Article Figures & Data
Figures
- Figure 1.
Calcinosis cutis in the soft tissue at the tip of the finger.
- Figure 2.
Liquified calcinosis draining from the soft tissue proximal to the fingernail.
Tables
Type of Calcification Pathogenesis Serum Calcium and/or Phosphorus Levels Associated Diseases Clinical Presentation Dystrophic calcification Secondary to tissue damage Normal Systemic sclerosis
Dermatomyositis
Lupus erythematosus
Lupus panniculitisPresent as nodules, plaques, extensive small dermal, or large subcutaneous deposits Metastatic calcification Calcium precipitation in the skin Abnormal Chronic kidney failure
Hyperparathyroidism
Hypervitaminosis D sarcoidosisSeen occasionally in the subcutaneous tissue as hard nodules located mainly in the vicinity of large joints Idiopathic calcification Unknown; no previous damage to skin or metabolic disturbances Normal Tumoral calcinosis
Calcified subepidermal nodules (Winer’s nodular calcinosis)
Scrotal calcinosisMultiple, asymptomatic nodules, which begin to appear in childhood or in early adult life Tumoral calcification In patients with an elevated serum phosphorus level but normal calcium level Presents as large subcutaneous calcium deposits near joints and pressure areas Calciphylaxis Calcification of the small vessel walls in the dermis and subcutaneous tissue, with subsequent ischemia Abnormalities can be observed Chronic kidney failure
Other nonuremic causesSubcutaneous nodules of infarction and necrotizing skin ulcers Mechanism Evidence Chronic inflammation Increased production of TNF, IL-1, IL-6, and other proinflammatory cytokines Vascular hypoxia (ischemia) Hypoxia-induced imbalance between angiogenic factors (such as VEGF, platelet-derived growth factors) and antiangiogenic factors (such as angiostatin, endostatin)
Increased expression of the hypoxia-associated GLUT-1
Hypoxia-induced osteoclast activityRecurrent trauma Presence or history of digital ulcers
Calcification occurs at sites of chronic trauma/stress, suggesting a role of pressure or recurrent traumaGLUT-1: glucose transporter 1; IL: interleukin; TNF: tumor necrosis factor; VEGF: vascular endothelial growth factor.
Treatment Dosage Study Design Partial Response, n (%) Complete Response, n (%) First Author, Year No. of Patients (Diseases) Outcomes Warfarin 1 mg/d RCT 0 (0) 0 (0) Berger, 198749,a 8 (4 placebo; 4 DM, SSc) No regression of calcinosis 1 mg/d R 0 (0) 0 (0) Lassoued, 198850 6 (DM, SSc) Worsening of calcinosis, 1 stable 1 mg/d R 0 (0) 2 (66) Cukierman, 200451 3 (SSc) 2 complete regressions of calcinosis NA R 1 (25) 0 (0) Balin, 201244 4 (SSc, DM) 1 partial response in calcinosis NA R 0 (0) 0 (0) Fredi, 201545 2 (DM) No response in calcinotic lesion Diltiazem 60 mg tid R 3 (25) 0 (0) Vayssairat, 19988 12 (SSc) 3 radiographic improvement < 480 mg/d R 9 (53) 0 (0) Balin, 201244 17 (SSc, DM) 10 cutaneous lesion improvement NA R 0 (0) 0 (0) Fredi, 201545 12 (DM) No response in calcinotic lesion 240-480 mg/d CS 2 (50) 2 (50) Palmieri, 199542 4 (CTD) Regression of calcific lesion 120 mg bid CR NA 1 (100) Dolan, 199543 1 (SSc) Remission of calcinosis 240 mg/d CR 1 (100) NA Farah, 199041 1 (SSc) Regression of calcinotic lesion Rituximab 0.575-1 g/m2 wk 0/1 RCT NA 1 (14) Aggarwal, 201756,b 76 (DM), 48 (JDM) No improvement in calcinosis 500 mg/m2 wk 0/2 P 0 (0) 3 (100) Moazedi-Fuerst, 201552 3 (SSc) Regression of calcinotic lesion 500mg/m2 wk 0/2 P 4 (36) NA Narváez, 201453 9 (SSc) Reduction in calcinotic lesion 375 mg/m2/wk × 4 P 3 (50) NA Giuggioli, 201554 10 (SSc) Improvement in calcinosis in 3/6 patients 2 × 500 mg/m2 P 0 (0) 0 (0) Bader-Meunier, 201155 6 (JDM) No calcinosis improvement in 6 patients 375 mg/m2 × 4 CR NA 1 (100) Daoussis, 201257 1 (SSc) Calcinosis significantly improved and pain resolved Bisphosphonate NA R 1 (20) 0 (0) Balin, 201244 5 (DM, SSc) 1 partial response, 3 had no response IV 1 mg/kg/d R 2 (66) 1 (33) Marco Puche, 201062 3 (JDM) Reduction and remission of calcinosis IV 1 mg/kg/d R 2 (33) 2 (33) Tayfur, 201561 6 ( JDM) Resolution of calcinosis in 4/6 patients 10 mg/kg/d CR 1 (100) NA Rabens, 197564 1 (SSc) Partial regression of calcinosis 10 mg/d CR 1 (100) NA Masza Mukamel, 200163 2 (JDM) Complete resolution of calcified lesions Initial dose 10 mg/kg/d, then 20 mg/kg/d CR 0 (0) 0 (0) Metzger, 197465 6 (SSc, DM) Progression of calcinosis Surgical excision NA R 3 (27) 8 (73) Balin, 201244 11 (DM, SSc) Complete response in 8/11 patients Extracorporeal shock wave lithotripsy NA P 4 (100) 0 (0) Blumhardt, 201691 4 (SSc) Reduction of calcinosis NA P 1 (33) 0 (0) Sultan-Bichat, 201290 4 (venous insufficiency), 1 (DM), 3 (SSc) Reduction of calcinotic lesion Carbon dioxide laser P P 5 (83) NA Bottomley, 199689 6 (SSc) Pain reduction Iontophoresis of acetic acid Iontophoresis with 2-5% acetic acid at 10 microA for 20 minsc P 0 (0) 0 (0) Shetty, 200577 3 (SSc) Reduction in the intensity of calcinosis in imaging, but no clinical benefits Surgical excision (microdrilling) NA P 12 (80) NA Fahmy, 199888 15 (SSc) Improvement of calcinosis in 12/15 digits ↵aIn Berger et al,49 4 patients received placebo, 3 received low-dose warfarin, and 1 was excluded for noncomplianace. The outcome was extent of calcinosis based on clinical and radiographic examination.
↵bIn Aggarwal et al,56 the primary endpoint was the cutaneous lesions (skin rashes) and not the calcinosis.
↵cIontophoresis was followed by ultrasound at 1.5 W/cm2 for 8 min occurring 9 times over a 3-week period. Bid: twice daily; CR: case report; CS: case series; CTD: connective tissue diseases; DM: dermatomyositis; IV: intravenous; JDM: juvenile dermatomyositis; NA: not applicable; P: prospective case series; PCT: placebo-controlled trial; R: retrospective case series; RCT: randomized controlled trial; SSc: systemic sclerosis; tid: three times daily.
Treatment Rationale Warfarin Warfarin antagonizes vitamin K and therefore reduces the levels of MGP by preventing carboxylation of glutamic acid Diltiazem Decrease in the influx of calcium ions into cells leading to correction of an abnormal imbalance of intracellular calcium concentration that may lead to crystal formation Rituximab Anti-CD20 antibody that depletes B lymphocytes Bisphosphonates Inhibit macrophage proinflammatory cytokine production and reduce calcium turnover Sodium thiosulfate Potent antioxidant and vasodilator that also chelates and dissolves calcium deposits IVIG Through decreasing inflammation, possibly through inhibition of macrophage function Minocycline Tetracycline antibiotic with antiinflammatory and calcium-binding properties Colchicine Antiinflammatory effect by disrupting leukocyte chemotaxis and phagocytosis through inhibiting microtubule polymerization IVIG: intravenous Ig; MGP: matrix gamma-carboxyglutamic acid protein.
