Abstract

Acral inflammatory dermatoses are commonly biopsied to distinguish between palmoplantar psoriasis (PP), hyperkeratotic palmoplantar eczema (HPE), and sometimes mycosis fungoides palmaris et plantaris (MFPP). While some cases are easily diagnosed using histopathological features, other cases may be more challenging to classify. Biomarkers reflecting the underlying immunology and molecular treatment targets of these disorders have the potential to provide diagnostic clarity; however, immunologic changes of these dermatoses on acral sites and how this relates to non-acral sites have not been intensively investigated. Eczema/atopic dermatitis is driven by T helper 2 (Th2)-skewed inflammation, while psoriasis demonstrates a Th1/Th17 immune bias. We therefore evaluated whether RNA in situ hybridization for markers of Th1 (IFNG), Th2 (IL13), and Th17 (IL17A) inflammation could distinguish PP and HPE. We also evaluated these markers in MFPP. To this end, we stained formalin-fixed paraffin-embedded skin biopsies from patients with HPE (n=12), PP (n=8), MFPP (n=8), and clinically normal acral skin (n=9), comparing staining patterns among the groups as well as to non-acral sites. We found that IL17A staining was significantly increased in PP compared to HPE, MFPP, and normal acral cases. IL17A epidermal staining in particular was effective at distinguishing PP, with 88% of PP cases demonstrating strong IL17A epidermal staining compared to 25% of HPE, 25% of MFPP, and 0% of normal acral cases. Unexpectedly, IFNG and IL13 were expressed at comparable levels among HPE, PP, and MFPP, contrasting with non-acral eczema (IL13 predominant, no/low IFNG) and psoriasis (IFNG/IL17A predominant, no/low IL13). These findings demonstrate the utility of these biomarkers for diagnosis of acral inflammatory dermatoses, suggest a unique immunology of these entities on acral sites, and imply the potential value of this approach for selecting cytokine-directed therapies for these patients.

Financial Disclosure:
No current or relevant financial relationships exist.