Comparison of skin barrier function and sensory nerve electric current perception threshold between IgE-high extrinsic and IgE-normal intrinsic types of atopic dermatitis

Abstract

Background Two types of atopic dermatitis (AD) have been proposed, with different pathophysiological mechanisms underlying this seemingly heterogeneous disorder. The extrinsic type shows high IgE levels presumably as a consequence of skin barrier damage and feasible allergen permeation, whereas the intrinsic type exhibits normal IgE levels and is not mediated by allergen-specific IgE. Objectives To investigate the relationship between pruritus perception threshold and skin barrier function of patients with AD in a comparison between the extrinsic and intrinsic types. Methods Enrolled in this study were 32 patients with extrinsic AD, 17 with intrinsic AD and 24 healthy individuals. The barrier function of the stratum corneum was assessed by skin surface hydration and transepidermal water loss (TEWL), and pruritus perception was evaluated by the electric current perception threshold (CPT) of sensory nerves upon neuroselective transcutaneous electric stimulation. Results Skin surface hydration was significantly lower and TEWL was significantly higher in extrinsic AD than intrinsic AD or normal controls. Although there was no statistically significant difference in CPT among extrinsic AD, intrinsic AD and normal controls, CPT was significantly correlated with skin surface hydration and inversely with TEWL in intrinsic AD and normal controls, but not extrinsic AD. Finally, CPT was correlated with the visual analogue scale of itch in the nonlesional skin of patients with extrinsic but not intrinsic AD. Conclusions Patients with extrinsic AD have an impaired barrier, which increases the pre-existing pruritus but rather decreases sensitivity to external stimuli. In contrast, patients with intrinsic AD retain a normal barrier function and sensory reactivity to external pruritic stimuli.

Pruritus intensity assessment: challenge for clinicians

“…This suggestion may be supported by the observation that CPT was significantly correlated with skin surface hydration and inversely with transepidermal water loss in intrinsic atopic dermatitis, as well as with the VAS scoring of itch in extrinsic atopic dermatitis [42]. Our group also observed a significant correlation between CPT and pruritus severity.…”

“…However, not all studies were able to demonstrate [41]. Accordingly, Mori et al observed no statistically significant difference in CPT among extrinsic atopic dermatitis, intrinsic atopic dermatitis and normal controls [42]. In contrast, our group found an even higher sensory threshold to electric current stimulation in patients with atopic dermatitis or psoriasis than in healthy volunteers, although no significant differences were found between subjects with atopic dermatitis and psoriasis [43].…”

“…In addition, the basal skin blood flow level fluctuated more in itchy skin areas than in the healthy skin areas of nodular prurigo patients, suggesting an abnormal spontaneous activity of nociceptive peripheral nerve fibers and a consequent release of vasoactive agents from their terminals (axon reflex) [37]. It was also demonstrated that electric stimulation might evoke pruritus in patients with chronic itch, making the threshold assessment relatively easy in clinical settings [41][42][43]. Kobayashi et al observed that patients with atopic dermatitis, a chronic inflammatory skin disease accompanied by severe itching, showed a lower barrier function and lower current perception threshold (CPT) than normal individuals, and the CPT was found to be inversely correlated with transepidermal water loss levels, a measurement of epidermal barrier disruption [38].…”

Atopic Dermatitis and the Nervous System

“…Skin sensitivity to electric current is decreased in patients with extrinsic atopic dermatitis but not in patients with the intrinsic form. This phenomenon appears to be related to an impaired skin barrier in patients with the extrinsic form [77]. In contrast to healthy subjects, neuroselective transcutaneous electrical stimulation preferentially evokes itch in atopics [78].…”

Animal Models of Allergic Diseases

“…The intrinsic form tends to develop in older patients and filaggrin mutations are not a characteristic of this form [8]. Studies investigating skin barrier function in patients diagnosed with intrinsic AD have shown that normal function and sensory reactivity to external stimuli is retained in these individuals, which is different from patients with the extrinsic form [9]. Immunologically, lower expression of T helper (Th)2 cytokines such as Interleukin (IL)-4, 5, and 13 are found in affected individuals.…”