Overexpression of the T cell cytokine IL-22 is linked to the development of some chronic diseases, but little is known about IL-22 deficiency in humans. As demonstrated in this study, acne inversa (AI; also designated as Hidradenitis suppurativa) lesions show a relative deficiency of IL-22 and IL-20, but not of IL-17A, IL-26, IFN-γ, IL-24, or IL-1β. Moreover, AI lesions had reduced expression of membranous IL-22 and IL-20 receptors and increased expression of the natural IL-22 inhibitor, IL-22 binding protein. AI is a chronic inflammatory skin disease with prevalence up to 4% of the population and in which cutaneous bacterial persistence represents an important pathogenetic factor. Accordingly, we also found a relative deficiency of antimicrobial proteins (AMPs) in AI lesions and a positive correlation between lesional IL-22 and IL-20 versus AMP levels. IL-22, like its tissue cell downstream mediator IL-20, upregulated AMPs in reconstituted human epidermis and was critical for increased AMP levels under inflammatory conditions. The relative IL-22 deficiency in AI was not linked to lesional T cell numbers or Th22/Th1/Th17 subset markers and -inducing cytokines. However, IL-10 was highly expressed in AI lesions and correlated negatively with IL-22 expression. Moreover, IL-10 inhibited IL-22 but not IL-17 production in vitro. The IL-10 overexpression, in turn, was not associated with an elevated presence of regulatory T cells but with the enhanced presence of an IL-10–inducing cytokine. We conclude that IL-22 deficiency may contribute to the pathogenesis of certain chronic disorders as postulated in this paper for AI.

Lichen sclerosus et atrophicus is a chronic dermatosis of unknown etiology and pathogenesis. Lichen sclerosus et atrophicus associated skin lesions show T cell enriched infiltrates, sometimes resembling the histologic picture of early mycosis fungoides. It is supposed that the infiltrating T cells participate in the pathogenesis of atrophy and sclerosis. We investigated skin biopsies from 39 lichen sclerosus et atrophicus patients by histology, immunohistochemistry and, in order to establish the status of T cell clonality, by polymerase chain reaction amplifying the T cell receptor-gamma rearrangements. A stage-dependent shift of the CD3-positive T cells was observed from a predominantly CD4-positive to a predominantly CD8-positive phenotype. The increase of CD8-positive cells was associated with more pronounced epidermotropism and basal degeneration. Nearly all CD8-positive cells expressed cytotoxic granules (TIA1), possibly causing the basal destruction. In the late fibrotic stage of the disease, only a weak or no infiltrate was found. Regarding the T cell receptor-gamma polymerase chain reaction, the presence of clonally expanded T cells was demonstrated in 19 of 39 patients (49%) by at least one of two different high resolution electrophoresis techniques applied to separate the amplification products. Thus, for the first time clonally expanded infiltrating T cells were detected in lichen sclerosus et atrophicus. Furthermore, this is one of the first reports on the detection of clonally expanded infiltrating T cells in an inflammatory skin disease. The clonal T cells could not be assigned to the CD4 or CD8 subtype. Most likely, their presence is not the result of a malignant transformation but a response to an as yet unknown lichen sclerosus et atrophicus associated antigen.

Combined US and FNAC provides important information prior to SLNB in that both procedures identify metastases in the lymph nodes (sensitivity > 80%). Patients with positive FNAC may proceed directly to complete lymph node dissection (cLND) instead of having initial SLNB. Thus, combined US and FNAC may prevent unnecessary anesthesia and surgical management as well reduce costs. In our study 16% (19/121) fewer SLNB procedures were carried out, subsequently replaced by cLND. For patients with a negative combination of in vivo US and FNAC, SLNB remains the best diagnostic option.