UK consultant rheumatologists' access to biological agents and views on the BSR Biologics Register.

OBJECTIVES: The British Society for Rheumatology Biologics Register (BSRBR) is a prospective cohort study to determine the efficacy and toxicity of biological agents in rheumatoid arthritis (RA) patients compared with RA controls. Entry of patients to the register is a condition of use of anti-tumour necrosis factor (anti-TNF) therapy in the UK, but little is known of clinicians' views of its usefulness. Data from the register suggest uneven provision of anti-TNF-alpha therapy. METHODS: A questionnaire was sent on behalf of the BSRBR to all UK consultant rheumatologists concerning provision and use of anti-TNF-alpha therapy and their experience of working with the BSRBR. RESULTS: Response rate was 49.5% representing 252 consultants. Fourty-six per cent had some limitation of access to anti-TNF-alpha drugs, usually a financial cap (70%), even for RA patients meeting National Institute for Health and Clinical Excellence (NICE) criteria. Sixty-seven per cent could prescribe for ankylosing spondylitis (AS) or psoriatic arthritis (PsA) in some circumstances but only 25 and 35%, respectively, could prescribe according to BSR guidance. More than 50% found the workload involved in submitting data to the registry at least difficult, but most had favourable impressions of the BSRBR and thought similar registries desirable or essential for PsA, AS and rituximab. CONCLUSIONS: Access to anti-TNF therapy for patients with inflammatory arthritis is variable in the UK, even for RA where it is NICE-approved. Access is more limited for conditions where NICE has not yet issued guidance. The BSRBR generates a significant workload for rheumatology staff but is generally well-regarded.

A study of the prevalence of systemic sclerosis in northeast England.

OBJECTIVES: We aimed to obtain an estimate of the prevalence and demographics of systemic sclerosis (SSc) and its subtypes at the turn of the millennium. METHODS: Case finding from multiple sources from a defined geographical area. Diagnosis confirmed by clinical examination. RESULTS: The crude prevalence of SSc in northeast England was 8.8 (95% CI: 6.8-10.8) per 100,000. The prevalence when adjusted for the entire UK is 8.2 (95% CI: 6.2-9.8) per 100,000. The ratio of women to men was 5.2:1. The median age of patients was 57.1 yr. The ratio of limited cutaneous SSc to diffuse cutaneous SSc was 4.7:1. Limited cutaneous SSc is associated with the presence of anticentromere antibodies; diffuse cutaneous SSc is associated with anti-Scl 70 antibodies, but either antibody was found in either form of SSc. CONCLUSIONS: SSc appears to be more common in northeast England than was found in the West Midlands in 1986. This may reflect changes in the diagnostic definition of SSc.

Cervical myelopathy and rheumatoid arthritis: a retrospective analysis of management.

BACKGROUND: Although a number of recent studies have described the outcome of surgical treatment of patients with rheumatoid cervical myelopathy, few have reported outcome in those unable to have surgery. We sought to examine the outcome in this group of patients regardless of surgical intervention. DESIGN: Retrospective and descriptive. SETTING: Department of Rheumatology, Freeman Hospital, Newcastle upon Tyne, UK. METHODS: Retrospective review of case notes of 40 patients (31 females, 9 males) with rheumatoid cervical myelopathy diagnosed 1988-1997. RESULTS: The mean age was 64 years (range 36-80 years). The mean duration of rheumatoid arthritis (RA) before the development of myelopathy was 21 years (range 5-44 years). The common impairments were paraesthesia in the arms, neck pain and weakness. Twenty-five patients (60%) were deemed fit for surgery (group I). Twenty-two patients successfully had operative treatment and the others refused. Twelve of the 15 patients who reported pain preoperatively obtained pain relief. Six of the 11 patients who were nonambulant (Ranawat class IIIB) were able to walk postoperatively. There were two deaths within six months (9% mortality) after primary surgery due to pneumonia and sepsis. Seven of the 15 patients managed conservatively (group II) because of coexisting medical complications died within six months of presentation (47% mortality). CONCLUSIONS: The study confirms the overall benefit of surgical intervention in those who are medically stable. Following surgery some functional improvement may occur even in patients with severe myelopathy.

An association between the CTLA4 exon 1 polymorphism and early rheumatoid arthritis with autoimmune endocrinopathies.

OBJECTIVE: To examine the allelic association of the single nucleotide polymorphism (CTLA4A/G) in exon 1 of the cytotoxic T lymphocyte antigen-4 (CTLA4) gene with early rheumatoid arthritis (RA). METHODS: One hundred and twenty-three unrelated white probands with early RA from the north-east of England and 349 local ethnically matched controls were studied. The CTLA4A/G polymorphism was genotyped with a polymerase chain reaction (PCR) method and digestion with the restriction enzyme Bst71I. Probands were also screened by allele-specific PCR for alleles HLA DRB1*01 and DRB1*04. RESULTS: The frequency of the G allele at CTLA4A/G was significantly increased in probands with early RA compared with controls [43 vs 36%; P=0.028, odds ratio (OR) 1.35, 95% confidence interval (CI) 1.01-1.82]. Most of this increased frequency was attributable to RA individuals with coexisting autoimmune thyroid disease or type 1 diabetes (58 vs 36% in controls; P=0.005, OR 2.50, CI 1.29-4.84). The frequency of the G allele in RA patients without autoimmune endocrinopathy was 40%, which was not significantly different from that in controls (P=0.140). CONCLUSION: The association between the CTLA4 G allele and early RA is largely explained by individuals with RA who have coexisting autoimmune endocrinopathies.

Clinical features of a novel TIMP-3 mutation causing Sorsby's fundus dystrophy: implications for disease mechanism.

AIMS: To describe the phenotype in three family members affected by a novel mutation in the gene coding for the enzyme tissue inhibitor of metalloproteinase-3 (TIMP-3). METHODS: Three members of the same family were seen with a history of nyctalopia and visual loss due to maculopathy. Clinical features were consistent with Sorsby's fundus dystrophy. Exon 5 of the gene coding for TIMP-3 was amplified by the polymerase chain reaction, single strand conformation polymorphism analysis undertaken and exon 5 amplicons were directly sequenced. RESULTS: Onset of symptoms was in the third to fourth decade. Five of six eyes had geographic macular atrophy rather than neovascularisation as a cause for central visual loss. Peripheral retinal pigmentary disturbances were present. Scotopic ERGs were abnormal in all three. Mutation analysis showed a G-->T transversion in all three resulting in a premature termination codon, E139X, deleting most of the carboxy terminal domain of TIMP-3. CONCLUSIONS: The patients described had a form of Sorsby's fundus dystrophy which fell at the severe end of the spectrum of this disease. Postulated disease mechanisms include deposition of dimerised TIMP-3 protein.

Ten year follow up of pulmonary function in patients with primary Sjögren's syndrome.

OBJECTIVES: To follow up a previous report on the lung function of patients with primary Sjögren's syndrome (SS), and describe the findings having followed up this cohort for a median duration of 10 years (range 8-12 years). METHODS: 30 patients fulfilling Fox's criteria for definite or probable primary SS were assessed within six months of diagnosis and after a median duration of four and then 10 years by a clinical examination, chest radiograph, and lung function studies (FEV(1), FVC, TLCO, and KCO). RESULTS: At baseline, symptomatic dyspnoea was a common finding, reported by 13/30 patients, of whom two had evidence of fibrosing alveolitis on plain chest radiograph. Five patients had a carbon monoxide transfer factor (TLCO) more than two standardised residuals below the predicted value. After four years' follow up two further patients developed radiological fibrotic changes and there were significant reductions in TLCO (p<0.02) and transfer coefficient (KCO) (p<0.02) compared with the baseline measurements. At 10 years' follow up four patients had died and four were lost to follow up. One patient with fibrosing alveolitis had died from chest disease. There were no further cases of pulmonary fibrosis identified on plain chest radiograph. The lung function studies showed no further deterioration from the results found at year four with significant improvements in both TLCO (p<0.001) and KCO (p<0.001). Those patients who were anti-Ro antibody positive had significantly lower transfer factors than patients with primary SS without this serological marker (p<0.02). CONCLUSION: This long term follow up of lung disease in primary SS is reassuring, and suggests that most patients do not develop progressive lung disease. Pulmonary disease occurs predominantly in anti-Ro antibody positive patients and presents early in the course of the disease.

Primary Sjögren's syndrome in the North East of England: a long-term follow-up study.

OBJECTIVE: Although primary Sjogren's syndrome is often a benign condition, characterized by lymphocytic infiltration of salivary and lacrimal glands, some patients develop systemic features. We have previously found that anti-Ro antibodies identified patients with more systemic disease, with increased incidence of parotid swelling, lymphadenopathy and lymphoma. METHODS: We have followed up a cohort of 100 patients over 10 yr, to establish whether the phenotypic expression of disease changed, and whether the different autoantibody patterns expressed at presentation could be used to predict outcome. RESULTS: While seronegative patients (ANA, RF, Ro and La negative) remained polysymptomatic, they did not develop systemic complications or serological changes. Thirty-nine per cent of ANA- or RF-positive patients who were negative for Ro and La were given revised diagnoses over the follow-up period, including rheumatoid arthritis, systemic lupus erythematosus, mixed connective tissue disease and scleroderma. Parotid swelling and lymphadenopathy were more common in Ro/La-positive patients, where the relative risk of developing non-Hodgkin's lymphoma was 49.7. CONCLUSION: Both HLA B8 and DR3 were present in 79% of Ro/La-positive patients, but were found together in only 4% of seronegative patients, supporting the view that these clinical subgroups of primary Sjogren's syndrome are both serologically and immunogenetically distinct. Patients who are initially autoantibody (including Ro and La) negative do not evolve into 'systemic' Sjogren's syndrome or other connective tissue diseases.

The treatment of sicca features in Sjögren's syndrome: a clinical review.

Patients with SS often suffer considerable distress due to sicca symptoms and the complications of mucosal dryness. Although there are many topical treatments available, the literature on their use is scant. This paper describes the treatments available and suggests a rationale for the choice of product.

Six-year follow-up of multiple joint replacement surgery to the lower limbs.

We report a 6-yr follow-up study of an original population of 50 patients who had three or more major joints (hips and knees) replaced. Thirty-one of 32 surviving patients were still ambulant in the community, and all patients described significant pain relief. No RA patient was requiring permanent inpatient or residential care and the family remained the main social support. They remained a very disabled group with a median Health Assessment Questionnaire score of 2.75. Ten required revision surgery: three hips and seven knees; four patients required their fourth lower limb joint (hip/knee) replaced and seven patients required surgery to the upper limbs and nine feet during the follow-up period. The median 10-yr survival of hip and knee arthroplasties in multiple joint replacement (MJR) patients with RA was 90.5 and 78.6% respectively. There was an increased incidence of cervical myelopathy in MJR patients 16.9%. The mortality rate was higher than expected (standardized mortality ratio = 590) but the actual surgery was not implicated. MJR therefore appears to be a worthwhile policy, even at long-term follow-up.

Menstrual arthritis.

The menstrual cycle is characterised by variations in the absolute and relative concentrations of the hormones of the hypothalamic pituitary ovarian axis, which in turn affect cell function and cytokine and heat shock protein production. Menstruation involves the shedding of the secretory endometrium, which is part of the mucosal associated lymphoid tissue and hence is rich in immunologically competent cells such as CD8 T cells and macrophages. The case is reported here of a patient presenting with a recurrent but transient symmetrical inflammatory polyarthritis which only occurred at menstruation with no residual damage. The disease was suppressed by danazol. Endometrial degradation products are suggested as the trigger of this 'menstrual arthritis'.

Levels of CD5+ B cells are not increased in probands or relatives in a family study of primary Sjögren's syndrome.

Levels of CD5+ B lymphocytes were assayed in a large family study of Primary Sjögren's syndrome. There was no significant difference in CD5 expression by index cases or their relatives when compared to controls. No association between CD5 expression, serological abnormalities or HLA haplotype was found and, furthermore, no evidence of linkage with HLA was observed. There was, however, variation in the expression of CD5+ B cells between the families. Levels in spouses were lower and reached statistical significance. The role for genetic and environmental factors influencing CD5 expression is discussed. Any genetic influence does not appear to involve the HLA region or genes in linkage disequilibrium.

Referrals to a rheumatology unit: an evaluation of the views of patients, general practitioners, and consultants.

One hundred and twelve randomly selected patients referred to a rheumatology unit were studied, using structured questionnaires, to gain the views of patients, general practitioners (GPs), and the consultants. There were differences in perception between these respondents on the reason for referral. Major diagnostic changes were made in less than 10% of cases. Nearly all patients claimed that some aspect of their disease had been improved as a result of the appointment. Satisfaction with the communication aspects of the appointment contributed more to patients' overall satisfaction than did improvement in pain or disability. General practitioners' objectives were also met if communication with patients was satisfactory. In the management of chronic disease communication is important and should be recognised as such.