Teloptosis and Kenogen: Two New Concepts in Human Trichology
Archives of Dermatology
Recently, 2 new important concepts have been introduced in human trichology. They are exogen/teloptosis and kenogen. As it is customary when new concepts have to be accepted, some perplexity and confusion originated. We will try to clarify what exogen/teloptosis and kenogen mean and what importance they may gain in hair physiology and pathology.
Exogen is a term coined by Stenn1 and indicates the moment in which the club hair is shed from the follicle that is already occupied by a new terminal anagen hair. In Stenn’s view, exogen, as the term suggests, is a new phase of the hair cycle. Its duration, however, is too short for deserving the privilege of a “phase” and, as Piérard-Franchimont and Piérard2 remarked, the term might rather suggest a biological exogenous process opposite to an endogenous one. They proposed instead the term teloptosis derived from the Greek o (falling off) to indicate the same phenomenon.
Far from being pushed off by the underlying new anagen hair, as quite simplistically thought before, the teloptotic hair is the result of the loss of adhesion between cells of the club hair and those of its epithelial envelope. The anchorage of telogen hairs to the follicular epithelium is due to desmosomes between the keratinocytes “surrounding the hair club and the basal layer of the outer root sheath,” as Koch et al3 put it. This same area of the hair follicle, in both mice and humans, shows intense reactivity for desmoglein 33 and, by electron microscopy, the mooring cells of the teloptotic root show intercellular separation suggesting a proteolytic process in the final shedding step.4 In fact, desmoglein 3 knockout mice lose their telogen hair prematurely.3
The concept of exogen/teloptosis is supported also by morphological findings. According to Piérard-Franchimont and Piérard,2 at least 2 types of telogen hairs on a trichogram can be distinguished, one whose club is still surrounded by its epithelial envelope and another whose club is naked. The former corresponds to a hair in its early telogen phase that only the forceful plucking of a trichogram can take off from its follicle. The naked club hair, instead, is the physiological result of teloptosis. Actually, the types of telogen roots are more numerous and diversified and their microscopical analysis and interpretation are still in progress (B. M. Piraccini, oral communication, European Hair Research Society conference, Barcelona, Spain, June 2003).
Teloptosis may be important also from the pathological point of view. According to Piérard-Franchimont and Piérard,2 early and synchronized teloptosis would result in increased hair shedding clinically presenting as telogen effluvium. This effluvium would be due to an anticipated teloptosis rather than a premature entrance into telogen phase as in other telogen effluvia. This may suggest that a distinction among various types of telogen effluvium could be established. Multifarious agents are likely to be at work in anticipated teloptosis, though sharing the same mechanism of damage to desmoglein 3. Mechanical (brushing, shampooing, chemical lotions), actinic, and inflammatory (eg, seborrheic dermatitis) factors may account for some telogen shedding.
Kenogen (from the Greek ó meaning empty) indicates with a single word what is has been called lag phase, latency period, or empty follicle phenomenon.5 The hair growth cycle is generally recognized to comprise phases of growth (anagen), regression (catagen), and rest (telogen). That this sequence does not recur regularly in women with androgenetic alopecia has been found in 1986 when Guarrera and Ciulla6 observed by phototrichogram periods in which the follicle was free from the hair shaft. Those periods coincided with the interval between teloptosis and the emergence of a new anagen. Later, Courtois et al7 observed the same phenomenon in men. Their “latency period” lasted about 4 months, increasing significantly up to about 7 months (10%-125%). Over the same period, kenogen affected 80% of all hair follicles.6 In 2 women with progressing androgenetic alopecia studied for 2 years with phototrichogram,8 kenogen involved 22% of the hair follicles, lasting a variable time in the same patient (from 3 months to 1 year). Both frequency and duration were greater in the patient with more severe alopecia. These findings agree with the observation that in women with diffuse androgenetic alopecia a proportion of growth-inhibited (dormant) follicles exists.9
Kenogen affects also prepubertal children,10 however. In an 8-year-old boy, with normal serum androgen level for his age, studied for 1 year, it involved 8% of hairs and lasted about 2 months.
The kenogen concept raises several questions. Its presence in a prepubertal child, in whom 5 reductase is not activated and androgenetic alopecia is not therefore present, suggests that the phenomenon is physiological. Kenogen, therefore, may be the true resting phase of hair cycle. In telogen, in fact, the "epithelial remnants (distal outer sheath, secondary hair germ, bulge) are still engaged in biochemical activity and even some degree of proliferation."11
Once accepted that kenogen is a physiological phenomenon, it remains to understand whether it affects all the follicles or groups of follicles simultaneously, or, as it seems more likely to us, it affects on rotation one follicle in a particular group of follicles. Thus, kenogen would be a sort of “rest shift” within a follicular unit. In addition, it suggests there may be 2 different pathways in the hair cycle: The classic one that advances from early anagen to telogen, the latter coincident with the new early anagen and terminating with teloptosis, and the alternative one in which the telogen phase, not accompanied by the coincident new early anagen phases, ends with teloptosis but leaves the follicle empty.5
Although it is unclear whether it depends on androgens and 5 reductase, kenogen may be important also in the pathogenesis of androgenetic alopecia. Its higher frequency and longer duration in progressing androgenetic alopecia suggest that hair miniaturization may be not the only mechanism at work in this disease.