C4d immunostaining facilitates differentiation of pemphigoid nodularis from prurigo nodularis

Pemphigoid nodularis and prurigo nodularis have similar clinicopathological features and are difficult to distinguish. Enzyme-linked immunosorbent assays (ELISA) and direct/indirect immunofluorescence can support the diagnosis of pemphigoid nodularis, but sometimes show contradictory results or are unavailable. We aimed to develop a practical method for differentiating between pemphigoid nodularis and prurigo nodularis. We analyzed the results of ELISA, direct immunofluorescence (DIF), and C3d and C4d immunohistochemistry (IHC) in 15 and 25 cases of pemphigoid nodularis and prurigo nodularis, respectively. C3d and C4d IHC results were positive in 8/15 (53.3 %) and 13/15 (86.7 %) patients with pemphigoid nodularis, respectively, and negative in all 25 patients with prurigo nodularis. The highest sensitivity (86.7 %) and negative predictive values (92.6 %) were observed in both C4d IHC and anti-BP180 ELISA, whereas C3d IHC exhibited the lowest sensitivity (53.3 %) and negative predictive values (78.1 %). Therefore, anti-BP180 ELISA and C4d IHC were the most sensitive markers to diagnose pemphigoid nodularis. The combination of DIF, ELISA, and C4d IHC is a relatively accurate panel of investigations for distinguishing pemphigoid nodularis from prurigo nodularis.