Hyperkeratotic hand eczema: Eczema or not?

Klaziena Politiek,Hendri H Pas,Gilles F.H Diercks,Peter C Van Den Akker,Laura Loman,Sabrina Z Jan,Henny H Lemmink,Maria C Bolling,Marie L.A Schuttelaar

doi:10.1111/cod.13572

Abstract

BackgroundHyperkeratotic hand eczema (HHE) is a typical clinical hand eczema subtype with a largely unknown pathophysiology.ObjectiveTo investigate histopathology, expression of keratins (K), epidermal barrier proteins, and adhesion molecules in HHE.MethodsPalmar skin biopsies (lesional and perilesional) were obtained from seven HHE patients and two healthy controls. Moreover, 135 candidate genes associated with palmoplantar keratoderma were screened for mutations.ResultsImmunofluorescence staining showed a significant reduction of K9 and K14 in lesional skin. Upregulation was found for K5, K6, K16, and K17 in lesional skin compared with perilesional and healthy palmar skin. Further, upregulation of involucrin and alternating loricrin staining, both in an extracellular staining pattern, was found. Filaggrin expression was similar in lesional, perilesional, and control skin. No monogenetic mutations were found.ConclusionCurrently, the phenotype of HHE is included in the hand eczema classification system; however, it can be argued whether this is justified. The evident expression of filaggrin and involucrin in lesional skin does not support a pathogenesis of atopic eczema. The upregulation of K6, K16, and K17 and reduction of K9 and K14 might contribute to the underlying pathogenesis. Unfortunately, comparison with hand eczema studies is not possible yet, because similar protein expression studies are lacking.

Highlights

Hyperkeratotic hand eczema (HHE) is defined by sharply demarcated areas of hyperkeratosis or thick scaling on the palms, possibly extending to the palmar aspects of the fingers.[1,2] There is little or no redness, and vesicles are absent
K6/16/17 are early barrier alarmins and upregulation of these keratins is seen in both wounding and exposure to irritants, which results in keratinocyte hyperproliferation and hyperkeratosis.[19]
HHE patients have a pre-existent skin barrier problem where exposure to irritating agents and factors eventually leads to secondary dysregulation of the immune system.[22]

Summary

Introduction

Hyperkeratotic hand eczema (HHE) is defined by sharply demarcated areas of hyperkeratosis or thick scaling on the palms, possibly extending to the palmar aspects of the fingers.[1,2] There is little or no redness, and vesicles are absent. There is a male predominance and patients are mainly middle aged.[3] This phenotype is currently included in the classification system of hand eczema. Methods: Palmar skin biopsies (lesional and perilesional) were obtained from seven HHE patients and two healthy controls. Filaggrin expression was similar in lesional, perilesional, and control skin. Conclusion: Currently, the phenotype of HHE is included in the hand eczema classification system; it can be argued whether this is justified. The evident expression of filaggrin and involucrin in lesional skin does not support a pathogenesis of atopic eczema. Comparison with hand eczema studies is not possible yet, because similar protein expression studies are lacking

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