Pathophysiology of nocturnal scratching in childhood atopic dermatitis: the role of brain-derived neurotrophic factor and substance P

Abstract

Childhood atopic dermatitis (AD) is a distressing disease associated with pruritus and sleep disturbance. The pathophysiology of pruritus is complex and various neuropeptides may be involved. To evaluate whether or not brain-derived neurotrophic factor (BDNF) and substance P are associated with disease severity, quality of life and nocturnal scratching in AD. Patients with AD aged under 18 years were recruited. Disease severity was assessed with the SCORing Atopic Dermatitis (SCORAD) index, and quality of life with the Children's Dermatology Life Quality Index (CDLQI). Concentrations of plasma BDNF, substance P, AD-associated chemokines [cutaneous T-cell attracting cytokine (CTACK), thymus and activation regulated chemokine (TARC)], serum total IgE and eosinophil counts were measured in these patients. All children were instructed to wear the DigiTrac monitor on their dominant wrist while sleeping. The monitor was programmed to record limb motion between 22.00 and 08.00 h the following morning. Twenty-eight children with AD [mean (SD) age 11.1 (3.3) years] were recruited. The mean (SD) SCORAD was 48.1 (21.5) and CDLQI was 8.7 (5.4) in the patients with AD. Their mean (SD) plasma concentrations of BDNF, substance P, CTACK and TARC were 1798 (935), 94 (42), 1424 (719) and 824 (1000) pg mL(-1), respectively. BDNF was significantly correlated with SCORAD (r = 0.478, P = 0.010) and CDLQI (r = 0.522, P = 0.004), whereas substance P showed significant correlation only with CDLQI (r = 0.441, P = 0.019). BDNF and substance P were also significantly correlated with the average (r = 0.905, P < 0.001 and r = 0.925, P < 0.001) and frequency-specific (r = 0.826, P < 0.001 and r = 0.870, P < 0.001) nocturnal wrist activities measured by DigiTrac. However, there was no correlation between BDNF or substance P and the subjective symptoms of pruritus or sleep-loss scores as reported by the parents in the SCORAD. In contrast, serum total IgE levels showed significant correlations with the subjective symptoms of pruritus (r = 0.576, P = 0.001) and sleep loss (r = 0.419, P = 0.027). Serum levels of BDNF and substance P correlate with the clinical score and quality of life score in patients with AD. The strong correlations with nocturnal wrist movements suggest that they may be the pathogenic factors of the annoying symptoms of scratching.