Table 1.

Potential biochemical mechanisms causing epidermal dysfunction in SLS.

Lipid Abnormality	Possible Pathogenic Mechanism
Fatty aldehydes accumulate.	Aldehyde adducts target intracellular lamellar body membrane lipids (PE) and epidermal proteins.
	Aldehydes activate signaling pathways and apoptosis.
Accumulation of straight-chain fatty alcohols or their metabolic products (alkyl- diacylglycerol, wax esters).	Lipids intercalate into lamellar body membranes and disrupt LB cargo membranes or LB exocytosis
	Fatty alcohols and/or neutral ether lipids affect PKC activity and keratinocyte differentiation
Isoprenols (farnesol, geranylgeroniol) accumulate and/or isoprenoic acids are deficient.	Inhibition of HMG-CoA reductase and decreased mevalonate pathway products (cholesterol, dolichols) result in abnormal LB formation.
	Disruption of PPAR-dependent epidermal gene expression and keratinocyte differentiation.
	Abnormal protein prenylation interferes with cell signaling pathways, vesicle trafficking and cell proliferation.
Accumulation of ω-oxidation lipids (eicosanoids, fatty acids, isoprenols) or deficiency of key products of ω-oxidation	Lipids intercalate into and disrupt LB and SC membranes. Deficient critical dicarboxylic acid?
Deficient acylceramide (ceramide-1) and ceramide-6	Abnormal SC multilamellar membranes cause leaky water barrier.
Polyunsaturated fatty acid deficiency	Abnormal LB and SC membranes?