Dickkopf 1 and Neuregulin 1 as cutaneous biomarkers for dermal pigmentation activity in acquired dermal macular hyperpigmentation (ADMH): a case control study.

Lichen planus pigmentosus (LPP), ashy dermatosis, and Riehl's melanosis are all referred to by the general term acquired dermal macular hyperpigmentation (ADMH). These conditions are distinguished clinically by hyperpigmented macules and patches of unknown cause. Melanogenesisis regulated by multiple dermal factors secreted by fibroblasts and among them are neuregulin1 (NRG1) and dickkopf1 (DKK1). This study was designed to study NRG1 and DKK1 as cutaneous biomarkers for activity of dermal pigmentation in ADMH and to correlate their activity with acquired dermal macular hyperpigmentation area and severity index (DPASI) score. A total of 35 clinically diagnosed ADMH patients and 10 healthy controls along with 4 positive controls of melasma patients were included in the study and DPASI score was calculated using Dermlite (DL4) dermatoscope to assess the disease severity. Skin biopsy samples were taken and immunofluorescence and qPCR were performed to measure the expression of NRG1 and DKK1. A correlation of NRG1 expression, DKK1 expression with DPASI score was assessed. NRG1 expression had a linear positive correlation with DPASI score with a correlation coefficient (r = 0.97) (p < 0.001), while DKK1 showed an inverse correlation with a correlation coefficient (r=-0.69) (p < 0.001). NRG1 and DKK1 expression regulates pigmentation in ADMH and they can be used as an objective tool to assess the disease activity and probably guide therapy.