Atopic dermatitis and skin diseaseIntrinsic atopic dermatitis shows similar TH2 and higher TH17 immune activation compared with extrinsic atopic dermatitis
Section snippets
Patient population
For this study, we grouped several cohorts of patients with AD previously published by our group,7, 19, 20, 21, 22, 23 as well as 3 new patients (n = 51). Chronic lesional (>72 hours duration with lichenification) and nonlesional (≥10 cm from active lesions) AD skin biopsy specimens and serum samples were collected for these studies under institutional review board–approved protocols. Patients were stratified into extrinsic (42 total; 23 male and 19 female patients; age, 15-81 years; mean age,
Results
We studied a group of 51 patients, of whom 42 were classified as having extrinsic AD and 9 as having intrinsic AD. The disease severity was very similar among these groups (mean SCORAD score, 53 and 54 for extrinsic and intrinsic AD, respectively; P = .46; see patient characteristics in Tables I and E1). In the extrinsic AD group a significant correlation was found between increased IgE levels and higher disease activity, as detected by using the SCORAD score (r = 0.76, P = 3.7 × 10−7); such a
Discussion
Although intrinsic AD represents a minority of patients with AD, it is important to clarify whether it represents a single disease spectrum along with extrinsic AD or whether different immune mechanisms underlie the 2 variants.
Numerous studies have tried to define differences and similarities in pathogenic mechanisms of extrinsic and intrinsic AD.2, 4, 14, 16, 28, 29, 30 Such studies have suggested common disease features of epidermal hyperplasia and increased infiltration of T cells and DC
References (61)
- et al.
Contrasting pathogenesis of atopic dermatitis and psoriasis—part I: clinical and pathologic concepts
J Allergy Clin Immunol
(2011) - et al.
Inhibition of programmed eosinophil death: a key pathogenic event for eosinophilia?
Immunol Today
(1995) - et al.
Delayed eosinophil programmed cell death in vitro: a common feature of inhalant allergy and extrinsic and intrinsic atopic dermatitis
J Allergy Clin Immunol
(1997) - et al.
Progressive activation of T(H)2/T(H)22 cytokines and selective epidermal proteins characterizes acute and chronic atopic dermatitis
J Allergy Clin Immunol
(2012) - et al.
Th2 cytokines act on S100/A11 to downregulate keratinocyte differentiation
J Invest Dermatol
(2008) - et al.
Loricrin and involucrin expression is down-regulated by Th2 cytokines through STAT-6
Clin Immunol
(2008) - et al.
Mechanism of HBD-3 deficiency in atopic dermatitis
Clin Immunol
(2006) - et al.
Elevated levels of IL-10 in intrinsic (IAD) and extrinsic atopic dermatitis (EAD) is associated with deficiency in anti-microbial peptide (AMP) production
J Allergy Clin Immunol
(2004) - et al.
A group of atopic dermatitis without IgE elevation or barrier impairment shows a high Th1 frequency: possible immunological state of the intrinsic type
J Dermatol Sci
(2012) Extrinsic and intrinsic types of atopic dermatitis
J Dermatol Sci
(2010)
Atopy patch test reactions show a rapid influx of inflammatory dendritic epidermal cells in patients with extrinsic atopic dermatitis and patients with intrinsic atopic dermatitis
J Allergy Clin Immunol
T cells and T cell-derived cytokines as pathogenic factors in the nonallergic form of atopic dermatitis
J Invest Dermatol
Major differences in inflammatory dendritic cells and their products distinguish atopic dermatitis from psoriasis
J Allergy Clin Immunol
Blockade of CD11a by efalizumab in psoriasis patients induces a unique state of T-cell hyporesponsiveness
J Invest Dermatol
Human interleukin-19 and its receptor: a potential role in the induction of Th2 responses
Int Immunopharmacol
Interleukin-19: multiple roles in immune regulation and disease
Cytokine Growth Factor Rev
IL-22-producing “T22” T cells account for upregulated IL-22 in atopic dermatitis despite reduced IL-17-producing TH17 T cells
J Allergy Clin Immunol
Contrasting pathogenesis of atopic dermatitis and psoriasis—part II: immune cell subsets and therapeutic concepts
J Allergy Clin Immunol
Possible pathogenic role of Th17 cells for atopic dermatitis
J Invest Dermatol
Polarized in vivo expression of IL-11 and IL-17 between acute and chronic skin lesions
J Allergy Clin Immunol
Allergic and nonallergic forms of atopic diseases
J Allergy Clin Immunol
The role of leukocytes, keratinocytes, and allergen-specific IgE in the development of atopic dermatitis
J Invest Dermatol
Interleukin-10 downregulates anti-microbial peptide expression in atopic dermatitis
J Invest Dermatol
IL-23-mediated epidermal hyperplasia is dependent on IL-6
J Invest Dermatol
Dichotomic nature of atopic dermatitis reflected by combined analysis of monocyte immunophenotyping and single nucleotide polymorphisms of the interleukin-4/interleukin-13 receptor gene: the dichotomy of extrinsic and intrinsic atopic dermatitis
J Invest Dermatol
Modulation of filaggrin by Th2 cytokines in the skin of atopic dermatitis (AD)
J Allergy Clin Immunol
Cytokine modulation of atopic dermatitis filaggrin skin expression
J Allergy Clin Immunol
Immunological differences between intrinsic and extrinsic types of atopic dermatitis
Clin Exp Allergy
Epidemiology, clinical features, and immunology of the “intrinsic” (non-IgE-mediated) type of atopic dermatitis (constitutional dermatitis)
Allergy
Differential in vivo cytokine mRNA expression in lesional skin of intrinsic vs. extrinsic atopic dermatitis patients using semiquantitative RT-PCR
Clin Exp Allergy
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J.G.K., M.S.-F., and N.D. were supported by grant no. 5UL1RR024143-02 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and the NIH Roadmap for Medical Research. E.G.-Y. was supported by the Dermatology Foundation Physician Scientist Career Development Award.
Disclosure of potential conflict of interest: C. de Guzman Strong has received payment for lectures from Rockefeller University Seminar. J. G. Krueger has received grants from Rockefeller University, Amgen, Centocor, Lilly, Merck, and Pfizer and has consultant arrangements with Centocor, Lilly, and Pfizer. E. Guttman-Yassky has consultant arrangements with Leo Pharma, Celgene, Stiefel, Bristol Meyers Squibb, GlaxoSmithKline, Regeneron, Jannsen, and Merck and has received payment for lectures from Celgene and Merck. The rest of the authors declare that they have no relevant conflicts of interest.