The impact of COVID-19 on rheumatology patients in a large UK centre using an innovative data collection technique: prevalence and effect of social shielding.

OBJECTIVES: We sought to gain insight into the prevalence of COVID-19 and the impact stringent social distancing (shielding) has had on a large cohort of rheumatology (RD) follow-up patients from a single large UK centre. METHODS: We linked COVID-19-related deaths, screening and infection rates to our RD population (1.2.20-1.5.20) and audited active rheumatology follow-up patients through survey data communicated via a linked mobile phone SMS message. We assessed epidemiology, effect of stringent social distancing (shielding) and quality of life (HRQoL) by Short Form 12 (SF12). RESULTS: There were 10,387 active follow-up patients, 7911 had linked mobile numbers. 12/10,387 RD patients died from COVID-19 (0.12%); local population 4131/7,415,149 (0.12%). For patients with mobile phones, 1693/7911 (21%) responded and of these, 1605 completed the SF12. Inflammatory arthritis predominated 1174/1693 (69%); 792/1693 (47%) were shielding. Advice on shielding/distancing was followed by 1372/1693(81%). 61/1693 (4%) reported COVID-19 (24/61 shielding); medication distribution was similar in COVID and non-COVID patients. Mental SF12 (MCS) but not physical (PCS) component scores were lower in COVID (60) vs. non-COVID (1545), mean differences: MCS, - 3.3; 95% CI - 5.2 to - 1.4, P < 0.001; PCS, - 0.4; 95% CI, - 2.1 to 1.3). In 1545 COVID-negative patients, those shielding had lower MCS (- 2.1; 95% CI - 2.8 to - 1.4) and PCS (- 3.1, 95% CI - 3.7 to - 2.5), both P < 0.001. CONCLUSIONS: Our full RD cohort had no excess of COVID deaths compared to the general local population. Our survey data suggest that shielding adversely affects both mental and physical health in RD. These data broaden our understanding of shielding, indicating need for further study.

Measurement of natural killer cell cytotoxicity by area under a cytotoxic curve. A method suitable for rheumatoid arthritis.

Calculation of the area under a curve derived from a 51Cr cellular release assay gives a reproducible expression of cellular cytotoxicity and correlates well with results at fixed lymphocyte-to-target cell ratios and with lytic units at 20% and 30% cytotoxicity. This method is suitable for quantifying the low cytotoxicity seen in rheumatoid arthritis. The area under the cellular cytotoxic curve may be calculated using a simple mathematical formula or by computer analysis.

Rheumatoid arthritis and chronic lymphatic leukaemia.

There is evidence for an increased incidence of lymphoproliferative disorders in patients with rheumatoid arthritis (RA). We present the clinical features of 4 patients with RA and chronic lymphatic leukaemia (CLL) which, occurring in a population of 1505 RA patients, represents a significantly increased prevalence of CLL (p less than 0.05) compared to the general population. These patients had significantly lower natural killer cell activity than matched rheumatoid controls (p less than 0.05) or normal controls (p less than 0.01) and we discuss this as a possible mechanism of association.

The effect of bed rest and intra-articular steroids on the acute phase response in rheumatoid arthritis.

The impact of therapeutic interventions on the disease process in patients with rheumatoid arthritis (RA) is complex. The effect on the acute phase response was studied in 25 in-patients on imposed bed rest, who were randomised to treatment with (n = 12) or without (n = 13) intra-articular steroids. C-reactive protein (CRP), ESR and IgA alpha-1 antitrypsin complex levels were measured on admission and on days 3 and 5. Levels at onset were not different between groups. At day 3 and day 5, a significant (p < 0.001) fall in CRP was seen only in the intra-articular steroid group. Other cytokine and disease parameter measures did not alter during the study period (although IL-6 and CRP correlated at onset in all 25 patients). The mean duration of the hospital stay was longer for the patients treated with bed rest only. Thus, bed rest when combined with intra-articular steroids produced a rapid systemic effect, while bed-rest alone did not have an effect on the acute phase response over this short time scale.

Improving the response to gold or D-penicillamine by addition of sulphasalazine. A pilot study in 25 patients with rheumatoid arthritis.

In a 6-month open pilot study 25 patients with Rheumatoid Arthritis (RA) whose disease was refractory to Gold or D-Penicillamine (DPA) were given Sulphasalazine (SAS) in addition. Three patients withdrew because of nausea. Twenty-two patients who completed therapy showed significant improvement in clinical and laboratory measures of disease activity.

von Willebrand factor: increased levels are related to poor prognosis in systemic sclerosis and not to tissue autoantibodies.

von Willebrand factor, C-reactive protein, rheumatoid factor, major organ involvement, antibodies to extractable nuclear antigen, anti-cardiolipin antibodies, anti-centromere antibodies and anti-nuclear antibodies were measured in 33 patients with systemic sclerosis. After five years, the nine patients who had died had initial levels of von Willebrand factor significantly higher (median 288 IU/dL, range 150-1170) than levels in the 24 who were still alive (median 148 IU/dL, range 65-262, Mann Whitney P = 0.0002). Increased levels of von Willebrand factor correlated with the time interval from blood sampling until the patient's death (Spearman's r = 0.73, P = 0.02). Levels of C-reactive protein, rheumatoid factor, and tissue autoantibodies, and age or the number of organs involved were unable to predict this outcome. We suggest that endothelial perturbation, as indicated by increased levels of von Willebrand factor, is a strong indicator of a poor prognosis in systemic sclerosis.

Chest pain--a common feature of ankylosing spondylitis.

We compared the incidence, nature and frequency of chest pain in a group of 45 ankylosing spondylitis patients with an age and sex matched group of normals. Twenty-five ankylosing spondylitis patients had experienced recurrent chest pain compared to three normals, and had a significantly reduced chest expansion. The presence of chest pain in ankylosing spondylitis can be an early presenting feature of the disease (eight patients had chest pain before spinal symptoms), and is associated with more severe disease.

Venostasis, subclinical vasculitis and von Willebrand factor antigen.

Von Willebrand factor antigen (VW FAg) has been used as a marker for vasculitis and raised levels have been shown to correlate with active disease. The use of VW FAg levels in the diagnosis of vasculitic disorders has been proposed. However, certain cases of vasculitis have normal VW FAg levels and are difficult to diagnose; this is of importance because of the high mortality associated with these disorders. It has been suggested that venostatic stress can be used as a provocative test for stimulating VW FAg release, thereby improving the speed and sensitivity of diagnosis. We tested this hypothesis in a mixed group of 35 patients with vasculitis, systemic lupus erythematosus and rheumatoid arthritis and 16 controls. At baseline, although the levels were not outside the laboratory range, the disease groups had raised VW FAg compared with the simultaneously tested controls. Venostatic stress increased VW FAg activity in all disease groups, control levels also increased and differences between controls and disease groups diminished in significance. Therefore venostatic stress with VW FAg measurement does not produce a more sensitive test for vasculitis. Venostasis should be avoided when measuring VW FAg levels.

Identification of risk factors for future fracture in patients following distal forearm fracture.

The challenge for healthcare systems around the world is delivering timely preventative strategies to subjects most likely to develop fragility fractures. The success or failure of national campaigns will be determined at local level, and many studies to date have found under-utilization of osteoporosis treatment strategies due to reduced public and healthcare professional awareness. An important link between the at-risk patients and their appropriate therapy is their identification and assessment. In the context of a medium sized secondary care provider, this study examined the efficiency of a nurse-led service for assessing women following distal forearm fracture, looking for additional risk factors for future fracture and also looking at uptake of the assessment programme among the target population. Two hundred and two women, median (range) age 69 (50-91) years presented with distal forearm fracture over a 9-month period. Fifty-four subjects did not participate in the study: they were significantly older than those who did ( P<0.002). One hundred and forty-eight subjects underwent assessment of falls risk, future hip fracture risk and calcaneal ultrasound attenuation measurement: 107 attended for assessment at the hospital and 41 required a health professional to visit at their place of residence-the latter group were significantly older ( P<0.0002). Of 148 subjects assessed, 76 (51%) had one or more risk factors for a fall: these subjects were significantly older ( P<0.0002) and more likely to have required a home visit ( P<0.002). Twenty-seven (18%) were considered at risk of a future hip fracture: again they were older and more likely to have required a home visit ( P<0.0005). Ninety-one subjects (61%) had a calcaneal ultrasound attenuation T-score below -2.0, and were referred for bone densitometry: again, they were older ( P<0.0002) and more likely to have required a home visit ( P<0.05). Bone densitometry demonstrated osteoporosis in 47 (52%) of those with low attenuation, osteopenia in 31 and normal bone density in 13. Of 76 subjects deemed to be at risk of falls, 31 (41%) had osteoporosis demonstrated on bone densitometry and of those at risk of future hip fracture, 12 (44%) had osteoporosis. Only nine (22%) subjects who received home visits had no risk factors for falls or hip fracture and normal bone density, compared to 45 (42%) of those who attended hospital. This study has demonstrated that the efficiency of a program to assess additional risk of future fracture in a population who have already fractured may be influenced by where the assessment is delivered: it may be that the patients at greatest risk did not avail of the service.

Sjögren's syndrome in women presenting with chronic dyspareunia.

OBJECTIVE: To identify cases of Sjögren's syndrome among women with chronic dyspareunia who did not already have a diagnosed rheumatological disorder. DESIGN: Prospective recruitment over 12 months. SETTING: Tertiary referral service for the assessment of vulval disease. PARTICIPANTS: Women with chronic dyspareunia who had musculoskeletal symptoms, Raynaud's phenomenon or symptoms of ocular or oral dryness. METHODS: The women underwent a Schirmer tear test and a comprehensive auto-antibody screen including latex fixation test for rheumatoid factor, antinuclear, anti-Ro, anti-La and anti-salivary duct antibodies. A labial salivary gland biopsy and vaginal biopsy were taken for routine histological analysis. MAIN OUTCOME MEASURES: Cases of definite and probable Sjögren's syndrome were identified using the European criteria. RESULTS: Eleven women were assessed for features of Sjögren's syndrome. Four had definite primary Sjögren's syndrome, two had probable primary Sjögren's syndrome and one had probable secondary Sjögren's syndrome. Among these seven women the median duration of vaginal symptoms was seven years (range 0.25-20), of ocular symptoms was one year (range 0.25-2) and of oral symptoms was 1.5 years (range 0-6). In all but one woman dyspareunia presented before ocular or oral symptoms, often by many years. CONCLUSIONS: Although well-recognised as a feature of established Sjögren's syndrome, this study emphasises that chronic dyspareunia can be a presenting feature in these women, antedating the emergence of ocular or oral symptoms by many years. Symptoms of ocular or oral dryness, Raynaud's phenomenon or musculoskeletal symptoms should be sought in women with chronic dyspareunia to identify those who merit further investigation.

Comparison and evaluation of a disease activity index for use in patients with rheumatoid arthritis.

An algorithm (Stoke index) has been designed to give a global measure of disease activity in rheumatoid arthritis. This algorithm has been created as an easy to use flow diagram based on two objective laboratory measures (C-reactive protein and erythrocyte sedimentation rate), one subjective and two semi-objective clinical measures (morning stiffness, synovitis score and Ritchie articular index). Results of six clinical markers and seven laboratory markers of disease activity on a cohort of 371 rheumatoid patients have been used to evaluate the algorithm and compare it with a previously described index of disease activity (Mallya-Mace index). Principal component analysis validates its ability to measure disease activity. Sensitivity is described by the distribution of patients between the two index scores. Change in index score by patients over a 6-month period indicates reversibility. The Stoke index demonstrates greater sensitivity and reversibility than the Mallya-Mace index. These findings indicate that the algorithm described provides a useful index of global disease activity for use in the assessment of rheumatoid arthritis.