Malignancy in scleroderma patients from south west England: a population-based cohort study.

The pathophysiological relationship between scleroderma and malignancy remains poorly understood. Although some previous studies have demonstrated an increased malignancy risk in patients with scleroderma, others have been inconclusive. We aimed to determine if patients with scleroderma had an increased risk of malignancy compared to an age- and sex-matched local South West England population, and if there were any important differences between scleroderma patients with and without malignancy. Methods of this study are as follows. Notes were obtained on all local scleroderma patients (n = 68) locally, and those diagnosed with malignancy verified by contacting each patient's general practitioner. Expected malignancy figures were obtained from age- and sex-stratified regional prevalence data provided by the South West Cancer Intelligence Service registry. Among the patients, 22.1% with scleroderma were identified with concurrent malignancy. Affected sites were of the breast (n = 5), haematological system (n = 5), skin (n = 4), and unknown primary (n = 1). Overall, malignancy risk was found to be increased in scleroderma (RR = 3.15, 95% CI 1.77-5.20, p = 0.01). In particular, this risk was the highest for haematological malignancies (RR = 18.5, 95% CI 6-43, p = 0.03), especially for non-Hodgkin's lymphoma (RR = 25.8, 95% CI 5-75, p = 0.10). The majority of patients (86.7%) developed malignancy after the onset of scleroderma (mean = 6.9 years). Age of >70 and patients with limited scleroderma were significant risk factors for a patient with scleroderma to have a concurrent malignancy; however, no increased risk was found in patients with any particular pattern of organ involvement, cytotoxic usage or serology. To conclude, in this small patient cohort, we have found that scleroderma is associated with an increased risk of malignancy. This risk is statistically significant in patients with limited scleroderma. Patients who are elderly and those with limited disease should be closely scrutinized at follow-up appointments.

Is there still a role for computerized strain gauge plethysmography in the assessment of patients with suspected deep vein thrombosis?

INTRODUCTION: Although deep vein thromboses (DVTs) are common, only a minority of patients referred with suspected DVT will have the condition. Various strategies exist to allow rapid and safe discharge of low-risk patients, thus precluding the need for imaging. AIMS AND OBJECTIVES: We aimed to investigate the accuracy of clinical risk assessment, D-Dimer analysis, computerized strain gauge plethysmography (CSGP) or a combination of the above in the assessment of outpatients with suspected DVT. METHODS: We performed a prospective cohort study on outpatients referred with suspected DVT to our medical assessment unit. Patients systematically underwent clinical risk assessment, D-Dimer analysis, CSGP and imaging with ultrasonography and/or venography. RESULTS: One hundred and eighty patients with suspected DVT were included in the analysis. Using a threshold of 0.6 mg/l, D-Dimer had a sensitivity and negative predictive value (NPV) of 100% for detecting DVT. Incorporating D-Dimer analysis with clinical risk assessment increased the specificity of the test. The sensitivity and NPV of CSGP were poor at 52.8 and 86.7%, respectively. Incorporating CSGP with D-Dimer did not influence decision making. Although the sensitivity of CSGP was higher for above knee (73.7%) than below knee DVT (29.4%), neither was sufficient for use as a screening tool. CONCLUSION: Our study did not support the role of CSGP either as a stand-alone screening tool or in conjunction with clinical risk scoring. As the evidence base for CSGP is conflicting, its accuracy should first be assessed before being incorporated into hospital algorithms as a DVT exclusion tool. However, our results support the current practice for D-Dimer use either alone or in conjunction with clinical assessment tool in the assessment of lower limb DVT.

Prevention of vascular damage in scleroderma and autoimmune Raynaud's phenomenon: a multicenter, randomized, double-blind, placebo-controlled trial of the angiotensin-converting enzyme inhibitor quinapril.

OBJECTIVE: To evaluate the efficacy and tolerability of prolonged administration of quinapril, a long-acting angiotensin-converting enzyme inhibitor, in the management of the peripheral vascular manifestations of limited cutaneous systemic sclerosis (lcSSc) and in the prevention of the progression of visceral organ involvement in the disease. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled study evaluating quinapril 80 mg/day, or the maximum tolerated dosage, in 210 patients with lcSSc or with Raynaud's phenomenon (RP) and the presence of SSc-specific antinuclear antibodies. Treatment was for 2-3 years. The primary outcome measure was the number of new ischemic ulcers appearing on the hands; secondary measures were the frequency and severity of RP attacks, skin score, treatments for ischemia, health status (measured by the Short Form 36 instrument), measures of kidney and lung function, and echocardiographic estimates of pulmonary artery pressure. An intent-to-treat analysis was used. RESULTS: Quinapril did not affect the occurrence of digital ulcers or the frequency or severity of RP episodes. It did not alter the treatments that were prescribed for either infected ulcers or severe RP symptoms. There was no apparent effect on the estimated tricuspid gradient. Health status was not affected by quinapril, and one-half of the patients who believed they had benefited from the trial treatment were in the placebo arm. Quinapril was not tolerated by one-fifth of the patients, with dry cough being the most frequent side effect. CONCLUSION: Administration of quinapril for up to 3 years had no demonstrable effects on the occurrence of upper limb digital ulcers or on other vascular manifestations of lcSSc in this patient population.

Reduction in heart rate variability in patients with systemic lupus erythematosus.

OBJECTIVE: To determine whether heart rate variability and cardiovascular reflex tests are abnormal in patients with systemic lupus erythematosus (SLE). METHODS: We measured heart rate variability (24 h ambulatory recordings), and used baroreflex sensitivity testing and cardiovascular reflex tests in a cross sectional, case-control study. Those taking drugs with cardiovascular activity were excluded. RESULTS: Determination of heart rate variability was simple to perform, well tolerated, and found to be reduced in the patients with lupus, but not strongly related to disease activity or duration. CONCLUSION: This may reflect underlying autonomic dysfunction; longitudinal studies will determine full clinical relevance.

Neridronate preferentially suppresses the urinary excretion of peptide-bound deoxypyridinoline in postmenopausal women.

ELISAs for measuring the urinary excretion of collagen crosslinks and related peptides appear to show marked differences in sensitivity to anti-resorptive therapy. This presumably reflects variations in specificity of the anylate being detected in these assays, and the way in which they respond to treatment. To clarify these points, we used HPLC analysis to assess the effect of four weeks treatment with the amino-bisphosphonate, neridronate, on free and peptide-bound fractions of the collagen cross-links deoxypyridinoline (Dpd) and pyridinoline (Pyd). Six postmenopausal women, in whom two hour morning urine samples were obtained at baseline (x2), and one, two and four weeks after commencing treatment, were included. We found that neridronate had relatively little effect on peptide-bound or free urinary Pyd. but markedly reduced peptide-bound urinary Dpd. However, urinary excretion of free Dpd was not significantly affected. As a consequence of these differential effects on collagen cross-link excretion, neridronate led to a striking increase in the free/total Dpd ratio, and in the peptide-bound Pyd/Dpd ratio. We conclude that neridronate, and presumably other bisphosphonates, selectively suppresses peptide-bound Dpd excretion, possibly reflecting altered processing of collagen crosslinks released during bone resorption.

Aminohexane bisphosphonate suppresses bone turnover in postmenopausal women more rapidly than oestrogen-gestagen therapy.

Although animal studies suggest that there may be major differences between the effects of bisphosphonates and ovarian hormones on skeletal metabolism, whether this also holds for their actions in patients is unknown. To address this question, we compared the effects of 12 weeks treatment with HRT on bone turnover markers in osteopenic postmenopausal women with those of an amino-bisphosphonate. Women within 15 yr of the menopause, with a lumbar and/or femoral neck bone mineral density 1 S.D. below the predicted value, received either oestradiol valerate 2 mg and dydrogesterone 5 mg (E/D; n = 16) or aminohexane bisphosphonate 400 mg (AHBP; n = 9). Urine and serum samples were collected on two separate occasions before starting treatment, and 1, 2, 4, 8 and 12 weeks afterwards. To assess bone resorption, we measured the urinary deoxypyridinoline/creatinine ratio (DPD/crea), while serum alkaline phosphatase (ALP), osteocalcin and C-terminal propeptide of type I collagen (CICP) were analysed to assess bone formation. Repeated measures analysis of variance revealed a highly significant decrease in DPD/crea over the treatment period. Furthermore, this pattern of response differed significantly between the two treatment groups, since DPD/crea was maximally suppressed within 2 weeks of starting AHBP, while E/D showed little decrease until 8 weeks. AHBP was also found to suppress ALP, osteocalcin and CICP more rapidly than E/D, the former reducing these markers by 8 weeks, while E/D caused little inhibition even by 12 weeks. We conclude that, in the doses used in this study, AHBP appears to suppress bone turnover significantly more rapidly than E/D, suggesting that clinically important differences may exist in the effects of bisphosphonates and ovarian hormones on bone metabolism.

Development of a 'Charcot-like joint' in tophaceous gout.

We report an unusually severe case of ulcerating tophaceous gout in which inflammation due to gout, infection and excessive alcohol intake resulted in complete destruction of an ankle joint.

Cerebral venous thrombosis and acquired protein S deficiency: an uncommon cause of headache in systemic lupus erythematosus.

A 42-yr-old woman with hypertension and renal involvement due to systemic lupus erythematosus (SLE) developed unilateral headache followed by the sudden onset of confusion and a grand mal convulsion. Cerebral computed tomography was normal. A magnetic resonance imaging angiogram revealed cerebral venous thrombosis and a venous infarct. Nephrotic syndrome had resulted in an acquired protein S deficiency. A review of previous cases suggests that either renal disease with proteinuria or features of the antiphospholipid syndrome are prerequisites for the development of cerebral venous thrombosis in SLE. Low free-protein S levels may be an additional risk factor. Furthermore it is likely that this condition is underdiagnosed.

Sulphasalazine-induced autoimmune abnormalities in patients with rheumatic disease.

Sulphasalazine is a commonly used second line agent in rheumatoid arthritis (RA) and other inflammatory joint diseases and is reported to be one of the least toxic of this group of drugs. Recently a severe allergic reaction and cases of lupus-like disease have been described in patients with RA after treatment with sulphasalazine. We describe five patients, all with inflammatory arthropathy who developed cutaneous vasculitis, lupus-like disease or atypical serology after exposure to sulphasalazine. Three of four cases investigated were found to have the slow acetylator phenotype. These reactions can complicate the diagnosis and delay discontinuation of the drug. Moreover, present guidelines for the diagnosis of drug-induced lupus do not apply to the majority of patients with sulphasalazine-induced lupus.