American Journal of Clinical Dermatology (2018) 19:733–757

https://doi.org/10.1007/s40257-018-0368-3

REVIEW ARTICLE

Keratosis Pilaris and its Subtypes: Associations, New Molecular

and Pharmacologic Etiologies, and Therapeutic Options
Jason F. Wang1   · Seth J. Orlow1 

Published online: 24 July 2018

© Springer Nature Switzerland AG 2018

Abstract
Keratosis pilaris is a common skin disorder comprising less common variants and rare subtypes, including keratosis pilaris
rubra, erythromelanosis follicularis faciei et colli, and the spectrum of keratosis pilaris atrophicans. Data, and critical analysis
of existing data, are lacking, so the etiologies, pathogeneses, disease associations, and treatments of these clinical entities are
poorly understood. The present article aims to fill this knowledge gap by reviewing literature in the PubMed, EMBASE, and
CINAHL databases and providing a comprehensive, analytical summary of the clinical characteristics and pathophysiology
of keratosis pilaris and its subtypes through the lens of disease associations, genetics, and pharmacologic etiologies. Histo-
pathologic, genomic, and epidemiologic evidence points to keratosis pilaris as a primary disorder of the pilosebaceous unit
as a result of inherited mutations or acquired disruptions in various biomolecular pathways. Recent data highlight aberrant
Ras signaling as an important contributor to the pathophysiology of keratosis pilaris and its subtypes. We also evaluate data
on treatments for keratosis pilaris and its subtypes, including topical, systemic, and energy-based therapies. The effectiveness
of various types of lasers in treating keratosis pilaris and its subtypes deserves wider recognition.

Key Points  1 Introduction

Keratosis pilaris (KP) is strongly associated with both
atopy and its related genetic abnormalities and with obe-
sity and its related hormonal abnormalities; it is also a
cutaneous manifestation of many hereditary syndromes,
including various neuro-cardio-facial-cutaneous syn-
dromes, ectodermal dysplasias, and neurodevelopmental
disorders.
Several systemic medications, including cyclosporine
and targeted inhibitors of B-Raf and tyrosine kinases,
can cause widespread KP-like eruptions.
Several types of lasers are effective in treating the ery-
thema, skin roughness, and pigmentary issues of KP and
its subtypes.
* Seth J. Orlow
seth.orlow@nyumc.org
1
The Ronald O. Perelman Department of Dermatology, New
York University School of Medicine, 240 East 38th Street,
11th Floor, New York, NY 10016, USA
Keratosis pilaris (KP), colloquially known as “chicken skin,”
is a common skin disorder characterized by keratotic pap-
ules in a folliculocentric distribution. Management of KP is
often sub-optimal, partly because of the fragmented nature
of the medical literature relating to the condition; the last
review article on the subject was published 10 years ago
[1]. The high prevalence of KP contrasts with the relative
lack of attention paid to it; KP is often dismissed as a cos-
metic issue. Despite the lack of attention, new data on the
condition, its syndromic associations, medications that can
cause or exacerbate the condition, and therapeutic options
are available. Our intent is to critically review this literature
and provide a comprehensive update. We also hope to direct
further attention to KP from those who develop therapeu-
tic agents and devices. To accomplish this, we performed a
literature review of KP using the PubMed, EMBASE, and
CINAHL medical databases using the search term keratosis
pilaris. Only peer-reviewed articles available in English were
included.

Vol.:(0123456789)

734 J. F. Wang, S. J. Orlow

1.1 Epidemiology results from abnormal keratinization of the follicular epi-

KP is the most common follicular disorder in children [2,
3]. The pediatric epidemiology of KP has been explored by
several groups (Table 1), but there appear to be large fluc-
tuations in the reported prevalence rates among and even
within countries or ethnicities, ranging from 0.75 to 34.4%
[4–15]. In addition, a cross-sectional study of 12,657 Korean
male military conscripts aged 19 years reported higher rates
of KP in the subjects than did results from hospital-based
studies [16]. The prevalence of KP was 11.9% (178/1502) in
a cross-sectional study of 1502 German adults [17]. In a pro-
spective study of 1107 Spanish and 1267 immigrant patients
aged < 60 years, KP was more prevalent in the immigrant
population (p = 0.04) [18]. KP also occurs more frequently
in individuals with skin scaling and dryness [7, 19], regard-
less of whether they have a diagnosis of ichthyosis vulgaris
(IV) or atopic dermatitis (AD) [20].
2 Clinical Overview, Pathophysiology,
and Histopathology of Keratosis Pilaris
(KP) and its Subtypes
The clinical features and natural history of KP are summa-
rized 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 pathophysi-
ology of KP is not completely understood. One hypothesis
proposes that the keratotic infundibular plug found in KP
thelium [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 ear-
lier step in the pathophysiology of KP [24]. We discuss these
and other hypotheses in greater depth.
2.1 KP Atrophicans and Erythromelanosis
Follicularis Faciei et Colli
KP atrophicans (KPA) has a variety of clinical and histo-
pathologic 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]. Con-
versely, it has been suggested that, rather than one heteroge-
neous 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

Table 1  Publications providing evidence on the epidemiology of keratosis pilaris in the pediatric population
Study Study design Nationality or ethnicity Subject age Subjects (N) Percentage of sub-
range, years jects with KP (N)

Brown et al. [4] 2009 Cross-sectional British 7–9 792 34.4 (273)
Anand et al. [5] 2012 Cross-sectional India 5–15 988 20 (198)
Dogra and Kumar [6] 2003 Cross-sectional India 6–14 12,586 1.3 (160)
Yosipovitch et al. [7] 2000 Cross-sectional Jewish 17–18 202 16 (33)
Tay et al. [8] 2002 Cross-sectional Singapore 7–16 12,323 13 (1602)
Inanir et al. [9] 2002 Cross-sectional Turkey 6–14 785 12.5 (98)
Popescu et al. [10] 1999 Cross-sectional Romania 6–12 1114 4 (45)
Del Pozzo-Magana et al. [11] 2012 Retrospective Mexico 0–18 5250 3.7 (192)
Al-Saeed et al. [12] 2006 Cross-sectional Saudi Arabia 6–17 2239 2.2 (50)
Figueroa et al. [13] 1996 Cross-sectional Ethiopia 5–16 112 1.8 (2)
Fung and Lo [14] 2000 Cross-sectional Hong Kong 6–21 1006 1.3 (13)
Bechelli et al. [15] 1981 Cross-sectional Brazil 6–16 9955 0.75 (75)

KP keratosis pilaris
Table 2  Clinical and histopathologic descriptions of keratosis pilaris and its subtypes
Condition Description Onset Clinical findings Natural history Histopathologic findings

KP Common follicular Typically during Spiny keratotic papules, approximately 1 mm Improves in 35% of patients by the late Orthokeratotic keratin plugs in fol-
skin disorder [1] childhood and in size, mostly distributed on the extensor teens but remains unchanged in 43% licular orifices, which may contain
adolescence; may surfaces of the proximal extremities [22]. of patients and worsens in 22% [22]. twisted hairs, dilate the infundibu-
also appear in infants Involvement of the distal extremities, face, In a survey of 49 British patients with lum, creating the papules of KP [1].
and adults [21] trunk, and buttocks may also occur [23]. KP aged 2–40 years, incidence was While the epidermis exhibits mild
Papules can be scattered or grouped together, most common during the first decade hyperkeratosis, hypogranulosis, and
Keratosis Pilaris and its Subtypes

sometimes with subtle perifollicular ery- of life and decreased with age [22]. follicular plugging, the upper dermis
thema [1]. Dermoscopic findings: follicular KP improved in the summer and and perifollicular areas contain
hyperkeratosis, dermal vascular ectasia, wid- worsened in the winter for approxi- mild perivascular lymphohistiocytic
ened follicular orifices, hyperpigmentation, mately half the patients; however, of infiltrates [24, 25]. There may be
perifollicular erythema, scaling, and thin and the patients with worsening KP in the focal parakeratosis within the SC
short hair shafts in lesional skin [24, 27–29]. summer, only 60% improved during [25]. Sebaceous glands are strikingly
Mild KP may have coiled or twisted vellus the winter [22]. In one case of biopsy- absent from KP lesions but are
hairs, either singular or in groups of two or proven KP, a 25-year-old man had present in unaffected skin from the
three, encircled by peripilar casts [24, 28]. profuse alopecia on KP-affected sites, same patient [24]
The vellus hairs in more severe KP appear but after 3 months, his KP spontane-
coiled and are impacted in the horny layer ously cleared with complete hair
[24, 28]. KP is usually asymptomatic but regrowth without scarring or atrophy
may be pruritic and cosmetically undesir- [26]
able [1]
KPA A rare, scarring Childhood [32] In addition to the finding of KP mostly on the Progressive scarring and destruction of Hyperkeratosis in the follicular
subtype of KP that extensor extremities, KPA and its subtypes the follicles, which over time manifest ostia and hypergranulosis of the
includes a spectrum present with perifollicular keratosis and as alopecia from the follicular papules infundibulum and isthmus, causing
of clinical variants [32] variable inflammation that result in atrophic [34]. With scalp involvement, there is chronic inflammation and deposition
scarring, usually starting on the face in expanding fibrosing alopecia [34] of cellular debris, disintegrating the
childhood and potentially involving the follicle [34]
scalp after puberty [32–34]
KPAF Variant of KPA also First months of life Small, follicular, keratotic papules and ery- Disease course typically ends after Keratosis of the pilosebaceous infun-
known as ulerythema [33] thema on the lateral third of the eyebrows, puberty, but permanent alopecia and dibulum with sebaceous gland and
ophryogenes [32] potentially extending to the forehead and atrophy may have already manifested hair follicle atrophy, surrounded by
cheeks and eventually leading to scarring [32] an inflammatory infiltrate [38]
alopecia [3, 32, 33]. KP is often present on
extensor surfaces [3]. Follicular atrophy
may also occur in advanced EFFC, suggest-
ing overlap between the two diseases [35].
Overlap has also been reported with KFSD
[36, 37]
AV Variant of KPA also Usually between 5 Begins with follicular, keratotic papules, Like KPAF, perifollicular inflamma- There is epidermal atrophy, capil-
known as and 12 years [38]. erythema, and milia on the cheeks and heals tion tends to stop after puberty, but lary dilation, and dermal collagen
honeycomb Rarely presents in with reticular, atrophic pitting of the cheeks, progression is also possible [32]. The sclerosis [41]. The pilosebaceous
atrophy [32] late adolescence [39] creating a worm-eaten or honeycomb appear- erythema and reticulated atrophy tend unit is abnormal, and sebaceous
ance [32, 38]. Usually spares the scalp and to improve spontaneously and gradu- glands are atrophic or absent [42].
eyebrows but may extend to the ears, upper ally [42] There are fewer elastic fibers in the
lip, neck, and extremities [3, 32, 40] dermis [43]
735


Table 2  (continued)
736

Condition Description Onset Clinical findings Natural history Histopathologic findings

KFSD Variant of Typically begins in Malar, follicular, keratotic, sometimes erythe- X-linked dominant KFSD tends to remit There is variable acanthosis and
KPA [32] infancy [31] matous papules that can progress to involve after puberty [32] papillomatosis, hair follicles are
the eyebrows, eyelashes, neck, extremities, dilated and contain keratin plugs and
scalp, and even axillae and pubic areas with trapped hair shafts, and there is peri-
scarring, patchy alopecia [3, 32, 38, 44, 45]. adnexal inflammatory infiltrate in
Other cutaneous findings include widespread the dermis comprising lymphocytes,
KP, palmoplantar keratoderma, prominent diffusely scattered plasma cells, and
cuticles, and hyperkeratosis of the calcaneal multinucleated giant cells [47–49]
heels and knees [3, 45]. Extracutaneous
manifestations may include blepharitis,
keratitis, corneal dystrophy, photophobia,
and enamel hypoplasia [45, 46]
FSD Variant of Childhood to Desquamation and pustular inflammation of Exacerbates after puberty with recurrent Follicular plugging, follicular and
KFSD [32] adolescence [44] the scalp [32, 44]. KP can also be present flares [32] interfollicular hyperkeratosis, mild
[50] inflammation, and focal scarring
[50]
EFFC Rare subtype Usually between Bilateral hyperpigmentation, follicular Disease duration varies from 2 to Follicular plugging, hyperkeratosis,
of KP [54] ages 8 and 12 years papules, and erythema on the cheeks and 14 years after onset [54] increased basal membrane pigmen-
[54] temples, potentially progressing to the tation, periadnexal and perivascular
submandibular neck and preauricular areas inflammatory infiltrate, and vascular
[54, 56]. Affected skin is rough with fewer dilation in the upper dermis [54,
vellus hairs, but there is neither scarring 57]. The degree of basal membrane
nor atrophy [54]. Associated KP can be pigmentation and the percent area
seen in 88% (22/25) of patients, often of blood vessels in the upper dermis
exhibits perifollicular erythema, and most correlate with disease severity [57]
commonly affects the arms and upper
back and sometimes lower or entire body
[54–56]. Typically asymptomatic, although
photosensitivity is possible [54]
KPR Common variant of KP Conflicting KP with more overt erythema and a larger dis- Erythema persists during puberty and Follicular infundibular plugging and
[23] data [23, 58] tribution of skin involvement, most often the can even worsen [23] mild perifollicular inflammation and
lateral cheeks and proximal extremities [23] fibrosis [23]

AV atrophoderma vermiculatum, EFFC erythromelanosis follicularis faciei et colli, FSD folliculitis spinulosa decalvans, KFSD keratosis follicularis spinulosa decalvans, KP keratosis pilaris,
KPA keratosis pilaris atrophicans, KPAF keratosis pilaris atrophicans faciei, KPR keratosis pilaris rubra, SC stratum corneum
J. F. Wang, S. J. Orlow
Keratosis Pilaris and its Subtypes
papillomavirus may exacerbate KPAF [52]. Because KPA
shares many clinical and histological features, including fol-
licular 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].
2.2 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 hyper-
pigmentation or atrophy associated with other KP variants,
it does appear to be more common than them but less com-
mon 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 indi-
vidual 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, demar-
cated 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
737
arising before 18 months of age [21]. A study of 11 patients
found that the lesions in PPPKP were larger and more exten-
sive and had an earlier onset than those of KP; the authors
opined that the condition is greatly underreported. In con-
trast 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.
3 Cellular and Biochemical Characterization
The epidermal permeability barrier consists of corneocytes
and the extracellular, hydrophobic lamellar bilayers of the
stratum corneum (SC), formed from the secretions of the
lamellar bodies (LBs) [24]. This is aided by tight junctions
in the underlying granular layer and by corneodesmosomes
[24, 73, 74]. These structures protect against the inward
entry of pathogens and the outward loss of water and elec-
trolytes [24, 75]. Although skin surface pH is normal in KP,
baseline transepidermal water loss is increased in patients
with KP (p < 0.01) [24]. The follicular and interfollicular
SC appears to have an abnormal permeability barrier in KP
lesions. In KP lesional skin, non-lamellar domains disrupt
lamellar membrane arrays. Lipid processing in the upper
parts of hair follicles and in the interfollicular epidermis may
be delayed. LB internal structures are abnormal, which can
affect loading into organelles.
A few groups have attempted to characterize KP and
its subtypes on a molecular level. Trichohyalin is weakly
expressed in lesional KP [76]. In a flow-cytometric investi-
gation, both KP- and KFSD-affected skin had lower propor-
tions of cells positive for involucrin and higher proportions
of cells positive for keratin 4 than normal skin [77]. Elevated
levels of cellular retinoic acid-binding protein have also been
found in lesions of KFSD, which may account in part for
the responsiveness of KP (at least in some individuals) to
retinoid therapy [78].
4 Genomics
A family history of KP is present in roughly 39% of patients,
indicating a potential genetic etiology with autosomal domi-
nant inheritance [22]. In a genomic analysis of 13 consan-
guineous Pakistani patients with KPA, KP1245R, a novel
homozygous missense variant of LRP1, was identified as
pathogenic in autosomal recessive KPA and KP [51]. LRP1
has endocytic functions within the LDL family, and its levels
are reduced in the fibroblasts of patients with this mutation,
as is cellular uptake of its ligand, α2-macroglobulin [79].
There is also evidence that mutations in desmoglein 4 can
contribute to the pathogenesis of autosomal recessive KPA
[80].

738
KPAF tends to be inherited in an autosomal dominant
pattern with incomplete penetrance, but sporadic cases have
also been documented [3]. AV can also be inherited in an
autosomal dominant fashion, but most cases are sporadic
[3, 42]. There have been a few pedigrees affected by KFSD
with the c.1523A > G mutation in the MBTPS2 gene in the
literature [45, 81, 82]. Mutations in this gene also cause
ichthyosis follicularis, alopecia, and photophobia syndrome
(IFAPS), which shares clinical features with KFSD [45,
81]. MBTPS2 also regulates TRPV3, the gene responsible
for Olmsted syndrome, which can present with widespread
KP [83, 84]. The pattern of inheritance varies, as there are
reports of X-linked patterns, autosomal dominant patterns,
and sporadic patterns [3, 32, 46, 81, 85]. While KFSD typi-
cally presents in males, there have been reports in females
[86–88]. FSD has been shown to be inherited in a primarily
autosomal dominant fashion [89].
The role of genetics in EFFC is unclear. Autosomal
recessive inheritance patterns have been observed [90], and
chromosomal instability may also play a role [91]. A family
history of KP is common in EFFC, and familial occurrence
of EFFC has been reported, supporting a genetic etiology
[54, 92, 93]. Although EFFC affects all races, Asian popu-
lations are more likely to be affected [60]. Disease onset
ranges between ages 2 and 43 years in reported cases, but
EFFC mostly affects adolescents. The male-to-female ratio
is about 2:1.
5 Disease Associations
5.1 Atopy, Hereditary Ichthyoses, and Filaggrin
Mutations
A history of atopy has been shown to be associated with KP
(p = 0.001), with one survey reporting it in 37% of patients
with KP [7, 22]. The association of AD and KP may stem
from abnormalities of the permeability barrier of the epi-
dermis [24]. KP is sometimes considered a minor diagnostic
criterion for AD, although there was poor diagnostic agree-
ment on KP among physicians in a study of 14 physicians
from a United Kingdom AD diagnostic criteria working
party trying to correctly diagnose AD in 15 patients [94].
Studies from several groups also present conflicting informa-
tion about the prevalence and diagnostic relevance of KP in
AD (Table 3) [8, 20, 95–99]. In childhood AD, the presence
of KP may be associated with more severe disease [100].
Subgroups have been proposed within AD, such as intrinsic
AD, which lacks allergen-specific immunoglobulin E (IgE)
and is less associated with KP (p < 0.05) [101]. KP in the
setting of AD may differ from KP without AD, as shown
by a study in which patients with AD with KP-like papules
developed pustular patch test reactions to 5% nickel sulfate,
J. F. Wang, S. J. Orlow
but patients with KP without AD had no reaction [102]. KP
is also associated with IV in the context of filaggrin muta-
tions [2]. Like AD, the prevalence data and diagnostic value
of KP in IV and other hereditary ichthyoses is conflicting
among several studies (Table 3) [3, 20, 103–106].
Although several genomic analyses have shown that
filaggrin mutations, especially R501X and 2282del4, are
associated with KP (p < 0.01 for each), they do not account
for the entire KP phenotype [4, 17, 24, 107]. For example,
in a genomic analysis of 40 subjects with KP, only 35%
(7/20) had filaggrin mutations [24]. Yet this is much higher
than the up to 9% general prevalence rate of filaggrin vari-
ants in Caucasians [24, 108]. In a genomic analysis of 459
patients, filaggrin mutations were associated with an odds
ratio approaching 2 in terms of having KP (p < 0.05) [109].
However, not all studies support the association of filag-
grin mutations with KP [110]. Filaggrin mutations may also
contribute to KP by downregulating sebocyte proliferation,
causing atrophy of the sebaceous glands, and disrupting the
epithelial barrier [24, 111, 112]. Targeted next-generation
sequencing has the potential to identify specific filaggrin
mutations in patients with KP, as it has already been used
for this purpose in IV [113].
5.2 Obesity, Diabetes, Pregnancy, and Related
Hormonal Abnormalities
High body mass index (BMI) and related conditions, includ-
ing diabetes, pregnancy, and hormonal abnormalities, are
often associated with KP [114]. While several studies have
found that KP is associated with high BMI and obesity, the
prevalence of this phenomenon is variable (Table 4) [7,
115–118]. The data on whether grade of obesity is directly
associated with likelihood of concomitant KP are conflict-
ing, as one study found no correlation [118] while others
showed a significant correlation [117, 119]. It is suspected
that obesity-related hyperinsulinemia and insulin resistance
contribute to KP pathophysiology, as suggested by a case
series of 13 women with acanthosis nigricans and insulin
resistance, nine of whom had KP [120].
KP is common in patients with type 1 diabetes melli-
tus (T1DM) and develops early in the disease course [121].
Evidence supports an association between KP and T1DM
(Table 4) [121, 122]. Downregulation of sebocyte prolif-
eration, a potential contributor to the pathogenesis of KP,
may be due in part to low insulin-like growth factor 1 or
insulin [24, 123]. Peroxisome proliferator-activated receptor
α, a regulator of ketogenesis, and peroxisome proliferator-
activated receptor γ1, a regulator of glucose metabolism and
fatty acid storage, are also expressed in sebocytes; decreased
activation of these receptors downregulates sebocyte prolif-
eration [24, 123, 124]. Hereditary EFFC may also be linked
to diabetes [91].
Table 3  Publications providing evidence for the association of keratosis pilaris with atopic dermatitis and ichthyoses
Study Study design Nationality or ethnic- Subject age, ­yearsa Subjects (N) Conclusions
ity

Cheng et al. [95] 2016 Questionnaire and Han Chinese AD cases: 5.4 ± 7.7 4321 total: 2205 AD KP was present in 13.1% (289/2205) of AD pts.
cross-sectional Controls: 27.5 ± 12.6 cases, 2116 controls The A allele of rs6780220 on chromosome
with genomic analysis 3p21.33 is potentially less frequent in AD pts
with KP than those without KP (p < 0.024, not
significant after Bonferroni correction)
Keratosis Pilaris and its Subtypes

Chen et al. [96] 2011 Cross-sectional Singaporean Chinese IV cases: NR 92 total in the filaggrin KP was present in 7.1% (30/425) of AD pts. KP
with genomic AD cases without mutation discovery was present in 10% (7/69) of IV pts, but this was
analysis IV: “adult” cohort: 69 IV cases, similar to the 13% (3/23) prevalence of KP in
AD cohort: 1–21 23 AD cases without IV. the AD without IV cohort. KP is associated with
Controls: 1–80 865 total in the AD filaggrin mutations (p = 0.001). AD pts without
cohort: 425 AD KP are unlikely to carry filaggrin-null muta-
cases, 440 controls tions, as the positive and negative predictive
values of KP for such mutations were 31.6% and
79.3%, respectively
Mevorah et al. [20] 1985 Cross-sectional Switzerland AD cohort: 0.5–59 343 total: 61 AD cases KP was present in 42.6% (26/61) of AD pts with-
IV cohort: 35–70 without IV, 35 IV cases out IV, which was lower than the 74.3% (26/35)
Controls: 1–74 without AD, 247 controls prevalence of KP in IV pts (p < 0.001) but
without AD or IV of which similar to the 41.7% (103/247) prevalence of KP
155 were examined for in controls. KP is associated with scaling among
scaling (40 with scaling, 115 controls without AD or IV, present in 62.5%
without scaling) (25/40) of controls with scaling and 38.3%
(44/115) of controls without scaling (p < 0.01).
KP is not helpful to the diagnosis of AD but is
part of the phenotype of dominant IV
Tay et al. [8] 2002 Questionnaire Singapore 7, 12, or 16 12,323 total students: KP was present in 13.4% (343/2563) of AD pts,
and cross-sectional (Chinese, Malays, 2563 with AD but this was similar to the 13% (1602/12323)
Indians, and others) prevalence of KP in the study population. KP is
not more common in AD pts
Wahab et al. [97] 2011 Descriptive Bangladesh 1–12 210 with AD KP was present in 14.8% (31/210) of AD pts
Macharia et al. [98] 1993 Cross-sectional with Kenya 0.25–10.25 54 with AD KP was present in 72% (39/54) of AD pts
consecutive sampling
Kwon et al. [99] 2004 Survey and cross- South Korea 12–40 48 with AD KP was present in 43% (21/48) of AD pts
sectional
Bremmer et al. [103] 2008 Cross-sectional USA 0–33 898 with valid data points KP was present in 52.9% (147/278) of IV pts,
for hyperlinear palms/KP which was more common than in those without
and IV: 278 IV cases, 620 IV (28.4%, 176/620; p < 0.001). KP supports
without IV a diagnosis of IV but is nonessential to the
diagnosis
739

740 J. F. Wang, S. J. Orlow

KP may be an underrecognized dermatosis of pregnancy.

autosomal recessive ichthyosis. KP was not pre-

hyperkeratosis, 23 with auto- X-linked ichthyosis, and 4.3% (1/23) in pts with
p < 0.0001). However, presence of KP does not

sent in either of the two pts with epidermolytic

A case series of five women with KP demonstrated that its

(13/25) in pts with IV, 9.1% (1/11) in pts with

primary hereditary ichthyoses, including 52%
than pts with X-linked ichthyosis (21%, 7/33;
somal dominant ichthyosis (proportion NR)
KP was more likely to occur in pts with auto-
onset or severity may be linked to hormone changes during

KP was present in 24.6% (15/61) of pts with

rule out a diagnosis of X-linked ichthyosis
pregnancy [125]. In all five women, KP improved within

KP was present in 6.3% (5/79) of IV pts

9 months of delivery. In addition, a 29-year-old woman
developed unilateral KP during her second pregnancy [64].
This may be explained by increased androgens and insulin
resistance associated with pregnancy. In addition, in a cross-
sectional study of 156 women, hyperandrogenism in the set-
ting of obesity was associated with increased incidence and

hyperkeratosis
severity of KP (p < 0.001) [126]. After controlling for hyper-
Conclusions

androgenism, obese women with KP were more likely to

have cutaneous features of virilism than obese women with-
out KP. This may be explained by androgen stimulation of
the pilosebaceous infundibulum causing hyperkeratinization.
85 total: 33 with X-linked, 52

X-linked recessive ichthyo-

sis, two with epidermolytic
61 total: 25 with IV, 11 with

somal recessive ichthyosis

with autosomal dominant

5.3 Primary Cicatricial Alopecias

Primary cicatricial alopecias (PCAs) are a group of hair

disorders such as KFSD with permanent hair loss due to
Subjects (N)

ichthyosis

79 with IV

destruction of follicular structures. Graham-Little-Piccardi-

Lasseur syndrome (GLPLS) is rare and characterized by KP
on the trunk and extremities, cicatricial alopecia of the scalp,
and non-scarring alopecia of the axillae and pubis [127].
Although KP is usually the last symptom to manifest, two
cases of GLPLS in patients with androgen-insensitivity syn-
drome, a 40-year-old and a 29-year-old, presented with KP
Nationality or ethnic- Subject age, ­yearsa

as the initial manifestation of GLPLS [127, 128]. Without

AD atopic dermatitis, IV ichthyosis vulgaris, KP keratosis pilaris, NR not reported, pts patients

androgen-insensitivity syndrome as a comorbidity, GLPLS

typically presents in postmenopausal women, as demon-
0.25–75

strated by a case of a 75-year-old woman [129]. There are

3–70

NR

very few reports of GLPLS in men [130]. Genetics may play

a role in the etiology of GLPLS [131]. These cases serve
to highlight a hormone imbalance as contributory towards
the pathophysiology of KP. There have been two reports
Switzerland

of KP associated with acne keloidalis, a chronic inflamma-

tory disorder of hair follicles on the nape and occipital scalp
Saudi
India

[132, 133]. KP was found in 5.6% (1/18) of patients with

ity

frontal fibrosing alopecia (FFA) in a retrospective study of

 Age given as mean ± standard deviation or as range

18 patients [134].

5.4 Other Disease Associations

Cross-sectional

Cross-sectional
Retrospective
Study design

There are rare reports of KP as a sign of malignancy.

Acquired hypertrichosis lanuginosa, a sign of internal
malignancy, appeared simultaneously with KP and furrowed
Mevorah et al. [104] 1991

tongue in a 32-year-old woman with metastatic adenocarci-

Ghosh et al. [105] 2017
Al-Akloby [106] 2004

noma of the liver [135]. KP appeared suddenly in a 14-year-

Table 3  (continued)

old girl in association with stage III Hodgkin’s lymphoma

and resolved after chemotherapy-induced remission [136].
A possible association exists between KP and thyroid dis-
ease in children [137, 138]. A cross-sectional study found
Study

KP in 27.9% of 61 children with anorexia nervosa [139].

a
Keratosis Pilaris and its Subtypes
Moderate-to-severe KP on the arms is associated with
a lower prevalence and reduced severity of acne vulgaris
(p < 0.01), demonstrated by a cross-sectional study of 158
patients aged 14–34 years, perhaps due to the sebaceous
gland deficits in KP [140]. There has been a case of AV
in association with Melkersson–Rosenthal syndrome, a
rare disorder characterized by facial nerve palsy, orofacial
edema, and lingua plicata [141]. KSFD has been associ-
ated with psychomotor retardation in a case report [142]. In
addition, three sporadic cases of KPR have been reported
in association with psychomotor retardation and precocious
canities [143]. EFFC with KP has been reported in associa-
tion with erythrosis pigmentosa mediofacialis in a 12-year-
old girl [144].
6 Hereditary and Syndromic Associations
6.1 Syndromes with Intellectual Disability
KP has been linked to a variety of genetic syndromes that
involve intellectual disability (ID) (Table 5). Several groups
have examined the rate of KP and its subtypes in patients
with Down syndrome (DS) [145–151]. Cabezas syndrome
is a form of X-linked ID caused by a mutation in CUL4B
that may be associated with KP [152]. Smith–Magenis
syndrome (SMS) is a rare genetic disorder with facial and
skeletal abnormalities, ID, developmental delay, and self-
injurious behavior that can present with extensive KP [153].
Cornelia de Lange syndrome is a rare disorder characterized
by ID, neurodevelopmental delay, congenital malformations,
and growth retardation that may be associated with KPAF
[154]. Rubinstein–Taybi syndrome (RTS) is a rare disorder
characterized by ID, facial abnormalities, and broad thumbs
and great toes also potentially associated with KPAF [155].
6.2 Neuro‑Cardio‑Facial‑Cutaneous Syndromes
Neuro-cardio-facial-cutaneous syndromes, also known as
RASopathies, are a group of syndromes with abnormali-
ties in the Ras signal transduction pathway (Table 5). Most
RASopathies are characterized by cardiac defects, abnor-
mal facies, ID, and dermatologic abnormalities [156].
Among the RASopathies, KP is more common in patients
with SOS1, SHOC2, and BRAF mutations [157]. KP is
a cardinal dermatologic feature in cardio-facio-cutaneous
syndrome (CFCS) [158–164]. However, histologic find-
ings have only been reported in three cases of CFCS and
one case of undifferentiated CFCS or Costello syndrome
(CS) [156, 161, 165, 166]. KP also occurs in CS but less
frequently than in CFCS [167]. KPAF is also very com-
mon in CFCS but not in CS [163, 167, 168]. In addition,
KP and KPAF affect patients with Noonan syndrome (NS)
741
[38, 169–175]. KP has also been reported in three fam-
ily members with Noonan-like syndrome and a PTPN11
mutation [176]. However, a direct comparison of RASo-
pathic patients with SOC1 and PTPN11 mutations found
that SOC1 was significantly more likely to be associated
with KP [177].
6.3 Ectodermal Dysplasias
Ectodermal dysplasias (EDs) are a group of syndromes with
ectodermal abnormalities, including CFCS, that have been
associated with KP (Table 5). Palmoplantar keratoderma-
congenital alopecia syndrome (PKCAS) is a rare genoder-
matosis with a mild autosomal dominant form (type 1) and
a recessive form (type 2) with more severe hand involve-
ment [178]. A total of 19 patients have been documented as
having PKCAS [178, 179]. Both forms include widespread
and severe KP, dystrophic nails, palmoplantar keratoderma
(PPK), and congenital alopecia (CA). In a report of two
patients with PKCAS type 2 (PKCAS2), the main features
were universal CA, diffuse KP, facial erythema, and a spe-
cific PPK that involved the fingertips and foot and hand
borders with worsening sclerodactyly, contractures, and
pseudoainhum [178]. The genetic basis of PKCAS2 is not
yet known.
Hereditary mucoepithelial dysplasia (HMD) is a rare
autosomal dominant disorder characterized by chronic
mucosal lesions and is associated with non-scarring alo-
pecia, perineal intertrigo, keratitis, and KP (Table 5) [180,
181]. Pachyonychia congenita (PC) is a rare genodermato-
sis with abnormal keratinization and dystrophic nails and
has been associated with KP [182, 183]. Monilethrix is rare
genetic disorder of the hair shaft and may present with KP
[184–187]. In addition, IFAPS, a rare X-linked congenital
ectodermal dysplasia (ED), may also present with KP [79,
188].
In a previously undescribed form of ED, four fam-
ily members presented with a syndrome characterized by
trichodysplasia, onychodysplasia, retrognathia, abnormal
dermatoglyphics, ID, and sometimes KP (Table 5) [189]. In
a cross-sectional study of 20 patients from seven families, an
autosomal recessive syndrome was characterized by pili torti
with corkscrew hairs, KP, palmoplantar keratoderma, xero-
sis, dental abnormalities, onychodysplasia, and facial abnor-
malities [190]. There has also been a report of an unnamed
disorder in a family presenting as congenital hypotrichosis in
all locations except the scalp hair, which appeared as coarse,
tidy, and shiny, as if “auto-combed,” with dystrophic nails
and KP [191]. Another unnamed ectodermal dysplasia pre-
sented with KP, ID, corkscrew hairs, syndactyly, abnormal
facies, dental aberrations, dermatoglyphic hypoplasia, and
low numbers of epidermal ridge sweat pores [192].

Table 4  Publications providing evidence for the association of keratosis pilaris with high body mass index and type 1 diabetes mellitus
Study
Yosipovitch et al. [7] 2000
Boza et al. [115] 2012
Nazik et al. [116] 2016
Garcia-Hidalgo et al. [117] 1999
Plascencia Gomez et al. [118] 2014
Guida et al. [119] 2010
Pavlovic et al. [121] 2007
Yosipovitch et al. [122] 1998
BMI body mass index, KP keratosis pilaris, OR odds ratio, pts patients, T1DM type 1 diabetes mellitus
a
 Age given as mean ± standard deviation or as range
742
Study design Nationality Subject age, ­yearsa Subjects (N) Conclusions
or ethnicity
Questionnaire and Jewish 17–18 202 students: 33 with KP, 169 without KP BMI was higher in those with KP (mean BMI 24.8)
cross-sectional vs. without KP (mean BMI 21.7; p < 0.001).
KP was present in 39% (14/36) of subjects with
BMI > 25, which was higher than those with
BMI ≤ 25 (11%, 19/166; p < 0.001), OR 4.9
Cross-sectional Brazil Obese cases: 49.7 ± 15.6 148 total: 76 obese pts, 72 normal-weight After controlling for atopy, KP still had a higher
Controls: 49.1 ± 14.5 controls prevalence in obese individuals (23.7%, 18/76)
vs. controls (5.5%, 4/72) with an adjusted preva-
lence ratio of 11.15 (p = 0.006)
Cross-sectional Turkey Obese cases: 29.8 ± 16.4 510 volunteers: 230 obese (BMI > 30.0), 130 KP was present in 21.2% (108/510) of overweight
Overweight cases: 44.9 ± 13.4 overweight (25.0 ≤ BMI ≤ 29.9), 150 controls and obese subjects
Controls: 32.1 ± 10.9 (BMI < 25.0)
Cross-sectional Mexico 16–89 156 obese patients: 28 grade I (10–25% excess KP was present in 21.2% (33/156) of obese pts and
weight), 34 grade II (26–50% excess weight), was more common in those with obesity grades
29 grade III (51–75% excess weight), 30 grade IV and V (32.3%, 31/65) than those with obesity
IV (76–100% excess weight), 35 grade V grades I, II, and III (13.2%, 12/91; p < 0.007),
(> 100% excess weight) OR 3.14
Cross-sectional Mexico 8–69 109 overweight patients KP was present in 42.2% (46/109) of overweight
pts but was not associated with grade of obesity
Cross-sectional Italy Obese cases: 37.1 ± 13.1 80 total: 60 obese (36 class I [30 < BMI < 35], KP was present in 13.3% (8/60) of obese subjects
Controls: 41.0 ± 12.3 14 class II [35 < BMI < 40], 10 class III and none of the controls. KP was associated with
[BMI ≥ 40]), 20 normal weight grade of obesity and was present in 6% (2/36) of
class I, 14% (2/14) of class II, and 40% (4/10) of
class III (p = 0.01)
Cross-sectional Serbia 2–22 408 total: 212 T1DM pts, 196 age- and sex- KP was more common in pts with T1DM (11.7%,
matched controls 27/212) than controls (1.5%, 3/196; p < 0.01) and
was more common in patients aged > 10 years
(21/27). Ichthyosiform skin changes were associ-
ated with KP in T1DM pts (p < 0.001), OR 1.53
Cross-sectional Israel T1DM pts: 12–44 360 total: 238 T1DM pts, 122 healthy controls KP was more prevalent in T1DM pts (21%, 50/238)
Controls: 16–36 than controls (9%, 11/122). T1DM pts also had
more extensive KP mostly on the extensor limbs,
and the presence of KP was associated with
higher BMI (p < 0.0001)
J. F. Wang, S. J. Orlow
Keratosis Pilaris and its Subtypes
6.4 Hereditary Skin Appendage Disorders
Several hereditary skin appendage disorders are associated
with KP and its subtypes (Table 5). Woolly hair (WH), a
congenital structural defect of scalp hair, may present with
KP either in the presence or in the absence of a neuro-cardio-
facial-cutaneous syndrome [170, 193–196]. KPAF and WH
can also occur together [195, 196], both in the setting and
in the absence of NS [170]. Hypotrichosis with KP is a rare
congenital disorder with short, brittle, sparse hair and KP on
the scalp. The brittleness of hair in this disorder may be due
to an altered fibrous protein composition [197]. Hereditary
koilonychia (HK) is a rare, hereditary nail deformity and is
associated with KP both in the setting of monilethrix and
in isolation [198, 199]. Leukonychia totalis (LT) is a rare
disorder characterized by complete white discoloration of
the nails that has also been associated with KP [200, 201].
6.5 Zouboulis Syndrome and Chromosome 18
Abnormalities
Zouboulis syndrome (ZS) is an ultra-rare disorder character-
ized by KP, KPAF, and monosomy 18p (Table 5), suggest-
ing that the gene for follicular keratinization is on the short
arm of chromosome 18 [202–207]. Laminin α1 deficiency
may contribute to the pathophysiology of ZS, as patients
neither have sebaceous glands nor express laminin α1 in
hair follicles, dermal nerves, or skin vessels [208]. Located
on chromosome 18p11.3, LAMA1 is missing in 18p mono-
somy, resulting in deficient laminin α1, which may lead to
abnormal sebaceous glands and hair follicles [202, 208].
Consideration should be given to testing children presenting
with both KP and KPAF for a partial 18p monosomy.
6.6 Other Syndromes
Patients with collagen VI-related myopathies, including
Ullrich congenital muscular dystrophy and Bethlem myo-
pathy, with mutations in COL6A1, COL6A2, and COL6A3,
may present with KP (Table 5) [209, 210]. Peeling skin
syndromes are a group of genodermatoses characterized
by spontaneous exfoliation and may present with KP [211].
Olmsted syndrome is a very rare disorder characterized
by symmetric, mutilating PPK, symmetric hyperkeratotic
plaques around body orifices, and sometimes widespread KP
[84]. BTG1, a ubiquitously expressed gene that downregu-
lates cell proliferation, may be an important contributor to
the pathogenesis of KP, as interstitial deletions in 12q21-q22
comprise a very rare syndrome characterized by KP, facial
dysmorphisms, growth retardation, and global developmen-
tal delay [212]. Dyschromatosis universalis hereditaria is
an autosomal dominant disorder characterized by scattered
hyperpigmented and hypopigmented macules and may be
743
associated with KP [213]. There has been a report of three
family members presenting with widespread KP, pediat-
ric alopecia, premature cataracts, and psoriasis [214]. One
patient presented with KP, palmoplantar keratoderma, and
ainhum [215].
Rombo syndrome is a very rare, autosomal dominant
genodermatosis characterized by AV, milia, telangiectasias,
hypotrichosis, trichoepitheliomas, proclivity for developing
basal cell carcinomas, and peripheral vasodilation with cya-
nosis (Table 5) [216]. Loeys–Dietz syndrome (LDS) is an
autosomal dominant connective tissue disorder caused by
mutations in the TGFBR1 or TGFBR2 genes and is charac-
terized by arterial tortuosity, hypertelorism, bifid uvula, and
aortic aneurysms [217]. TGFBR2-related LDS may present
with AV, suggesting a potential role for transforming growth
factor β signaling in the pathogenesis of the scarring of AV
[217, 218]. AV has also been associated with steatocystoma
multiplex [32].
7 Medications Causing KP‑Like Lesions
7.1 Cyclosporine
KP may arise in patients receiving cyclosporine (Table 6)
[219]. Graft-versus-host disease (GVHD) is a common com-
plication in transplant recipients, and cutaneous manifesta-
tions, including KP, are frequently the presenting symptoms.
A retrospective study of 100 patients with chronic GVHD
after hematopoietic stem cell transplantation found KP in
1% (1/100) of the cohort; however, many of these patients
were receiving cyclosporine, a known cause of KP [220].
7.2 B‑Raf Inhibitors
Generalized eruptions of diffuse follicular keratotic papules
are common in patients treated with inhibitors of the ser-
ine/threonine kinase B-Raf (Table 6) [221–223]. In patients
treated with the B-Raf inhibitor dabrafenib, KP is more
likely to develop in younger patients (p = 0.02), and it seems
to be protective against developing seborrheic keratoses
(p = 0.05) [223]. Although combined treatment with mito-
gen-activated protein kinase (MAPK) inhibitors prevents
some skin toxicities, it does not prevent KP. Vemurafenib
may also cause KP [224–228], potentially because of activa-
tion of downstream protein kinase R-like endoplasmic retic-
ulum kinase (pERK) in follicular epithelial cells [229]. Para-
doxical activation of the MAPK pathway by vemurafenib
is another possible mechanism, affecting both keratinocyte
differentiation and melanocyte proliferation, as shown by a
case report of KP, eruptive melanocytic nevi, and hidrad-
enitis suppurativa in a patient receiving vemurafenib [230].

744 J. F. Wang, S. J. Orlow

Table 5  Syndromic and hereditary associations with keratosis pilaris and its subtypes
Association Evidence

Neurodevelopmental disorders
DS and KP KP was found in 46% (51/110) of males with DS, mostly between the ages of 20 and 40 years, but was rela-
tively rare in females [145]. In a couple of other studies, KP was found in 14% (8/57) and 11.8% (24/203)
of DS pts [146, 147]. However, the rate of KP was only 4% (4/100) in a cross-sectional study of 100 DS
pts aged 3–20 years [148]. In addition, a couple of studies have found similarly low rates of KP in DS pts,
such as 3.2% (7/213) and 2.8% (2/71) [149, 150]
DS and KFSD DS occurring with KFSD has been reported [151]
Cabezas syndrome and KP A case series of three brothers with Cabezas syndrome found KP in one [152]
SMS and KP In a cross-sectional study of 20 pts with SMS, extensive KP was present in 65% (13/20) of pts, mostly
adults [153]
Cornelia de Lange syndrome and KPAF KPAF has been reported in Cornelia de Lange syndrome [154]
RTS and KPAF There has been a case report of KPAF in a pt with RTS [155]
Neuro-cardio-facial-cutaneous syndromes
CFCS and KP In addition to several case reports [158–162], KP was present in 80% (49/61) of pts in a survey of 61 CFCS
pts aged 16 months–31 years with MEK1, MEK2, BRAF, and KRAS mutations [163] and 73% (19/26) of
pts in a survey of 38 CFCS pts aged 1–23 years [164]
CFCS and KPAF KPAF was present in 90% (55/61) of CFCS pts in a survey of 61 pts [163]. This association has also been
documented in several case reports [168]
CS and KP In a cross-sectional study of 46 pts with CS, the frequency of KP was 32.6% (15/46), which is less frequent
than in CFCS (80.3%, 49/61; p = 0.001) [167]. No CS pts had KPAF [167]
NS and KP There have been reports of KP occurring in pts with NS [169, 170]. A cross-sectional study of 129 pts with
NS found facial KP in 50% (8/16) of pts with an SOC1 mutation [171]
NS and KPAF There have been several cases of NS occurring with KPAF, two of which were proven to be caused by an
SOC1 mutation [38, 170, 172–175]
EDs
PKCAS and KPAF Both type 1 and type 2 include widespread, severe KP [178, 179]
HMD and KP The frequency of KP among published cases of HMD is 77% (23/30) [180]
PC and KP PC is often associated with KP in case reports [182, 183]
Monilethrix and KP There are several reports of KP occurring in pts with monilethrix [184–187]
IFAPS and KP There are reports of IFAPS presenting with KP [79, 188]
Skin appendage disorders
WH and KP A few reports have associated WH with KP [170, 193–196]
WH and KPAF KPAF and WH have also been reported in association within a few families [195, 196]
Hypotrichosis and KP There has been a case of a 19-year-old Japanese male with this disorder [197]
HK and KP KP has been reported in association with HK [198, 199]
LT and KP In two cases, a brother and sister presented with LT, KP, and hyperhidrosis [200]. In three different cases, a
mother and her two daughters have been reported to have an unnamed syndrome characterized by LT, KP,
palmoplantar keratoderma, and hypotrichosis [201]
Other syndromes
ZS, KP, and KPAF There have been very few reported cases of ZS [202–207]
Collagen VI-related myopathies and KP In a case series, KP was reported in eight children with Ullrich congenital muscular dystrophy with
mutations in COL6A1, COL6A2, or COL6A3 and one adult with Bethlem myopathy with a mutation in
COL6A3 [210]
Peeling skin syndromes and KP An association with KP was found by a retrospective study of 21 pts with a peeling skin syndrome [211]
Olmsted syndrome and KP Olmsted syndrome sometimes presents with widespread KP [84]
Dyschromatosis universalis hereditarian and KP A case of KP associated with dyschromatosis universalis hereditaria was reported in a 16-year-old Indian
boy [213]
Rombo syndrome and AV A couple of cases of Rombo syndrome occurring with AV have been reported [216]
LDS and AV AV has been reported in three cases of TGFBR2-related LDS [217, 218]
Steatocytoma multiplex and AV A case of AV was reported in association with steatocytoma multiplex [32]

AV atrophoderma vermiculatum, CFCS cardio-facial-cutaneous syndrome, CS Costello syndrome, DS Down syndrome, ED ectodermal dyspla-
sia, HK hereditary koilonychia, HMD hereditary mucoepithelial dysplasia, IFAPS ichthyosis follicularis alopecia and photophobia syndrome,
KFSD keratosis follicularis spinulosa decalvans, KP keratosis pilaris, KPAF keratosis pilaris atrophicans faciei, LDS Loeys–Dietz syndrome, LT
leukonychia totalis, NS Noonan syndrome, PC pachyonychia congenita, PKCAS palmoplantar keratoderma-congenital alopecia syndrome, pts
patients, RTS Rubinstein–Taybi syndrome, SMS Smith–Magenis syndrome, WH woolly hair, ZS Zouboulis syndrome
Keratosis Pilaris and its Subtypes 745

B-Raf inhibitors are thought to induce aberrant signaling in 8 Environmental Exposures

the MAPK pathway, another plausible mechanism for the
development of KP [231].
7.3 Tyrosine Kinase Inhibitors
Nilotinib is a second-generation selective inhibitor of the
Bcr-Abl tyrosine kinase that has been known to induce both
KP and KPA (Table 6) [232–237]. The pathogenesis of this
reaction is unclear; nilotinib may affect the tyrosine kinase
receptors of hair follicles, affect the c-Kit receptor in basal
skin cells, or have off-target effects against Raf, which could
explain its shared toxicity with B-Raf inhibitors [232, 234,
238]. Dasatinib, another second-generation Bcr-Abl tyros-
ine kinase inhibitor (TKI), can also induce KP [235]. In a
case series of nine patients receiving single or combination
TKI therapy, six receiving nilotinib, three receiving dasat-
inib, and two receiving ponatinib, all developed KP-like
lesions, which resolved with dose reduction, cessation, or
TKI switching [238].
Erlotinib is a TKI that inhibits epidermal growth factor
receptor (EGFR) and may induce KP, perhaps due to the
role of EGFR in the skin and hair follicle signaling [239].
Sorafenib is a TKI with several targets, including vascular
endothelial growth factor receptor, platelet-derived growth
factor receptor, and several Raf kinases, the latter of which
most likely explains why a number of patients receiving
sorafenib in one study developed generalized KP [240].
Rarely, environmental exposures have been reported to
induce KP. For example, a 55-year-old machinist developed
clinical and histological KP on areas of his skin exposed to
cutting oil at the bolt manufacturing plant where he worked
[241]. Deliberate application of the cutting oil reproduced
clinical and histological KP on a previously unexposed area.
While more typically associated with chloracne, 2,3,7,8-tet-
rachlorodibenzo-p-dioxin exposure has been linked to AV in
a few cases [242].
9 Therapeutic Options and New Procedures
9.1 Topical Therapies and Systemic Drugs
Several topical therapies are commonly used to treat KP
and its subtypes with variable success (Table 7). Lactic acid
(LA) is a topical keratolytic agent that modulates skin kerati-
nization and, as shown in a prospective, randomized, clini-
cal study, is potentially more effective at treating KP than
salicylic acid (SA), another topical keratolytic agent that
may reduce cohesion between keratinocytes [243]. High-
frequency conductance can measure the hydration state of
the skin surface, and both LA and SA have been shown to
increase conductance in patients with KP. In a prospective
cohort study, LA has also been used in combination with
propylene glycol with partial benefit in treating KP [21].
Urea, another keratolytic agent, has been shown to be effec-
tive in treating KP in a few small studies and is often used

Table 6  Medications causing keratosis pilaris-like eruptions

Medication Evidence

Cyclosporine and KP In a cross-sectional study of 67 renal transplant recipients receiving cyclosporine and methylprednisolone, 21% (14/67)
developed KP [219]
Dabrafenib and KP In a prospective study of 59 pts treated with vemurafenib, dabrafenib, or a combination of dabrafenib and trametinib,
32.2% (19/59) pts, all of whom were receiving dabrafenib, developed KP no earlier than 27 days after starting therapy
[223]
Vemurafenib and KP There have been several reported cases of KP-like lesions occurring with vemurafenib therapy, along with a study of 28
pts with metastatic melanoma receiving vemurafenib, which found KP in 43% (12/28) pts [224–228, 230]. When vemu-
rafenib was undergoing phase II trials, three of seven enrolled pts developed KP [229]
Nilotinib and KP There have been several case reports of pts with CML developing KP-like eruptions after treatment with nilotinib, one of
which resolved after switching to dasatinib [232–236, 238]
Nilotinib and KPA In one case, a 46-year-old with CML developed KPA 2 months after initiating nilotinib therapy [237]
Dasatinib and KP There are several reports of KP-like lesions developing in pts treated with dasatinib [235, 238]
Ponatinib and KP There are two cases of ponatinib causing KP-like lesions [238]
Erlotinib and KP In a 60-year-old woman with stage IV lung cancer, scattered KP developed 5 months after discontinuing erlotinib therapy
[239]
Sorafenib and KP In one study examining two cohorts of pts receiving sorafenib, generalized KP developed in 21% (5/24) of pts in the
prospective cohort and in 41% (17/41) of the cohort of pts consulted after developing a dermatologic adverse event to
sorafenib [240]

CML chronic myeloid leukemia, KP keratosis pilaris, KPA keratosis pilaris atrophicans, pts patients

Table 7  Publications providing evidence for the treatment of keratosis pilaris and its subtypes
Treatment
Topical and systemic therapies
LA vs. SA
LA, SA, tretinoin, topical
corticosteroids, systemic
antibiotics, and/or isotretinoin
SA and urea
Aquaphor vs. tacrolimus
Tazarotene
Tretinoin
LA, urea, propylene glycol,
emollients, surgras soap,
topical corticosteroids, oral
corticosteroids, and
antihistamines
Calcipotriol
Combination peel with incorpo-
rated fractional prickle coral
calcium
Study
Kootiratrakarn et al. [243] 2015
Baden and Byers [34] 1994
Novick [244] 1984
Breithaupt et al. [248] 2011
Gerbig [247] 2002
Patel et al. [238] 2016
Castela et al. [21] 2012
Kragballe et al. [252] 1995
Park et al. [249] 2014
746
Study design Subject age Sub- Conclusions
jects
(N)
Prospective, randomized, NR 50 10% LA or 5% SA BID for 12 weeks: reduction of KP
clinical lesions in 66% of LA group and 52% of SA group
(p < 0.05 for each). Conductance improved with
both, but no effect on transepidermal water loss.
Adverse effects: mild local irritation
Prospective cohort 12–48 years 21 KPA: SA and LA smoothened skin without complete
clearing. 14 used topical corticosteroids, with/with-
out tretinoin: helped partially. Five used systemic
antibiotics: minimal, transient improvement. Three
received isotretinoin: minimal responses, one flared
Treatment recommendation NR 30 Combined with short showers and topical corticoster-
oids for inflammation, SA and urea QD are effective
for widespread, atypical KP. 75–100% clearance
achieved in 2–3 weeks
Double-blind, bilateral 2–16 years 30 27 pts completed study, Aquaphor to one limb and
paired comparison tacrolimus to the other BID for 4 weeks: improved
investigator’s global assessment score was 81% for
tacrolimus and 78% for Aquaphor, both improved
vs. baseline (tacrolimus: p < 0.001, Aquaphor:
p < 0.005). Tacrolimus more likely to have marked
effect. Adverse events: mild and transient
Open with consecutive NR 20 KP improved with QD application as early as 2 weeks,
recruitment gradually fading from 4–8 weeks
Case series 55–56 years 3 Three cases of KP induced by nilotinib, dasatinib, or
ponatinib: slight improvement
Prospective cohort 10 months–3  11 Not effective: emollients, topical corticosteroids, oral
years corticosteroids, antihistamines, surgras soap. Par-
tially effective: propylene glycol, LA, urea
Randomized, double-blind, vehicle- 16–45 years 9 KP appears unresponsive to calcipotriol
controlled, right/left comparative
Pilot 12–41 years 16 Five treatments of KP on upper arms at 2-week
intervals: improvement in erythema (p = 0.011) and
melanin (p = 0.006) index of mexameter relative to
baseline, maintained at 2-month follow-up. Adverse
events: mild and transient, including erythema,
pruritus, stinging
J. F. Wang, S. J. Orlow
Table 7  (continued)
Treatment
Ammonia-oxidizing bacteria
(Nitrosomonas eutropha) spray-
on mist
Chlorine dioxide complex
cleanser
Energy-based therapies
Photopneumatic therapy
Intense pulsed light
 < 600 nm: KTPL and PDL
Combination of 595-nm PDL,
long-pulsed 755-nm alexandrite
laser, and microdermabrasion
810 nm: long-pulsed diode laser
Study Study design
Lee et al. [250] 2018 Double-blinded, placebo-controlled,
split-arm
Zirwas and Fichtel [251] 2018 Case series
Ciliberto et al. [254] 2013 Pilot
Rodríguez-Lojo et al. [255] 2010 Case series
Schoch et al. [256] 2016 Case series
Alcántara González et al. [257] 2010 Case series
Clark et al. [258] 2000 Prospective cohort
Kaune et al. [259] 2009 Case report
Dawn et al. [59] 2002 Case report
Lee et al. [261] 2013 Retrospective
Lee et al. [260] 2012 Case series
Ibrahim et al. [262] 2015 Split-body, rater-blinded, parallel-
group, balanced (1:1), placebo-
controlled RCT​
Subject age Sub- Conclusions
jects
(N)
18–65 years 24 4 weeks of BID treatment for KP: larger % reduction
in height of follicular papules by quantitative digital
topographic analysis in the treatment group (18% vs.
15.2%; p = 0.007)
Keratosis Pilaris and its Subtypes
11–28 years 5 90–100% of KP papules resolved from 2 days to
1 month with QD treatment
13–45 years 10 One treatment: erythema and skin texture of KP
improved for at least 1 month (skin types I–III).
Adverse events: transient hypopigmentation, purpura
14–20 years 4 5–9 sessions for KPA: reduced erythema 75–100%,
reduced skin roughness with no adverse effects, no
recurrence after 10 months
14–16 years 8 1–4 treatments with PDL: all pts reported improved
erythema in KPR. Six pts sustained results up to
19 months
8–35 years 10 2–7 sessions of PDL: all pts with KPR (8/10) or KPAF
(2/10) had marked reduction in erythema, low inci-
dence of adverse events
5–23 years 12 2–8 treatments: PDL reduced KPA-associated ery-
thema (p < 0.05) and may improve skin roughness,
minimal adverse events
17 years 1 Erythema and follicular hyperkeratosis of severe KPR
and KPAF: marked improvement with PDL every
6 weeks, remained stable for 9 months
15 years 1 Topical clobetasone butyrate: minimal effect, but
seven treatments of KTPL at 6- to 8-week intervals
reduced erythema, cleared keratotic papules of KPR
19–45 years 26 51.7% of KP pts, all type IV skin: marked improve-
ment or total clearance in erythema, skin texture,
brownish dyschromias without significant side
effects, except scaling with microdermabrasion
23 and 2 4 months after final treatment: marked improvement in
28 years KP, satisfied with results
18–65 years 23 18 KP pts with skin types I–III completed study: three
treatments induced improvement in overall severity
(p = 0.005), skin texture (p = 0.004), but erythema
did not improve (p = 0.11)
747

Table 7  (continued)
Treatment
1064 nm: Q-switched Nd:YAG
laser
Combination of 1064 nm:
Q-switched Nd:YAG laser and
topical urea
10,600 nm: fractional carbon
dioxide laser
BID twice a day, KP keratosis pilaris, KPA keratosis pilaris atrophicans, KPAF keratosis pilaris atrophicans faciei, KPR keratosis pilaris rubra, KTPL potassium titanyl phosphate laser, LA lactic
acid, Nd:YAG​neodymium-doped yttrium aluminum garnet, NR not reported, PDL pulsed dye laser, pts patients, QD once a day, RCT​randomized controlled trial, SA salicylic acid
Study
Saelim et al. [263] 2013
Park et al. [264] 2011
Kim [245] 2011
Vachiramon et al. [265] 2016
748
Study design Subject age Sub- Conclusions
jects
(N)
Split-body RCT​ 15–42 years 18 Three treatments at 4-week intervals: 17 KP pts com-
pleted trial, improvement in erythema (p = 0.009),
global assessment (p = 0.007), quantity of keratotic
papules (p = 0.009). All reported improvement,
satisfaction
Pilot 18–35 years 12 Ten treatments once every 2 weeks for KP: skin tex-
ture, dyspigmentation improved > 25% in 11/12 pts,
texture improved > 50% in 6/12 pts, dyspigmentation
improved > 50% in 5/12 pts. 11/12 pts satisfied. No
significant adverse events
Pilot 19–29 years 10 Five weekly laser treatments, urea emollient applica-
tion BID: all pts (skin types IV–V) improved in post-
inflammatory hyperpigmentation associated with KP
(p < 0.05). Minimal adverse events
Prospective, randomized, single- 19–32 years 24 All pts reported improvement in KP after one
blinded, intraindividual compara- treatment. 30% of 20 pts completed study: moder-
tive ate–good improvement by physician’s assessment
at 12 weeks. Hyperpigmentation, keratotic papules
responded better than erythema. Darker skin types
may develop transient pigment changes
J. F. Wang, S. J. Orlow
Keratosis Pilaris and its Subtypes
in combination with other therapies [21, 244, 245]. Glycolic
acid and Jessner solution have been recommended for treat-
ing KP, but data to support these therapies are lacking [246].
Tazarotene, a topical retinoid, has antiproliferative effects,
alters keratinocyte differentiation, and may be effective in
treating KP, as shown by an open study with consecutive
recruitment [247]. Tretinoin, another topical retinoid, has
shown slight effectiveness in treating drug-induced KP in
a case series [238]. Topical steroids may be useful in KPA,
but two prospective cohort studies did not find them to be
useful in KP [21, 34]. One double-blind, bilateral paired
comparison study found that tacrolimus, a topical calcineu-
rin inhibitor, and Aquaphor each treat KP effectively [248],
but not all emollients have been found to be helpful [21]. In
addition, a pilot study found that a combination peel incor-
porating fractional prickle coral calcium (an extract made
from mineral-rich coral and algae that facilitates SC pen-
etration), niacinamide, arbutin, Centella asiatica, papain,
and several acids showed efficacy in treating KP [249]. In
an attempt to restore the skin microbiome, a double-blind,
placebo-controlled, split-arm study demonstrated the safety
and efficacy of a spray-on mist containing the ammonia-
oxidizing bacteria Nitrosomonas eutropha in the treatment
of KP; this organism potentially replenishes physiologic
levels of nitric oxide in the skin, decreasing keratinocyte
proliferation [250]. Chlorine dioxide complex cleanser is a
stable compound with antimicrobial and keratolytic prop-
erties that has been shown in a case series to induce rapid
improvement of KP [251]. However, calcipotriol, a vitamin
D derivative approved for the treatment of psoriasis, has
not been effective in treating KP in a randomized, double-
blind, vehicle-controlled, right/left comparative study [252],
despite a flow-cytometric study that found that calcipotriol
decreases the percentage of epidermal cells in the SG2 M
phase in lesional KP skin [77]. Limited data on the use of
surgras soap from a prospective cohort study did not show
effectiveness in treating KP [21].
Very little data exist on the use of systemic drugs in KP
and its subtypes (Table 7). A prospective cohort study found
that various systemic antibiotics were minimally effective
for KPA [34] and also found that isotretinoin was minimally
effective in treating KPA and may even have caused it to
worsen. However, a case report showed that isotretinoin may
be effective in the treatment of KFSD [133]. Systemic anti-
histamines were not shown to be effective in the treatment
of KP in a prospective cohort study [21]. Of note, a 45-year-
old man with chronic fatigue syndrome who experienced
marked improvement in his KP and AD after treatment with
dextroamphetamine sulfate has been reported [253].
749
9.2 Energy‑Based Therapies
Data from two small pilot studies (Table 7) of light-based
therapies suggest therapeutic promise for photopneumatic
therapy, which stretches and elevates the skin with a pneu-
matic handpiece while delivering light from 400 to 1200 nm
[254], and for intense pulsed light, which delivers broad-
spectrum visible light [255], in the treatment of KPA. Recent
reports address the use of lasers in the treatment of KP and
its subtypes (Table 7). For lasers with wavelengths < 600 nm,
most data are on pulsed dye laser (PDL), which, in a case
report, two case series, and a prospective cohort study,
showed efficacy in the treatment of KPR and KPA, including
KPAF [256–259]. The 532-nm potassium titanyl phosphate
laser (KTPL) does not cause bruise-like discoloration after
treatment, a side effect of PDL, but the therapeutic value of
KTPL in treating KPR has only been examined in one case
report [59]. PDL has also been combined with long-pulsed
755-nm alexandrite laser and microdermabrasion to effec-
tively treat KP in a case series and a retrospective study [260,
261]. In addition, 810-nm long-pulsed diode laser is effec-
tive in treating KP, as shown by a randomized controlled
trial (RCT) [262]. With the Q-switched neodymium-doped
yttrium aluminum garnet (Nd:YAG) laser, both monother-
apy and combination therapy with topical urea have been
shown in two pilot studies and an RCT to effectively treat
KP [245, 263, 264]. In a prospective, randomized, single-
blinded, intraindividual comparative study, fractional carbon
dioxide laser was also shown to be effective in treating KP
[265]. In a case of KFSD, hair removal with five treatments
of long-pulsed non-Q-switched ruby laser at 6-week inter-
vals resulted in reduced inflammation and hair growth that
persisted at 8 months of follow-up [266].
9.3 Other Therapeutic Modalities and Options
for Scarring
Microdermabrasion, a mild treatment that induces epidermal
injury without extending into the dermis, has been recom-
mended to treat KP, but data only exist in combination with
laser therapy from a case series and a retrospective study
[260, 261, 267]. Use of a pumice stone with prior treatment
with a keratolytic agent has also been recommended in treat-
ing KP in a commentary [268]. KPA with scarring alopecia,
once dormant, may be cosmetically treated with reconstruc-
tive procedures, as shown in the case of a 33-year-old man
with dormant KPA who underwent eyebrow reconstruction
with individual hair follicle micrografts and maintained cos-
metic satisfaction at 4 years of follow-up [269].

750
10 Conclusion
KP is a very common skin condition in children and adults.
It is often dismissed as a cosmetic issue, but this can lead
to missed diagnoses of a variety of associated diseases,
hereditary syndromes, and adverse events from medica-
tions as well as inadequate treatment. Further characteriza-
tion of these associations will shed much needed light on the
pathophysiology of KP and its subtypes, which can lead to a
better understanding of how to develop effective therapies.
More data on the effectiveness of old and new therapies are
necessary to update treatment guidelines. Based on our com-
prehensive review of the literature, we present the following
conclusions:
• KP is common, but prevalence appears to vary with eth-
nicity. Genetics appear to play a major role in KP and its
subtypes.
• KP typically presents during childhood; spontaneous
improvement during adolescence is common.
• Diagnosis of KP is usually made clinically, but dermos-
copy and biopsy can aid with diagnosis.
• KPA is a rare, scarring, atrophic subtype of KP poten-
tially due to a mutation in LRP1; KPA comprises a
spectrum of clinical entities with variable overlap and
pediatric onset that tend to improve during adolescence,
including KPAF, AV, KFSD, and—potentially—FSD.
• EFFC is a rare, pigmented subtype of KP without scar-
ring or atrophy but with pediatric onset and clinical over-
lap with KPR.
• KPR and PPPKP are common but underreported vari-
ants of KP, while unilateral presentations of KP and its
subtypes are rare.
• Although the pathogenesis of KP has not yet been fully
elucidated, many factors, including histopathologic find-
ings, the tendency of KP to improve during adolescence,
the association of KP with filaggrin mutations and 18p
monosomy, the effects of androgen and insulin dysregu-
lation, and reduced prevalence of KP in patients with
acne vulgaris, support KP as a disorder of the sebaceous
gland, which in turn disrupts the permeability barrier
of the SC and causes aberrant keratinization and hair
abnormalities.
• The association of KP with atopy and IV may stem from
a defect in the permeability barrier partially caused by
filaggrin mutations. However, given the etiological het-
erogeneity and high prevalence of both disorders, the
presence of KP should not be considered a diagnostic
criterion for AD.
• Changes in androgen and insulin levels that manifest in
obesity, diabetes, and pregnancy can directly affect sebo-
cytes and contribute to the pathogenesis of KP.
J. F. Wang, S. J. Orlow
• KP is associated with several PCAs, including GLPLS,
acne keloidalis, and FFA.
• Of the syndromes with ID as a cardinal feature, the asso-
ciation of KP and DS is the most evidence-based.
• Of the RASopathies, KP and KPAF are more common
in cardio-facial-cutaneous syndrome than in CS or NS.
Because KP is also caused by B-Raf inhibitors, aberrant
signaling in the Ras pathway may be crucial to the patho-
genesis of KP.
• KP is associated with several EDs, including PKCAS,
HMD, PC, and monilethrix, and hereditary skin append-
age disorders, including WH, hypotrichosis, HK, and LT.
• Medications known to cause KP-like eruptions include
cyclosporine, the B-Raf inhibitors dabrafenib and vemu-
rafenib, and the TKIs nilotinib, dasatinib, ponatinib, erlo-
tinib, and sorafenib.
• Sudden KP-like eruptions warrant a thorough medical
evaluation, with special attention to medications.
• LA, SA, urea, topical retinoids, tacrolimus, Aquaphor,
fractional prickle coral calcium, spray-on Nitrosomonas
eutropa mist, and chorine dioxide complex cleanser have
been shown to be at least partially effective in treating
KP.
• The data on systemic drugs for the treatment of KP and
its subtypes are sparse and conflicting.
• Preliminary data suggest that photopneumatic therapy is
effective in treating KP and intense pulsed light is effec-
tive in treating KPA.
• Lasers that are effective in treating KP or its subtypes
include PDL, KTPL, alexandrite laser, long-pulsed diode
laser, Q-switched Nd:YAG laser, and fractional carbon
dioxide laser.
Since KP is so common, it is difficult to distinguish true
associations from those that occur by chance, especially with
environmental exposures and rare diseases. More studies
are necessary to cement disease associations, gain further
insight into the pathophysiology of KP, and establish effec-
tive treatment guidelines.
Compliance with Ethical Standards 
Funding  JFW was supported in part by the Clinical and Translational
Science Award grant UL1TR001445 to New York University from
the National Center for Advancing Translational Sciences, National
Institutes of Health.
Conflicts of interest  JFW and SJO have no conflicts of interest.
References
1. Hwang S, Schwartz RA. Keratosis pilaris: a common follicular
hyperkeratosis. Cutis. 2008;82(3):177–80.
Keratosis Pilaris and its Subtypes
2. Sandilands A, O’Regan GM, Liao H, Zhao Y, Terron-Kwiat-
kowski A, Watson RM, et al. Prevalent and rare mutations in
the gene encoding filaggrin cause ichthyosis vulgaris and pre-
dispose individuals to atopic dermatitis. J Invest Dermatol.
2006;126(8):1770–5.
3. Sardana K. Follicular disorders of the face. Clin Dermatol.
2014;32(6):839–72.
4. Brown SJ, Relton CL, Liao H, Zhao Y, Sandilands A, McLean
WHI, et al. Filaggrin haploinsufficiency is highly penetrant
and is associated with increased severity of eczema: Fur-
ther delineation of the skin phenotype in a prospective epi-
demiological study of 792 school children. Br J Dermatol.
2009;161(4):884–9.
5. Anand BK, Marwaha MPS, Prakash B. Prevalence of skin disor-
ders in school children. Internet J Health. 2012;13(1):1.
6. Dogra S, Kumar B. Epidemiology of skin diseases in school
children: a study from northern india. pediatric dermatology.
2003;20(6):470–3.
7. Yosipovitch G, Mevorah B, Mashiach J, Chan YH, David M.
High body mass index, dry scaly leg skin and atopic conditions
are highly associated with keratosis pilaris. Dermatology (Basel,
Switzerland). 2000;201(1):34–6.
8. Tay YK, Kong KH, Khoo L, Goh CL, Giam YC. The prevalence
and descriptive epidemiology of atopic dermatitis in Singapore
school children. Br J Dermatol. 2002;146(1):101–6.
9. Inanir I, Turhan Sahin M, Gunduz K, Dinc G, Turel A, Serap
Ozturkcan D. Prevalence of skin conditions in primary school
children in Turkey: differences based on socioeconomic factors.
Pediatr Dermatol. 2002;19(4):307–11.
10. Popescu R, Popescu CM, Williams HC, Forsea D. The prevalence
of skin conditions in Romanian school children. Br J Dermatol.
1999;140(5):891–6.
11. Del Pozzo-Magana BR, Lazo-Langner A, Gutierrez-Castrellon
P, Ruiz-Maldonado R. Common dermatoses in children referred
to a specialized pediatric dermatology service in Mexico: a
comparative study between two decades. ISRN Dermatol.
2012;2012:351603.
12. Al-Saeed WY, Al-Dawood KM, Bukhari IA, Bahnassy AA. Prev-
alence and pattern of skin disorders among female schoolchildren
in Eastern Saudi Arabia. Saudi Med J. 2006;27(2):227–34.
13. Figueroa JI, Fuller LC, Abraha A, Hay RJ. The prevalence of
skin disease among school children in rural Ethiopia—a pre-
liminary assessment of dermatologic needs. Pediatr Dermatol.
1996;13(5):378–81.
14. Fung WK, Lo KK. Prevalence of skin disease among school
children and adolescents in a student health service center in
Hong Kong. Pediatr Dermatol. 2000;17(6):440–6.
15. Bechelli LM, Haddad N, Pimenta WP, Pagnano PM, Melchior E
Jr, Fregnan RC, et al. Epidemiological survey of skin diseases in
schoolchildren living in the Purus Valley (Acre State, Amazonia,
Brazil). Dermatologica. 1981;163(1):78–93.
16. Pyo JY, Kim SD, Lee WJ, Koo DW. An epidemiological study
of dermatoses of conscriptees in Kangwon Province, 2001.
[Korean]. Korean. J Dermatol. 2003;41(9):1149–56.
17. Novak N, Baurecht H, Schafer T, Rodriguez E, Wagenpfeil S,
Klopp N, et al. Loss-of-function mutations in the Filaggrin gene
and allergic contact sensitization to nickel. J Investig Dermatol.
2008;128(6):1430–5.
18. Albares MP, Belinchon I, Ramos JM, Sanchez-Paya J, Betl-
loch I. Epidemiologic study of skin diseases among immigrants
in Alicante, Spain. [Spanish]. Actas Dermo-Sifiliograficas.
2012;103(3):214–22.
19. Sergeant A, Campbell LE, Hull PR, Porter M, Palmer CN, Smith
FJ, et al. Heterozygous null alleles in filaggrin contribute to clini-
cal dry skin in young adults and the elderly. J Invest Dermatol.
2009;129(4):1042–5.
751
20. Mevorah B, Marazzi A, Frenk E. The prevalence of accentuated
palmoplantar markings and keratosis pilaris in atopic dermati-
tis, autosomal dominant ichthyosis and control dermatological
patients. Br J Dermatol. 1985;112(6):679–85.
21. Castela E, Chiaverini C, Boralevi F, Hugues R, Lacour JP. Papu-
lar, profuse, and precocious keratosis pilaris. Pediatr Dermatol.
2012;29(3):285–8.
22. Poskitt L, Wilkinson JD. Natural history of keratosis pilaris. Br
J Dermatol. 1994;130(6):711–3.
23. Marqueling AL, Gilliam AE, Prendiville J, Zvulunov A,
Antaya RJ, Sugarman J, et  al. Keratosis pilaris rubra: a
common but underrecognized condition. Arch Dermatol.
2006;142(12):1611–6.
24. Gruber R, Sugarman JL, Crumrine D, Hupe M, Mauro TM,
Mauldin EA, et al. Sebaceous gland, hair shaft, and epidermal
barrier abnormalities in keratosis pilaris with and without filag-
grin deficiency. Am J Pathol. 2015;185(4):1012–21.
25. Sallakachart P, Nakjang Y. Keratosis pilaris: a clinico-histo-
pathologic study. J Med Assoc Thailand Chotmaihet thangphaet.
1987;70(7):386–9.
26. Drago F, Maietta G, Parodi A, Rebora A. Keratosis pilaris decal-
vans non-atrophicans. Clin Exp Dermatol. 1993;18(1):45–6.
27. Silverberg NB. A pilot trial of dermoscopy as a rapid assessment
tool in pediatric dermatoses. Cutis. 2011;87(3):148–54.
28. Panchaprateep R, Tanus A, Tosti A. Clinical, dermoscopic, and
histopathologic features of body hair disorders. J Am Acad Der-
matol. 2015;72(5):890–900.
29. Thomas M, Khopkar US. Keratosis pilaris revisited: is it more
than just a follicular keratosis? Int J Trichol. 2012;4(4):255–8.
30. Schneider MR, Paus R. Deciphering the functions of the hair
follicle infundibulum in skin physiology and disease. Cell Tissue
Res. 2014;358(3):697–704.
31. Rand R, Baden HP. Keratosis follicularis spinulosa decalvans.
Report of two cases and literature review. Arch Dermatol.
1983;119(1):22–6.
32. Callaway SR, Lesher Jr JL. Keratosis pilaris atrophicans: case
series and review. Pediatr Dermatol. 2004;21(1):14–7.
33. Davenport DD. Ulerythema ophryogenes; review and report of
a case. Discussion of relationship to certain other skin disorders
and association with internal abnormalities. Arch Dermatol.
1964;89:74–80.
34. Baden HP, Byers HR. Clinical findings, cutaneous pathology, and
response to therapy in 21 patients with keratosis pilaris atrophi-
cans. Arch Dermatol. 1994;130(4):469–75.
35. Volks N, Folster-Holst R. Erythromelanosis follicularis faciei-a
variant of keratosis pilaris? JDDG. 2015;13(1):51–4.
36. Stojanovic S, Vuckovic N, Jovanovic M. Overlap between ulery-
thema ophryogenes and keratosis follicularis spinulosa decal-
vans: a case report. Serb J Dermatol Venereol. 2015;7(3):129–38.
37. Selvaag E, Krohn-Hansen D. Keratosis follicularis spinulosa
decalvans. Eur J Pediatr Dermatol. 1996;6(2):69–72.
38. Pierini DO, Pierini AM. Keratosis pilaris atrophicans faciei
(ulerythema ophryogenes): a cutaneous marker in the Noonan
syndrome. Br J Dermatol. 1979;100(4):409–16.
39. Luria RB, Conologue T. Atrophoderma vermiculatum: a case
report and review of the literature on keratosis pilaris atrophi-
cans. Cutis Cutaneous Med Pract. 2009;83(2):83–6.
40. Frosch PJ, Brumage MR, Schuster-Pavlovic C, Bersch A.
Atrophoderma vermiculatum. Case reports and review. J Am
Acad Dermatol. 1988;18(3):538–42.
41. Das A, Podder I. Atrophoderma vermiculatum. Indian Pediatr.
2014;51(8):679.
42. Barron DR, Hirsch AL, Buchbinder L, Pomeranz JR. Follicu-
litis ulerythematosus reticulata: a report of four cases and brief
review of the literature. Pediatr Dermatol. 1987;4(2):85–9.

752
43. Jansen T, Sander CA, Altmeyer P. Atrophodermia vermiculata:
case report and review of the literature. J Eur Acad Dermatol
Venereol. 2003;17(1):70–2.
44. Oranje AP, van Osch LD, Oosterwijk JC. Keratosis pilaris atroph-
icans. One heterogeneous disease or a symptom in different clini-
cal entities? Arch Dermatol. 1994;130(4):500–2.
45. Fong K, Wedgeworth EK, Lai-Cheong JE, Tosi I, Mellerio JE,
Powell AM, et al. MBTPS2 mutation in a British pedigree with
keratosis follicularis spinulosa decalvans. Clin Exp Dermatol.
2012;37(6):631–4.
46. Oosterwijk JC, Nelen M, van Zandvoort PM, van Osch LD,
Oranje AP, Wittebol-Post D, et al. Linkage analysis of kera-
tosis follicularis spinulosa decalvans, and regional assign-
ment to human chromosome Xp21.2-p22.2. Am J Hum Genet.
1992;50(4):801–7.
47. Malvankar DD, Sacchidanand S. Keratosis follicularis spi-
nulosa decalvans: a report of three cases. Int J Trichol.
2015;7(3):125–8.
48. Romine KA, Rothschild JG, Hansen RC. Cicatricial alopecia and
keratosis pilaris. Keratosis follicularis spinulosa decalvans. Arch
Dermatol. 1997;133(3):381, 4.
49. Maroon M, Tyler WB, Marks VJ. Keratosis pilaris and scarring
alopecia. Keratosis follicularis spinulosa decalvans. Arch Der-
matol. 1992;128(3):397, 400.
50. Di Lernia V, Ricci C. Folliculitis spinulosa decalvans: an uncom-
mon entity within the keratosis pilaris atrophicans spectrum.
Pediatr Dermatol. 2006;23(3):255–8.
51. Klar J, Schuster J, Khan TN, Jameel M, Mabert K, Forsberg L,
et al. Whole exome sequencing identifies LRP1 as a pathogenic
gene in autosomal recessive keratosis pilaris atrophicans. J Med
Genet. 2015;52(9):599–606.
52. Dianzani C, Pizzuti A, Gaspardini F, Bernardini L, Rizzo B,
Degener AM. Ulerythema ophryogenes, a rare and often misdi-
agnosed syndrome: analysis of an idiopathic case. Int J Immu-
nopathol Pharmacol. 2011;24(2):523–7.
53. Turegano MM, Sperling LC. Lichenoid folliculitis: a unifying
concept. J Cutan Pathol. 2017;44(7):647–54.
54. Rather S, Yaseen A, Mukhija M. Erythromelanosis follicularis
faciei et colli—a cross-sectional, descriptive study. Indian J Der-
matol. 2016;61(3):308–13.
55. Sardana K, Relhan V, Garg V, Khurana N. An observational
analysis of erythromelanosis follicularis faciei et colli. Clin Exp
Dermatol. 2008;33(3):333–6.
56. Arif T, Adil M, Amin SS, Tahseen M, Dorjay K, Mohtashim M,
et al. Erythromelanosis follicularis faciei et colli: a clinicoepide-
miologic study. Pediatr Dermatol. 2018;35(1):e70–1.
57. Kim MG, Hong SJ, Son SJ, Song HJ, Kim IH, Oh CH, et al.
Quantitative histopathologic findings of erythromelanosis fol-
licularis faciei et colli. J Cutan Pathol. 2001;28(3):160–4.
58. Voss M. Keratosis follicularis–new genetic aspects. Hautarzt.
1991;42(5):319–21.
59. Dawn G, Urcelay M, Patel M, Strong AM. Keratosis rubra pilaris
responding to potassium titanyl phosphate laser. Br J Dermatol.
2002;147(4):822–4.
60. Al Hawsawi K, Aljuhani O, Niaz G, Fallatah H, Alhawsawi A.
Erythromelanosis follicularis faciei: a case report and review of
the literature. case reports in dermatology. 2015;7(3):335–9.
61. Augustine M, Jayaseelan E. Erythromelanosis follicularis faciei
et colli: relationship with keratosis pilaris. Indian J Dermatol
Venereol Leprol. 2008;74(1):47–9.
62. Watt TL, Kaiser JS. Erythromelanosis follicularis faciei et colli.
A case report. J Am Acad Dermatol. 1981;5(5):533–4.
63. Ehsani A, Namazi MR, Barikbin B, Nazemi MJ. Unilaterally
generalized keratosis pilaris. JEADV. 2003;17(3):361–2.
64. Zhu JW, Lu ZF, Zheng M. Unilateral generalized keratosis pilaris
following pregnancy. Cutis. 2014;94(4):203–5.
J. F. Wang, S. J. Orlow
65. Ma H, Xu Q, Zhu G, Su X, Yin S, Lu C, et al. Unilateral kera-
tosis pilaris occurring on linear hypopigmentation patches:
a new variant of keratosis pilaris in an Asian? J Dermatol.
2015;42(4):437–8.
66. Rozum LT, Mehregan AH, Johnson SA. Folliculitis ulerythe-
matosa reticulata. A case with unilateral lesion. Arch Dermatol.
1972;106(3):388–9.
67. Arrieta E, Milgram-Sternberg Y. Honeycomb atrophy on the
right cheek. Folliculitis ulerythematosa reticulata (atrophoderma
vermiculatum). Arch Dermatol. 1988;124(7):1101, 4.
68. Jayaraman M, Somasundaram V. Unilateral atropho-
derma vermiculatum. Indian J Dermatol Venereol Leprol.
1996;62(5):320–1.
69. Nico MM, Valente NY, Sotto MN. Folliculitis ulerythematosa
reticulata (atrophoderma vermiculata): early detection of a case
with unilateral lesions. Pediatr Dermatol. 1998;15(4):285–6.
70. Hsu S, Nikko A. Unilateral atrophic skin lesion with features of
atrophoderma vermiculatum: a variant of the epidermal nevus
syndrome? J Am Acad Dermatol. 2000;43(2 Pt 1):310–2.
71. Bhoyrul B, Jones H, Blackford S. Extensive unilateral atropho-
derma vermiculatum associated with ipsilateral congenital cata-
ract. Clin Exp Dermatol. 2016;41(2):159–61.
72. Dajani ZAW, Kerns MJ, Mutasim DF. Unilateral keratosis pilaris
atrophicans faciei mimicking follicular mucinosis. J Am Acad
Dermatol. 2011;64(5):e71–2.
73. Haftek M, Simon M, Kanitakis J, Marechal S, Claudy A, Serre
G, et al. Expression of corneodesmosin in the granular layer and
stratum corneum of normal and diseased epidermis. Br J Derma-
tol. 1997;137(6):864–73.
74. Kirschner N, Houdek P, Fromm M, Moll I, Brandner JM. Tight
junctions form a barrier in human epidermis. Eur J Cell Biol.
2010;89(11):839–42.
75. Feingold KR, Schmuth M, Elias PM. The regulation of
permeability barrier homeostasis. J Invest Dermatol.
2007;127(7):1574–6.
76. Lee SC, Lee JB, Seo JJ, Kim YP. Expression of trichohyalin in
dermatological disorders: a comparative study with involucrin
and filaggrin by immunohistochemical staining. Acta Dermato-
venereol. 1999;79(2):122–6.
77. Lucker GPH, Steijlen PM, Suykerbuyk EJA, Kragballe K, Bran-
drup F, Van De Kerkhof PCM. Flow-cytometric investigation of
epidermal cell characteristics in monogenic disorders of kerati-
nization and their modulation by topical calcipotriol treatment.
Acta Dermato-Venereol. 1996;76(2):97–101.
78. Siegenthaler G, Saurat JH, Salomon D, Merot Y. Skin cellular
retinoid-binding proteins and retinoid-responsive dermatoses.
Dermatologica. 1986;173(4):163–73.
79. Akay BN, Parlak N, Saral S, Akyol A. The case of ichthyosis fol-
licularis, alopecia and photophobia syndrome with retinal detach-
ment. [Turkish]. Turkderm Deri Hastaliklari ve Frengi Arsivi.
2014;48(2):108–10.
80. Cohen-Barak E, Danial-Farran N, Hammed H, Aleme O, Krauz
J, Gavish E, et al. Desmoglein 4 Mutation Underlies Autosomal
Recessive Keratosis Pilaris Atrophicans. Acta Dermato-venereol.
2018. https​://doi.org/10.2340/00015​555-2976.
81. Aten E, Brasz LC, Bornholdt D, Hooijkaas IB, Porte-
ous ME, Sybert VP, et  al. Keratosis follicularis spinulosa
decalvans is caused by mutations in MBTPS2. Hum Mutat.
2010;31(10):1125–33.
82. Zhang J, Wang Y, Cheng R, Ni C, Liang J, Li M, et al. Novel
MBTPS2 missense mutation causes a keratosis follicularis spi-
nulosa decalvans phenotype: mutation update and review of the
literature. Clin Exp Dermatol. 2016;41(7):757–60.
83. Nemer G, Safi R, Kreidieh F, Usta J, Bergqvist C, Ballout
F, et  al. Understanding the phenotypic similarities between
IFAP and Olmsted syndrome from a molecular perspective:
Keratosis Pilaris and its Subtypes
the interaction of MBTPS2 and TRPV3. Arch Dermatol Res.
2017;309(8):637–43.
84. Perry HO, Su WP. Olmsted syndrome. Semin Dermatol.
1995;14(2):145–51.
85. Bellet JS, Kaplan AL, Selim MA, Olsen EA. Keratosis folli-
cularis spinulosa decalvans in a family. J Am Acad Dermatol.
2008;58(3):499–502.
86. Sequeira FF, Jayaseelan E. Keratosis follicularis spinulosa decal-
vans in a female. Indian journal of dermatology, venereology and
leprology. 2011;77(3):325–7.
87. Chauhan RK, Sankhwar S, Tripathi R, Pandey SS. A rare pres-
entation of keratosis follicularis spinulosa decalvans in female
twins. Indian J Dermatol Venereol Leprol. 2017. https​://doi.
org/10.4103/ijdvl​.IJDVL​_524_16.
88. Khumalo NP, Loo WJ, Hollowood K, Salvary I, Graham RM,
Dawber RPR. Keratosis pilaris atrophicans in mother and
daughter. J Eur Acad Dermatol Venereol. 2002;16(4):397–400.
89. Castori M, Covaciu C, Paradisi M, Zambruno G. Clinical and
genetic heterogeneity in keratosis follicularis spinulosa decal-
vans. Eur J Med Genet. 2009;52(1):53–8.
90. Yanez S, Velasco JA, Gonzalez MP. Familial erythromelanosis
follicularis faciei et colli—an autosomal recessive mode of
inheritance. Clin Exp Dermatol. 1993;18(3):283–5.
91. Tuzun Y, Wolf R, Tuzun B, Ozdemir M, Demirkesen C,
Deviren A, et al. Familial erythromelanosis follicularis and
chromosomal instability. JEADV. 2001;15(2):150–2.
92. Lalit G, Anubhav G, Kumar KA, Asit M. Familial erythromela-
nosis follicularis faciei et colli with extensive keratosis pilaris.
Int J Dermatol. 2011;50(11):1400–1.
93. Ermertcan AT, Ozturkcan S, Sahin MT, Turkdogan P, Sacar
T. Erythromelanosis follicularis faciei et colli associated
with keratosis pilaris in two brothers. Pediatr Dermatol.
2006;23(1):31–4.
94. Williams HC, Burney PG, Strachan D, Hay RJ. The U.K.
Working Party’s Diagnostic Criteria for Atopic Dermatitis. II.
Observer variation of clinical diagnosis and signs of atopic der-
matitis. Br J Dermatol. 1994;131(3):397–405.
95. Cheng F, Zhao JH, Tang XF, Cheng H, Sheng YJ, Jiang XY,
et al. Association of the chromosome 11p13.5 variant and atopic
dermatitis with a family history of atopy in the Chinese Han
population. Asian Pac J Allergy Immunol. 2016;34(2):109–14.
96. Chen H, Common JEA, Haines RL, Balakrishnan A, Brown
SJ, Goh CSM, et  al. Wide spectrum of filaggrin-null muta-
tions in atopic dermatitis highlights differences between Sin-
gaporean Chinese and European populations. Br J Dermatol.
2011;165(1):106–14.
97. Wahab MA, Rahman MH, Khondker L, Hawlader AR, Ali A,
Hafiz MA, et al. Minor criteria for atopic dermatitis in children.
MMJ. 2011;20(3):419–24.
98. Macharia WM, Anabwani GM, Owili DM. Clinical presentation
of atopic dermatitis in Negroid children. Afr J Med Med Sci.
1993;22(4):41–4.
99. Kwon JA, Roh KY, Koh BK, Kim JW. Clinical characteristics
of adolescence and adult atopic dermatitis in Korea. [Korean].
Korean J Dermatol. 2004;42(8):949–54.
100. Choi YS, You CE, Park MY, Son SJ, Whang KU. A study
on clinical features and laboratory findings according to the
severity of atopic dermatitis. [Korean]. Korean J Dermatol.
2006;44(7):824–9.
101. Brenninkmeijer EEA, Spuls PI, Legierse CM, Lindeboom R,
Smitt JHS, Bos JD. Clinical differences between atopic and
atopiform dermatitis. J Am Acad Dermatol. 2008;58(3):407–14.
102. Uehara M, Takahashi C, Ofuji S. Pustular patch test reactions in
atopic dermatitis. Arch Dermatol. 1975;111(9):1154–7.
103. Bremmer SF, Hanifin JM, Simpson EL. Clinical detection of
ichthyosis vulgaris in an atopic dermatitis clinic: implications for
753
allergic respiratory disease and prognosis. J Am Acad Dermatol.
2008;59(1):72–8.
104. Mevorah B, Krayenbuhl A, Bovey EH, van Melle GD. Autoso-
mal dominant ichthyosis and X-linked ichthyosis. Comparison
of their clinical and histological phenotypes. Acta Dermato-
venereol. 1991;71(5):431–4.
105. Ghosh A, Ahar R, Chatterjee G, Sharma N, Jadhav SA.
Clinico-epidemiological Study of Congenital Ichthyosis in
a Tertiary Care Center of Eastern India. Indian J Dermatol.
2017;62(6):606–11.
106. Al-Akloby OM. Association of atopic dermatitis with primary
hereditary ichthyoses. Saudi Med J. 2004;25(8):1097–9.
107. Brown SJ, Relton CL, Liao H, Zhao Y, Sandilands A, Wilson
IJ, et al. Filaggrin null mutations and childhood atopic eczema:
a population-based case-control study. J Allergy Clin Immunol.
2008;121(4):940–46.e3.
108. Palmer CN, Irvine AD, Terron-Kwiatkowski A, Zhao Y, Liao
H, Lee SP, et al. Common loss-of-function variants of the epi-
dermal barrier protein filaggrin are a major predisposing factor
for atopic dermatitis. Nat Genet. 2006;38(4):441–6.
109. Landeck L, Visser M, Kezic S, John SM. Genotype-phenotype
associations in filaggrin loss-of-function mutation carriers.
Contact Dermat. 2013;68(3):149–55.
110. Cai SC, Chen H, Koh WP, Common JE, van Bever HP, McLean
WH, et al. Filaggrin mutations are associated with recurrent
skin infection in Singaporean Chinese patients with atopic der-
matitis. Br J Dermatol. 2012;166(1):200–3.
111. Thyssen JP, Thuesen B, Huth C, Standl M, Carson CG,
Heinrich J, et al. Skin barrier abnormality caused by filag-
grin (FLG) mutations is associated with increased serum
25-hydroxyvitamin D concentrations. J Allergy Clin Immunol.
2012;130(5):1204–7.e2.
112. Sato T, Imai N, Akimoto N, Sakiguchi T, Kitamura K, Ito A.
Epidermal growth factor and 1alpha,25-dihydroxyvitamin D3
suppress lipogenesis in hamster sebaceous gland cells in vitro. J
Invest Dermatol. 2001;117(4):965–70.
113. Chen S, Kong X, Wei X, Sun Y, Yin D, Zhang Q, et al. Targeted
next-generation sequencing identifies 9 novel FLG variants in
Chinese Han patients with ichthyosis vulgaris. Br J Dermatol.
2017;177(5):e202–3.
114. Baselga Torres E, Torres-Pradilla M. Cutaneous manifestations
in children with diabetes mellitus and obesity. Actas Dermo-
sifiliograficas. 2014;105(6):546–57.
115. Boza JC, Trindade EN, Peruzzo J, Sachett L, Rech L, Cestari TF.
Skin manifestations of obesity: a comparative study. J Eur Acad
Dermatol Venereol. 2012;26(10):1220–3.
116. Nazik H, Kokcam I, Demir B, Gul FC. Skin findings in over-
weight and obese individuals. [Turkish]. Turkderm Deri Hasta-
liklari ve Frengi Arsivi. 2016;50(2):59–64.
117. Garcia-Hidalgo L, Orozco-Topete R, Gonzalez-Barranco J, Villa
AR, Dalman JJ, Ortiz-Pedroza G. Dermatoses in 156 obese
adults. Obes Res. 1999;7(3):299–302.
118. Plascencia Gomez A, Vega Memije ME, Torres Tamayo M,
Rodriguez Carreon AA. Skin disorders in overweight and obese
patients and their relationship with insulin. Actas Dermo-sifili-
ograficas. 2014;105(2):178–85.
119. Guida B, Nino M, Perrino NR, Laccetti R, Trio R, Labella S,
et al. The impact of obesity on skin disease and epidermal perme-
ability barrier status. JEADV. 2010;24(2):191–5.
120. Barth JH, Ng LL, Wojnarowska F, Dawber RPR. Acanthosis nig-
ricans, insulin resistance and cutaneous virilism. Br J Dermatol.
1988;118(5):613–9.
121. Pavlovic MD, Milenkovic T, Dinic M, Misovic M, Dakovic
D, Todorovic S, et al. The prevalence of cutaneous manifes-
tations in young patients with type 1 diabetes. Diabetes Care.
2007;30(8):1964–7.

754
122. Yosipovitch G, Hodak E, Vardi P, Shraga I, Karp M, Sprecher
E, et al. The prevalence of cutaneous manifestations in IDDM
patients and their association with diabetes risk factors and
microvascular complications. Diabetes Care. 1998;21(4):506–9.
123. Zouboulis CC, Schagen S, Alestas T. The sebocyte culture:
a model to study the pathophysiology of the sebaceous gland
in sebostasis, seborrhoea and acne. Arch Dermatol Res.
2008;300(8):397–413.
124. Alestas T, Ganceviciene R, Fimmel S, Muller-Decker K, Zou-
boulis CC. Enzymes involved in the biosynthesis of leukotriene
B4 and prostaglandin E2 are active in sebaceous glands. J Mol
Med (Berlin, Germany). 2006;84(1):75–87.
125. Jackson JB, Touma SC, Norton AB. Keratosis pilaris in preg-
nancy: an unrecognized dematosis of pregnancy? West Vir-
ginia Med J. 2004;100(1):26–8.
126. Barth JH, Wojnarowska F, Dawber RPR. Is keratosis pilaris
another androgen-dependent dermatosis? Clin Exp Dermatol.
1988;13(4):240–1.
127. Donovan JC. Graham Little-Piccardi-Lassueur syndrome in a
patient with androgen insensitivity syndrome. Int J Dermatol.
2016;55(4):e211–2.
128. Vega Gutierrez J, Miranda-Romero A, Perez Milan F, Martinez
Garcia G. Graham Little-Piccardi-Lassueur syndrome associ-
ated with androgen insensitivity syndrome (testicular feminiza-
tion). JEADV. 2004;18(4):463–6.
129. Yorulmaz A, Artuz F, Er O, Guresci S. A case of Graham-
Little-Piccardi-Lasseur syndrome. Dermatol Online J.
2015;21(6):12.
130. Laszlo FG. Graham-Little-Piccardi-Lasseur syndrome: case
report and review of the syndrome in men. Int J Dermatol.
2014;53(8):1019–22.
131. Viglizzo G, Verrini A, Rongioletti F. Familial Lassueur-Gra-
ham-Little-Piccardi syndrome. Dermatology (Basel, Switzer-
land). 2004;208(2):142–4.
132. Janjua SA, Iftikhar N, Pastar Z, Hosler GA. Keratosis fol-
licularis spinulosa decalvans associated with acne keloida-
lis nuchae and tufted hair folliculitis. Am J Clin Dermatol.
2008;9(2):137–40.
133. Goh MS, Magee J, Chong AH. Keratosis follicularis spinu-
losa decalvans and acne keloidalis nuchae. Austral J Dermatol.
2005;46(4):257–60.
134. Tan KT, Messenger AG. Frontal fibrosing alopecia: clinical pres-
entations and prognosis. Br J Dermatol. 2009;160(1):75–9.
135. Sindhuphak W, Vibhagool A. Acquired hypertrichosis lanugi-
nosa. Int J Dermatol. 1982;21(10):599–601.
136. Thomsen K, Nyfors A. Keratosis pilaris: skin marker of Hodgkin
disease? Arch Dermatol. 1973;107(4):629–30.
137. Brazzelli V, Larizza D, Prestinari F, Barbagallo T, Lauriola MM,
Calcaterra V, et al. Thyroid diseases and skin disorders in pedi-
atric patients. Giornale Italiano di Dermatologia e Venereologia.
2005;140(5):485–9.
138. Forman L. Keratosis pilaris associated with myxoedema. Proc R
Soc Med. 1951;44(8):683–4.
139. Ziora K, Pindycka-Piaszczynska M, Wszolek M, Oswiecimska J,
Swider M, Ziora-Jakutowicz K, et al. Prevalence of skin lesions
in children and adolescents with anorexia nervosa. [Polish].
Pediatria Polska. 2011;86(6):612–9.
140. Schmitt JV, Lima BZ, Souza MC, Miot HA. Keratosis pilaris
and prevalence of acne vulgaris: a cross-sectional study. Anais
Brasileiros de Dermatologia. 2014;89(1):91–5.
141. Kose O, Safali M, Riza Gur A. Atrophoderma vermicula-
tum with Melkersson-Rosenthal syndrome. Dermatology.
2005;210(1):76–7.
142. Masood Q, Manzoor S, Hassan I, Majid I. Psychomotor
retardation—an unusual association of keratosis follicularis
J. F. Wang, S. J. Orlow
spinulosa decalvans. Indian J Dermatol Venereol Leprol.
2000;66(6):320–1.
143. Macotela Ruiz E, Cantu JM. Keratosis pilaris rubra, precocious
canities and psychomotor retardation. A new syndrome. Mod-
ProblPaediat. 1975;17:60.
144. Kalwaniya S, Morgaonkar M, Gupta S, Jain SK. Co-occurrence
of erythrosis pigmentosa mediofacialis and erythromelanosis
follicularis faciei et colli associated with keratosis pilaris in an
adolescent female. Indian J Dermatol. 2016;61(4):467.
145. Finn OA, Grant PW, McCallum DI, Raffle EJ. A singular derma-
tosis of mongols. Arch Dermatol. 1978;114(10):1493–4.
146. Camacho FM, Mazuecos J, Ferrandiz L, Cantalejo C,
Cabello A. Phenotypical and dermatological findings of
down syndrome in Southern Spain. Eur J Pediatr Dermatol.
2014;24(1):7–12.
147. Schepis C, Barone C, Siragusa M, Pettinato R, Romano C. An
updated survey on skin conditions in Down syndrome. Derma-
tology. 2002;205(3):234–8.
148. Daneshpazhooh M, Nazemi TM, Bigdeloo L, Yoosefi M.
Mucocutaneous findings in 100 children with Down syndrome.
Pediatr Dermatol. 2007;24(3):317–20.
149. Carter DM, Jegasothy BV. Alopecia areata and Down syn-
drome. Arch Dermatol. 1976;112(10):1397–9.
150. Ercis M, Balci S, Atakan N. Dermatological manifestations
of 71 Down syndrome children admitted to a clinical genetics
unit. Clin Genet. 1996;50(5):317–20.
151. Alfadley A, Al Hawsawi K, Hainau B, Al Aboud K. Two broth-
ers with keratosis follicularis spinulosa decalvans. J Am Acad
Dermatol. 2002;47(5 SUPPL.):S275–S8.
152. Badura-Stronka M, Jamsheer A, Materna-Kiryluk A, Sowinska
A, Kiryluk K, Budny B, et al. A novel nonsense mutation in
CUL4B gene in three brothers with X-linked mental retardation
syndrome. Clin Genet. 2010;77(2):141–4.
153. Guerin-Moreau M, Colin E, Nguyen S, Andrieux J, De Leer-
snyder H, Bonneau D, et al. Dermatologic features of Smith-
Magenis syndrome. Pediatr Dermatol. 2015;32(3):337–41.
154. Florez A, Fernandez-Redondo V, Toribio J. Ulerythema ophry-
ogenes in Cornelia de Lange syndrome. Pediatr Dermatol.
2002;19(1):42–5.
155. Gomez Centeno P, Roson E, Peteiro C, Mercedes Pereiro M,
Toribio J. Rubinstein–Taybi syndrome and ulerythema ophryo-
genes in a 9-year-old boy. Pediatr Dermatol. 1999;16(2):134–6.
156. Bryan ZT, Missall TA, Stieren S, Siegfried E, Burkemper
NM. Clinicopathologic evaluation of cardiofaciocutaneous
syndrome: overcoming the challenges of diagnosing a rare
genodermatosis. Pediatr Dermatol. 2015;32(1):e23–e8.
157. Digilio MC, Lepri F, Baban A, Dentici ML, Versacci P, Cap-
olino R, et al. RASopathies: clinical diagnosis in the first year
of life. Mol Syndromol. 2011;1(6):282–9.
158. Weiss G, Confino Y, Shemer A, Trau H. Cutaneous manifesta-
tions in the cardiofaciocutaneous syndrome, a variant of the
classical Noonan syndrome. Report of a case and review of the
literature. J Eur Acad Dermatol Venereol. 2004;18(3):324–7.
159. Grebe TA, Clericuzio C. Neurologic and gastrointestinal dys-
function in cardio-facio-cutaneous syndrome: Identification of
a severe phenotype. Am J Med Genet. 2000;95(2):135–43.
160. Schepis C, Greco D, Romano C. Cardiofaciocutaneous (CFC)
syndrome. Austral J Dermatol. 1999;40(2):111–5.
161. Borradori L, Blanchet-Bardon C. Skin manifestations of
cardio-facio-cutaneous syndrome. J Am Acad Dermatol.
1993;28(5 II):815–9.
162. Verloes A, Le Merrer M, Soyeur D, Kaplan J, Pangalos C,
Rigo J, et al. CFC syndrome: a syndrome distinct from Noonan
syndrome. Ann Genet. 1988;31(4):230–4.
163. Siegel DH, McKenzie J, Fr ieden IJ, Rauen KA.
D e r m a to l o g i c a l f i n d i n g s i n 6 1 m u t a t i o n - p o s i t i ve
Keratosis Pilaris and its Subtypes
individuals with cardiofaciocutaneous syndrome. Br J Der-
matol. 2011;164(3):521–9.
164. Armour CM, Allanson JE. Further delineation of cardio-facio-
cutaneous syndrome: clinical features of 38 individuals with
proven mutations. J Med Genet. 2008;45(4):249–54.
165. Nanda S, Rajpal M, Reddy BS. Cardio-facio-cutaneous syn-
drome: report of a case with a review of the literature. Int J
Dermatol. 2004;43(6):447–50.
166. Zanjani KS, Zeinaloo AA, Radmehr H. Ross operation in a
neuro-cardio-facial-cutaneous syndrome patient. Indian J Hum
Genet. 2011;17(3):229–31.
167. Siegel DH, Mann JA, Krol AL, Rauen KA. Dermatological phe-
notype in Costello syndrome: consequences of Ras dysregulation
in development. Br J Dermatol. 2012;166(3):601–7.
168. Manci EA, Martinez JE, Horenstein MG, Gardner TM, Ahmed A,
Mancao MC, et al. Cardiofaciocutaneous syndrome (CFC) with
congenital peripheral neuropathy and nonorganic malnutrition:
an autopsy study. Am J Med Genet Part A. 2005;137(1):1–8.
169. Kondo RN, Martins LM, Lopes VC, Bittar RA, Araujo FM. Do
you know this syndrome? Noonan syndrome. Anais brasileiros
de dermatologia. 2013;88(4):664–6.
170. Neild VS, Pegum JS, Wells RS. The association of keratosis
pilaris atrophicans and woolly hair, with and without Noonan’s
syndrome. Br J Dermatol. 1984;110(3):357–62.
171. Tartaglia M, Pennacchio LA, Zhao C, Yadav KK, Fodale V,
Sarkozy A, et al. Gain-of-function SOS1 mutations cause a dis-
tinctive form of Noonan syndrome. Nat Genet. 2007;39(1):75–9.
172. Li K, Ann Thomas M, Haber RM. Ulerythema ophryogenes, a
rarely reported cutaneous manifestation of noonan syndrome:
case report and review of the literature. J Cutan Med Surg.
2013;17(3):212–8.
173. Guidry JA, Rees A, Chan AJ, Shuja F, Hsu S. Ulerythema
ophryogenes and Noonan syndrome. Dermatol Online J.
2013;19(2):14.
174. Denayer E, Devriendt K, de Ravel T, Van Buggenhout G, Smeets
E, Francois I, et al. Tumor spectrum in children with Noonan
syndrome and SOS1 or RAF1 mutations. Genes Chromosom
Cancer. 2010;49(3):242–52.
175. Gulec AT, Karaduman A, Seckin D. Noonan syndrome: a case
with recurrent keloid formation. Cutis. 2001;67(4):315–6.
176. Ekvall S, Hagenas L, Allanson J, Anneren G, Bondeson ML.
Co-occurring SHOC2 and PTPN11 mutations in a patient with
severe/complex Noonan syndrome-like phenotype. Am J Med
Genet Part A. 2011;155(6):1217–24.
177. Zenker M, Horn D, Wieczorek D, Allanson J, Pauli S, Van Der
Burgt I, et al. SOS1 is the second most common Noonan gene but
plays no major role in cardio-facio-cutaneous syndrome. J Med
Genet. 2007;44(10):651–6.
178. Castori M, Morlino S, Sana ME, Paradisi M, Tadini G, Angioni
A, et al. Clinical and molecular characterization of two patients
with palmoplantar keratoderma-congenital alopecia syndrome
type 2. Clin Exp Dermatol. 2016;41(6):632–5.
179. Castori M, Valiante M, Ritelli M, Preziosi N, Colombi M, Para-
disi M, et al. Palmoplantar keratoderma, pseudo-ainhum, and
universal atrichia: a new patient and review of the palmoplantar
keratoderma-congenital alopecia syndrome. Am J Med Genet
Part A. 2010;152(8):2043–7.
180. Boralevi F, Haftek M, Vabres P, Lepreux S, Goizet C, Leaute-
Labreze C, et al. Hereditary mucoepithelial dysplasia: clinical,
ultrastructural and genetic study of eight patients and literature
review. Br J Dermatol. 2005;153(2):310–8.
181. Scheman AJ, Ray DJ, Witkop CJ Jr, Dahl MV. Hereditary
mucoepithelial dysplasia. Case report and review of the litera-
ture. J Am Acad Dermatol. 1989;21(2 Pt 2):351–7.
755
182. Duarte GV, Cunha R. Do you know this syndrome? Pach-
yonychia congenita. Anais brasileiros de dermatologia.
2011;86(6):1222–7.
183. Cardinali C, Torchia D, Caproni M, Petrini N, Fabbri P. Case
study: pachyonychia congenita: a mixed type II-type IV presenta-
tion. Skinmed. 2004;3(4):233–5.
184. Leitner C, Cheung S, De Berker D. Pitfalls and pearls in the
diagnosis of monilethrix. Pediatr Dermatol. 2013;30(5):633–5.
185. Singh A, Ambujam S, Srikanth S, Uma A. Monilethrix: one step
more on the ladder of cytogenetics. Int J Trichol. 2010;2(1):18–9.
186. Erbagci Z, Erbagci I, Erbagci H, Erkilic S, Tuncel AA. Severe
monilethrix associated with intractable scalp pruritus, posterior
subcapsular cataract, brachiocephaly, and distinct facial fea-
tures: a new variant of monilethrix syndrome? Pediatr Dermatol.
2004;21(4):486–90.
187. Bajaj AK, Swarup V, Gupta SC, Shukla SR, Pande RC, Gupta
OP. Monilethrix. Dermatologica. 1978;156(5):292–5.
188. Nagakeerthana S, Rangaraj M, Karthikeyan K. Ichthyosis fol-
licularis, alopecia, and photophobia syndrome. Int J Trichol.
2017;9(2):67–9.
189. Halal F, Setton N, Wang NS. A distinct type of hidrotic ectoder-
mal dysplasia. Am J Med Genet. 1991;38(4):552–6.
190. Abramovits-Ackerman W, Bustos T, Simosa-Leon V, Fernandez
L, Ramella M. Cutaneous findings in a new syndrome of autoso-
mal recessive ectodermal dysplasia with corkscrew hairs. J Am
Acad Dermatol. 1992;27(6 I):917–21.
191. Shelleh HH, Dawood S. “Auto-combed hair”. A clinicopatho-
logical study of a possibly “de novo” hair defect. Eur J Pediatr
Dermatol. 2007;17(2):93–7.
192. Argenziano G, Monsurro MR, Pazienza R, Delfino M. A case of
probable autosomal recessive ectodermal dysplasia with cork-
screw hairs and mental retardation in a family with tuberous
sclerosis. J Am Acad Dermatol. 1998;38(2 II):344–8.
193. Vasudevan B, Verma R, Pragasam V, Badad A. A rare case of
woolly hair with unusual associations. Indian Dermatol Online
J. 2013;4(3):222–4.
194. Torres T, Machado S, Selores M. Generalized woolly hair: case
report and literature review. [Portuguese]. Anais Brasileiros de
Dermatologia. 2010;85(1):97–100.
195. Chien AJ, Valentine MC, Sybert VP. Hereditary woolly
hair and keratosis pilaris. J Am Acad Dermatol. 2006;54(2
SUPPL.):S35–9.
196. McHenry PM, Nevin NC, Bingham EA. The association of
keratosis pilaris atrophicans with hereditary woolly hair. Pediatr
Dermatol. 1990;7(3):202–4.
197. Dekio S, Nagashima T, Watanabe Y, Jidoi J. Hypotrichosis with
keratosis pilaris: electrophoretical study of hair fibrous proteins
from a patient. Dermatologica. 1989;179(3):118-22.
198. Thai KE, Sinclair RD. Keratosis pilaris and hereditary
koilonychia without monilethrix. J Am Acad Dermatol.
2001;45(4):627–9.
199. Gebhardt M, Fischer T, Claussen U, Wollina U, Elsner P. Monile-
thrix—improvement by hormonal influences? Pediatr Dermatol.
1999;16(4):297–300.
200. Galadari I, Mohsen S. Leukonychia totalis associated with kera-
tosis pilaris and hyperhidrosis. Int J Dermatol. 1993;32(7):524–5.
201. Basaran E, Yilmaz E, Alpsoy E, Yilmaz GG. Keratoderma,
hypotrichosis and leukonychia totalis: a new syndrome? Br J
Dermatol. 1995;133(4):636–8.
202. Liakou AI, Esteves De Carvalho AV, Nazarenko LP. Trias of
keratosis pilaris, ulerythema ophryogenes and 18p monosomy:
zouboulis syndrome. J Dermatol. 2014;41(5):371–6.
203. Zouboulis CC, Stratakis CA, Rinck G, Wegner RD, Gollnick H,
Orfanos CE. Ulerythema ophryogenes and keratosis pilaris in a
child with monosomy 18p. Pediatr Dermatol. 1994;11(2):172–5.

756
204. Horsley SW, Knight SJ, Nixon J, Huson S, Fitchett M, Boone
RA, et al. Del(18p) shown to be a cryptic translocation using a
multiprobe FISH assay for subtelomeric chromosome rearrange-
ments. J Med Genet. 1998;35(9):722–6.
205. Nazarenko SA, Ostroverkhova NV, Vasiljeva EO, Nazarenko
LP, Puzyrev VP, Malet P, et al. Keratosis pilaris and ulerythema
ophryogenes associated with an 18p deletion caused by a Y/18
translocation. Am J Med Genet. 1999;85(2):179–82.
206. Carvalho CA, de Carvalho AVE, Kiss A, Paskulin G, Gotze FM.
Keratosis pilaris and ulerythema ophryogenes in a woman with
monosomy of the short arm of chromosome 18. Anais Brasileiros
de Dermatologia. 2011;86(4 SUPPL. 1):42–5.
207. Patrizi A, Bianchi T, Orlandi C, Mazzanti L. Ulerythema ophryo-
genes and keratosis pilaris. Eur J Dermatol. 2002;12(6):572.
208. Zouboulis CC, Stratakis CA, Gollnick HP, Orfanos CE. Kera-
tosis pilaris/ulerythema ophryogenes and 18p deletion: is it
possible that the LAMA1 gene is involved? J Med Genet.
2001;38(2):127–8.
209. Lettmann S, Bloch W, Maass T, Niehoff A, Schulz JN, Eckes
B, et al. Col6a1 null mice as a model to study skin phenotypes
in patients with collagen VI related myopathies: expression of
classical and novel collagen VI variants during wound healing.
PLoS ONE. 2014;9(8):e105686.
210. Sabatelli P, Gara SK, Grumati P, Urciuolo A, Gualandi F, Curci
R, et al. Expression of the collagen VI alpha5 and alpha6 Chains
in normal human skin and in skin of patients with collagen VI-
related myopathies. J Investig Dermatol. 2011;131(1):99–107.
211. Kose O, Safali M, Koc E, Arca E, Acikgoz G, Ozmen I, et al.
Peeling skin diseases: 21 cases from Turkey and a review of the
literature. JEADV. 2012;26(7):844–8.
212. Al-Maawali A, Marshall CR, Scherer SW, Dupuis L, Mendoza-
Londono R, Stavropoulos DJ. Clinical characteristics in patients
with interstitial deletions of chromosome region 12q21-q22 and
identification of a critical region associated with keratosis pilaris.
Am J Med Genet Part A. 2014;164(3):796–800.
213. Udayashankar C, Nath AK. Dyschromatosis universalis heredi-
taria: a case report. Dermatol Online J. 2011;17(2):2.
214. Appell ML, Sherertz EF. A kindred with alopecia, keratosis pila-
ris, cataracts, and psoriasis. J Am Acad Dermatol. 1987;16(1
PART I):89–95.
215. Singh G. Ainhum with keratoderma palmaris et plantaris
with keratosis pilaris in an Indian female. J Trop Med Hyg.
1966;69(12):282–4.
216. Michaelsson G, Olsson E, Westermark P. The Rombo syn-
drome: a familial disorder with vermiculate atrophoderma,
milia, hypotrichosis, trichoepitheliomas, basal cell carcinomas
and peripheral vasodilation with cyanosis. Acta Derm Venereol.
1981;61(6):497–503.
217. Lloyd BM, Braverman AC, Anadkat MJ. Multiple facial
milia in patients with Loeys-Dietz syndrome. Arch Dermatol.
2011;147(2):223–6.
218. van Dijk FS, Brittain H, Boerma R, Robert ML, Cobben JM.
Atrophoderma vermiculatum: a cutaneous feature of Loeys-Dietz
syndrome. JAMA Dermatol. 2015;151(6):675–7.
219. Bencini PL, Montagnino G, Sala F. Cutaneous lesions in 67
cyclosporin-treated renal transplant recipients. Dermatologica.
1986;172(1):24–30.
220. Kim SJ, Choi JM, Kim JE, Cho BK, Kim DW, Park HJ. Clinico-
pathologic characteristics of cutaneous chronic graft-versus-host
diseases: a retrospective study in Korean patients. Int J Dermatol.
2010;49(12):1386–92.
221. Hauschild A, Grob JJ, Demidov LV, Jouary T, Gutzmer R, Mill-
ward M, et al. Dabrafenib in BRAF-mutated metastatic mela-
noma: a multicentre, open-label, phase 3 randomised controlled
trial. Lancet. 2012;380(9839):358–65.
J. F. Wang, S. J. Orlow
222. Sinha R, Edmonds K, Newton-Bishop JA, Gore ME, Larkin J,
Fearfield L. Cutaneous adverse events associated with vemu-
rafenib in patients with metastatic melanoma: practical advice
on diagnosis, prevention and management of the main treatment-
related skin toxicities. Br J Dermatol. 2012;167(5):987–94.
223. Erfan G, Puig S, Carrera C, Arance A, Gaba L, Victoria I, et al.
Development of cutaneous toxicities during selective anti-BRAF
therapies: preventive role of combination with MEK inhibitors.
Acta Dermato-Venereol. 2017;97(2):258–60.
224. Peters S, Bouchaab H, Zimmerman S, Bucher M, Gaide O, Leto-
vanec I, et al. Dramatic response of vemurafenib-induced cutane-
ous lesions upon switch to Dual BRAF/MEK inhibition in a met-
astatic melanoma patient. Melanoma Res. 2014;24(5):496–500.
225. Braunstein I, Gangadhar TC, Elenitsas R, Chu EY. Vemu-
rafenib-induced interface dermatitis manifesting as radiation-
recall and a keratosis pilaris-like eruption. J Cutan Pathol.
2014;41(6):539–43.
226. Rinderknecht JD, Goldinger SM, Rozati S, Kamarashev J, Kerl
K, French LE, et al. RASopathic Skin eruptions during vemu-
rafenib therapy. PLoS ONE. 2013;8(3):e58721.
227. Wang CM, Fleming KF, Hsu S. A case of vemurafenib-induced
keratosis pilaris-like eruption. Dermatol Online J. 2012;18(4):7.
228. Huang V, Hepper D, Anadkat M, Cornelius L. Cutaneous toxic
effects associated with vemurafenib and inhibition of the BRAF
pathway. Arch Dermatol. 2012;148(5):628–33.
229. Van Der Kooi K, Glass LF, Messina JL, Trimble JS. Keratosis
pilaris-like eruption observed during the experimental PLX 4032
studies. J Am Acad Dermatol. 2012;67(6):e286–7.
230. Ma L, Dominguez AR, Collins GR, Kia KF, Cockerell CJ.
Hidradenitis suppurativa, eruptive melanocytic nevi, and kera-
tosis pilaris-like eruption in a patient treated with vemurafenib.
Arch Dermatol. 2012;148(12):1428–9.
231. Boyd KP, Vincent B, Andea A, Conry RM, Hughey LC. Non-
malignant cutaneous findings associated with vemurafenib use
in patients with metastatic melanoma. J Am Acad Dermatol.
2012;67(6):1375–9.
232. Leong WM, Aw CW. Nilotinib-induced keratosis pilaris. Case
Rep Dermatol. 2016;8(1):91–6.
233. Chang CH, Shih LY, Lu PH. A case of nilotinib-induced kera-
tosis pilaris-like perifollicular fibrosis with a brief review of the
literature. Dermatol Sin. 2017;35(3):163–5.
234. Shimizu A, Hattori M, Takeuchi Y, Ishikawa O. Generalized ker-
atosis pilaris-like eruptions in a chronic myelogenous leukemia
patient treated with nilotinib. J Dermatol. 2016;43(9):1100–1.
235. Drucker AM, Wu S, Busam KJ, Berman E, Amitay-Laish I,
Lacouture ME. Rash with the multitargeted kinase inhibitors
nilotinib and dasatinib: meta-analysis and clinical characteriza-
tion. Eur J Haematol. 2013;90(2):142–50.
236. Tawil MH, El Khoury R, Tomb R, Ghosn M. Nilotinib-induced
keratosis pilaris associated with alopecia areata and eyebrow
thinning. Int J Trichol. 2017;9(2):87–9.
237. Khetarpal S, Sood A, Billings SD. Nilontinib induced keratosis
pilaris atrophicans. Dermatol Online J. 2016;22(8):8.
238. Patel AB, Solomon AR, Mauro MJ, Ehst BD. Unique cutaneous
reaction to second- and third-generation tyrosine kinase inhibi-
tors for chronic myeloid leukemia. Dermatology (Basel, Switzer-
land). 2016;232(1):122–5.
239. Okereke UR, Colozza S, Cohen DE. A case of new onset kerato-
sis pilaris after discontinuation of erlotinib. J Drugs Dermatol.
2014;13(11):1410–1.
240. Kong HH, Turner ML. Array of cutaneous adverse effects associ-
ated with sorafenib. J Am Acad Dermatol. 2009;61(2):360–1.
241. Georgouras K. Oil contact keratosis pilaris. Austral J Dermatol.
1985;26(3):108–12.
Keratosis Pilaris and its Subtypes
242. Gianotti F. Chloracne due to tetrachloro-2,3,7,8-dibenzo-p-
dioxin in children (author’s transl). Ann Dermatol Venereol.
1977;104(12):825–9.
243. Kootiratrakarn T, Kampirapap K, Chunhasewee C. Epidermal
permeability barrier in the treatment of keratosis pilaris. Derma-
tol Res Pract. 2015;2015:5. https​://doi.org/10.1155/2015/20501​
2.
244. Novick NL. Practical management of widespread, atypical kera-
tosis pilaris. J Am Acad Dermatol. 1984;11(2 Pt 1):305–6.
245. Kim S. Treatment of pigmented keratosis pilaris in Asian patients
with a novel Q-switched Nd:YAG laser. J Cosmet Laser Ther.
2011;13(3):120–2.
246. Reserva J, Champlain A, Soon SL, Tung R. Chemical peels: indi-
cations and special considerations for the male patient. Dermatol
Surg. 2017;43(Suppl 2):S163–s173.
247. Gerbig AW. Treating keratosis pilaris. J Am Acad Dermatol.
2002;47(3):457.
248. Breithaupt AD, Alio A, Friedlander SF. A comparative trial com-
paring the efficacy of tacrolimus 0.1% ointment with aquaphor
ointment for the treatment of keratosis pilaris. Pediatr Dermatol.
2011;28(4):459–60.
249. Park KY, Son IP, Choi SY, Seo SJ, Hong CK. Combination
peel with incorporated fractional prickle coral calcium for the
treatment of keratosis pilaris: a pilot study. J Dermatol Treat.
2014;25(4):314–8.
250. Lee NY, Ibrahim O, Khetarpal S, Gaber M, Jamas S, Gryllos I,
et al. Dermal microflora restoration with ammonia-oxidizing bac-
teria nitrosomonas eutropha in the treatment of keratosis pilaris:
a randomized clinical trial. JDD. 2018;17(3):285–8.
251. Zirwas MJ, Fichtel J. Chlorine dioxide complex cleanser:
a new agent with rapid efficacy for keratosis pilaris. JDD.
2018;17(5):554–6.
252. Kragballe K, Steijlen PM, Ibsen HH, Van de Kerkhof PCM,
Esmann J, Sorensen LH, et al. Efficacy, tolerability, and safety
of calcipotriol ointment in disorders of keratinization: results of a
randomized, double-blind, vehicle-controlled, right/left compara-
tive study. Arch Dermatol. 1995;131(5):556–60.
253. Check JH, Chan S. Complete eradication of chronic long standing
eczema and keratosis pilaris following treatment with dextroam-
phetamine sulfate. Clin Exp Obstet Gynecol. 2014;41(2):202–4.
254. Ciliberto H, Farshidi A, Berk D, Bayliss S. Photopneumatic
therapy for the treatment of keratosis pilaris. J Drugs Dermatol.
2013;12(7):804–6.
255. Rodriguez-Lojo R, Pozo JD, Barja JM, Pineyro F, Perez-Varela
L. Keratosis pilaris atrophicans: treatment with intense pulsed
light in four patients. J Cosmet Laser Ther. 2010;12(4):188–90.
757
256. Schoch JJ, Tollefson MM, Witman P, Davis DM. Successful
treatment of keratosis pilaris rubra with pulsed dye laser. Pediatr
Dermatol. 2016;33(4):443–6.
257. Alcantara Gonzalez J, Boixeda P, Truchuelo Diez MT, Fleta Asin
B. Keratosis pilaris rubra and keratosis pilaris atrophicans faciei
treated with pulsed dye laser: report of 10 cases. J Eur Acad
Dermatol Venereol. 2011;25(6):710–4.
258. Clark SM, Mills CM, Lanigan SW. Treatment of keratosis pilaris
atrophicans with the pulsed tunable dye laser. J Cutan Laser Ther.
2000;2(3):151–6.
259. Kaune KM, Haas E, Emmert S, SchOn MP, Zutt M. Successful
treatment of severe keratosis pilaris rubra with a 595-nm pulsed
dye laser. Dermatol Surg. 2009;35(10):1592–5.
260. Lee SJ, Chung WS, Kim J, Cho SB. Combination of 595-nm
pulsed dye laser, long-pulsed 755-nm alexandrite laser and
microdermabrasion treatment for keratosis pilaris. J Dermatol.
2012;39(5):479–80.
261. Lee SJ, Choi MJ, Zheng Z, Chung WS, Kim YK, Cho SB.
Combination of 595-nm pulsed dye laser, long-pulsed 755-nm
alexandrite laser, and microdermabrasion treatment for keratosis
pilaris: retrospective analysis of 26 Korean patients. J Cosmet
Laser Ther. 2013;15(3):150–4.
262. Ibrahim O, Khan M, Bolotin D, Dubina M, Nodzenski M,
Disphanurat W, et al. Treatment of keratosis pilaris with 810-
nm diode laser a randomized clinical trial. JAMA Dermatol.
2015;151(2):187–91.
263. Saelim P, Pongprutthipan M, Pootongkam S, Jariyasethavong
V, Asawanonda P. Long-pulsed 1064-nm Nd:YAG laser signifi-
cantly improves keratosis pilaris: a randomized, evaluator-blind
study. J Dermatol Treat. 2013;24(4):318–22.
264. Park J, Kim BJ, Kim MN, Lee CK. A pilot study of Q-switched
1064-nm Nd:YAG Laser treatment in the keratosis pilaris. Ann
Dermatol. 2011;23(3):293–8.
265. Vachiramon V, Anusaksathien P, Kanokrungsee S, Chanpra-
paph K. Fractional carbon dioxide laser for keratosis pilaris: a
single-blind, randomized, comparative study. BioMed Res Int.
2016;2016:6.
266. Chui CT, Berger TG, Price VH, Zachary CB. Recalcitrant scar-
ring follicular disorders treated by laser-assisted hair removal: a
preliminary report. Dermatol Surg. 1999;25(1):34–7.
267. Rubin MG. Microabrasion: an epidermal abrasion. Aesthet Surg
J. 2003;23(2):137–9.
268. Baden HP. The pumice stone in dermatologic therapy. J Am Acad
Dermatol. 1980;2(1):29–30.
269. Miranda BH, Farjo N, Farjo B. Eyebrow reconstruction in dor-
mant keratosis pilaris atrophicans. J Plast Reconstr Aesthet Surg.
2011;64(12):e303–5.