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Mineral Depositions of Calcifying Skin Disorders are Predominantly Composed of Carbonate Apatite

Michael FRANZEN 1, Elena MORÉ 1, Janne CADAMURO 2, Josef KOLLER 4, Wolfgang SALMHOFER 5, Iris WOHLMUTH-WIESER 4, Cornelia KRONBERGER 3 and Hermann SALMHOFER 1

1

Nephrology Unit, Department of Internal Medicine I, Departments of 2 Laboratory Medicine, 3 Pathology and 4 Dermatology, Paracelsus Medical University, Salzburg, and 5 Department of Dermatology, Medical University Graz, Graz, Austria

Subcutaneous calcifications can lead to complications, including pain, inflammation, ulceration and immobilization. Studies on the pathophysiology of mineral compositions and effective treatment modalities are limited. We therefore studied 14 patients with subcutaneous calcifications. Mineral material was collected and analysed by Fourier transform infrared spectrometry. Blood analyses were run to evaluate systemic alterations of mineral metabolism. Carbonate apatite( CAP) was found to be the single constituent in the majority of patients( n = 9, 64.3 %), 3 cases( 21.4 %) had a composition of CAP and calcium oxalate dihydrate and one case had a combination of CAP and magnesium ammonium phosphate, whereas CAP was the major component in all 4 cases. Only one case showed predominantly calcium oxalate. Thus, CAP was found to be the only or predominant component in most cases of subcutaneous calcifications. Chemical analyses of the mineral compositions may aid in the development of new treatment regimes to improve the solubility of mineral components and to decrease extraosseous calcifications.

Key words: subcutaneous calcifications; tumoural calcinosis; carbonate apatite.

Accepted Jun 28, 2017; Epub ahead of print Jun 29, 2017 Acta Derm Venereol 2017; 97: 1178 – 1181.

Corr: Hermann Salmhofer, Nephrology Unit, Department of Internal Medicine I, Paracelsus Medical University, Müllner Hauptstrasse 48, AT-5020 Salzburg, Austria. E-mail: h. salmhofer @ salk. at

Dystrophic calcification arises from inflammation or cell death and nucleation of mineral deposition at sites of tissue damage or alterations of collagen and elastin fibres. This may occur in various diseases, including connective tissue disease, cutaneous neoplasms, infections

Table I. Mechanisms of extraosseous calcification and related diseases

Metastatic

Dystrophic

Idiopathic

Genetic

Systemic alteration of calcium phosphate metabolism Precipitation of calcium in cutaneous and subcutaneous tissues

Inflammation / cell death or mineral deposition at sites of tissue damage or alteration of collagen and elastin fibres Serum calcium and phosphate levels are within normal ranges

No underlying tissue damage or metabolic disorder

Inherited disorders leading to skin calcification

Adapted from: Reiter et al.( 2).

• Chronic kidney disease

• Calciphylaxis

• Hyperparathyroidism

• Neoplasms

• Sarcoidosis

• Connective tissue diseases( e. g. CREST syndrome)

• Cutaneous neoplasms

• Infection

• Trauma

• Tumoural calcinosis

• Subepidermal calcified nodules

• Pseudoxanthoma elasticum

• Werner Syndrome

• Ehlers-Danlos syndrome

• Familial tumoural calcinosis

and trauma. The nature of idiopathic calcifications is unclear, since no systemic or local trigger has yet been identified( 3, 4). Additional knowledge of promoters and inhibitors of extraosseous calcification has arisen from mouse models without human counterpart( 3).

Clinically, end-stage renal disease and connective tissue disease predominate among calcifying disorders. However, the pathogenesis of some forms of cutaneous or subcutaneous calcinoses remains unclear.

In biological systems, a variety of calcium phosphate compounds may be found: carbonate apatite( CAP), amorphous calcium phosphate, calcium pyrophosphate, Whitlockite, di-calcium phosphate dihydrate and octacalcium phosphate( 5). Changes in pH or solution composition may induce transformation of calcium phosphate phases; formation and transformation may further be influenced by organic or inorganic moieties( 5).

To date, only a few reports on the pathogenesis and mineral composition of various extraosseous calcifications have been published, including the discovery of CAP depositions in calcific periarthritis, uraemic tumoural calcinosis, idiopathic inflammatory myopathies, calcified mitral valves, calcified calculi of hydrocele, in atherosclerosis, as well as in the cervical spine of a patient with CREST( calcinosis, Raynaud’ s phenomenon, oesophageal dysmotility, sclerodactyly, and telangiectasia) syndrome( 5 – 14).

In order to determine the composition of calcium precipitations in a variety of calcifying skin diseases, doi: 10.2340 / 00015555-2739 Acta Derm Venereol 2017; 97: 1178 – 1181

This is an open access article under the CC BY-NC license. www. medicaljournals. se / acta Journal Compilation © 2017 Acta Dermato-Venereologica.