Pathophysiology of Nocturnal Scratching in Childhood Atopic Dermatitis: The Role of Brain-Derived Neurotrophic Factor and Substance P

Abstract

Hon KL, Lam MC, Wong KY, Leung TF, Ng PC. Br J Dermatol. 2007;157(5):922–925 PURPOSE OF THE STUDY. To determine if brain-derived neurotrophic factor (BDNF) and substance P are associated with disease severity, quality of life, and nocturnal scratching in atopic dermatitis (AD). STUDY POPULATION. This was a prospective study of 28 children with AD (mean age: 11.1 ± 3.3 years) recruited from a pediatric dermatology clinic at a university teaching hospital in Hong Kong. Eighty-nine percent had moderate-to-severe AD on the basis of Scoring Atopic Dermatitis (SCORAD) scores. METHODS. AD severity, as well as pruritus and sleep loss (in the preceding 3 days), was evaluated by using the SCORAD index. The Children's Dermatology Life Quality Index (CDLQI) was used to measure the quality of life over the preceding 7 days. Serum BDNF, substance P, AD-associated chemokine (cutaneous T-cell–attracting cytokine [CTACK] and thymus and activation-regulated chemokine [TARC]), total immunoglobulin E (IgE), and eosinophil counts were measured. Patients wore a DigiTrac monitor (IM Systems, Baltimore, MD) on their dominant wrist while sleeping to record limb motion from 10 pm to 8 am the following morning. On the basis of the group's previous work showing that the wrist activities between 1 and 3 Hz for the first 3 hours of sleep were indicators of AD severity of children, the same parameters were used for analyses of correlations. RESULTS. The mean SCORAD score was 48.1 ± 21.5, and mean CDLQI score was 8.7 ± 5.4. The mean plasma concentrations of BDNF, substance P, CTACK, and TARC were 1798 ± 935, 94 ± 42, 1424 ± 719, and 824 ± 1000 pg/mL, respectively. BDNF correlated significantly with both the SCORAD (P = .010) and CDLQI (P = .004) scores, whereas substance P had a significant correlation only with the CDLQI score (P = .019). Both BDNF and substance P were highly significantly correlated with average (P < .001) and frequency-specific (P < .001) wrist activities measured by the DigiTrac. In contrast, the chemokine (CTACK and TARC), serum total IgE, and eosinophil counts did not correlate with scratching. It is interesting to note that there was no correlation between BDNF or substance P level and pruritus or sleep-loss scores reported by the parents in the SCORAD. CONCLUSIONS. Serum levels of BDNF and substance P were significantly linked to disease activity, quality of life, and levels of nocturnal scratching. REVIEWER COMMENTS. Pruritus can be very distressing for children with AD. Unfortunately, the pathophysiology of nocturnal itching and the mediators involved have not been well elucidated. This article is the first to demonstrate that BDNF and substance P levels are significantly linked to nocturnal scratching. Certainly additional studies are needed to show that these neuropeptides are the causative factors in itching. Inclusion of control groups and those with other dermatologic conditions that also cause pruritus would be helpful. However, this article also suggests that perceived symptoms of itch, especially by parents of those with AD, may not be precise and that perhaps the extent of nocturnal itching has been underappreciated.