Relationship between calcinosis cutis in epidermal necrolysis and caspofungin, a physicochemical investigation

Abstract

Epidermal necrolysis (EN) is a rare life-threatening condition, usually drug-induced and characterised by a diffuse epidermal and mucosal detachment. Calcinosis cutis is reported in various skin diseases, occurring preferentially with tissue damage, but has never been described in EN. Clinical, biological and histopathological characteristics of three patients were retrospectively obtained from medical charts. Immunohistochemistry of classical osteogenic markers was used to explore the pathogenesis of the calcifications; their chemical composition was determined by μFourier transform infra-red (μFTIR) spectroscopy and their localization and morphology by field-emission scanning electron microscopy (FE-SEM). In a recent letter, part of the results of this investigation has been already presented. In this contribution, we have added original data to this previous letter. We have investigated a set of biopsies corresponding to patients who presented atypical healing retardation due to calcinosis cutis. Through FE-SEM observations at the nanometre scale, we describe different areas where are present voluminous calcifications at the surface, submicrometre spherical entities within the papillary dermis and then large “normal” fibres. FE-SEM observations show clearly that “large” calcifications are the result of an agglomeration of small spherical entities. Moreover, micrometre scale spherical entities are the results of an agglomeration of nanometer scale spherical entities. Finally, the last set of data seems to show that the starting point of the calcifications process is “distant” from the epidermis in part of the dermis which appears undamaged. Regarding the chemical composition of large calcifications, different μFTIR maps which underlined the presence of calcium-phosphate apatite have been gathered. Moreover, histopathology indicates that these pathological calcifications are not induced following a trans-differentiation of the skin cells into an osteochondrogenic phenotype. The association of caspofungin administration, known to induce in vitro intracellular calcium influx, and inflammation, induced by EN, known to favor dystrophic calcifications in various inflammatory skin diseases, could explain this never-before reported occurrence of calcinosis cutis.