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

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 $\mu$Fourier transform infra-red ($\mu$FTIR) 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 $\mu$FTIR 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

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

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 $\mu$Fourier transform infra-red ($\mu$FTIR) 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 $\mu$FTIR 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

French referral center management of Stevens–Johnson syndrome/toxic epidermal necrolysis

Drug-induced adverse reactions represent major health problems, with the skin being one of the most common targets. Approximately 2% of all drug-induced skin reactions are considered serious. Stevens–Johnson syndrome/toxic epidermal necrolysis corresponds to rare and acute life-threatening mucocutaneous reactions characterized by extensive necrosis and epidermal detachment. This review focuses on the management of these severe cutaneous reactions in the French Referral Center for Toxic Bullous Diseases. Early referral to a specialized unit, early diagnosis of severe cutaneous adverse reactions, prompt withdrawal of the culprit drug, improved symptomatic management, and specific dermatological care have contributed to better survival in the past 10 years and also has limited sequelae

Primary Cutaneous Follicle Center Lymphomas Expressing BCL2 Protein Frequently Harbor BCL2 Gene Break and May Present 1p36 Deletion

International audienceThe classification of cutaneous follicular lymphoma (CFL) into primary cutaneous follicle center lymphoma (PCFCL) or secondary cutaneous follicular lymphoma (SCFL) is challenging. SCFL is suspected when tumor cells express BCL2 protein, reflecting a BCL2 translocation. However, BCL2 expression is difficult to assess in CFLs because of numerous BCL2+ reactive T cells. To investigate these issues and to further characterize PCFCL, we studied a series of 25 CFLs without any extracutaneous disease at diagnosis, selected on the basis of BCL2 protein expression using 2 BCL2 antibodies (clones 124 and E17) and BOB1/BCL2 double immunostaining. All cases were studied using interphase fluorescence in situ hybridization with BCL2, BCL6, IGH, IGK, IGL breakapart, IGH-BCL2 fusion, and 1p36/1q25 dual-color probes. Nineteen CFLs were BCL2 positive, and 6 were negative. After a medium follow-up of 24 (6 to 96) months, 5 cases were reclassified as SCFL and were excluded from a part of our analyses. Among BCL2+ PCFCLs, 60% (9/15) demonstrated a BCL2 break. BCL2-break-positive cases had a tendency to occur in the head and neck and showed the classical phenotype of nodal follicular lymphoma (CD10+, BCL6+, BCL2+, STMN+) compared with BCL2-break-negative PCFCLs. Del 1p36 was observed in 1 PCFCL. No significant clinical differences were observed between BCL2+ or BCL2- PCFCL. In conclusion, we show that a subset of PCFCLs harbor similar genetic alterations, as observed in nodal follicular lymphomas, including BCL2 breaks and 1p36 deletion. As BCL2 protein expression is usually associated with the presence of a BCL2 translocation, fluorescence in situ hybridization should be performed to confirm this hypothesis

Clinical and histological features of fixed drug eruption: a single-centre series of 73 cases with comparison between bullous and non-bullous forms

International audienc

Patch tests in nonimmediate cutaneous adverse drug reactions: The importance of late readings on day 4

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Clinical relevance of interdental papilla biopsy in chronic erosive gingivitis (desquamative gingivitis): retrospective bicentric study of 148 specimens

International audienceBackground: Chronic erosive gingivitis, also called desquamative gingivitis, defines a clinical picture that can be generated by several inflammatory and immune diseases. Pathology is therefore essential for the differential diagnosis. However, when the gingival lesion is initial, exclusive or predominant, selecting the biopsy site and protocol may be problematic due to tissue fragility. Especially since there are few studies on the subject, the aim of our study was to assess the protocol, diagnostic relevance and tolerance of an original protocol using interdental papilla biopsy. Methods: We conducted a retrospective bicentric study, from October 2011 to July 2019, including all patients with a chronic erosive gingivitis who had received, for diagnostic purposes, a interdental papilla biopsy. Results: The contribution levels for the two hospital departments were 94.7% and 97.1%, respectively. No postoperative complication was recorded in the short or long term. Conclusion: The interdental papilla biopsy protocol is perfectly adapted to the anatomopathological examinations required to establish differential diagnosis of chronic erosive gingivitis. This surgical protocol is simple to perform, non iatrogenic with a very good tolerance and and accessible to all clinicians. It is highly efficient with an excellent contribution level