Calcinosis is associated with digital ulcers and osteoporosis in patients with systemic sclerosis: A Scleroderma Clinical Trials Consortium study
Introduction
Calcinosis is a rare disorder characterized by deposition of calcium in skin and subcutaneous tissues [1]. It is associated with connective tissue diseases including systemic sclerosis (SSc) and dermatomyositis (DM). Two general mechanisms of calcification in soft tissues have been described: (1) metastatic calcification, where the deposition of calcium occurs in normal cutaneous or subcutaneous tissue in the presence of elevated levels of serum calcium and/or phosphate, and (2) dystrophic calcification—the most common presentation of calcinosis occurring in association with SSc—where the deposition of calcified material happens in diseased tissues, and associated with normal serum calcium and phosphate levels [2]. Calcinosis is often painful and may be associated with recurrent episodes of local inflammation or infection, leading to considerable functional impairment [3].
Calcinosis in patients with SSc is a late manifestation, most often occurring more than 7.5 years after the diagnosis [1]. It typically involves the hands and feet, particularly the fingers [4]. Calcinosis in SSc has been associated with male gender [5], digital ulcers [5], [6], [7], digital tip pitting scars [6], acro-osteolysis [8], late nailfold videocapillaroscopy pattern [7], anticentromere antibody (ACA) [9], and anti-PM/Scl antibody [10].These findings are primarily derived from small single-center studies, and the effects of confounding variables were not taken into account.
We previously found an overall frequency of calcinosis of 22% in a multicenter international cohort of 7056 SSc patients (data unpublished). Given that calcinosis is a frequent, debilitating complication of SSc with no effective therapies, we sought to identify clinical associations of calcinosis that may shed light on the underlying pathogenesis, and provide novel therapeutic targets.
Section snippets
Study design
This is a retrospective multicenter cohort study of 5218 patients with SSc from 9 cohorts within the United States (Stanford University, University of Pittsburgh, Northwestern University, and Rutgers-RWJMS), Australia, Canada, United Kingdom, Italy, and Mexico. We collected information on demographics, clinical findings, internal organ involvement, co-morbid diseases (osteoporosis, renal disease), and serum autoantibodies. We defined diffuse cutaneous SSc as skin thickness proximal to elbows
Patient characteristics and calcinosis
Of 5218 patients with SSc, 4428 (84.9%) were female, and racial distribution was 81.7% Caucasian, 6.1% Hispanic, 2.6% Asian, and 0.9% African-American. Overall, 61.4% had limited cutaneous SSc, and 38.4% had diffuse cutaneous SSc. Mean age at last visit was 57.4 ± 13.3 years, and mean disease duration from first non-Raynaud phenomenon (RP) symptom was 9.4 ± 9.7 years.
A total of 1290 patients (24.7%) had calcinosis. Patients with calcinosis were older than patients without calcinosis, more
Discussion
Calcinosis is a common manifestation in patients with SSc, and has a substantial impact on quality of life. Our large database was able to confirm with high statistical certainty prior studies showing an association between calcinosis and digital ulcers, as well as other ischemic manifestations of SSc, including digital tip pitting scars, loss of digital pulp, nailfold capillary changes, and acro-osteolysis. One study of 103 patients with SSc found that a history of digital ulcers was a
Acknowledgments
Investigators of the Canadian Scleroderma Research Group: J. Pope, London, Ontario; M. Baron, Montreal, Quebec; J. Markland, Saskatoon, Saskatchewan; D. Robinson, Winnipeg, Manitoba; N. Jones, Edmonton, Alberta; N. Khalidi, Hamilton, Ontario; P. Docherty, Moncton, New Brunswick; E. Kaminska, Calgary, Alberta; A. Masetto, Sherbrooke, Quebec; E. Sutton, Halifax, Nova Scotia; J-P. Mathieu, Montreal, Quebec; M. Hudson, Montreal, Quebec; S. Ligier, Montreal, Quebec; T. Grodzicky, Montreal, Quebec;
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