Pemphigus vulgaris (PV) is a rare immunobullous disease. Although it classically presents as generalized flaccid blisters affecting the skin and mucosae, atypical cases of PV can be diagnostically challenging. Herein, we report an underrecognized non-blistering manifestation of pemphigus vulgaris, which we call mounded and refractory keratoses (MARK). MARK presents as exuberant scaling plaques on the scalp, often in the skin of color. When MARK features are present, pemphigus vulgaris is prone to misdiagnosis, clinically and histopathologically, leading to delays in appropriate treatment. Specifically, biopsies from these patients may resemble acantholytic dyskeratosis, resulting in initial misdiagnosis. Thus, recognizing this presentation may aid physicians in diagnosing and monitoring the recurrence of pemphigus vulgaris.

Necrobiosis is a histologic term used to describe abnormal deposits of degenerating collagen within the skin. It can be found as an incidental finding in various granulomatous conditions, but is a hallmark of necrobiosis lipoidica (NL) and necrobiotic xanthogranuloma (NXG). There is limited prior research on necrobiosis. Here, we employed single-cell analysis of lesional and nonlesional skin to study the pathophysiology of necrobiosis. Our findings demonstrate that necrobiotic lesional skin is characterized by SPP1hi macrophages expressing MARCO; NKG7-expressing effector CD8+ T cells coexpressing CCL5, IFNG, GZMs, and PRF1; CCL5hi fibroblasts coexpressing CXCL9, diverse collagens (e.g., COL4A4, COL11A1, COL8A1), and TIMP1; and IGHM-expressing plasma cells. Integrative analysis of signaling ligands and receptor expression identified strong cell-cell communication between NKG7+ T cells, CCL5hi fibroblasts, and SPP1-expressing macrophages. In contrast, these cell populations were not dominant features of systemic sclerosis, another collagen deposition disease. Furthermore, although SPP1-expressing macrophages were detectable in sarcoidosis, IFNG-expressing T cells were a more defining feature of sarcoidosis compared with NL and NXG. From these findings, we speculate that necrobiosis results from the deposition of diverse collagens and ECM proteins through a process driven by CCL5-expressing fibroblasts and SPP1-expressing macrophages.