Non-segmental vitiligo (NSV) comprises different clinical subtypes including acrofacial, generalized, mucosal (multifocal) and universal types. In most cases of NSV, there is a preferential targeting of epidermal but not follicular melanocytes and, in a recent study, leukotrichia has been found in only 18% of patients with NSV (Mazereeuw-Hautier et al., 2010). Follicular melanocyte involvement is, on the contrary, in segmental vitiligo (Taïeb and Picardo, 2009).
In July 2011, a 13-yr-old African native boy was seen at the vitiligo clinic of our department for the assessment of a 2-yr history of depigmented macules of the midface including the nose, lips and glabella (Figure 1A), left and right peri-auricular areas (Figure 1B) and complete whitening of the eyelashes. There was no evidence of inflammatory skin condition prior to the onset of the lesions. The skin texture was normal, although cutaneous examination showed a complete whitening of body hair with progressive whitening of scalp hairs. Upon questioning, the patient and his parents acknowledged involvement of the midface, the lips with progressive whitening of eyelashes as the primary event 2 yr ago. Body hair whitening appeared later, at the onset of puberty, and progressively evolved towards complete whitening (Figure 1C). A treatment with pimecrolimus applied twice a day for 3 months allowed partial repigmentation of all vitiligo macules. There was no other abnormality, in particular no visual or hearing dysfunction. Laboratory investigations for thyroid function were normal. Family history was remarkable for a history of premature hair graying (PHG) in all four sisters of the boy’s mother as well as in his maternal grandmother (Figure 2). Biopsy taken close (1 cm) to a depigmented macule of the peri-auricular area confirmed the clinical diagnosis of vitiligo. Skin samples were stained with hematoxylin and eosin (HE), silver (Fontana–Masson stain), and Melan-A and showed a loss of melanin pigment in the basal layer of the follicle compared with the adjacent epidermis (Figure 3A,B) which was associated with a loss of follicular melanocytes (demonstrated by immunostaining with Melan-A antibody Figure 3C). We therefore propose naming this condition ‘follicular vitiligo’.
Repigmentation of vitiligo depends on the mobilization of melanocytes from three possible sources: the hair follicle, the border of vitiligo lesions, and unaffected melanocytes within depigmented areas (Parsad et al., 2004). Among these, the hair follicle is the main source of melanocytes. To the best of our knowledge, this is the first report of a case of NS vitiligo early and massively affecting the body and hair follicle compartment, in contrast to limited interfollicular compartment involvement. This finding may be less remarkable in individuals with a fair skin complexion. However, as opposed to our patient’s history, premature leukotrichia/canities is not a usual feature in NSV patients and preferential targeting of hair follicle melanocytes with sparing of skin melanocytes has not been described previously. Indeed, in most cases of NSV, there is a preferential targeting of epidermal but not follicular melanocytes, which may correspond to different antigenic profiles. Some of these immunologic differences are likely to reflect the fact that amelanotic pigment cell precursors reside in the immune-privileged proximal anagen hair bulb (Christoph et al., 2000; Ito et al., 2008; Westgate et al., 1991).
Moreover, in our patient there was a strong family history of premature hair graying, which is known to be an inherited trait. Hair graying is probably linked to an early reduction in tyrosinase activity within hair bulb melanocytes associated with inappropriate melanocyte–cortical keratinocyte interactions and defective migration of melanocytes to the hair bulb (Ito et al., 2008; Tobin, 2011). An autoimmune cause is usually not considered for PHG (Ezzedine et al., 2012). In mice, a number of alleles have been identified that explain the coat color diversity (Bennett and Lamoreux, 2003). Nishimura et al. (2005) reported that immature MITF-positive melanoblasts in the bulge area (which show similar features to mouse melanocyte stem cells) are decreased in number with aging. In the same study, the analysis of mutant Bcl2-deficient mice has revealed that the loss of melanocyte stem cells precedes the loss of hair matrix melanocytes and hair graying (Nishimura et al., 2005). Their finding is consistent with another study in which the authors showed that not only hair bulb melanocytes but also PMEL17-positive immature melanoblasts on the outer root sheath (which show a similar destribution pattern to MITF-positive melanoblasts in the bulge area) are depleted in aged hair follicles which grow white hair (Commo et al., 2004). Hair graying may be induced by melanocyte stem cell depletion because of deficiencies in a critical gene or genes with subsequent hair graying (Nishimura, 2011). Indeed, the family history of PHG that we found in our patient suggests that further epidemiological investigations on vitiligo and PHG should be conducterd, as previously suggested (Taïeb and Picardo, 2007). A recent genome-wide association study has found a susceptibility variant for NSV in the tyrosinase gene (TYR) in European whites, rarely found in melanoma patients (Jin et al., 2010), suggesting a genetic dysregulation of immunosurveillance against the melanocytic system. A subset of PHG might thus be reconsidered as an immune process inappropriately targeting the hair follicle melanocytic compartment. If confirmed, such a finding should also prompt a search for PHG in the context of risk of melanoma. However, the immune targeting of the hair follicle reservoir by vitiligo in our patient may also be the consequence, due to intrinsic melanocyte fragility, of an independent non-immune PHG predisposing trait.
In conclusion, our patient seems to be affected by a form of generalized vitiligo targeting mostly, if not primarily, hair follicle melanocytes, in the context of familial canities. We propose calling this particular form of vitiligo ‘follicular vitiligo’.