TNF-α mediated keratinocyte expression and release of matrix metalloproteinase 9: putative mechanism of pathogenesis in Stevens-Johnson syndrome/ toxic epidermal necrolysis.

Stevens Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are severe cutaneous adverse drug reactions (ADRs) characterised by widespread keratinocyte cell-death and epidermal detachment. At present, there is little understanding of how the detachment occurs or how it is abrogated by the TNF-α inhibitor etanercept, an effective SJS/TEN treatment. RNA-sequencing was used to identify upregulated transcripts in formalin-fixed paraffin-embedded SJS/TEN skin biopsies. Epidermal matrix metalloproteinase 9 (MMP9) expression was assessed by immunohistochemistry in skin biopsies and cultured human skin explants exposed to serum from cutaneous ADRs patients. TNF-α-induced MMP9 expression and activity, and its abrogation by etanercept was determined using the HaCaT immortalised keratinocyte cell-line. Epidermal MMP9 expression was significantly higher in SJS/TEN skin (70.6%) vs. healthy control skin (0%, p=0.0098) and non-bullous skin reactions (10.7%, p=0.0002). SJS/TEN serum induced significant MMP9 expression and collagenase activity in healthy skin explants, which was reduced by etanercept. Etanercept was also able negate the TNF-α induced MMP9 expression in the HaCaT cell line. Data suggest that elevated epidermal MMP9 expression and collagenase activity is a putative pathogenic mechanism in SJS/TEN, which is limited by etanercept. Modulation of MMP9 expression and activity represents to our knowledge a previously unreported therapeutic target for the treatment of SJS/TEN

Multiple eruptive clear cell acanthomas successfully treated with CO2 laser ablation

Clear cell acanthoma (CCA) is a rare, benign epidermal lesion of clear glycogen-containing keratinocytes. The exact etiology is unknown. Although CCA usually appear as solitary lesions, cases of multiple CCAs have also been described. The rare eruptive CCA variant describes cases with more than 30 lesions. Current therapeutic evidence for the management of multiple CCAs is limited. CO2 laser remains the most widely used laser in clinical practice. However, literature describing its effectiveness on CCA is sparse, and previous reports have described its use for a maximum of three lesions. To our knowledge, this is the first report of successful CO2 laser treatment of the multiple eruptive CCA variant with an excellent cosmetic outcome. Our case adds to the evidence that CO2 laser is an effective treatment for this condition. Particularly in those patients with refractory or multiple eruptive CCAs, or for those who may not tolerate repeated courses of cryotherapy, or who are concerned about scarring and cosmetic outcome