Atopic Dermatitis-like Graft-versus-host Disease and Lichen Planus-like Graft-versus-host Disease

Abstract

Background:Graft-versus-host disease (GVHD) is a common complication of hematopoietic stem cell transplantation. Skin barrier disruption could induce thymic stromal lymphopoietin (TSLP) expression, and the expression of TSLP was increased in lesions of atopic dermatitis (AD)-like GVHD and lichen planus (LP)-like GVHD. This study attempted to investigate the skin barrier function of AD-like GVHD and LP-like GVHD and possible mechanisms.Methods:Eighteen AD-like GVHD patients, 12 LP-like GVHD patients, and 14 healthy volunteers were enrolled in this study. Skin biopsy was done in five AD-like GVHD patients, eight LP-like GVHD patients, and eight healthy volunteers. The intensity of pruritus was assessed by visual analog scale itch score and detailed pruritus score. Transepidermal water loss (TEWL) was measured using Tewameter® TM 300. Immunohistochemistry was used to observe the expression of loricrin, involucrin, LL37, and human β-defensins 2 (hBD2) in skin lesions. Western blot analysis was used for analyzing the protein levels of loricrin and involucrin in skin lesions. Real-time polymerase chain reaction was performed to assess the mRNA levels of LL37 and hBD2 in skin lesions.Results:Pruritus score was higher in patients with AD-like GVHD (11.33 ± 5.35) than that of patients with LP-like GVHD (2.58 ± 3.09, P < 0.001). Compared with healthy controls (HCs, 4.52 ± 1.24 g·m−2·h−1), TEWL was increased in AD-like GVHD (26.72 ± 9.02 g·m−2·h−1, P < 0.001) and LP-like GVHD patients (18.78 ± 4.57 g·m−2·h−1, P < 0.001), and expressions of loricrin and involucrin were also increased in skin lesions of AD-like GVHD and LP-like GVHD patients (all P < 0.05). LL37 mRNA expression was decreased in lesions of AD-like GVHD and LP-like GVHD patients (P = 0.005 and P = 0.008, vs. HCs, respectively). hBD2 mRNA expression was increased in skin lesions of AD-like GVHD and LP-like GVHD patients (P = 0.002 and P < 0.001, vs. HCs, respectively).Conclusions:Skin barrier dysfunction is present in AD-like GVHD and LP-like GVHD. The immunoreactions, but not the congenital defect, are considered to be the primary cause of skin barrier impairment in AD-like GVHD and LP-like GVHD.

Human β-defensin 2 ameliorates acute GVHD by limiting ileal neutrophil infiltration and restraining T cell receptor signaling

“…Eriguchi et al (31,32) described that Paneth cells are targeted and markedly reduced during murine GVHD, resulting in decreased α-defensin production. In patients, the expression of defensins during GVHD has been analyzed in only a few studies with limited patient numbers and with controversial results regarding the correlation of defensin expression and GVHD patient outcomes (33)(34)(35). The therapeutic effect of the α-defensin cryptdin-4 (Crp-4) has been investigated in an aGVHD mouse model.…”

Eczematous graft‐vs‐host disease: A report of three cases and review of the literature

“…In addition, the majority of previously reported cases of eczema‐like GVHD did not have a history of atopy in either recipient or donor 10,11,13 . Of interest, by studying 18 patients with atopic dermatitis‐like GVHD, Li et al demonstrated that similar to patients with spontaneous atopic dermatitis, skin permeability, and antimicrobial barriers are impaired in these patients; however, the mechanism involved is different from that of spontaneous atopic dermatitis 20 . They did not provide a detailed case‐by‐case clinicopathological description of their patients.…”

Pruritus in cutaneous graft‐versus‐host disease: A systematic review

“…In another study of 193 cGVHD patients, pruritus intensity was not associated with cGVHD severity and the presence of pruritus was not associated with survival. 11 In a small observational study from China, Li et al 13 defined the 'pruritus score' as the sum of the VAS (range 0-10) plus a modified duo score (range 0-23) and reported that the mean pruritus score in patients with atopic dermatitis (AD)-like cGVHD (n = 18) was 8.75 higher (11.33 vs. 2.58) than in patients with lichen planus (LP)-like cGVHD (n = 12). However, we did not find any studies that looked in more detail at the average onset of itch or its potential triggers, how patients perceived the quality of itch and how they coped with it.…”

“…Of the analysed 13 studies, 9 (69.2%) used binary outcomes ('pruritus' vs. 'no pruritus') to assess pruritus. Only four studies used assessment tools to specify pruritus, including the visual analogue scale (VAS), 13 duo score, 13 numerical ratings scale (NRS) 11,14 and grading scales for pruritus mentioned in the common terminology criteria for adverse events (CTCAE) version 4.0. 15 The VAS and NRS were both scored on a 0-10 scale (0 = no pruritus, 10 = worst pruritus imaginable).…”