Pyoderma gangrenosum (PG) lacks consensus regarding treatment, and no prior studies assess treatment satisfaction in PG. The objective of this study was to determine patient-reported satisfaction in the treatment of PG, and associations with satisfaction. Methodology was a multicenter cross-sectional survey for patients who received systemic medication(s) to treat PG. Thirty-five patients completed the survey (mean age: 54.0 years, 65.7% female, response rate: 81.4%). Mean (± SD)

Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are caused by type IV allergic drug reaction and thereby believed to be primarily mediated by T cells. Hence, the involvement of innate immune cells in the pathogenesis of SJS/TEN has been not expected. Here we show an involvement of neutrophils in the pathogenesis of SJS/TEN. We analyzed skin specimens and peripheral blood from SJS/TEN patients. Isolated circulating neutrophils from SJS/TEN patients showed neutrophil extracellular trap (NET) formation. Likewise, immunostaining analysis showed a massive neutrophil infiltration accompanied with NET formation in the early lesional epidermis of SJS/TEN. Analysis of skin specimens and in vitro studies using sera from SJS/TEN patients showed that these NETotic neutrophils released LL-37, an antimicrobial peptide, and subsequently induced formyl peptide receptor 1 (FPR1) on keratinocytes (KCs). FPR1-expressing KCs underwent necroptosis, a programmed form of necrosis, in a monocyte-derived annexin-A1 dependent manner. By using peripheral blood from patients who recovered from SJS/TEN, we revealed that lipocalin-2 produced by causative drug-specific CD8 + T cells induced NETs in neutrophils in the upstream of these processes. Importantly, these mechanisms were specific in patients with SJS/TEN among patients with adverse drug reactions. In summary, we revealed that 1) lipocalin-2 produced by drugspecific CD8 + T cells induced NET formation in neutrophils. 2) LL-37 in NET induced FPR1 on KCs. 3) FPR1-expressing KCs underwent necroptosis through the interaction with monocyte-derived annexin-A1. In conclusion, we proposed that this CD8 + T cellseneutrophils axis acts as an "igniter" upon the onset of SJS/TEN.