A case-control study addressing the population of epidermal and dermal inflammatory infiltrate including neural milieu in primary prurigo nodularis using S-100 and toluidine blue stain and its therapeutic implications

Background The pathogenesis of prurigo nodularis (PN) is considered to be multifactorial, with numerous cells and cytokines confabulating to produce an aberrant immune response.Methods A cross-sectional observational study was done in cases of untreated primary prurigo nodularis cases with histopathological assessment in 49 cases from lesional and nonlesional skin with assessment of epidermal and dermal changes, dermal infiltrate, S-100 and toluidine blue staining to assess the expression of nerve and mast cells.Results The most common histological changes seen in lesional skin were hyperkeratosis (98%), irregular hyperplasia (69.4%), hypergranulosis (69.4%), subepidermal clefting (6%), vertical collagen bundles (51.0%), and dermal fibrosis (48.9%). Chronic inflammatory infiltrate was seen in all cases (100%) predominantly of lymphocytes (100%) followed by eosinophils (18.4%), plasma cells (8.2%), and neutrophils (2.0%). There was a marked increase in the expression of S-100 (6.92 +/- 3.40 vs. 3.94 +/- 2.15, P < 0.001) and toluidine blue (4.99 +/- 4.47 vs. 1.22 +/- 1.28, P < 0.001) in the lesional skin as compared to the nonlesional skin.Conclusion We can infer that the epidermal and dermal pathology in PN is related to the infiltrate of lymphocytes, mast cells, and neural hyperplasia which perpetuate the pathogenesis by triggering the itch-inflammation cycle. Thus, apart from immunosuppressive agents that target lymphocytes and their cytokines, therapy targeted at mast cells and neural proliferation may be needed to treat prurigo nodularis.