Bullous mycosis fungoides associated with an extensive ulcer and a severe leukemoid reaction

This report presents a case of bullous mycosis fungoides associated with an extensive ulcer and a severe leukemoid reaction. The rash began as indurated erythema which was always followed by ulceration. The rashes initially responded to radiation therapy, but multiple recurrences appeared. Several bullae appeared on the trunk during the course of the illness, without any evidence of paraneoplastic pemphigus. Finally, the ulcer covered a large part of the trunk, and the patient died of sepsis with an extreme leukocyte count of 118,000/μL. A bone marrow analysis revealed a leukemoid reaction and an autopsy revealed pseudomembranous colitis

Methylation in pericytes after acute injury promotes chronic kidney disease

The origin and fate of renal myofibroblasts is not clear after acute kidney injury (AKI). Here, we demonstrate that myofibroblasts were activated from quiescent pericytes (qPericytes) and the cell numbers increased after ischemia/reperfusion injury-induced AKI (IRI-AKI). Myofibroblasts underwent apoptosis during renal recovery but one-fifth of them survived in the recovered kidneys on day 28 after IRI-AKI and their cell numbers increased again after day 56. Microarray data showed the distinctive gene expression patterns of qPericytes, activated pericytes (aPericytes, myofibroblasts), and inactivated pericytes (iPericytes) isolated from kidneys before, on day 7, and on day 28 after IRI-AKI. Hypermethylation of the Acta2 repressor Ybx2 during IRI-AKI resulted in epigenetic modification of iPericytes to promote the transition to chronic kidney disease (CKD) and aggravated fibrogenesis induced by a second AKI induced by adenine. Mechanistically, transforming growth factor-β1 decreased the binding of YBX2 to the promoter of Acta2 and induced Ybx2 hypermethylation, thereby increasing α-smooth muscle actin expression in aPericytes. Demethylation by 5-azacytidine recovered the microvascular stabilizing function of aPericytes, reversed the profibrotic property of iPericytes, prevented AKI-CKD transition, and attenuated fibrogenesis induced by a second adenine-AKI. In conclusion, intervention to erase hypermethylation of pericytes after AKI provides a strategy to stop the transition to CKD