Pruritus and Neuropsychiatric Symptoms Among Patients with Darier Disease-An Overlooked and Interconnected Challenge

(1) Background: Darier disease (DD) is a rare autosomal dominant disorder caused by mutations in ATP2A2, a gene that encodes the sarco(endo)plasmic reticulum calcium-ATPase 2 enzyme, which disrupts calcium homeostasis in keratinocytes. Pruritus, a frequently overlooked symptom in DD, can lead to physical and emotional complications, especially in patients with DD who are genetically predisposed to psychiatric comorbidities. (2) Methods: This study aimed to analyze pruritus and other related symptoms in patients with DD and explore their correlation with neuropsychiatric conditions, psychological challenges, disease severity, and body surface area (BSA) involvement through a retrospective review of a tertiary center. (3) Results: Data from 76 patients (equal gender distribution, mean age 44 years) revealed a prevalence of pruritus of 90.8%, surpassing symptoms such as pain (34.3%) and malodor (43.4%). Burning sensations due to DD lesions were significantly correlated with the diagnosis of comorbid neuropsychiatric conditions (p = 0.047) and psychiatric medication use (p = 0.019). While pruritus correlated with disease severity and %BSA involvement, the findings were not statistically significant. Patients reporting pruritus had a significantly higher Dermatology Life Quality Index symptom score (2.4 ± 1.0), which is defined as the presence of itch, soreness, pain, or stinging, than those who did not (1.5 ± 0.6), indicating accurate symptom reporting. (4) Conclusions: In conclusion, a striking majority of patients with DD experience pruritus, with higher prevalence among those with neuropsychiatric challenges, severe Darier disease, and greater %BSA skin involvement. Clinicians should recognize pruritus as a key therapeutic target and adopt comprehensive treatment approaches that both address the neuropsychiatric comorbidities and the added psychological burden of pruritus in patients with DD.