The Hardening Phenomenon in Irritant Contact Dermatitis: Cosmetic Implications

By: Howard I. Maibach, MD, University of California School of Medicine, San Francisco and Shannon A. Watkins, MD, Yale New Haven Hospital

Posted: October 30, 2009, from the November 2009 issue of Cosmetics & Toiletries.

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Changes in Permeability and Vascular Reactivity
Another theory to explain the hardening phenomenon is that repetitive irritation induces increased permeability and vascular reactivity, thereby allowing for the faster removal of irritants in hardened skin.^{2, 7} McOsker et al. showed in an animal model that adapted skin was more permeable to irritants than normal skin, yet with less irritant reaction.⁷ The researchers resolved this apparent dichotomy by purposing two theories.

The first theory proposes that in hardened skin, the irritant could be reacting less with skin components and is therefore removed more rapidly via blood and lymph. Concentrations of the irritant remaining in the tissues are thus insufficient to induce a reaction. This theory assumes that a certain threshold level of irritant is necessary to induce a reaction, even in accommodated cells.

In a second theory, the resistance of hardened skin to irritants is the result of a reduced permeability in the individual cells. This concept can be reconciled with an overall increase in skin permeability in hardened skin but only if normal skin favors a slower intracellular route of absorption while accommodated skin favors a faster, alternative intercellular route of absorption.^{2, 7} To date, no known experiments have yet been performed to assess the validity of these theories.

Systemic Changes with Hardening
Evidence also supports that hardening is not locally limited as once thought and that it has global effects, perhaps mediated through cytokines and humoral factors.^{2, 9} Similarly, exposure to UV light is a more widely known localized skin reaction that has systemic implications. UV exposure can result in systemic immunologic suppression via multiple mechanisms.¹⁰ Studies suggest a similar global process may also occur with hardening.

In 1987, Lamintausta et al. showed that repeated SLS applications on the right scapula of human subjects induced a post-irritant hypo-reactive state at a distant site on the left scapula during repeat testing six weeks later.¹¹ In 1990, Wulfhorst et al. provided further support for systemic effects of hardening by again showing that low-dose levels of irritant can induce a globally hyporeactive state.² While the localized changes observed with hardening are well-documented, more studies are required to explore the possible global effect of this phenomenon, as well as its mechanisms.