ECZEMA IMMUNOPATHOGENSIS

The immunopathogenesis of atopic eczema involves decreased cutaneous mediated immunity (Bos et al.). While not fully understood, substance P (SP) and C nerve fibers are implicated in pruitoceptive itch and nociceptive pain. Eczematous lesions expose C nerve fibers creating a pathway for reaction to the application of topical products. Through cell-learning, these reactions subside allowing for continuation of topical treatments involved in reduction symptoms and lesional activity. This paper will elucidate C nerve fiber and SP involvement.

Pruritoceptive itch and nociceptive pain have been shown to be caused by the activation of very small nonmyelinated C nerve endings from large A? and A? myelinated nerve fibers. The C fiber’s free nerve endings are located near the dermoepidermal junction and are conducted centripetally by afferent nerves entering the spinal cord through the dorsal roots. Some research has shown that the itch responses is elicited in the C fiber nerve endings located in the epidermis, while the pain response is elicited in the dermal C fiber endings (Bigliardi-Qi et al.). Once activated, the primary neurons of the C fibers synapse to secondary neurons whose axons cross via the tractus spinothalamicus and arrive at the laminar nuclei of the thalamus. Finally, the laminar nuclei relay the signal to the cerebral cortex. The primary afferent neurons of C fibers have low conduction velocities of approximately 0.5 m/s and extend across innervation territories measuring up to 85 mm in the lower leg (Schmelz et al.).

SP is a proinflammatory neuropeptide produced in dorsal ganglia and transported to periphery via A? and C nerve fibers. SP is from a group of neuropeptides called the tachykinins, which also include neurokinin A (NKA) and neurokinin B (NKB). SP is abundant in pruitoceptive C bibers and can release histamine from mast cell granules and provoke itch. The neuropeptide binds to a dermal mast cell, the mast cell degranulates, histamine is released and vasodilatation occurs. SP also releases tumor necrosis factor-alpha (TNF?) and increases the production of leukotriene (LK) and prostaglandins (PG) in keratinocytes.

REMEDY WITH OLIVAMINE

Olivamine-based skin care products contain several specialized nutrients that effectively modulate the biochemical abnormalities associated with pruritus/pain. The anti-pruritic nutrients include hydroxytyrosol (HT), or 3,4-dihydroxyphenyl ethanol, which is a simple phenol found predominantly in Olea europea, or the olive plant. HT is an extremely potent free radical scavenger that stimulates significant anti-inflammatory activity in skin (Bitler et al.). Numerous studies have established that topically applied antioxidants substantially reduce pruritus by inhibiting the secondary biochemical factors present in infected and inflamed skin (Hadshiew et al.). In particular, HT inhibits leukotriene B4 (LKB4) generation by modulating the enzymatic oxidation of AA through the 5-lipoxygenase pathway Petroni et al., Kohyama et al.). Altogether, the phenolics found in HT possess an array of beneficial LK-inhibitory, PG-sparing, and antioxidant properties (de la Puetra et al.).

In addition, Olivamine containing products provide aloe barbadensis leaf juice, niacinamide (NA), pyridoxine (PO) and retinyl palmitate (RP). Aloe barbadensis leaf juice contains the glycoprotein alprogen, which has been found to inhibit multiple signals throughout the biochemical cascade responsible for deranulated mast cell (DMC) degranulation. Most notably, alprogen inhibits HA activity and prevents the release of LKB4 (Ro et al.). NA and PO induce a similar inhibitory activity of DMC degranulation and HA release (Graf et al.). Furthermore, NA has been shown to significantly inhibit cyclic adenosine monophosphate (cAMP) at the dermal-epidermal junction, thus reducing the excitation of pruritic C-nerve fibers (Bisset et al.). RP reduces pruritic symptoms associated with vitamin A deficient inflammation. Numerous studies show that vitamin A deficiency aggravates the clinical manifestations of inflammatory reactions, thereby increasing the release of pruritic inducing PGs and LKs (Gatica et al.). The topical application of RP prevents vitamin A deficiency and subsequently reduces inflammation and pruritus.

Nutrashield Cream and Skin Repair Cream are composed of advanced silicones that prevent the excessive transepidermal water loss (e-TEWL) responsible for dry, irritated skin. Transepidermal water loss (TEWL) is a measure of cutaneous barrier function reflecting skin water content and is defined as grams of water lost per square meter of skin per hour (Ostlere et al.). TEWL decreases stratum corneum hydration and activates a pruritic inflammatory response in the epidermis and dermis (Fujii et al.). In addition, scratching dry, irritated skin further increases TEWL and intensifies the associated pruritus (Miyamoto et al.). An independent in vitro study found that silicone-based Nutrashield Cream and Skin Repair Cream significantly reduced e-TEWL, conserving nearly four times the quantity of water as the control(McCord). Reducing TEWL and conserving stratum corneum hydration is the key to reducing the dry, irritated skin responsible for inflammation and pruritus (Grubauer et al.).