not improve on stopping the anti-tumor necrosis factor (TNF) agent. Few cases of demyelinating disease occurring after more than 2 years of treatment with anti-TNF agents have been reported in patients with AS. Opthalmologists, internists, neurologists, and rheumatologists need to be aware of these adverse events, as patients may present to any of these specialties many years after treatment.     

How should clinicians manage osteoporosis in ankylosing spondylitis?

Osteoporosis is a common complication of AS, with an incidence between 18.7% and 62%. The prevalence of osteoporosis is greater in males, and increases with increasing patient age and disease duration. Osteoporosis is also more common in patients with syndesmophytes, cervical fusion, and peripheral joint involvement. These variables are not all independent, as they may be indicators of disease duration. Osteoporosis in patients with AS is largely confined to the axial skeleton, in contrast to the pattern of osteoporosis seen in rheumatoid arthritis. BMD at the lumbar spine and femoral neck may be severely reduced, while most studies indicate that carpal and radial BMD remain within normal limits. The development of syndesmophytes in late AS can lead to difficulties in the use of DEXA scanning to determine lumbar BMD, as the extraspinal bone may obscure osteoporotic vertebrae. Under these circumstances more accurate assessment of lumbar BMD, and one that correlates better with femoral neck BMD, may be obtained by quantitative CT scanning or DEXA scanning of the lateral aspect of the L3 vertebra. Osteoporosis in AS significantly increases the risk of vertebral compression fractures within 5 years of the diagnosis of AS. The risk of a vertebral compression fracture occurring over a 30 year period following the diagnosis of AS is 14%, compared to 3.4% for population controls. In patients with vertebral osteoporosis relatively minor trauma, such as slipping, can lead to spinal fracture and dislocatior with subsequent damage to the spinal cord. There is a higher incidence of spinal cord injury following spinal fracture dislocations in patients with AS, and the resulting neurological deficit can range from mild sensory loss to complete paraplegia. Cytokines such as TNF-alpha and IL-6 may play an important part in the pathogenesis of osteoporosis in early AS, and IL-6 levels have been correlated with markers of disease activity and severity. In late AS, mechanical factors such as decreased mobility and the support provided by extraspinal bone may play a role in vertebral osteoporosis. Screening patients with AS for the presence of osteoporosis is an important, but contentious subject. This and subsequent monitoring needs to be considered in all patients, but longterm studies are needed to determine with confidence which patients should undergo screening, by which methods, and how often. The treatment of osteoporosis in AS is at present similar to that used for primary osteoporosis, except that due to the male predominance and a relatively young age of patients, there is a limited role for hormone replacement therapy. Exercise regimens and bisphosphonates are widely used, but a study of the relative efficacy of different bisphosphonate agents in patients with AS is required.     

Is disease severity in ankylosing spondylitis genetically determined?

OBJECTIVE: To assess the role of genes and the environment in determining the severity of ankylosing spondylitis. METHODS: One hundred seventy-three families with >1 case of ankylosing spondylitis were recruited (120 affected sibling pairs, 26 affected parent-child pairs, 20 families with both first- and second-degree relatives affected, and 7 families with only second-degree relatives affected), comprising a total of 384 affected individuals. Disease severity was assessed by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and functional impairment was determined using the Bath Ankylosing Spondylitis Functional Index (BASFI). Disease duration and age at onset were also studied. Variance-components modeling was used to determine the genetic and environmental components contributing to familiality of the traits examined, and complex segregation analysis was performed to assess different disease models. RESULTS: Both the disease activity and functional capacity as assessed by the BASDAI and the BASFI, respectively, were found to be highly familial (BASDAI familiality 0.51 [P = 10(-4)], BASFI familiality 0.68 [P = 3 x 10(-7)]). No significant shared environmental component was demonstrated to be associated with either the BASDAI or the BASFI. Including age at disease onset and duration of disease as covariates made no difference in the heritability assessments. A strong correlation was noted between the BASDAI and the BASFI (genetic correlation 0.9), suggesting the presence of shared determinants of these 2 measures. However, there was significant residual heritability for each measure independent of the other (BASFI residual heritability 0.48, BASDAI 0.36), perhaps indicating that not all genes influencing disease activity influence chronicity. No significant heritability of age at disease onset was found (heritability 0.18; P = 0.2). Segregation studies suggested the presence of a single major gene influencing the BASDAI and the BASFI. CONCLUSION: This study demonstrates a major genetic contribution to disease severity in ankylosing spondylitis. As with susceptibility to ankylosing spondylitis, shared environmental factors play little role in determining the disease severity.     

Retroperitoneal fibrosis and ankylosing spondylitis: which links?

OBJECTIVES: To report a case of retroperitoneal fibrosis (RPF) in a patient with ankylosing spondylitis (AS) and to review the medical literature for similar cases to detect possible links between the 2 diseases. METHODS: The presentation, clinical course, diagnostic work-up, and treatment of our patient are described, and the English and French medical literature from 1960 to 2000 is reviewed using a MEDLINE search for cases with coexisting RPF and spondyloarthritis. RESULTS: Our patient with AS had RPF, which mimicked rectal cancer with retroperitoneal and vertebral metastases. Special attention is paid to the unusual clinical presentation, the multistep diagnostic process, and the therapeutic strategy which was both radiologically and histologically successful. Literature review revealed 18 cases of concomitant RPF and spondyloarthritis, mainly AS. Patients were more frequently male (M/F, 3/1) and developed spondyloarthritis several years before RPF. CONCLUSIONS: RPF may result from a local immune response to products of aortic atheromatous plaques, with subsequent periaortic deposition of fibrous tissue. However, the clinical features and the frequent association with other fibrosing disorders suggest that RPF is a systemic inflammatory condition. The role of AS-associated aortitis in the development of RPF warrants consideration.     

Is disease severity in ankylosing spondylitis genetically determined?

Objective

To assess the role of genes and the environment in determining the severity of ankylosing spondylitis.

Methods

One hundred seventy‐three families with >1 case of ankylosing spondylitis were recruited (120 affected sibling pairs, 26 affected parent–child pairs, 20 families with both first‐ and second‐degree relatives affected, and 7 families with only second‐degree relatives affected), comprising a total of 384 affected individuals. Disease severity was assessed by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and functional impairment was determined using the Bath Ankylosing Spondylitis Functional Index (BASFI). Disease duration and age at onset were also studied. Variance‐components modeling was used to determine the genetic and environmental components contributing to familiality of the traits examined, and complex segregation analysis was performed to assess different disease models.

Results

Both the disease activity and functional capacity as assessed by the BASDAI and the BASFI, respectively, were found to be highly familial (BASDAI familiality 0.51 [P = 10⁻⁴], BASFI familiality 0.68 [P = 3 × 10⁻⁷]). No significant shared environmental component was demonstrated to be associated with either the BASDAI or the BASFI. Including age at disease onset and duration of disease as covariates made no difference in the heritability assessments. A strong correlation was noted between the BASDAI and the BASFI (genetic correlation 0.9), suggesting the presence of shared determinants of these 2 measures. However, there was significant residual heritability for each measure independent of the other (BASFI residual heritability 0.48, BASDAI 0.36), perhaps indicating that not all genes influencing disease activity influence chronicity. No significant heritability of age at disease onset was found (heritability 0.18; P = 0.2). Segregation studies suggested the presence of a single major gene influencing the BASDAI and the BASFI.

Conclusion

This study demonstrates a major genetic contribution to disease severity in ankylosing spondylitis. As with susceptibility to ankylosing spondylitis, shared environmental factors play little role in determining the disease severity.

     

Is retardation of radiologic progression of ankylosing spondylitis possible?

In the introduction is the author dealing with problems of early diagnosis of ankylosing spondylitis and he is explaining the advantages of new ASAS/EULAR criteria for diagnosis of axial spondylarthritis. Than he continues with discussion about new "Recommendations for treatment of ankylosing spondylitis", stressing the modification of recommendations for anti-TNF therapy. Despite the fact, that high symptomatic efficacy of anti-TNF therapy was confirmed, there is no clear evidence that anti-TNF drugs delay radiologic progression. On the contrary, study with nonsteroidal antirheumatic drugs in duration 24 months was performed and have documented that patients treated continuously by celecoxib had smaller radiographic progression than patients treated with celecoxib on demand. Anti-TNF therapy delays radiographic progression in rheumatoid arthritis, but not NSAID, in ankylosing spondylitis it is opposite. The differences may be caused by different pathophysiology of rheumatoid arthritis and ankylosing spondylitis as it is explained in the next part of publication. Combination therapy of AS with anti-TNF and continuous celecoxib therapy could be very interesting.     

Behçet's syndrome coexisting with clinically occult ankylosing spondylitis

The case of a 36-year old man with Beh?et's disease (BS) for 16 years had low back pain and stiffness in the cervical and lumbar spine. He was diagnosed as having ankylosing spondylitis (AS). In this report we wish to emphasize the clinically occult co-existence of AS in BS and revelation of AS after a long time of BS diagnose.     

The coexistence of Behçet's disease and ankylosing spondylitis

We present the case of a young woman suffering from both ankylosing spondylitis and Behçet's disease, associated with a severe inflammatory arthritis. Although the HLA phenotype was positive for HLA-B27 and negative for HLA-B5, the clinical findings, especially the joint manifestations of Behçet's disease, seem to appear dominantly. The meaning of this rare combination was discussed with a review of the literature.     

Familial versus sporadic ankylosing spondylitis. two different diseases?

Objective. To define potential differences and the possible contribution of susceptibility or severity genes in familial versus sporadic ankylosing spondylitis (AS). Methods. Three hundred twenty patients with AS were studied: 160 who had first-degree relatives with AS (familial) and 160 age- and sex-matched controls who had no first-degree relative with the disease (sporadic). Disease expression in the two groups was evaluated using an index of physical, psychological, and social functioning (the Arthritis Impact Measurement Scales [AIMS]) and an assessment of spinal mobility. Results. Familial disease was significantly milder than sporadic disease as assessed by all measures, e.g., spinal mobility score (mean 4.08 versus 4.65, P < 0.038), AIMS overall impact score (mean 2.63 versus 3.59, P = 0.002), AIMS physical activity score (4.19 versus 5.10 [P = 0.004]), AIMS social function score (4.02 versus 4.60, P = 0.023), and AIMS pain score (4.15 versus 5.33, P = 0.002). Conclusion. The greater prevalence of AS in at-risk families may be explained by the occurrence of more AS “susceptibility” genes in those families, whereas the more severe disease, seen in patients with sporadic AS, is conferred by the presence of more “severity” genes than “susceptibility” genes.     

Sjögren’s syndrome in patients with ankylosing spondylitis

There are few reports about the coexistence of Sjögren’s syndrome (SS) and ankylosing spondylitis (AS). To evaluate the frequency of SS in patients with AS. We studied 70 patients with AS presenting to the university outpatient clinic between January 2002 and November 2003. All the patients were asked about sicca symptoms by using sicca questionnaire. Rheumatoid factor, anti-nuclear antibody, anti-Ro, and anti-La antibodies were examined for each of the patients. Salivary flowmetry for the existence of xerostomia, Schirmer’s test, and break-up time for the existence of xerophtalmia were performed in all patients with AS. Minor salivary gland biopsy was performed on the patients with at least three positive responses to the sicca questionnaire and positive xerostomia/ xerophtalmia tests. Biopsies were regarded as pathological when they showed focal grade III and grade IV sialoadenitis according to Chisholm grading criteria. Among 70 AS cases, 56 (80%) were men, 14 (20%) were women, and the mean age was 42 years old. Minor salivary gland biopsy was performed on the 16 patients. Of 16 minor salivary gland biopsies, 7 were assessed as pathological—5 of them showed grade III, and 2 of them showed grade IV sialoadenitis. Of these seven patients, one was anti-Ro-positive, and two were anti-La-positive. There was no patient with normal salivary gland biopsy and anti-Ro and/or anti-La positivity. In our study group, 7 (10%) of 70 AS patients had concomitant SS. Therefore, it seems likely that AS may have pathogenetic association with SS.     

Hodgkin’s lymphoma following treatment with etanercept in ankylosing spondylitis

It has been well known that anti-TNF drugs might increase lymphoma risk in rheumatoid arthritis (RA), where the rate of lymphoma has already been increased. However, unlike RA, an increased rate of lymphoma has not been reported in ankylosing spondylitis (AS). Hereby, we present a case with AS developing Hodgkin’s lymphoma (HL) following 6 months of etanercept treatment. Pathological analysis revealed mixed cellular type of HL. Although we report a single case, it should be kept in mind that anti-TNF drugs might cause lymphoma development not only in RA, but also in AS.