American Journal of Clinical Dermatology (2023) 24:81–88

https://doi.org/10.1007/s40257-022-00740-w

REVIEW ARTICLE

Beyond the Hot Comb: Updates in Epidemiology, Pathogenesis,

and Treatment of Central Centrifugal Cicatricial Alopecia from 2011
to 2021
Elisabeth A. George1 · Caneisaya Matthews2   · Fritzlaine C. Roche3,4 · Susan C. Taylor4,5,6

Accepted: 17 October 2022 / Published online: 18 November 2022

© The Author(s), under exclusive licence to Springer Nature Switzerland AG 2022

Abstract
Central centrifugal cicatricial alopecia (CCCA) is a form of scarring alopecia that predominantly affects middle-aged women
of African descent. Recent data suggest a multifactorial etiology of CCCA that is influenced by environmental and genetic
factors. Emerging evidence regarding the genetic basis of the condition may elucidate new therapies. While topical and
intralesional steroids and tetracycline antibiotics are the mainstay of treatment, refractory cases may be considered for hair
transplantation. Emerging therapies using platelet-rich plasma, botanical formulas, and cosmetic procedures have shown
promising results for the future management of CCA. As recent notable advances in CCCA have been achieved, this review
provides an update on the epidemiology, pathophysiology, and management of CCCA.

1 Introduction
In primary cicatricial alopecia (PCA), hair follicle destruc-
tion leads to irreversible fibrosis and scalp scarring [1]. Cen-
tral centrifugal cicatricial alopecia (CCCA) is a frequently
encountered PCA subtype that primarily affects middle-aged
women of African descent [2–4]. The condition is character-
ized by hair loss at the vertex that progresses in a symmetric,
centrifugal pattern [5–7]. While lymphocytic inflammatory
Elisabeth A. George and Caneisaya Matthews contributed equally.
* Susan C. Taylor
Susan.Taylor@pennmedicine.upenn.edu
1
Warren Alpert Medical School of Brown University,
Providence, RI 02903, USA
2
Florida State University College of Medicine, Tallahassee,
FL 32304, USA
3
The Children’s Mercy Hospital and Clinics, Kansas City,
MO 64108, USA
4
Division of Dermatology, Department of Medicine,
Washington University in St. Louis, St. Louis, MO 63110,
USA
5
Department of Dermatology, Perelman School of Medicine
at the University of Pennsylvania, Philadelphia, PA 19104,
USA
6 Within the last decade, understanding of CCCA etiology
Department of Dermatology, Perelman Center for Advanced
Medicine, 3400 Civic Center Blvd, Philadelphia, PA 19104,
USA
Key Points 
Over the past decade, there have been notable advance-
ments in discovering the epidemiology, pathogenesis,
and optimal management of central centrifugal cicatri-
cial alopecia.
Physicians should educate patients on the genetic nature
of the condition to bring awareness to the risk of CCCA
in relatives.
First-line therapies include corticosteroids, calcineurin
inhibitors, and tetracyclines, while hair transplantation
may be considered for stable disease.
infiltrate is identified on histology during the active dis-
ease stage, minimal inflammation is typically appreciated
clinically [5, 8, 9], which differentiates CCCA from other
forms of scarring alopecia. Since hair regeneration is rarely
observed, CCCA progression may lead to comorbid psy-
chiatric conditions, including anxiety and depression [10].
Central centrifugal cicatricial alopecia was first termed
“hot comb alopecia” since the predominant belief in the late
1960s was that common hair grooming practices in the Afri-
can–American community caused the condition [11–13].
and pathogenesis has dramatically advanced. Recent studies
have elucidated an autosomal dominant genetic etiology of

Vol.:(0123456789)

82
CCCA [14, 15]. The specific role of hair grooming practices
remains unclear, with some studies finding no association
[11, 16, 17], and others identifying certain grooming prac-
tices that may aggravate or trigger the condition [15].
In this review, we narratively summarize existing litera-
ture and highlight gaps in current understanding of CCCA
epidemiology, pathogenesis, and management. Scientific
studies published between 2011 and 2021 were identified
using the PubMed database with specific search terms of
“central centrifugal cicatricial alopecia” with “histology”,
“pathogenesis”, “treatment”, and “management”. A few key
scientific papers published prior to 2011 are also described
to provide historical context.
2 Epidemiology
While the prevalence of CCCA in the USA remains
unknown, the incidence of severe central scalp hair loss, that
was presumptively CCCA, was 5.6% in African–American
women in a southeastern US study [17]. Since symptoms
of CCCA are frequently absent, diagnosis is often delayed
[18–20]. Patients typically present during the third and
fourth decades of life, after irreversible scarring has already
occurred [14, 17, 19, 21]. There are limited data regarding
age of onset, but given the disease severity at presentation,
onset may occur during childhood. Eginli et al presented 6
pediatric cases of CCCA with a mean age of 14 years [19].
Dlova et al described biopsy-proven CCCA in an 11-year-old
African female and her 35-year-old mother [15]. The mother
was aware of her personal hair loss; however, her daughter’s
hair loss was unknown, since the lesions were obscured by
her thick, curly hair [15]. As these studies are limited, fur-
ther research on pediatric CCCA may elucidate the age of
onset and provide insight into diagnosing the disease at ear-
lier stages, which may ultimately improve clinical outcome.
Central centrifugal cicatricial alopecia patients may expe-
rience comorbidities including fibroproliferative disorders
(FPDs), breast cancer, and type II diabetes mellitus (DM2)
[5, 12, 22, 23], suggesting there may be a shared genetic
mutation that predisposes African–American women to
these conditions [22]. Aguh et al discovered that several
genes involved in regulating fibroblast proliferation in FPDs
were also upregulated in CCCA scalp samples [5]. However,
a case-control study including 74 African–American women
with CCCA found no significant association with fibroids, a
common FPD [24]. Brown-Korsah et al found that women
with CCCA were three times more likely to have a history of
breast cancer compared to controls [22]. Roche et al found
that the odds ratio (OR) for DM2 in women with CCCA was
four times higher than matched controls [25], which corrob-
orated prior findings of increased risk of severe central scalp
hair loss in DM2 patients [12, 23]. Narasimman et al also
E. A. George et al.
found that DM2 was one of the most common comorbidities;
however, there was no significant difference in DM2 preva-
lence among CCCA cases compared to controls who had
other hair loss conditions [24]. Despite conflicting findings,
screening for FPDs, breast cancer, and DM2 may improve
outcomes for CCCA patients.
3 Genetics
Genetics are a likely underpinning of CCCA pathogenesis [5,
14, 15, 19, 26]. Central centrifugal cicatricial alopecia has
been demonstrated, in some families, to be inherited in an
autosomal dominant pattern [14, 15, 19, 27]. Furthermore,
upregulation of genes involved in fibroblast proliferation,
collagen formation, and wound healing was demonstrated
in scalp biopsies of CCCA [5]. Other exome sequencing
studies have demonstrated that genes associated with lipid
metabolism and hair shaft formation may be downregulated
in CCCA patients [5, 26]. Malki et al observed a decrease
in PADI3 expression in CCCA scalp biopsies from women
of African descent compared to healthy controls matched
by ancestry, age, and sex [26]. Missense and splice PADI3
gene mutations may result in decreased enzymatic activity,
misfolded proteins, and abnormal protein localization, ulti-
mately leading to decreased hair follicle development and
hair shaft malformations [26].
4 Pathogenesis
There is an unclear relationship between hair grooming
practices and CCCA. Since hair grooming practices are
often utilized concurrently, parsing out the true impact of
each practice is difficult. In a retrospective chart review, the
majority of CCCA patients used chemical relaxers (84%),
cornrows/braids (50%), hot combs (42%), and weaves/exten-
sions (33%) at least one time [28]. In a 2020 case-control
study, current or prior chemical relaxer use was significantly
associated with CCCA (OR: 12.37, p-value < 0.001) [24]. In
contrast, chemical relaxers were not significantly associated
with CCCA in a 2009 case-control study that included 50
African–American women with CCCA [9]. Instead, Gath-
ers et al found that CCCA patients were more likely to have
worn traction inducing hairstyles and to have worn these
hairstyles for a longer duration compared to healthy controls
with no hair loss [9]. Central centrifugal cicatricial alopecia
patients were also significantly more likely to report uncom-
fortable pulling sensations when wearing cornrows/braids
with extensions and sewn-in hair weaves [9]. In contrast,
Narasimman et al found that tight braids, sewn-in weaves,
and hair extensions were not significantly associated with
CCCA [24]. Prior US and South African population studies
Epidemiology, Pathogenesis, and Treatment of Central Centrifugal Cicatricial Alopecia
have also found no association between chemical relaxers,
traction inducing hairstyles, traction-related symptoms, and
CCCA [11, 17]. Other factors such as hot combs [9, 11, 17],
curling irons [9], hair gels [9], hair oils [9], hair dyes [9],
frequency of hair washes [9, 24], and frequency of salon vis-
its [24] have not been significantly associated with CCCA.
Central centrifugal cicatricial alopecia severity does not
appear to be associated with use of hot combs, hair dyes,
hair extensions or chemical relaxers, but may be related to
traction inducing hairstyling [16]. In a cross-sectional study
of 310 African–American women with varying degrees of
central hair loss, participants were assigned central hair loss
grades (CHLG). The authors observed a positive trend, but
no significant difference, in the use of hot combs or chemi-
cal relaxers among people with probable CCCA (i.e., CHLG
3–5) and those with minimal to no hair loss (i.e., CHLG 0–1)
[12]. However, there was a statistically significant increase
in traction inducing hairstyles among people with probable
CCCA compared to those with less severe hair loss (i.e.,
CHLG 2) [12]. Nevertheless, hair grooming does not entirely
explain CCCA severity. In the first published study of CCCA
in Native Americans, the authors discussed two identical twin
Lumbee Indian patients who had worn braids as children and
regularly used chemical relaxers [27]. Although these sub-
jects had nearly identical grooming practices, the severity of
their hair loss and the observed histopathologic inflamma-
tory infiltrate differed between the subjects [27]. The authors
did not include a hypothesis for the varying CCCA severity.
However, they suggested that similar hair shaft structure and
grooming practices between the twins and women of African
descent may have contributed to CCCA development [27].
4.1 Dermatoscopy
Dermatoscopy should be used to identify characteristic
disease features that may help diagnose the condition and
exclude other hair disorders, as seen in Table 1 [21]. Visual-
izing peripilar white/gray halos is the most specific dermato-
scopic finding and highly sensitive for early- and late-stage
CCCA (Fig. 1) [29, 30]. Other specific dermatoscopic find-
ings include broken hairs, hair shaft variability, asterisk-like
interfollicular brown macules, and a “starry sky” pattern
of numerous, irregularly distributed, interfollicular pin-
point white macules [29]. Dermatoscopy may also be used
to guide biopsy of a scalp region with broken hairs, which
correlates with diagnostic inflamed follicular structures on
histopathology (Fig. 2) [29].
4.2 Histopathology
Diagnosing CCCA utilizing histopathological criteria can be
challenging due to shared histopathologic features with other
PCA subtypes, such as lichen planopilaris (LPP) [2, 36, 37].
83
While recent studies indicate distinctions [38–40], other stud-
ies highlight the similarities. These comparisons are high-
lighted in Table 1. In a scalp biopsy analysis of clinical CCCA
(n = 27) and LPP (n = 24), Jordan et al demonstrated similar
histopathological features, including basal vacuolization, lym-
phocyte exocytosis, dyskeratosis, and squamatization of the
basal layer of the follicle [36]. There were no significant dif-
ferences in terminal-to-vellus hair ratio, percentage of catagen/
telogen follicles, number of affected follicular units, degree
of perifollicular fibrosis, and density of lymphocytic infiltrate
[36]. Immunostaining demonstrated that CCCA and LPP have
indistinguishable immunophenotypes with CD4+ T-cell pre-
dominant inflammatory infiltrate and similar lymphocyte sub-
types at the follicular epithelium [36]. Most LPP and CCCA
samples were devoid of cells expressing cytokeratin-15, and all
samples lacked myeloperoxidase-positive neutrophils, CD68+
macrophages, and CD123+ plasmacytoid cells [36]. Of note,
the CD4+ T-cell predominant inflammatory infiltrate in LPP
identified by Jordan et al [36], contrasts with a prior study,
which described significant CD8+ T-cell predominant inflam-
matory infiltrate among 42 cases of LPP [40].
In a retrospective examination of scalp biopsies from 18
African–American females with clinical CCCA, Flamm et al
described the characteristic features of disease progression
[41]. Hair follicles with lymphocytic perifollicular inflam-
mation were categorized as “affected” if they met two or
more of the following criteria: (1) premature desquamation
of the inner root sheath, (2) mucinous fibroplasia with or
without perifollicular fibrosis, or (3) eccentric thinning of
the outer root sheath (Table 1) [41]. In both affected and
unaffected follicles, CD3+ T-cell infiltrate was predomi-
nantly perifollicular, with CD4+ predominance [41]. In
affected follicles, CD4+ T-cell predominance was even more
pronounced [41]. More CD1a+ Langerhans cells (LCs) and
an increased CD1a:CD3 ratio were detected within affected
follicles compared to unaffected follicles [41]. The average
distance between follicles and small blood vessel clusters
(BVCs) was also greater for affected follicles.
As concluded by the authors, these findings suggest that
antigen presentation may be involved in CCCA progression
[41]. Langerhans cell migration may lead to increased anti-
gen presentation, inducing a CD4+ T-cell response. Addi-
tionally, the authors posit that chronic inflammation may
promote perifollicular mucinous fibroplasia, which disrupts
BVCs that supply the fibrous sheath, leading to increased
single blood vessels and solitary endothelial cells around
affected follicles [41]. End-stage CCCA is marked by con-
centric perifollicular fibrosis, with distant small BVCs
remaining [41]. Increased stress is placed on follicular
keratinocytes with disrupted blood supply. Ultimately, the
CD4+ T-cell inflammatory response destroys keratinocyte
stem cells in the bulge region, leading to irreversible fol-
licular scarring [41].

84 E. A. George et al.

Table 1  Differentiating CCCA from other alopecia according to clinical presentation, dermatoscopy, and histology [31–35]
Clinical features Dermatoscopy Histology

CCCA​ Women of African descent aged 30–40 Perihilar white/gray halo Perifollicular concentric fibrosis
Patch of scarring alopecia on vertex that Loss of follicular ostia Premature desquamation of the inner root
slowly progresses centrifugally Perifollicular hyperpigmentation sheath
Broken hairs Polytrichia Eccentric thinning of the follicular epithe-
± dysesthesia of scalp Pin-point white macules lium
Perifollicular lymphocytic infiltrate
Classic LPP Caucasians aged 40–60 Perifollicular erythema, Subepidermal interface dermatitis
Predominantly multifocal, confluent hyperkeratosis, telangiectasias Lymphocytic infiltration of the infundibu-
alopecic patches starting at the parietal Peripilar casts lum and isthmus of hair follicle
scalp Loss of follicular ostia Concentric perifollicular lamellar fibrosis
± dysesthesia of scalp Violaceous-blue interfollicular spaces
FFA Mostly postmenopausal females Lymphocytosis, perifollicular dermatitis
Follicular hyperkeratosis and perifollicu-
Progressive recession of the fronto-tem- lar erythema with sparing of interfollicular epidermis
poral hairline in a band like pattern Absence of follicular ostia Lymphocytic infiltrate of isthmus and
Alopecia of the eyebrows Lone hairs infundibulum of hair follicle
Dysesthesia of scalp Red or gray dots distributed in eyebrows Perifollicular fibrosis
FPHL Bimodal: women aged 25–40 and 50–60 Diversity in the thickness of hairs Transverse section: increase ratio in minia-
Slowly progressive thinning of vertex Miniaturized hairs turized to terminal hairs
and bitemporal region with frontal Decrease in the number of hairs per fol- Vertical section: band of residual connec-
accentuation licular unit tive tissue in depth of the dermis, under
Symmetric hair loss Yellow dots miniaturized follicles
Increased shedding Terminal:vellus hair ratio of <4:1
Absence of scarring Discreet perifollicular lymphocytic infil-
Miniaturized hairs trate and fibrosis
DLE Adults aged 20–40 Perifollicular erythema Active lesion:
Women > men Follicular hyperkeratosis with follicular Perivascular and peri-adnexal lymphocytic
≥ 1 erythematous indurated patch with plugging, hyperpigmentation, depig- infiltrate
peripheral scaling and central scarring mentation, and telangiectasia Interface dermatitis
Starting at occipital and parietal scalp Follicular red dots Basilar vacuolar degeneration
Photosensitivity Necrotic keratinocytes and thickening of
Scalp and other sun exposed areas basement membrane
affected Chronic lesion:
Carpet tack sign Complete loss of follicular units
Perifollicular and interstitial fibrosis
Mucin deposit
Degeneration of elastic and collagen fibers
Direct immunofluorescence – IgG and C3
deposition in basement membrane
PPB Women aged 30–50 Loss of follicular ostia Thin epidermis with sclerotic dermis and
Irregular patches of alopecia beginning at Ivory white colored areas streamers of fibrosis
vertex or parietal scalp White dots Early lesion:
“Footprints in the snow” Solitary dystrophic hairs Sparse lymphocytic infiltrate around the
Epidermis w/o scaling or signs of inflam- infundibulum – absence of sebaceous
mation glands
Later lesions:
Atrophic follicular epithelium surrounded
by concentric lamellar fibroplasias
Markedly thickened elastic fibers on elastin
stain

CCCA​ central centrifugal cicatricial alopecia, DLE discoid lupus erythematosus, FFA frontal fibrosing alopecia, FPHL female pattern hair loss,
IgG immunoglobulin G, LPP lichen planopilaris, PPB pseudopelade of brocq

Histological examination of 836 punch biopsies from
African–American women with CCCA revealed that aging
may also contribute to inflammatory progression in CCCA.
Follicular density significantly decreased with advancing age
in the patient cohort [38]. Subset analysis of 30 randomly
selected biopsies revealed that perifollicular lymphocytic
inflammation also significantly decreased with advancing
age [38]. The authors noted that follicular density in the
early age cohort (18–38 years) was already approximately
25% less than that of healthy African–American females
[42], suggesting that many patients presented after signifi-
cant follicular destruction had occurred [38].
Epidemiology, Pathogenesis, and Treatment of Central Centrifugal Cicatricial Alopecia
Fig. 1  Dermatoscopic findings of central centrifugal cicatricial alo-
pecia (CCCA) include peripilar gray/white halo, disrupted pigmented
network, and loss of follicular openings [18]. Source: Clinical, Cos-
metic and Investigational Dermatology 2016:9, 175–181. Originally
published by and used with permission from Dove Medical Press Ltd
Fig. 2  Follicular scars and follicles with mucinous fibroplasia and
mild perifollicular lymphocytic inflammation
5 Management
Best practices involve approaching CCCA patients with
empathy and cultural understanding [43]. A certain degree
of knowledge and familiarity with common hair practices
is essential to strengthen the provider-patient relationship.
Diagnosing early CCCA requires a high index of suspicion,
85
as the condition may only present as hair breakage at the
scalp vertex [44]. A complete history must include hair and
scalp symptoms, hair grooming practices, obstetrical and
gynecological history, surgical history, medication use, and
dietary intake [21]. Patients with CCCA should be educated
on the genetic nature of the condition and encouraged to
share their diagnosis with their family members to promote
early intervention. Complete family history may identify
family members who would benefit from evaluation and
treatment. A study demonstrated the CCCA patients were
significantly more likely to have a sister who also experi-
enced hair loss [9].
There is no consensus regarding hair styling recommen-
dations for this patient population. Although the evidence
is conflicting, it is not unreasonable to err on the side of
caution and advise patients to abstain from chemical treat-
ments such as relaxers or hair dyes and to discontinue any
traction hairstyles [21, 45]. Gentle tension-free hairstyling
and reduced manipulation at the vertex should be encour-
aged [21, 46]. Camouflaging techniques such as braided lace
wigs and crochet styling are advertised to CCCA patients
on social media; however, patients should be counseled
that these styles may exacerbate damage if excess tension is
applied to the scalp (Table 2) [47]. Many of these hairstyles
are advertised as “protective styles” since natural hairs are
tucked away from damage such as constant manipulation and
environmental factors [47]. However, constant traction and
tension on hair follicles may promote inflammation. Alter-
native camouflaging techniques include synthetic makeup,
color match make-up and possible scalp micropigmentation
[48, 49].
5.1 Medical and Surgical Management
There is no randomized placebo controlled therapeutic stud-
ies of CCCA. Since the condition represents a type of scar-
ring alopecia, treatment options are more likely to slow or
modify disease progression when started early in the clinical
course. Treatment of the inflammatory disease stage should
focus on mitigating inflammation by using weekly anti-dan-
druff shampoo [50, 51], daily topical high-potency corticos-
teroids or monthly intralesional corticosteroids 5.0–7.5 mg/
cc [49], or anti-inflammatory oral tetracycline antibiotics
along with topical corticosteroids (Table 2) [21, 52]. Topi-
cal application of clobetasol 0.05% foam has demonstrated
substantial improvement in severe inflammation and perifol-
licular edema [51]. Chronic use of topical and intralesional
steroids, however, potentiates the risk of cutaneous atrophy
and hypopigmentation [31]. Tetracyclines modulate pro-
tease-activated receptor 2 downstream signaling in epider-
mal keratinocytes, which may relieve chronic pruritus that
affects some CCCA patients [53, 54]. Doxycycline hyclate
is preferred over minocycline, as minocycline has increased

86 E. A. George et al.

Table 2  Summary of CCCA medical, surgical, and behavioral therapies [21, 52, 57]

First-line therapy High potency topical steroid class I or II daily

± intralesional corticosteroid injection 5.0–7.5 mg/cc × 6 months
± oral tetracyclines (doxycycline, minocycline) 2–6 months
Second-line therapy Hydroxychloroquine 200 mg twice daily
Immunosuppressants (mycophenolate, cyclosporine)
Calcineurin inhibitors
Tacrolimus
Topical metformin 10%
Refractory therapy PRP, hair graft transplant
Maintenance therapy Mid potency topical steroids class III-V and reduce antibiotic dose by 50%
Calcineurin inhibitors
Minoxidil 5%
Behavioral therapies Gentle tension-free hair styling, refrain from chemical relaxers
Cosmetic therapies Wigs, hair pieces, hair powder, hair color, scalp micropigmentation for camouflaging

CCCA​central centrifugal cicatricial alopecia, PRP platelet-rich plasma

risk for severe drug hypersensitivity reaction [51]. Second-
line treatments such as hydroxychloroquine and calcineu-
rin inhibitors may also be considered for refractory disease
(Table 2) [49, 51, 55, 56].
Since clinical signs of inflammation such as erythema
or scale may be lacking, it may be challenging to identify
when active disease has stabilized. Performing repeat biop-
sies and examining the periphery of alopecic patches may
help determine disease activity. Patients may report cessa-
tion of hair loss. After active disease stabilization, which
generally takes at least six months, mid-potency topical
corticosteroids may be used as maintenance therapy up to
three times per week [52]. Topical minoxidil 5% foam daily
may stimulate viable hair follicles, convert vellus to terminal
hairs, and prolong the anagen phase of the hair cycle [58]. In
refractory cases, hair transplantation using the round punch
graft technique may be performed in patients who lack his-
topathologic features of inflammation after 12 months of
corticosteroid therapy and lack a history of keloid scarring
[52, 59]. Additionally, hair transplantation using the follicu-
lar unit excision technique has been successfully described
with 60% graft uptake [60, 61]. Emerging therapies for post-
inflammatory CCCA includes platelet-rich plasma (PRP)
[62]. Platelet-rich plasma is enriched with growth factors
and anti-inflammatory and proangiogenic cytokines that
subsequently promote hair growth [52, 57]. Platelet-rich
plasma use in androgenetic alopecies (AGA) has increased
in popularity with viable results, but its use in CCCA is not
well studied. In a recent case series of two patients with
PCA, a 53-year-old woman with biopsy-proven CCCA and
concomitant AGA received three sessions of PRP 4 weeks
apart with successful treatment [57]. Results showed a 50%
increase in the hair density at the vertex of the scalp and a
normal follicular density at the temporal scalp [57]. Topical
metformin may also play a role in the future of managing
CCCA. The literature has cited two case reports of African
American females with advanced CCCA who experienced
hair regrowth with daily topical metformin 10% cream after
4 to 6 months [51, 63]. Side effects included dryness and
irritated scalp, resolved with topical emollients and mois-
turizers [51, 63]. In light of increased consumer interest in
natural ingredients, Umar et al reported successful treat-
ment of refractory CCCA with a novel botanical formula
in a case series of four African–American women [64]. All
patients reported complete resolution of itching within 2
weeks of use and significant hair regrowth within 2 months
[64]. Turmeric and fenugreek oil were core ingredients in
the formula, proposed to have anti-inflammatory properties
and exert anti-fibrotic effects in down-regulating transform-
ing growth factor beta (TGFβ) and upregulating adenosine
monophosphate-activated protein kinase (AMPK) and per-
oxisome proliferator-activated receptor (PPAR). Assessment
of the efficacy of natural or botanical products through ran-
domized controlled trials should be the next step in evaluat-
ing their role in CCCA treatment options [65]. Additional
emerging therapies include low-level laser light therapy and
scalp micropigmentation [52].
6 Future Directions
While there have been advancements in understanding the
etiology and histopathologic progression of CCCA, much
of the pathogenesis remains unclear and requires further
exploration. It may be prudent to investigate the association
between CCCA and chemical relaxers and traction hairstyl-
ing in larger epidemiological studies, which may also help to
identify novel risk factors. Prevalence studies, randomized
placebo-controlled therapeutic studies, and analysis of the
inflammatory cytokine milieu may help to expand treatment
options.
Epidemiology, Pathogenesis, and Treatment of Central Centrifugal Cicatricial Alopecia
Identifying PADI3, a specific gene that is associated
with onset and progression of CCCA, in 25% of a cohort of
CCCA patients, demonstrates the genetic basis of the condi-
tion. Exploring genetic predisposition to CCCA in large epi-
demiological studies may help to further characterize disease
pathogenesis. As previous studies have suggested an auto-
somal dominant pattern of inheritance, screening teenagers
with a family history of CCCA may facilitate earlier disease
diagnosis, better treatment outcomes, and improved quality
of life. Advances in describing the histopathology and patho-
genesis of CCCA over the last decade may be reflected in an
updated CCCA classification system. Last, scarring alopecia
in African–American patients should be included in derma-
tology resident training, so that all physicians are equipped
to successfully diagnose and manage CCCA patients with
appropriate cultural competence.
Declarations  tol. 2013;52(12):1506–12.
Funding  Not applicable.
Conflict of interest  Not applicable.
Ethics approval  Not applicable.
Consent to participate  Not applicable.
Consent to publish  Not applicable.
Code availability  Not applicable.
Availability of data and materials  No data sets were generated or ana-
lyzed during the current study.
Author contributions  Dr. Fritzlaine Roche contributed to the manu-
script in leading the initiation of the research project, searching for rel-
evant references, and reviewing and editing the manuscript. Caneisaya
Matthews and Dr. Elisabeth George both worked diligently in preparing
the first draft of the manuscript. After review and editing by Dr. Roche
and Dr. Susan Taylor, Caneisaya Matthews and Dr. George revised the
draft and produced the final paper.
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