Keratosis pilaris atrophicans

INTRODUCTION — Keratosis pilaris atrophicans is a group of related disorders characterized by inflammatory keratotic papules that may result in alopecia and scarring. They include keratosis pilaris atrophicans faciei (also called ulerythema ophryogenes), atrophoderma vermiculatum, and keratosis follicularis spinulosa decalvans [1].

This topic will review the clinical presentation and management of keratosis pilaris atrophicans. Keratosis pilaris is discussed separately. (See "Keratosis pilaris".)

PATHOGENESIS — Keratosis pilaris atrophicans is caused by abnormal keratinization of the follicular infundibulum, resulting in obstruction of the growing hair shaft and inflammation. Chronic inflammation leads to fibrosis, atrophy, shrinkage of the hair bulb, and alopecia. The association with several congenital syndromes due to partial monosomy or deletion in chromosome arm 18p suggests that the genes regulating the follicular keratinization may be located on chromosome 18p. (See 'Associated syndromes' below.)

Autosomal recessive keratosis pilaris atrophicans has been shown to be due to a mutation in the desmoglein 4 gene [2].

PATHOLOGY — The histopathologic features of keratosis pilaris atrophicans are nonspecific. In the early stages, there is an orthokeratotic keratin plug that blocks and dilates the orifice and upper portion of the follicular infundibulum (picture 1) [3]. A twisted hair shaft may be trapped within this keratotic material, and a mild perivascular mononuclear cell infiltrate is usually present in the adjacent dermis. In later stages, dermal fibrosis and loss of hair follicles may be seen.

CLINICAL VARIANTS — There are three clinical variants of keratosis pilaris atrophicans: ulerythema ophryogenes (also called keratosis pilaris atrophicans faciei), atrophoderma vermiculatum, and keratosis follicularis spinulosa decalvans (KFSD) [4]. Clinical features common to all forms include involvement of the face, in particular of the lateral eyebrows and cheeks; prominent erythema; and progression to an atrophic stage with loss of hairs in the involved areas [5].

Ulerythema ophryogenes — Ulerythema ophryogenes (the prefix "ophryo-" refers to the eyebrow), also called "keratosis pilaris atrophicans faciei," primarily involves the eyebrow areas, resulting in atrophy and permanent loss of the involved hairs [5,6]. It usually occurs as a sporadic disease, but an autosomal dominant pattern of inheritance has been also reported [1].

Ulerythema ophryogenes typically begins in the first months of life, with erythema and tiny keratotic follicular papules involving the lateral one-third of the eyebrows (picture 2B). Over time, atrophy and loss of the eyebrows occur. The disorder may extend to the temples, cheeks, and forehead, resulting in a persistent facial erythema (picture 2A). The affected areas may feel rough on gentle palpation.

The condition typically improves after puberty, but the loss of the lateral eyebrows and resultant scarring is often permanent. Simple keratosis pilaris is often present on the extensor aspects of the limbs. (See "Keratosis pilaris".)

Associated syndromes — Ulerythema ophryogenes is considered a marker of several congenital syndromes, such as Noonan syndrome, Rubinstein-Taybi syndrome, Cornelia de Lange syndrome, cardiofaciocutaneous syndrome, and chromosome 18p deletion [7-12]. (See "Noonan syndrome" and "Microdeletion syndromes (chromosomes 12 to 22)", section on '16p13.3 deletion syndrome (Rubinstein-Taybi syndrome)' and "Microdeletion syndromes (chromosomes 12 to 22)", section on '18p deletion syndrome'.)

An association has also been reported with woolly hair (MIM #194300), a group of autosomal dominant hair shaft disorders characterized by fine and tightly curly hair [13].

Atrophoderma vermiculatum — Atrophoderma vermiculatum is a rare form of keratosis pilaris atrophicans, characterized by hyperkeratotic follicular papules with surrounding erythema on the cheeks, which evolve into coalescent follicular depressions in a honeycomb or worm-eaten pattern (picture 3) [14]. It usually begins during childhood and progresses until puberty. The cheeks and preauricular regions are predominantly involved, with sparing of the eyebrows, eyelashes, and scalp.

Atrophoderma vermiculatum is a feature of Rombo syndrome, a genetic syndrome characterized by facial follicular atrophy, multiple milia, hypotrichosis, peripheral vasodilation with cyanosis, trichoepitheliomas, and predisposition to develop basal cell carcinomas [15,16]. Atrophoderma vermiculatum has also been associated with Loeys-Dietz syndrome, a rare autosomal aortic aneurysm syndrome with multiple skeletal abnormalities and dysmorphic facial features, caused by mutations in the transforming growth factor-beta receptor gene (TGFBR) [17].

Keratosis follicularis spinulosa decalvans — Keratosis follicularis spinulosa decalvans (KFSD; MIM #308800) is an exceedingly rare variant of keratosis pilaris atrophicans characterized by follicular keratosis and progressive cicatricial alopecia involving the scalp, eyebrows, and eyelashes (picture 4A-B) [4]. KFSD affects predominantly males, suggesting an X-linked mode of inheritance [18]. Mutations in the membrane-bound transcription factor protease site 2 (MBTPS2) gene on Xp22.12-p22.11 have been found in patients from several families with KFSD [19-21]. However, autosomal dominant forms have also been reported [18,22].

KFSD presents with facial erythema and extensive keratosis pilaris of the face, scalp, extremities, and trunk during early childhood (picture 4B). Cicatricial alopecia of the scalp and eyebrows begins around puberty and slowly progresses with follicular inflammation and fibrosis.

Associated features include palmoplantar keratoderma, photophobia, blepharitis, and corneal dystrophy. Acne keloidalis nuchae and tufted hair folliculitis have been described in several patients with KFSD [23-25]. (See "Evaluation and diagnosis of hair loss", section on 'Cicatricial alopecia'.)

KFSD shares many clinical features with ichthyosis follicularis, congenital atrichia, and photophobia (IFAP) syndrome (MIM #308205), an X-linked condition caused by mutations in the MBTPS2 gene, in which affected neonates show widespread keratotic follicular papules with a sandpapery feel to the skin, atrichia or severe hypotrichosis, and photophobia [4,26].

DIAGNOSIS — The diagnosis of keratosis pilaris atrophicans is clinical. A skin biopsy is usually not necessary for the diagnosis. If performed, it shows nonspecific features including keratotic plugs in the pilosebaceous units and a mild perifollicular inflammatory infiltrate [6]. (See 'Pathogenesis' above.)

The differential diagnosis of keratosis pilaris atrophicans includes:

●Keratosis pilaris rubra faciei, a clinical variant of the common keratosis pilaris characterized by marked perifollicular erythema on the cheeks, forehead, and neck (picture 5). (See "Keratosis pilaris", section on 'Clinical variants'.)

●Erythromelanosis follicularis faciei et colli, another variant of keratosis pilaris presenting with erythema, hyperpigmentation, and follicular papules involving the cheeks, preauricular areas, and sides of the neck (picture 6). (See "Keratosis pilaris", section on 'Clinical variants'.)

TREATMENT — There are no effective therapies for keratosis pilaris atrophicans. The condition often improves with age. Ultraviolet (UV) protection is encouraged, since the condition is often photoexacerbated [6]. Topical corticosteroids, keratolytics, and topical retinoids are of limited benefit [27]. There are isolated reports of successful use of systemic retinoids for atrophoderma vermiculatum and keratosis follicularis spinulosa decalvans [28,29].

Pulsed dye laser and intense pulsed light have been reported as effective in reducing erythema in small series of patients [30,31]. Hair transplant surgery has been reported for dormant keratosis pilaris atrophicans [32].

SUMMARY AND RECOMMENDATIONS

●Definition – Keratosis pilaris atrophicans is a group of rare conditions characterized by follicular keratosis, chronic inflammation, and secondary scarring and alopecia. (See 'Introduction' above.)

●Clinical presentation – Keratosis pilaris atrophicans comprises three distinct entities: ulerythema ophryogenes (picture 2A-B) (also called keratosis pilaris atrophicans faciei), atrophoderma vermiculatum (picture 3), and keratosis follicularis spinulosa decalvans (picture 4A-B). Clinical features common to all forms include involvement of the face, in particular of the lateral eyebrows and cheeks; prominent erythema; and progression to an atrophic stage with loss of hairs in the involved areas. (See 'Clinical variants' above.)

●Treatment – There is no effective treatment for keratosis pilaris atrophicans. It often improves with age, but the loss of eyebrows and scarring are typically permanent. Topical therapies, including corticosteroids, keratolytics, and retinoids, are of limited benefit. Pulsed dye laser and intense pulsed light have been reported as effective in reducing erythema. (See 'Treatment' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Jennifer Perryman, MD, who contributed to an earlier version of this topic review.