American Journal of Clinical Dermatology

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 

© 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,” Keratosis pilaris (KP), thường được gọi là "da gà",
is a common skin disorder characterized by keratotic pap- là một chứng rối loạn da phổ biến được đặc trưng bởi các sẩn dày sừng trong phân bố
dạng nang.
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)
 J. F. Wang, S. J. Orlow
KP: dày sừng nang lôg - AD: viêm da dị ứng - IV: bong da vảy cá

Dịch tễ học 1.1 Epidemiology
KP is the most common follicular disorder in children [2,
KP (dày sừng) là rối loạn nang lông phổ biến nhất ở trẻ em [2,
3]. Dịch tễ học nhi khoa của KP đã được khám phá bởi 3]. The pediatric epidemiology of KP has been explored by
một số nhóm (Bảng 1), nhưng dường như có sự biến động lớn về tỷ lệ hiện several groups (Table 1), but there appear to be large fluc-
mắc được báo cáo giữa và thậm chí tuations in the reported prevalence rates among and even
trong phạm vi quốc gia hoặc dân tộc, dao động từ 0,75 đến 34,4% within countries or ethnicities, ranging from 0.75 to 34.4%
[4–15]. Ngoài ra, một nghiên cứu cắt ngang trên 12.657 nam Hàn Quốc 19
[4–15]. In addition, a cross-sectional study of 12,657 Korean
tuổi báo cáo tỷ lệ cao hơn về
KP ở các đối tượng so với kết quả từ bệnh viện male military conscripts aged 19 years reported higher rates
nghiên cứu [16]. Tỷ lệ phổ biến của KP là 11,9% (178/1502) ở of KP in the subjects than did results from hospital-based
một nghiên cứu cắt ngang trên 1502 người Đức trưởng thành [17]. studies [16]. The prevalence of KP was 11.9% (178/1502) in
Trong một nghiên cứu tiền cứu trên 1107 bệnh nhân Tây Ban Nha và a cross-sectional study of 1502 German adults [17]. In a pro-
1267 bệnh nhân nhập cư <60 tuổi, KP phổ biến hơn ở những người nhập spective study of 1107 Spanish and 1267 immigrant patients
cư (p = 0,04) [18]. KP cũng xảy ra thường xuyên hơn
ở những người có vảy da và khô da [7, 19], bất kể họ có được chẩn đoán
aged < 60 years, KP was more prevalent in the immigrant
mắc bệnh (da vảy cá) ichthyosis vulgaris hay không population (p = 0.04) [18]. KP also occurs more frequently
(IV) hoặc viêm da dị ứng (AD) [20] 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].
Tổng quan về lâm sàng, Sly bệnh + GP bệnh của KP(dày sừng)2 Clinical Overview, Pathophysiology,
và subtype and Histopathology of Keratosis Pilaris
(KP) and its Subtypes
The clinical features and natural history of KP are summa-
Các đặc điểm lâm sàng và diễn biến tự nhiên của KP được tóm tắt
trong Bảng 2; trong khi dấu hiệu mô bệnh học của KP là tăng sừng rized in Table 2; while the histopathological hallmark of KP
nang lông, thông tin thêm được cung cấp trong Bảng 2 [1, 3, 21–26]. is follicular hyperkeratosis, further information is provided
Mặc dù KP thường được chẩn đoán trên lâm sàng, soi da có thể hỗ in Table 2 [1, 3, 21–26]. Although KP is usually diagnosed
trợ trong việc hỗ trợ chẩn đoán và theo dõi đáp ứng với điều trị; Các clinically, dermoscopy can aid in supporting the diagnosis
phát hiện qua soi da cũng được tóm tắt trong Bảng 2 [24, 27–29]. and monitoring response to treatment; dermoscopic findings
Sinh lý bệnh của KP chưa được hiểu rõ hoàn toàn. Một giả thuyết đề
xuất rằng sừng hóa phễu nang lông được tìm thấy ở KP
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
results from abnormal keratinization of the follicular epi- là kết quả của sự sừng hóa bất thường của biểu mô nang lông[28].
thelium [28]. Another hypothesis proposes that, because Một giả thuyết khác đề xuất rằng, vì các thân lông được chiết xuất
hair shafts extracted with a needle from 25 patients with KP bằng kim từ 25 bệnh nhân KP vẫn giữ được hình dạng cuộn lại mặc
dù đã cắt bỏ nang, KP không phải là rối loạn nguyên phát của tế bào
retained their coiled shape despite removal from the follicle, sừng mà là rối loạn thân lông hoặc cổ nang lông; giả thuyết này
KP is not a primary disorder of keratinocytes but rather a cho rằng KP xảy ra khi các sợi lông cuộn lại làm vỡ biểu mô nang
hair shaft or infundibular disorder; this hypothesis suggests lông, gây ra hiện tượng sừng hóa nang lông bị lỗi và viêm [29, 30].
that KP occurs when coiled hair shafts rupture the follicular Người ta cũng đã công nhận rằng cả sự bất thường về sừng hóa và
epithelium, causing defective follicular keratinization and bất thường của thân lông có thể được giải thích là do sự vắng mặt
của các tuyến bã nhờn như một bước sớm hơn trong sinh lý bệnh
inflammation [29, 30]. It has also been postulated that both
của KP [24]. Chúng tôi thảo luận sâu hơn về những giả thuyết này
the abnormal keratinization and hair shaft abnormalities can và các giả thuyết khác
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
 nhìn chung là có đỡ giảm (35%), 10 năm đầu đời bị nhiều hơn, mùa đông bị nhiều hơn
mùa hè

Cải thiện ở 35% bệnh nhân ở

độ tuổi thanh thiếu niên
nhưng không thay đổi ở 43%
bệnh nhân và xấu đi ở 22%
[22]. Trong một cuộc khảo sát
trên 49 bệnh nhân người Anh
mắc KP từ 2–40 tuổi, tỷ lệ mắc
bệnh phổ biến nhất trong 10
Các sẩn dày sừng có gai, kích thước khoảng
năm đầu đời và giảm dần theo
1 mm, chủ yếu phân bố trên bề mặt duỗi
tuổi [22]. KP được cải thiện
của các đầu gần các chi [22]. Sự tham gia
vào mùa hè và trở nên tồi tệ
của các đầu xa chi, mặt, thân và mông cũng
hơn vào mùa đông đối với Chất sừng cắm trong các lỗ nang,
có thể xảy ra [23]. Các nốt sẩn có thể rải rác
khoảng một nửa số bệnh nhân; có thể chứa các lông xoắn, làm giãn
hoặc tập hợp lại với nhau, đôi khi có ban đỏ
tuy nhiên, trong số bệnh nhân phễu nang lông , tạo ra các u nhú
tinh vi quanh nang [1]. Các phát hiện qua
KP nặng hơn vào mùa hè, chỉ của KP [1]. Trong khi lớp thượng
soi da: tăng sừng nang lông, tăng sinh mạch
60% được cải thiện trong mùa bì có biểu hiện tăng sừng nhẹ, giảm
da, lỗ nang lông rộng, tăng sắc tố, ban đỏ
đông [22]. Trong một trường độ dày lớp hạt và tắc nang lông, thì
quanh nang lông, đóng vảy, và các sợi lông
hợp KP đã được chứng minh lớp trung bì trên và các vùng
mỏng và ngắn ở vùng da tổn thương [24,
bằng sinh thiết, một người đàn quanh nang chứa thâm nhiễm tế
27–29]. KP nhẹ có thể có lông cuộn hoặc
ông 25 tuổi bị rụng tóc nhiều ở bào lympho quanh mạch nhẹ [24,
xoắn, số ít hoặc nhóm hai hoặc ba, được bao
các vị trí bị ảnh hưởng bởi KP, 25]. Có thể có parakeratosis (Tb
bọc bởi các phôi quanh tương tự [24, 28].
nhưng sau 3 tháng, KP của anh sừng còn nhân) khu trú trong SC
Lông ở KP nặng hơn thì bị cuộn lại và bị
ấy tự nhiên hết với tóc mọc lại [25]. Các tuyến bã nhờn không có
dính vào lớp sừng [24, 28]. KP thường
hoàn toàn mà không để lại sẹo tổn thương KP nhưng lại có ở vùng
không có triệu chứng nhưng có thể ngứa và
hoặc teo [26] da không bị ảnh hưởng của cùng
không mong muốn về mặt thẩm mỹ [1]
một bệnh nhân [24]

Keratosis Pilaris and its Subtypes

Table 2  Clinical and histopathologic descriptions of keratosis pilaris and its subtypes
Condition Description mô tả Onset bắt đầu Clinical findings Natural history diễn biến tự nhiên 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-
RL sừng hóa da phổ 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].
biến 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
Điển hình là trong sometimes with subtle perifollicular ery- of life and decreased with age [22]. follicular plugging, the upper dermis
thời thơ ấu và thema [1]. Dermoscopic findings: follicular KP improved in the summer and and perifollicular areas contain
thời niên thiếu; có thể 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
cũng xuất hiện ở trẻ
perifollicular erythema, scaling, and thin and the patients with worsening KP in the focal parakeratosis within the SC
sơ sinh
short hair shafts in lesional skin [24, 27–29]. summer, only 60% improved during [25]. Sebaceous glands are strikingly
và người lớn [21 absent from KP lesions but are
Mild KP may have coiled or twisted vellus the winter [22]. In one case of biopsy-
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]


Table 2  (continued)
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
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 dj truyền
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].
--> Do lớp lipid giữa các tb sừng bị gián đoạn: nhất là khu vực giữa các nang lông + phần
trên của nang lông --> mất nước --> sừng hóa k đúng
TB và đặc điểm hóa sinh
Hàng rào thẩm thấu của thượng bì bao gồm các tế bào sừng và
thành phần ngoại bào, lớp kép kỵ nước của lớp sừng (SC), được
hình thành từ chất tiết của các thể phiến (LBs) [24]. Điều này
được hỗ trợ bởi các điểm nối chặt chẽ ở lớp hạt bên dưới và các
kết nối desmosomes [24, 73, 74]. Các cấu trúc này bảo vệ chống
lại sự xâm nhập vào bên trong của mầm bệnh và sự mất nước và
chất điện giải ra bên ngoài [24, 75]. Mặc dù ở KP, pH bề mặt da
bình thường nhưng sự mất nước qua thượng bì tăng lên ở
bệnh nhân KP (p <0,01) [24]. SC ở nang và giữa các nang
dường như có một hàng rào thấm bất thường trong tổn
thương KP (khiến nước bị mất). Ở vùng da tổn thương KP, các
vùng không thể phiến làm gián đoạn hàng rào thẩm thấu. Quá
trình xử lý lipid ở các phần trên của nang lông và trong biểu bì
giữa các nang lông có thể bị trì hoãn. Các cấu trúc bên trong LB là
bất thường, có thể ảnh hưởng đến việc vận chuyển vào các bào
quan trong da
Một vài nhóm đã cố gắng mô tả đặc điểm của KP và các trichohyalin ít
dạng subtype của nó ở cấp độ phân tử. Trichohyalin biểu
hiện yếu ở KP [76]. Trong một cuộc điều tra đo dòng chảy tb (+) involucrin thấp
tế bào, cả da bị ảnh hưởng bởi KP- và KFSD đều có tỷ lệ tế (+) keratin cao
bào dương tính với involucrin thấp hơn và tỷ lệ tế bào
dương tính với keratin 4 cao hơn so với da bình thường tăng proteiin liên kết axit retinoic
[77]. Mức độ tăng cao của protein liên kết axit retinoic tế
bào cũng đã được tìm thấy trong các tổn thương của
KFSD, điều này có thể giải thích một phần cho sự đáp ứng
của KP (ít nhất là ở một số người) với liệu pháp retinoid
[78].
Tiền sử gia đình mắc bệnh KP có ở khoảng 39% bệnh bệnh di truyền gen lặn trên NST
nhân, cho thấy căn nguyên di truyền tiềm ẩn với sự di thường
truyền trội trên NST thường [22]. Trong một phân tích bộ
gen của 13 bệnh nhân Pakistan cùng họ với KPA, đột biến LRP1 nhà LDL
KP1245R, một biến thể đồng hợp tử mới của LRP1, đã
được xác định là gây bệnh ở KPA và KP lặn trên NST đột biến desmoglein 4
thường [51]. LRP1 có chức năng nội bào trong họ LDL, và
mức độ của nó bị giảm trong nguyên bào sợi của những
bệnh nhân bị đột biến này, cũng như sự hấp thu tế bào
đối với phối tử của nó, α2-macroglobulin [79]. Cũng có
bằng chứng cho thấy các đột biến trong desmoglein 4 có
thể góp phần vào cơ chế bệnh sinh của KPA lặn trên NST
thường [80].

KPAF có xu hướng được di truyền theo kiểu trội với sự
xâm nhập không hoàn toàn, nhưng các trường hợp lẻ tẻ
cũng đã được ghi nhận [3]. AV cũng có thể được di truyền
theo kiểu trội, nhưng hầu hết các trường hợp là lẻ tẻ [3,
42]. Đã có một vài phả hệ bị ảnh hưởng bởi KFSD với đột
biến c.1523A> G trong gen MBTPS2 trong tài liệu [45, 81,
82]. Các đột biến trong gen này cũng gây ra bệnh trứng cá,
rụng tóc và hội chứng sợ ánh sáng (IFAPS), có chung các đặc
điểm lâm sàng với KFSD [45, 81]. MBTPS2 cũng điều chỉnh
TRPV3, gen gây ra hội chứng Olmsted, có thể biểu hiện với
KP phổ biến [83, 84]. Các kiểu thừa kế khác nhau, vì có báo
cáo về các kiểu liên kết X, kiểu trội trên NST thường và kiểu
rời rạc [3, 32, 46, 81, 85]. Trong khi KFSD thường biểu
hiện ở nam giới, đã có báo cáo ở nữ giới [86–88]. FSD đã
được chứng minh là được di truyền theo nhiễm sắc thể
thường [89].
KPAF: trội
AV: trội
KFSD cả nam và nữ
FSD: NST thường
Vai trò của di truyền trong EFFC là không rõ ràng. EFFC di truyền lặn
NST thường đã được quan sát thấy [90], và sự mất ổn định của nhiễm
sắc thể cũng có thể đóng một vai trò nào đó [91]. Tiền sử gia đình
mắc KP thường gặp ở EFFC, và sự xuất hiện trong gia đình của EFFC
đã được báo cáo, hỗ trợ căn nguyên di truyền [54, 92, 93]. Mặc dù
EFFC ảnh hưởng đến tất cả các chủng tộc, nhưng dân số châu Á có
nhiều khả năng bị ảnh hưởng hơn [60]. Bệnh khởi phát từ 2 đến 43
tuổi trong các trường hợp được báo cáo, nhưng EFFC chủ yếu ảnh
hưởng đến thanh thiếu niên. Tỷ lệ nam nữ là khoảng 2: 1.
EFFC: di truyền lặn NST thường, có yếu tố gia đình
dân châu á, nam, tuổi thiếu niên thường gặp
LIÊN QUAN TỚI CÁC BỆNH
Dị ứng, bệnh di truyền Ichthyoses và Đột biến gen Filaggrin
Tiền sử bệnh dị ứng đã được chứng minh là có liên quan đến KP
(p = 0,001), với một cuộc khảo sát báo cáo có TS dị ứng ở 37%
bệnh nhân KP [7, 22]. Sự liên kết của AD và KP có thể xuất phát
từ sự bất thường của hàng rào thấm của biểu bì [24]. KP đôi
khi được coi là một tiêu chuẩn chẩn đoán nhỏ cho AD, mặc dù
chưa có sự thống nhất chẩn đoán về KP giữa các bác sĩ trong một
nghiên cứu trên 14 bác sĩ từ một nhóm làm việc về tiêu chuẩn
chẩn đoán AD của Vương quốc Anh đang cố gắng chẩn đoán
chính xác AD ở 15 bệnh nhân [94]. Các nghiên cứu từ một số
nhóm cũng đưa ra thông tin trái ngược nhau về tỷ lệ phổ biến và
mức độ phù hợp chẩn đoán của KP trong AD (Bảng 3) [8, 20, 95–
99]. Trong AD thời thơ ấu, sự hiện diện của KP có thể liên quan
đến bệnh nặng hơn [100]. Các nhóm phụ đã được đề xuất trong
AD, chẳng hạn như AD nội tại, thiếu globulin miễn dịch đặc hiệu
với chất gây dị ứng E (IgE) và ít liên quan với KP (p <0,05) [101].
KP có AD có thể khác với KP không AD, như được chỉ ra trong
một nghiên cứu trong đó bệnh nhân AD với các nốt sẩn giống
KP đã phát triển các phản ứng thử nghiệm miếng dán với 5%
niken sulfat
liên quan giữa KP và AD
- bất thường hàng rào thấm
- bệnh nặng hơn
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].
nhưng bệnh nhân KP không có AD không có phản ứng [102]. KP cũng được kết
hợp với IV trong bối cảnh đột biến filaggrin [2]. Giống như AD, dữ liệu về tỷ lệ
hiện mắc và giá trị chẩn đoán của KP ở IV và các loại ichthyoses di truyền khác
là mâu thuẫn giữa một số nghiên cứu (Bảng 3) [3, 20, 103–106]
không hiểu gì
Mặc dù một số phân tích bộ gen đã chỉ ra rằng các đột biến filaggrin,
đặc biệt là R501X và 2282del4, có liên quan đến KP (p <0,01 cho mỗi
loại), chúng không chiếm toàn bộ kiểu hình KP [4, 17, 24, 107]. Ví dụ,
trong một phân tích bộ gen của 40 đối tượng có KP, chỉ có 35%
(7/20) có đột biến filaggrin [24]. Tuy nhiên, tỷ lệ này cao hơn nhiều
so với tỷ lệ phổ biến lên tới2 9% của các biến thể filaggrin ở người da
trắng [24, 108]. Trong một phân tích bộ gen của 459 bệnh nhân, đột
biến filaggrin có liên quan đến tỷ lệ chênh lệch gần bằng 2 khi có KP
(p <0,05) [109]. Tuy nhiên, không phải tất cả các nghiên cứu đều ủng
hộ sự liên quan của đột biến filaggrin với KP [110]. Các đột biến
Filaggrin cũng có thể góp phần vào KP bằng cách giảm sự tăng sinh
của tế bào bã nhờn, gây teo các tuyến bã nhờn và phá vỡ hàng rào
biểu mô [24, 111, 112]. Giải trình tự thế hệ tiếp theo được nhắm mục
tiêu có khả năng xác định các đột biến filaggrin cụ thể ở bệnh nhân
KP, vì nó đã được sử dụng cho mục đích này trong IV [113].
liên quan giữa đột biến fillaggrin và KP --> giảm tb bã nhờn, teo tuyến bã nhờn
Béo phì, Tiểu đường, Mang thai và Bất thường Nội tiết tố Liên quan
Béo phì, kháng insulin nguy cơ bị KP
Chỉ số khối cơ thể (BMI) cao và các tình trạng liên quan, bao
gồm bệnh tiểu đường, mang thai và các bất thường về nội tiết
tố, thường liên quan đến KP [114]. Trong khi một số nghiên cứu
đã phát hiện ra rằng ---KP có liên quan đến BMI cao và béo
phì---, tỷ lệ hiện tượng này có thể thay đổi (Bảng 4) [7, 115–
118]. Dữ liệu về việc mức độ béo phì có liên quan trực tiếp đến
khả năng mắc đồng thời KP có mâu thuẫn hay không, vì một
nghiên cứu không tìm thấy mối tương quan nào [118] trong khi
các nghiên cứu khác cho thấy mối tương quan có ý nghĩa [117,
119]. Người ta nghi ngờ rằng /tăng insulin/ máu liên quan đến
béo phì và //kháng insulin// góp phần vào sinh lý bệnh KP,
như được đề xuất bởi một loạt trường hợp gồm 13 phụ nữ bị
acanthosis nigricans và kháng insulin, 9 người trong số họ bị KP
[120].
Đái đường - tiết ít insulin - kháng insulin - giảm tb bã nhờn - kP
KP thường gặp ở bệnh nhân đái tháo đường týp 1 (T1DM) và
phát triển sớm trong quá trình bệnh [121]. Bằng chứng chứng
minh mối liên quan giữa KP và T1DM (Bảng 4) [121, 122].
//Giảm điều hòa tăng sinh tế bào bã nhờn//, một yếu tố tiềm
năng góp phần vào cơ chế bệnh sinh của KP, một phần có thể là
do //yếu tố tăng trưởng giống insulin 1// hoặc insulin thấp
trong máu [24, 123]. //Thụ thể α kích hoạt chất tăng sinh
peroxisome, một cơ quan điều hòa quá trình tạo ceton//, và
//thụ thể tăng sinh peroxisome γ1, một cơ quan điều hòa
chuyển hóa glucose và dự trữ axit béo//, cũng được biểu hiện
trong tế bào bã nhờn; //giảm hoạt hóa của các thụ thể// này
làm //giảm sự tăng sinh tế bào bã nhờn// [24, 123, 124].
EFFC di truyền cũng có thể liên quan đến bệnh tiểu đường [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
 J. F. Wang, S. J. Orlow

KP may be an underrecognized dermatosis of pregnancy. KP có thể là một bệnh da liễu không được phát hiện trong thai kỳ. Một loạt

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 trường hợp gồm 5 phụ nữ bị KP đã chứng minh rằng sự khởi phát hoặc

(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)
mức độ nghiêm trọng của nó có thể liên quan đến những //thay đổi

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
hormone trong thai kỳ\\ [125]. Ở tất cả năm phụ nữ, KP được// cải
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
thiện trong vòng 9 tháng sau khi sinh\\. Ngoài ra, một phụ nữ 29 tuổi
phát triển KP một bên khi mang thai lần thứ hai [64]. Điều này có thể được
giải thích là do //tăng nội tiết tố androgen và kháng insulin\\ liên quan
đến thai kỳ. Ngoài ra, trong một nghiên cứu cắt ngang trên 156 phụ nữ,
chứng //tăng tiết androgen trong bối cảnh béo phì\\ có liên quan đến
việc tăng tỷ lệ mắc và mức độ nghiêm trọng của KP (p <0,001) [126]. Sau
khi kiểm soát chứng tăng tiết androgen, phụ nữ béo phì có KP có nhiều khả
năng có các //bệnh trên da ``hơn những phụ nữ béo phì không có KP\\.

hyperkeratosis
severity of KP (p < 0.001) [126]. After controlling for hyper- Điều này có thể được giải thích là do kích thích //androgen của cổ nang

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.
lông gây tăng sừng hóa.\\
PN có thai thay đổi hormone androgen + kháng insulin có nguy cơ cao mắc KP
cơ chế: androgen cổ nang lông tăng sừng hóa

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
0.25–75 typically presents in postmenopausal women, as demon-
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)
[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
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
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].
 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

B-Raf inhibitors are thought to induce aberrant signaling in
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].
Table 6  Medications causing keratosis pilaris-like eruptions
Medication Evidence
8 Environmental Exposures Phơi nhiễm vs môi trường
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 thuốc bôi và thuốc uống
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
Hiếm khi, tiếp xúc với môi trường được báo cáo là gây ra
KP. Ví dụ, một thợ máy 55 tuổi đã phát triển KP mô học
và lâm sàng trên những vùng da tiếp xúc với dầu cắt gọt
tại nhà máy sản xuất bu lông nơi anh ta làm việc [241]. Cố
ý áp dụng dầu cắt gọt được tái tạo lại KP mô học và lâm
sàng trên một khu vực chưa được phơi sáng trước đó.
Trong khi thường liên quan đến chloracne, phơi nhiễm
2,3,7,8-tetrachlorodibenzo-p-dioxin có liên quan đến AV
trong một vài trường hợp [242].
dầu cắt kim loại, chloracne, phơi nhiễm dioxin --> liên quan đến KP
Opition điều trị và những phương pháp mới
Một số liệu pháp tại chỗ thường được sử dụng để điều trị KP và các
dạng subtype của nó với mức độ thành công khác nhau (Bảng 7).
Axit lactic (LA) là một tác nhân tiêu sừng tại chỗ giúp điều chỉnh
quá trình sừng hóa da và, như được thể hiện trong một nghiên cứu
lâm sàng, ngẫu nhiên, có khả năng điều trị KP hiệu quả hơn so với
axit salicylic (SA), một tác nhân tiêu sừng tại chỗ khác có thể làm
giảm sự gắn kết giữa tế bào sừng [243]. Độ dẫn tần số cao có thể
đo trạng thái hydrat hóa (độ ẩm) của bề mặt da, và cả LA và SA đã
được chứng minh là làm tăng độ dẫn điện ở da của bệnh nhân KP.
Trong một nghiên cứu đoàn hệ tiền cứu, LA cũng đã được sử dụng
kết hợp với propylene glycol với lợi ích một phần trong điều trị
KP [21]. Urê, một tác nhân tiêu sừng khác, đã được chứng minh là
có hiệu quả trong điều trị KP trong một vài nghiên cứu nhỏ và
thường được sử dụng
LA > SA về khả năng điều chỉnh sừng hóa da
dùng thêm propylên glycol
Ure`

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 Các ấn phẩm cung cấp bằng chứng về việc điều trị bệnh dày sừng pilaris và các dạng phụ của nó
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
10% LA hoặc 5% SA BID trong 12 tuần: giảm tổn thương
KP ở 66% nhóm LA và 52% nhóm SA (p <0,05 cho mỗi ca).
Độ dẫn điện được cải thiện với cả hai, nhưng không ảnh
hưởng đến sự mất nước qua biểu bì. Tác dụng ngoại ý: kích
ứng nhẹ tại chỗ
KPA: SA và LA làm mịn da mà không cần tẩy trang hoàn
toàn. 14 người đã sử dụng corticosteroid tại chỗ, có /
không có tretinoin: đã giúp đỡ một phần. Năm kháng sinh
toàn thân đã sử dụng: cải thiện tối thiểu, thoáng qua. Ba
nhận được isotretinoin: phản hồi tối thiểu, một phản ứng
bùng phát
SA và LA có tác dụng tốt trong điều trị KP`
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
J. F. Wang, S. J. Orlow
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
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)

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
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 9.2 Energy‑Based Therapies
kết hợp với các liệu pháp khác [21, 244, 245]. Axit glycolic acid and Jessner solution have been recommended for treat-
và dung dịch Jessner đã được khuyến cáo để điều trị KP, ing KP, but data to support these therapies are lacking [246]. Data from two small pilot studies (Table 7) of light-based
nhưng thiếu dữ liệu để hỗ trợ các liệu pháp này [246].
//Tazarotene, một loại retinoid\\ dùng tại chỗ, có tác Tazarotene, a topical retinoid, has antiproliferative effects, therapies suggest therapeutic promise for photopneumatic
dụng chống tăng sinh, thay đổi sự biệt hóa của tế bào sừng alters keratinocyte differentiation, and may be effective in therapy, which stretches and elevates the skin with a pneu-
và //có thể có hiệu quả\\ trong điều trị KP, như được chỉ ra treating KP, as shown by an open study with consecutive matic handpiece while delivering light from 400 to 1200 nm
bởi một nghiên cứu mở với việc tuyển dụng liên tiếp [247]. recruitment [247]. Tretinoin, another topical retinoid, has [254], and for intense pulsed light, which delivers broad-
//Tretinoin,\\ một loại retinoid bôi khác, đã cho thấy shown slight effectiveness in treating drug-induced KP in spectrum visible light [255], in the treatment of KPA. Recent
//hiệu quả nhẹ\\ trong điều trị KP do thuốc trong một loạt
a case series [238]. Topical steroids may be useful in KPA, reports address the use of lasers in the treatment of KP and
trường hợp [238]. //Steroid tại chỗ\ có thể hữu ích trong
KPA, nhưng hai nghiên cứu đoàn hệ tiền cứu không cho thấy but two prospective cohort studies did not find them to be its subtypes (Table 7). For lasers with wavelengths < 600 nm,
chúng hữu ích trong KP [21, 34]. Một nghiên cứu so sánh useful in KP [21, 34]. One double-blind, bilateral paired most data are on pulsed dye laser (PDL), which, in a case
song phương, mù đôi cho thấy //tacrolimus, một chất ức comparison study found that tacrolimus, a topical calcineu- report, two case series, and a prospective cohort study,
chế calcineurin tại chỗ và Aquaphor đều điều trị KP hiệu rin inhibitor, and Aquaphor each treat KP effectively [248], showed efficacy in the treatment of KPR and KPA, including
quả\\ [248], nhưng không phải tất cả các chất làm mềm đều
but not all emollients have been found to be helpful [21]. In KPAF [256–259]. The 532-nm potassium titanyl phosphate
hữu ích [21]. Ngoài ra, một nghiên cứu thử nghiệm cho thấy
một loại vỏ kết hợp bao gồm canxi san hô gai phân đoạn addition, a pilot study found that a combination peel incor- laser (KTPL) does not cause bruise-like discoloration after
(chiết xuất từ ​san hô giàu khoáng chất và tảo tạo điều kiện porating fractional prickle coral calcium (an extract made treatment, a side effect of PDL, but the therapeutic value of
cho sự xâm nhập của SC), //niacinamide, arbutin, Centella from mineral-rich coral and algae that facilitates SC pen- KTPL in treating KPR has only been examined in one case
asiatica, papain và một số axit cho thấy hiệu quả trong việc etration), niacinamide, arbutin, Centella asiatica, papain, report [59]. PDL has also been combined with long-pulsed
điều trị KP\\ [249]. Trong nỗ lực khôi phục hệ vi sinh vật and several acids showed efficacy in treating KP [249]. In 755-nm alexandrite laser and microdermabrasion to effec-
trên da, một nghiên cứu mù đôi, có đối chứng với giả dược,
đã chứng minh tính an toàn và hiệu quả của dạng phun
an attempt to restore the skin microbiome, a double-blind, tively treat KP in a case series and a retrospective study [260,
sương có chứa vi khuẩn amoniaoxy hóa /Nitrosomonas placebo-controlled, split-arm study demonstrated the safety 261]. In addition, 810-nm long-pulsed diode laser is effec-
eutropha\ trong điều trị KP; sinh vật này có khả năng bổ and efficacy of a spray-on mist containing the ammonia- tive in treating KP, as shown by a randomized controlled
sung mức độ sinh lý của oxit nitric trong da, làm giảm sự oxidizing bacteria Nitrosomonas eutropha in the treatment trial (RCT) [262]. With the Q-switched neodymium-doped
tăng sinh tế bào sừng [250]. Chất tẩy rửa phức hợp of KP; this organism potentially replenishes physiologic yttrium aluminum garnet (Nd:YAG) laser, both monother-
/Chlorine dioxide\ là một hợp chất ổn định có đặc tính
levels of nitric oxide in the skin, decreasing keratinocyte apy and combination therapy with topical urea have been
/kháng khuẩn và tiêu sừng\ đã được chứng minh trong
một loạt trường hợp để cải thiện nhanh chóng KP [251]. Tuy proliferation [250]. Chlorine dioxide complex cleanser is a shown in two pilot studies and an RCT to effectively treat
nhiên,/ calcipotriol, một dẫn xuất vitamin D\ được phê stable compound with antimicrobial and keratolytic prop- KP [245, 263, 264]. In a prospective, randomized, single-
duyệt để điều trị bệnh vẩy nến, đã không có hiệu quả trong erties that has been shown in a case series to induce rapid blinded, intraindividual comparative study, fractional carbon
điều trị KP trong một nghiên cứu so sánh ngẫu nhiên, mù improvement of KP [251]. However, calcipotriol, a vitamin dioxide laser was also shown to be effective in treating KP
đôi, có kiểm soát phương tiện, bên phải / bên trái [252], mặcD derivative approved for the treatment of psoriasis, has [265]. In a case of KFSD, hair removal with five treatments
dù một nghiên cứu đo dòng chảy cho thấy rằng calcipotriol
làm giảm tỷ lệ tế bào biểu bì ở pha SG2 M ở da KP bị tổn not been effective in treating KP in a randomized, double- of long-pulsed non-Q-switched ruby laser at 6-week inter-
thương [77]. Dữ liệu hạn chế về việc sử dụng xà phòng blind, vehicle-controlled, right/left comparative study [252], vals resulted in reduced inflammation and hair growth that
surgras từ một nghiên cứu thuần tập tiền cứu không cho despite a flow-cytometric study that found that calcipotriol persisted at 8 months of follow-up [266].
thấy hiệu quả trong điều trị KP [21] decreases the percentage of epidermal cells in the SG2 M
phase in lesional KP skin [77]. Limited data on the use of 9.3 Other Therapeutic Modalities and Options
surgras soap from a prospective cohort study did not show for Scarring
effectiveness in treating KP [21].
Thuốc toàn thân
Very little data exist on the use of systemic drugs in KP Microdermabrasion, a mild treatment that induces epidermal
Có rất ít dữ liệu về việc sử dụng thuốc toàn thân ở KP và các
phân nhóm của nó (Bảng 7). Một nghiên cứu đoàn hệ tiền cứu and its subtypes (Table 7). A prospective cohort study found injury without extending into the dermis, has been recom-
cho thấy nhiều loại kháng sinh toàn thân khác nhau có hiệu that various systemic antibiotics were minimally effective mended to treat KP, but data only exist in combination with
quả tối thiểu đối với KPA [34] và cũng phát hiện ra rằng for KPA [34] and also found that isotretinoin was minimally laser therapy from a case series and a retrospective study
isotretinoin chỉ có hiệu quả tối thiểu trong điều trị KPA và effective in treating KPA and may even have caused it to [260, 261, 267]. Use of a pumice stone with prior treatment
thậm chí có thể khiến bệnh trầm trọng hơn. Tuy nhiên, một worsen. However, a case report showed that isotretinoin may with a keratolytic agent has also been recommended in treat-
báo cáo trường hợp cho thấy isotretinoin có thể có hiệu quả
trong điều trị KFSD [133]. Thuốc kháng histamine toàn thân
be effective in the treatment of KFSD [133]. Systemic anti- ing KP in a commentary [268]. KPA with scarring alopecia,
được chứng minh là KHÔNG hiệu quả trong điều trị KP trong histamines were not shown to be effective in the treatment once dormant, may be cosmetically treated with reconstruc-
một nghiên cứu thuần tập tiền cứu [21]. Đáng chú ý, một of KP in a prospective cohort study [21]. Of note, a 45-year- tive procedures, as shown in the case of a 33-year-old man
người đàn ông 45 tuổi mắc hội chứng mệt mỏi mãn tính đã old man with chronic fatigue syndrome who experienced with dormant KPA who underwent eyebrow reconstruction
cải thiện đáng kể KP và AD sau khi điều trị bằng marked improvement in his KP and AD after treatment with with individual hair follicle micrografts and maintained cos-
dextroamphetamine sulfate (Có cải thiện) đã được báo cáo
dextroamphetamine sulfate has been reported [253]. metic satisfaction at 4 years of follow-up [269].
[253].

KP là một tình trạng da rất phổ biến ở trẻ em và người lớn. Nó
thường bị coi là một vấn đề thẩm mỹ (ít được quan tâm), nhưng
điều này có thể dẫn đến việc bỏ sót chẩn đoán nhiều loại bệnh
liên quan, hội chứng di truyền và các tác dụng phụ do thuốc cũng
như điều trị không đầy đủ. Việc mô tả thêm các đặc điểm của các
mối liên quan này sẽ làm sáng tỏ rất cần thiết về sinh lý bệnh của
KP và các dạng phụ của nó, từ đó có thể hiểu rõ hơn về cách phát
triển các liệu pháp hiệu quả. Cần có thêm dữ liệu về hiệu quả của
các liệu pháp cũ và mới để cập nhật các hướng dẫn điều trị. Dựa
trên đánh giá toàn diện của chúng tôi về tài liệu, chúng tôi xin
đưa ra các kết luận sau:
• KP là phổ biến, nhưng tỷ lệ hiện mắc bệnh dường như thay
đổi theo dân tộc. Di truyền dường như đóng một vai trò chính
trong KP và các subtype của nó.
• Tuổi mắc: KP thường xuất hiện trong thời thơ ấu; sự tự cải
thiện trong tuổi thanh niên là phổ biến.
• Chẩn đoán KP thường được thực hiện trên lâm sàng, nhưng
soi da và sinh thiết có thể hỗ trợ chẩn đoán.
• Mặc dù cơ chế bệnh sinh của KP vẫn chưa được
làm sáng tỏ đầy đủ, nhưng nhiều yếu tố, bao gồm các
phát hiện mô bệnh học, xu hướng cải thiện của KP ở
tuổi vị thành niên, mối liên quan của KP với đột biến
filaggrin và sự phân ly 18p, tác động của rối loạn điều
hòa androgen và insulin, và giảm Sự phổ biến của KP
ở những bệnh nhân bị mụn trứng cá, hỗ trợ KP như
một rối loạn của tuyến bã nhờn, do đó phá vỡ hàng
rào thẩm thấu của SC và gây ra hiện tượng sừng hóa
và bất thường về lông.
• Sự liên kết của KP với các bệnh: với atopy (viêm
da dị ứng) và IV (da vảy cá) có thể xuất phát từ một
khiếm khuyết trong hàng rào thấm một phần do đột
biến filaggrin gây ra. Tuy nhiên, với sự không đồng
nhất về căn nguyên và tỷ lệ phổ biến cao của cả hai rối
loạn, sự hiện diện của KP không nên được coi là
tiêu chí chẩn đoán AD.
• Những thay đổi về nồng độ androgen và insulin
biểu hiện trong bệnh béo phì, tiểu đường và mang
thai có thể ảnh hưởng trực tiếp đến các tế bào bã
nhờn và góp phần vào cơ chế bệnh sinh của KP.
10 Conclusion kết luận
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,
• LA, SA, urê, retinoids tại chỗ, tacrolimus, Aquaphor, canxi san hô
fractional prickle coral calcium, spray-on Nitrosomonas gai phân đoạn, phun sương Nitrosomonas eutropa, và chất tẩy rửa
eutropa mist, and chorine dioxide complex cleanser have phức hợp chorine dioxide đã được chứng minh là có ít nhất một
been shown to be at least partially effective in treating phần hiệu quả trong việc điều trị KP.
KP. • Dữ liệu về các loại thuốc toàn thân để điều trị KP và các phân
• The data on systemic drugs for the treatment of KP and nhóm của nó rất thưa thớt và mâu thuẫn. ít có hiệu quả
its subtypes are sparse and conflicting. • Dữ liệu sơ bộ cho thấy liệu pháp laser có hiệu quả trong điều trị
• Preliminary data suggest that photopneumatic therapy is KP và ánh sáng xung cường độ cao có hiệu quả trong điều trị KPA.
effective in treating KP and intense pulsed light is effec-
• Các loại laser có hiệu quả trong điều trị KP hoặc các loại phụ của
tive in treating KPA.
nó bao gồm PDL, KTPL, laser alexandrite, laser diode xung dài, laser
• Lasers that are effective in treating KP or its subtypes
Q-switched Nd: YAG và laser carbon dioxide phân đoạn.
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 Vì KP quá phổ biến, rất khó để xác định sự liên quan khi
associations from those that occur by chance, especially with tiếp xúc với môi trường và các bệnh hiếm. Cần có thêm
environmental exposures and rare diseases. More studies nhiều nghiên cứu để củng cố các mối liên hệ bệnh tật, no mean
are necessary to cement disease associations, gain further hiểu sâu hơn về sinh lý bệnh của KP, và thiết lập các
insight into the pathophysiology of KP, and establish effec- hướng dẫn điều trị hiệu quả.
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.
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