7 research outputs found

    Single-cell sequencing reveals Hippo signaling as a driver of fibrosis in hidradenitis suppurativa

    Get PDF
    Hidradenitis suppurativa (HS) is a chronic inflammatory disease characterized by abscesses, nodules, dissecting/draining tunnels, and extensive fibrosis. Here, we integrate single-cell RNA sequencing, spatial transcriptomics, and immunostaining to provide an unprecedented view of the pathogenesis of chronic HS, characterizing the main cellular players and defining their interactions. We found a striking layering of the chronic HS infiltrate and identified the contribution of 2 fibroblast subtypes (SFRP4+ and CXCL13+) in orchestrating this compartmentalized immune response. We further demonstrated the central role of the Hippo pathway in promoting extensive fibrosis in HS and provided preclinical evidence that the profibrotic fibroblast response in HS can be modulated through inhibition of this pathway. These data provide insights into key aspects of HS pathogenesis with broad therapeutic implications.</p

    Unusual drug reaction with features of colchicine toxicity in a patient on colchicine and allopurinol

    Full text link
    A 58-year-old woman was admitted for heart failure and concern for cardiogenic shock. The patient had been recently placed on colchicine and allopurinol, 4 months and 3 weeks, respectively, prior to admission. Upon admission, she had a cutaneous eruption that had started abruptly several days after allopurinol initiation. It included multiple erythematous papules with scant scale on the forearms and numerous erythematous papules on the legs. Because of the varied morphologic presentation, biopsies from both the thigh and forearm were performed for a suspected drug reaction. The specimen from the thigh showed a superficial-dermal, band-like lymphocytic infiltrate with dyskeratosis and numerous intraepidermal mitotic figures predominantly in metaphase. In addition, there were neutrophils with leukocytoclasia. The specimen from the forearm showed superficial perivascular lymphocytic inflammation and intraepidermal dyskeratosis with mitotic figures similar to the thigh biopsy specimen but without a dermal neutrophilic infiltrate. An unusual drug eruption with features of colchicine toxicity was favored. Colchicine toxicity is not a commonly encountered clinical scenario and cutaneous findings have only rarely been described. Herein we report an exceedingly rare case of an unusual drug reaction with “colchicine figures” (i.e., ring-shaped mitotic figures arrested in metaphase) consistent with colchicine toxicity.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/175075/1/cup14280_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/175075/2/cup14280.pd
    corecore