Analysis of Sebum Lipid Composition and the Development of Acneiform Rash before and after Administration of egfr Inhibitor

Abstract

Treatment with an epidermal growth factor receptor inhibitor (egfri) in patients having non-small-cell lung cancer can cause frequent and diverse skin toxicities, an acneiform rash being one of the commonest. Although the exact pathophysiology of this rash and its development mechanisms remain unknown, investigators have noted that egfriinduced skin toxicity might be partly associated with sebaceous gland function. Sebum is composed mainly of the lipids squalene (sq), wax ester (we), triglyceride, free fatty acid, and cholesterol, which are secreted mostly from the sebaceous glands and by keratinocytes. We therefore investigated the lipid composition of sebum before and after administration of egfri and whether sebum composition was associated with the development of acneiform rash. To investigate any associated changes in sebum gland activity, we focused especially on alterations in the amounts of sq and we, which are secreted solely from the sebaceous glands.In contrast to our expectations, we observed no substantial changes in the lipid composition of sebum before and after administration of egfri. Composition varies with the individual; however, the proportion of sq and we derived from the sebaceous glands was significantly lower in regions that did not develop acneiform rash than in regions that did. Our results suggest that development of an acneiform rash after administration of egfri could be related to sebaceous gland activity. Measurement of the lipid composition of sebum before therapy with egfri might predict which patients will be prone to acneiform rash.

Meibomian glands, meibum, and meibogenesis

“…It seems that further efforts of this nature, without addressing specific unanswered questions, would produce progressively less new information due to the universal law of diminishing returns. For comparison purposes, the lipid composition of a related secretion, namely sebum (Butovich et al, 2016) (Thiboutot, 2004) (Picardo et al, 2009) (Nakahara et al, 2015), is also presented in Table 1, from which one can conclude that sebum and meibum substantially differ from each other.…”

Sebum/Meibum Surface Film Interactions and Phase Transitional Differences

“…4,33 The concentration of SQ in sebum is 28%, 34–36 but meibum contains no 28 or very little (2%) SQ. 37–41 In addition to a higher level of SQ in sebum compared to meibum, sebum contains much more free cholesterol (10%–20%) 42,43 compared with meibum (0%–1%) 4 and more glycerides (25%–50%) 36,42,43 than meibum (1%–1.5%). 36,44,45 As would be expected, if sebum and meibum mixed, tears were found to contain more free cholesterol (6%–15%) 46,47 and more free glycerides (2.5%) 45 compared with meibum, further supporting the idea that meibum and sebum mix and contribute to the TFLL.…”

The investigation of the amounts and expressions of epidermal growth factor, epidermal growth factor receptor, and epidermal growth factor receptor gene polymorphisms in acne vulgaris

“…Excess sebum secretion proportional to acne severity is a well‐known trait in AV patients, 21 while those undergo EGFRI treatment do not complain from hyperseborrhea. One other discrepancy is the increased squalene and decreased linoleic acid content in AV, 21 whereas there was no change in the content of sebum after EGFRI treatment 22 . Finally, unlike AV, AF may cause itching which may be relieved by topical steroids 23 …”

“…One other discrepancy is the increased squalene and decreased linoleic acid content in AV, 21 whereas there was no change in the content of sebum after EGFRI treatment. 22 Finally, unlike AV, AF may cause itching which may be relieved by topical steroids. 23 Molecular genetic studies have been carried out for a long time to understand the AV genetic predisposition.…”