Abstract

Secondary syphilis is the early systemic manifestation of treponemal bacteremia, and produces a wide variety of multisystemic symptoms. Cutaneous secondary syphilis has great histologic variability including prominent perivascular lymphocytic infiltration, lichenoid/vacuolar interface dermatitis, psoriasiform dermatitis with plasma cells, granulomatous dermatitis, and alopecia with peribulbar lymphoplasmacytic infiltrate. Previous studies have qualitatively demonstrated the distribution of Treponema pallidum spirochetes across skin compartments, noting greater densities at the dermal-epidermal junction (DEJ) and dermal perivascular spaces. However, objective quantification of spirochete density within compartments has yet to be described. In this preliminary report, we measure spirochete density from whole slide images (WSI) of 17 skin biopsies using QuPath. Organism density was approximated by measuring the optical density of red chromogen in the anti-treponemal stains from normalized WSI within manually annotated epidermal, DEJ, dermal, perivascular, and adnexal compartments. Consistent with prior reports, we found nearly all cases had prominent perivascular involvement. Clustering analysis revealed distinct epidermotropic and adnexotropic profiles. These clusters may correlate with the predominant inflammatory pattern. Cases of syphilis involving a dermatofibroma and syphilitic alopecia were also evaluated. The mechanisms of tropism of spirochetes in cutaneous syphilis are largely unknown and may provide insight into the underlying pathophysiology. This study supplies the foundation to systematically semi-quantitatively measure T. pallidum localization to allow for comparisons across different disease states. Future work will investigate the degree of spirochete distributions in the wide variety of clinical presentations and inflammatory patterns seen in secondary syphilis.