IgE-independent pathophysiology of severe atopic dermatitis demonstrated in an IgE-deficient patient

About 20% of patients with the clinical diagnosis of atopic dermatitis (AD) have no IgE-sensitization to food or aeroallergens and have low to normal serum IgE levels, in contrast to archetypal AD patients, who show clinically relevant IgE-sensitization [ 1 Tokura Y. Extrinsic and intrinsic types of atopic dermatitis. J. Dermatol. Sci. 2010; 58: 1-7 Abstract Full Text Full Text PDF PubMed Scopus (250) Google Scholar , 2 Leung D.Y. Guttman-Yassky E. Deciphering the complexities of atopic dermatitis: shifting paradigms in treatment approaches. J. Allergy Clin. Immunol. 2014; 134: 769-779 Abstract Full Text Full Text PDF PubMed Scopus (303) Google Scholar ]. Based on the concept that these two forms of AD are distinct entities, the World Allergy Organization proposed the nomenclature of “atopic eczema” (AE) and “nonatopic eczema” (nonAE) [ [3] Johansson S.G. Bieber T. Dahl R. Friedmann P.S. Lanier B.Q. Lockey R.F. et al. Revised nomenclature for allergy for global use: report of the Nomenclature Review Committee of the World Allergy Organization, October 2003. J. Allergy Clin. Immunol. 2004; 113: 832-836 Abstract Full Text Full Text PDF PubMed Scopus (1876) Google Scholar ]. Alternatively, by borrowing the terminology of asthma classification, many dermatologists apply the terminology of “intrinsic AD” (IAD), to differentiate from IgE-associated AD, which is termed “extrinsic AD” (EAD) [ [1] Tokura Y. Extrinsic and intrinsic types of atopic dermatitis. J. Dermatol. Sci. 2010; 58: 1-7 Abstract Full Text Full Text PDF PubMed Scopus (250) Google Scholar ]. Other terminology, such as non-IgE-associated AD or atopiform dermatitis, has been proposed as well [ [4] Bieber T. Atopic dermatitis. Ann. Dermatol. 2010; 22: 125-137 Crossref PubMed Scopus (469) Google Scholar ]. The different pathophysiologies of AE/EAD and nonAE/IAD have been studied, although the extent to which they share common mechanisms remains unclear. Furthermore, a debate remains on whether IgE plays a pathogenic role in nonAE/IAD patients, because microbial allergen-specific IgEs that are not commonly tested in clinical practice may be detected in the sera of these patients [ [5] Casagrande B.F. Fluckiger S. Linder M.T. Johansson C. Scheynius A. Crameri R. et al. Sensitization to the yeast Malassezia sympodialis is specific for extrinsic and intrinsic atopic eczema. J. Invest. Dermatol. 2006; 126: 2414-2421 Abstract Full Text Full Text PDF PubMed Scopus (101) Google Scholar ]. Here we describe an adult patient with severe AD accompanied by total IgE deficiency, harboring a heterozygous FLG mutation.