Abundant immunoglobulin E-positive cells in skin lesions support an allergic etiology of atopic dermatitis in the elderly

Abstract

Background/objectives: Atopic dermatitis (AD) in the elderly is gradually increasing in industrialized countries in association with the aging of society. We report herein four cases of elderly AD {three extrinsic [immunoglobulin (Ig)E-mediated allergy]; one intrinsic (non-IgE-allergy)} in which we investigated the presence of IgE+ cells in lesional skin.

Methods/results: Single immunohistochemical and double immunofluorescence stainings were performed for skin biopsy specimens from AD patients and non-atopic control subjects with chronic eczema. In the lesional lichenified skin of patients with extrinsic elderly AD, numerous IgE+ cells were found among inflammatory cells infiltrates in the upper dermis. Comparative analysis of single immunohistochemistry results using serial paraffin and/or frozen sections found that many IgE+ cells showed identical distributions to tryptase+ mast cells. IgE+ cells coincident with CD1a+ Langerhans cells in the epidermis were found in small numbers only in frozen sections. Double immunofluorescence staining for IgE and CD11c revealed cells coexpressing IgE and CD11c with a dendritic morphology in the papillary and upper dermis. These IgE+ mast cells and IgE+ CD11c+ cells were also found in cured normal-looking skin from a patient with extrinsic elderly AD after successful treatment. Although only a few weakly positive IgE+ cells were detected, no IgE+CD11c+ cells were found in specimens from patients with intrinsic elderly AD or non-atopic chronic eczema.

Conclusion: IgE-mediated allergic inflammation may play an important role in the pathobiology of elderly AD, similar to other age groups of AD.

Figure 1

Skin manifestations of elderly AD: extrinsic form, Cases 1–3; intrinsic form, Case 4 (a) Lichenified eczema on the upper back (Case 1). (b) Facial erythema (atopic red face) with Hertogh’s sign (loss of lateral eyebrows) and Dennie-Morgan infraorbital folds (Case 2). (c) Dirty neck (Case 2). (d) Lichenified eczema around the scarcely involved elbow fold (reverse sign) (Case 2). (e) Eczematous erythroderma (Case 3). (f) Eczematous lesions mostly disappeared after successful treatment and the cured skin shows a normal appearance (Case 3). (g) Lichenified eczema of erythroderma on the trunk and neck (Case 4).

Figure 2

Single immunohistochemical staining with anti-mast-cell-tryptase antibody and with anti-IgE antibody using serial paraffin sections Sets of figures (a and c), and figures (b and d) represent serial sections. (a) Tryptase+ mast cell infiltration is increased in the papillary and upper dermis of a lichenified lesion from a patient with extrinsic elderly AD (Case 2). (b) Tryptase+ mast cells are scattered in a skin lesion from a patient with non-atopic chronic eczema (asteatotic dermatitis) (Case 5). (c) Numerous IgE+ cells are seen in inflammatory infiltrates of a lichenified lesion from a patient with extrinsic elderly AD (Case 2). (d) Few IgE+ cells are present in a skin lesion from a patient with non-atopic chronic eczema (Case 5). Note that, in specimens from cases with extrinsic elderly AD (a and c), most IgE+ cells and tryptase+ cells show the same morphology and localization (arrows). Original magnification: ×100.

Figure 3

Double immunofluorescence staining with anti-IgE and anti-CD11c mAbs (a) This figure clearly shows three types of cells coexisting in the dermal papillae and upper dermis of lichenified skin lesions of a patient with extrinsic elderly AD (Case 2): single IgE+ cells (red images), mostly representing IgE-bearing mast cells; single CD11c+ cells (green images), representing dermal dendritic cells; and double-positive IgE+CD11c+ cells (yellow images), representing IgE-bearing dermal dendritic cells. The box in the upper panel indicates a dendritic IgE+CD11c+ cell in the basal layer of the epidermis. (b) Only single CD11c+ cells (green images) are apparent in a skin lesion from a patient with non-atopic chronic eczema (asteatotic dermatitis) (Case 5). Nuclei are labeled with DAPI (blue images). Original magnification: ×200.

Figure 4

Double immunofluorescence staining with anti-IgE and anti-CD11c mAbs (a) Lichenified skin lesion from a patient with extrinsic elderly AD (Case 1). The majority of double-positive IgE+CD11c+ cells (yellow images) with a dendritic morphology are distributed in the papillary and upper dermis. Single IgE+ cells (red images) are seen in the upper dermis, but single CD11c+ cells (green images) are apparent in both the epidermis and dermis. (b) A lichenified skin lesion from a patient with intrinsic elderly AD (Case 4). Only a few single IgE+ cells (red images) and no double-positive IgE+CD11c+ cells are observed, although infiltrating single CD11c+ cells (green images) are seen in the upper dermis. (c) Cured normal-appearing skin of a patient with extrinsic elderly AD after successful treatment (Case 3). Cells coexpressing IgE and CD11c (yellow images) accompanied with single IgE+ cells (red images) and single CD11c+ cells (green images) are scattered among the dermis-infiltrating cells. Note that cells coexpressing IgE and CD11c (yellow images) lacked dendritic morphology. (d) Cells coexpressing IgE and CD11c are absent in normal skin from a non-atopic volunteer. Nuclei are labeled with DAPI (blue images). Original magnification: ×100.