pyrophosphate and Scleroderma--Systemic

The aim of this study was to provide updated information on the prevalence, pathogenesis, diagnostics and therapeutics of calcinosis cutis associated with systemic sclerosis (SSc).. Observational studies show ethnic and geographical differences in the prevalence of calcinosis. In addition to clinical and serological associations, biochemical studies and in-vivo models have attempted to explain theories behind its pathogenesis, including prolonged state of inflammation, mechanical stress, hypoxia and dysregulation in bone and phosphate metabolism. Long-term use of proton pump inhibitors may increase the risk for calcinosis in SSc. Few single-centre observational studies have shown mild benefit with minocycline and topical sodium thiosulfate.. Calcinosis cutis is the deposition of insoluble calcium in the skin and subcutaneous tissues. It affects up to 40% of SSc patients and causes significant morbidity. Long disease duration, features of vascular dysfunction and osteoporosis have been associated with calcinosis. Altered levels of inorganic pyrophosphate and fibroblast growth factor-23 have been implicated in dysregulated phosphate metabolism that may lead to calcinosis in SSc. Plain radiography can help with diagnosis and quantifying the calcinosis burden. Surgical treatment remains the most effective therapy when feasible. At present, no medical therapies have proven efficacy in large randomized controlled trials.

Topics: Calcinosis; Calcium; Diphosphates; Humans; Minocycline; Proton Pump Inhibitors; Scleroderma, Systemic

The pathogenesis of calcinosis cutis, a disabling complication of SSc, is poorly understood and effective treatments are lacking. Inorganic pyrophosphate (PPi) is a key regulator of ectopic mineralization, and its deficiency has been implicated in ectopic mineralization disorders. We therefore sought to test the hypothesis that SSc may be associated with reduced circulating PPi, which might play a pathogenic role in calcinosis cutis.. Subjects with SSc and age-matched controls without SSc were recruited from the outpatient rheumatology clinics at Rutgers and Northwestern Universities (US cohort), and from the Universities of Szeged and Debrecen (Hungarian cohort). Calcinosis cutis was confirmed by direct palpation, by imaging or both. Plasma PPi levels were determined in platelet-free plasma using ATP sulfurylase to convert PPi into ATP in the presence of excess adenosine 5' phosphosulfate.. Eighty-one patients with SSc (40 diffuse cutaneous, and 41 limited cutaneous SSc) in the US cohort and 45 patients with SSc (19 diffuse cutaneous and 26 limited cutaneous SSc) in the Hungarian cohort were enrolled. Calcinosis was frequently detected (40% of US and 46% of the Hungarian cohort). Plasma PPi levels were significantly reduced in both SSc cohorts with and without calcinosis (US: P = 0.003; Hungarian: P < 0.001).. Circulating PPi are significantly reduced in SSc patients with or without calcinosis. Reduced PPi may be important in the pathophysiology of calcinosis and contribute to tissue damage with chronic SSc. Administering PPi may be a therapeutic strategy and larger clinical studies are planned to confirm our findings.

Topics: Adult; Aged; Calcinosis; Diphosphates; Female; Humans; Male; Middle Aged; Scleroderma, Systemic

Recent advances in technology have lead to the development of a high-definition microfocal X-ray unit allowing macroradiographic examination of different parts of the body at x 5 to x 10 magnification and with a high spatial resolution. Its applications in the study of a number of arthritides, metabolic and some other bone diseases are described in terms of early detection of diagnostic features. Emphasis is placed on the advantages of direct accurate measurement of these features, providing a precise evaluation of disease progression and response to therapy.

Topics: Arthritis, Rheumatoid; Bone and Bones; Child; Diphosphates; Humans; Hyperparathyroidism; Male; Osteoarthritis; Radiation Dosage; Radiography; Scleroderma, Systemic; X-Ray Intensifying Screens

Scintigraphic examination of the myocardium, using 99mTc-labelled pyrophosphate, was carried out in 17 patients suffering from systemic sclerosis. This connective tissue disorder very often affects the myocardium secondarily. The results of the cardiac scan were compared with the information obtained from the electrocardiogram of systolic time intervals. In addition, spirometry was undertaken to detect a potential relation between cardiac and pulmonary involvement. The scan was found to be positive in seven patients and electrocardiographic findings were pathological in five patients only. The systolic time intervals were abnormal in three patients only. A ventilation disturbance was recorded in 10 patients. No clear relation was found between the results of the individual examinations. It is concluded that pyrophosphate heart scintigraphy may detect myocardial impairment in some cases of systemic sclerosis before it is manifested by heart failure. Examination of systolic time intervals is of little importance.

Topics: Adult; Aged; Diphosphates; Female; Heart; Humans; Lung; Male; Middle Aged; Radionuclide Imaging; Respiration; Scleroderma, Systemic; Systole

Topics: Adult; Aged; Cardiomyopathies; Diphosphates; Female; Humans; Lupus Erythematosus, Systemic; Middle Aged; Organotechnetium Compounds; Radionuclide Imaging; Scleroderma, Systemic; Sugar Acids; Technetium; Technetium Tc 99m Pyrophosphate