Onychodermis Containing Onychofibroblasts: A Crucial Concept in Nail Histopathology

In the August 2025 issue, I read with great interest the article reassessing the histologic validity of the onychodermis in both adult and polydactyly nail units.1 Although Perrin questioned the existence of the onychodermis and onychofibroblasts, our recent histologic, immunohistochemical, and molecular studies in both polydactyly and adult nail units provide compelling evidence supporting their presence.2–4 First, contrary to his suggestion that this concept represents an oversimplification, the recognition of the onychodermis and its resident onychofibroblasts is fundamental to nail biology. These structures play critical roles in nail formation and growth through the epithelial–mesenchymal interactions, and in the pathogenesis of nail tumors such as onychomatricoma.2–9 The onychodermis is a specialized mesenchymal region beneath the nail matrix and nail bed (Fig. 1), distinct from ordinary dermis in both structure and function. The onychodermis can be distinguished from the surrounding skin dermis, which contains conventional dermal fibroblasts and adnexal structures. The nail matrix onychodermis is composed of an upper dense collagenous layer and an underlying, less eosinophilic, loosely cellular zone known as the onychomatricodermis. The nail matrix onychodermis contributes to nail plate formation by interacting with the nail matrix. In contrast, the nail bed onychodermis appears as a dense collagenous layer including thick fibrous tissue that anchors the nail bed to the distal phalanx, primarily contributing to the mechanical support for the nail plate. Despite these histologic differences, both regions share common features in histology, immunohistochemistry, and gene expression. These similarities support the concept of the onychodermis as a distinct nail-specific mesenchymal tissue. RSPO4 is a key nail-specific gene involved in nail development, and mutations in RSPO4 are associated with anonychia.10 This gene is expressed in onychofibroblasts within the onychodermis of the nail matrix and nail bed. In addition, our recent spatial transcriptomic profiling demonstrated that both the onychodermis and the follicular dermal papilla expressed Wnt- and BMP-related signaling molecules, suggesting that the onychodermis serves as the nail unit's counterpart to the dermal papilla of hair follicles.4FIGURE 1.: Simplified illustration of the onychodermis in the human nail unit. Blue area shows Onychodermis.Second, Perrin repeatedly referred to the lower portion of the nail matrix onychodermis as the “matrix hypodermis.” However, this terminology is anatomically incorrect because this region belongs to the onychodermis rather than to the subcutaneous hypodermis although age-related fatty changes may be observed in the deeper portion of the nail matrix onychodermis in adult nail units. RSPO4 is expressed in onychofibroblasts within the nail matrix onychodermis, including the region he referred to as the “matrix hypodermis.” Third, he recently proposed the presence of so-called telocytes in the nail unit; however, both the terminology and the described cellular characteristics closely resemble those of previously described and extensively characterized onychofibroblasts. In conclusion, recognition of the onychodermis and its resident onychofibroblasts is essential for advancing our understanding of nail biology and pathology.