No abstract

Atopic dermatitis is a chronic inflammatory skin disease that causes significant morbidity in affected individuals. It is characterized by dysregulated immune responses that consist of an increased systemic Th2 response and a combination of Th2 and Th1 responses in the skin lesions. In this article, we review factors that contribute to these abnormal responses, including key effector cells of the immune system, chemokines, defective skin barrier, genetic predisposition, and environmental triggers. Understanding these pathomechanisms may improve our current therapies for atopic dermatitis.

KeywordsADEH; AMPs MADAM, Patients with atopic dermatitis (AD) with a history of eczema herpeticum (ADEH) represent a subset of individuals with AD who have more severe disease. 1 It has previously been shown that the skin of patients with AD has defects in its capacity to increase maximally the antimicrobial peptides (AMPs), cathelicidin, human β-defensin (HBD)-2 and HBD-3 in response to inflammation, in contrast to patients with psoriasis who also have inflammation of the skin, but no difficulty with AMP induction. 2,3 To date, however, previous studies have not examined HBD-2 and HBD-3 induction in the ADEH subset of patients. 4 We sought to examine if subjects with ADEH exhibit an inhibition in induction of AMPs, compared with subjects without ADEH. A total of 81 subjects were recruited into the study: 26 patients with psoriasis, 21 with AD and nine with ADEH and 25 healthy subjects with no history of skin disease (Table S1, see Supporting information). Two 2-mm punch biopsies were collected from lesional and nonlesional skin of the patients. Normal controls provided two 2-mm punch biopsies from the skin of their upper inner arm. Quantification of cathelicidin, interleukin (IL)-13, HBD-2 and HBD-3 in the skin was performed by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) (see supporting information), and their expression was calculated as relative to glyceraldehyde 3-phosphate dehydrogenase (GAPDH) mRNA. All statistical analyses were performed using SAS v9.1 or higher (SAS Institute, Cary, NC, U.S.A.) (see Supporting information).Compared with individuals with AD or psoriasis, patients with ADEH showed a lesser relative increase in cathelicidin, HBD-2 and HBD-3 mRNA in their lesional skin (Fig. 1). Immunohistochemical staining of LL-37 confirmed the RT-PCR data for this peptide product of the cathelicidin gene (Fig. S1, see Supporting information) and supported a prior report that cathelicidin is suppressed in subjects with ADEH. 4 This finding, combined with the novel observation of decreased inducibility of HBD-2 and HBD-3, suggests that HBD-2Correspondence: Tissa Hata and Richard Gallo. thata@ucsd.edu; rgallo@vapop.ucsd.edu . Conflicts of interest: none declared.Supporting information Additional supporting information may be found in the online version of this letter. and HBD-3 may further contribute to the increased incidence of secondary infection with herpes simplex virus (HSV) in ADEH. NIH Public AccessAs expected, due to low expression in normal skin, nonlesional skin revealed no differences in cathelicidin levels between the four groups (Fig. 2). 5 Interestingly, however, nonlesional HBD-2 levels were significantly higher in patients with ADEH compared with those with AD (P < 0.001) or psoriasis (P < 0.001) and normal controls (P = 0.001). Nonlesional HBD-3 levels were also higher in patients with ADEH compared with those with AD (P = 0.002) or psoriasis (P = 0.003). Upregulation of HBD-2 and HBD-3 has been shown to occur with proinflammatory stimuli such as tumour necrosis f...

These data suggest that defects in viral-induced IFN-γ from CD8+ T cells contribute to the ADEH+ phenotype.