In subjects under stress, diffuse hair thinning is often visible in thepost-frontal area almost all the way to the top. This is a fact, known to everyone actively involved in hair, but how this happens is not clear to anyone. Marino Salin spoke of “nervous incidence.” Daniele Campo speaks of “psychogenic alopecia.” Besides the classical one (activation of the hypothalamic-pituitary-cortical adrenal axis), there is an alternative, peripheral, cutaneous pathway in the stress response. This goes through a chain of neuropeptides, neurotransmitters and hormones that, released from the cutaneous nerve plexuses, have a direct effect on the skin: Nerve Growth Factor, Substance P and Catecholamines are the key mediators of the inhibitory effects on stress-induced hair growth.

Let’s see: the hair follicle possesses a rich nerve plexus. It is important and interesting to know that this follicular nerve plexus is in direct connection with the postcentral gyrus of the cerebral cortex. The follicular nerve plexus is partly composed of motor fibers but mainly of sensory fibers and by postganglionic fibers, sympathetic, amyelin, and noradrenergic free-terminating fibers.

The sensory plexus, under stimulation of Nerve Growth Factor, which increases under stress, is able to release Substance P. Substance P is believed to be the main mediator of pain signals from the periphery to nerve centers. Substance P activates mediators of inflammation, causes degranulation of macrophages and mast cells with production of lymphocyte inflammatory cytokines leading to induction of apoptosis and inhibition of proliferation of Keratinocytes in the hair follicle and on video-dermatoscope suggestive pictures appear, such as an erythematous, sunken halo surrounding the hair infundibules. We talk about neurogenic inflammation.

The sympathetic plexus, under stress, is able to release norepinephrine into the perifollicular intercellular spaces, and norepinephrine is a potent vasoconstrictor and powerful inhibitor of adenylyl cyclase which, when inhibited or blocked, inhibits or cascades the entire kinase system and with it glycolysis, the hexosomonophosphates and the Kebs cycle. Blocked glycolysis is blocked energy metabolism and with it mitosis of the hair matrix. The visible effect of noradrenaline release, which is known to all, is horripilation. But if there is excess adrenergic tone (i.e., norepinephrine) in the follicle system there is also vasoconstriction, ischemia, hypoxia, and under hypoxic conditions glycolysis leads to lactic acid formation.

Lactic acid is normally present in sweat and has, with glutamic acid and aspartic acid, a buffering function. Lactic acid formation, in the epidermis, which is equipped with the specific enzymes of glycolysis and the Krebs cycle, occurs from glucose and triglycerides. When lactic acid formation is supraphysiological, the pH of the system is lowered, the Kebs cycle (which has an ideal pH of 7.35) becomes slow and unable to dispose of pyruvic acid; thus lactic acid, similar to what occurs in a hypoxic and fatigued muscle, accumulates.

What influence does pH have in the development of these diseases?

Changes in pH are followed by changes in surface fatty acid composition. If there is excess adrenergic tone with the blockade of adenylyl cyclase there is, as mentioned above, no activation of protein kinase and thus of hormone-sensitive lipase that allows normal metabolism of triglycerides to fatty acids, and triglyceride metabolism, normally directed toward fatty acid formation, is diverted to acetyl-coenzyme A. Acetyl-coenzyme A cannot be disposed of in the Kebs cycle, because it is slowed by the acidity of the system, and takes the metabolic route of squalene, which accumulates, and further lactic acid formation, so the “short circuit” is self-maintaining.

Lo Squalene (so named because it was first isolated from shark liver) is an aliphatic acyclic hydrocarbon that, as mentioned above, is formed from lactic acid and/or triglycerides. Cholesterol is normally formed from squalene, and in the epidermis lipid biosynthesis is very active, so much so that only the epidermis can convert C14 acetate into cholesterol using precisely squalene as a precursor.

What happens with the degradation of hair sheaths?

A degradation of the hair sheaths is consistently observed in Alopecia Areata. This harm has in the past been attributed by non-medical Trichologists as Marcel Contier e Marino Salin to two “metabolic waste“: precisely lactic acid and squalene. Under these conditions, under a microscope in polarized light, in a high number of hairs extracted for trichogram we can see some, apparently strange, images. There is damage to the anchoring system of the inner sheath. According to Marino Salin, it is lactic acid that causes caustic damage to the inner sheath, which appears to be lifted from the hair cuticle. Under a polarized light microscope, what Contier and Salin believed to be lactic acid damage appears as a black spiral, a helical shape, between the hair cuticle and the inner epithelial sheath, which appears to be damaged by the “caustic” effect. The inner epithelial sheath appears to detach from the cuticle and “bag” while the outer epithelial sheath remains intact. Lactic acid (C3 H6 O3) would then lead to degradation of the inner sheath by caustic effect and hair loss, such as Telogen Effluvium, would be the consequence. Squalene, on the other hand, would appear to reach the hair shaft from the sebaceous gland and under a microscope in polarized light would appear as a dark spot that destroys the inner sheath from the outside. This phenomenon is attributable to the strong hygroscopicity of squalene, which damages the inner sheath by dehydration. In the expansion zone of Alopecia areata, damage to the inner epithelial sheath of all hairs is constantly found, and sheath damage appears to be the earliest sign of Alopecia Areata. We hypothesize that the initial damage of Alopecia Areata may be at the level of the inner epithelial sheath. This hypothesis allows us to understand how an Alopecia Areata can develop within a few hours, a fact that cannot be reconciled, in our opinion, with a strict autoimmune pathogenesis. The hair (and hairs) affected by the disease, after destruction of the sheath anchoring system, fall either in anagen than in catagen; that is, it appears that the hair attempts, unsuccessfully, to “escape into telogen,” a stage at which the pathogenic noxa at the origin of the disease can no longer strike. That portion of hair that falls into anagen appears to have suffered such extensive sheath damage that the follicle cannot even attempt to escape, through catagen, to telogen. This is in agreement with histological observations showing a marked increase in the proportion of catagen hair at the expanding edge of an Alopecia Areata. Autoimmunity would come into play only in the chronification of the disease. If this does not occur we have a Telogen Effluvium.