Keratosis Pilaris and its Subtypes

Associations, New Molecular and Pharmacologic Etiologies, and Therapeutic Options

Jason F. Wang; Seth J. Orlow

Disclosures

Am J Clin Dermatol. 2018;19(5):733-757. 

In This Article

Clinical Overview, Pathophysiology, and Histopathology of Keratosis Pilaris (KP) and its Subtypes

The clinical features and natural history of KP are summarized in Table 2; while the histopathological hallmark of KP is follicular hyperkeratosis, further information is provided in Table 2.[1,3,21–26] Although KP is usually diagnosed clinically, dermoscopy can aid in supporting the diagnosis and monitoring response to treatment; dermoscopic findings are also summarized in Table 2.[24,27–29] The pathophysiology of KP is not completely understood. One hypothesis proposes that the keratotic infundibular plug found in KP results from abnormal keratinization of the follicular epithelium.[28] Another hypothesis proposes that, because hair shafts extracted with a needle from 25 patients with KP retained their coiled shape despite removal from the follicle, KP is not a primary disorder of keratinocytes but rather a hair shaft or infundibular disorder; this hypothesis suggests that KP occurs when coiled hair shafts rupture the follicular epithelium, causing defective follicular keratinization and inflammation.[29,30] It has also been postulated that both the abnormal keratinization and hair shaft abnormalities can be explained by the absence of sebaceous glands as an earlier step in the pathophysiology of KP.[24] We discuss these and other hypotheses in greater depth.

KP Atrophicans and Erythromelanosis Follicularis Faciei et Colli

KP atrophicans (KPA) has a variety of clinical and histopathologic features (Table 2) and includes a spectrum of clinical variants:[31–34] keratosis pilaris atrophicans faciei (KPAF),[3,32,33,35–37] atrophoderma vermiculatum (AV),[3,32,38–43] and keratosis follicularis spinulosa decalvans (KFSD).[3,32,38,44–49] Whether folliculitis spinulosa decalvans (FSD), a KFSD variant, is a separate clinical entity is still debated (Table 2).[32,44,50] Conversely, it has been suggested that, rather than one heterogeneous disease, KPA is better defined as a finding shared by various clinical entities.[44] It has been hypothesized that the pathophysiology of KPA involves a mutation in the low-density lipoprotein (LDL) receptor-related protein 1 (LRP1),[51] causing keratinocytes to release cytokines in response to follicular plugs, leading to perifollicular inflammation that promotes fibrosis, alopecia, atrophy, and hair bulb shrinkage.[32,34] It is possible that cutaneous infection with human papillomavirus may exacerbate KPAF.[52] Because KPA shares many clinical and histological features, including follicular papules, cicatricial alopecia, and follicular vacuolar interface changes, with the lichen planopilaris subgroup, the simplifying term "lichen folliculitis" has been proposed to refer to both groups.[53] Erythromelanosis follicularis faciei et colli (EFFC) is a subtype of KP that lacks the scarring and atrophy of KPA and has been described by a few groups (Table 2).[54–57]

KP Rubra, Unilateral KP, and Papular, Profuse, Precocious KP

KP rubra (KPR) is a common variant of KP that has received little attention (Table 2).[23] Patients with significant facial involvement are often distressed by the appearance of their lesions. Although KPR does not typically exhibit the hyperpigmentation or atrophy associated with other KP variants, it does appear to be more common than them but less common than KP, with one study reporting KPR in up to 25% of patients with KP studied.[23,58] Conflicting data in the literature address the sex and age demographics of KPR. One study reported a female-to-male ratio of 2:1, with a higher incidence in adults.[58] Another study of a primarily pediatric population reported a female-to-male ratio of 1:2.[23] A familial component and connection to atopy have been suggested.[23,59] The pathophysiology of KPR is poorly understood. Because it fluctuates and can present in areas not significantly affected by keratotic papules, it has been hypothesized that the erythema of KPR may be due to flushing from an autonomic abnormality.[23] In lighter-skinned patients, KPR has significant clinical overlap with EFFC; they may represent a disease spectrum with individual differences in pigmentation.[60–62]

Rare case reports describe unilateral presentations of KP and its subtypes. In one case, a 2-year-old girl presented with KP on almost the entire left side of the body, demarcated by a sharp midbody line, a phenomenon potentially explained by a somatic mutation.[63] In another case, a 29-year-old pregnant woman developed generalized KP only on her right side.[64] An additional case of unilateral KP occurring in hypopigmented patches following the lines of Blaschko on the right chest wall of a 25-year-old Asian man has been reported.[65] KPA can also present unilaterally. There are six reported cases of AV occurring unilaterally, all presenting in childhood.[66–71] Two of these cases were associated with ipsilateral congenital cataracts, potentially comprising a variant of epidermal nevus syndrome.[70,71] There has also been a reported case of unilateral KPAF with childhood onset, clinically mimicking follicular mucinosis.[72] Unilateral EFFC is rare but also possible.[54]

Papular, profuse, precocious KP (PPPKP) is a KP variant with extensive involvement of the cheeks and extremities arising before 18 months of age.[21] A study of 11 patients found that the lesions in PPPKP were larger and more extensive and had an earlier onset than those of KP; the authors opined that the condition is greatly underreported. In contrast to other KP subtypes, PPPKP does not appear to be inherited. It appears to be associated with AD, and bacterial folliculitis is a potential complication.

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