ChapterPDF Available

Retinoids in Hair Disorders


Abstract and Figures

Vitamin A has been shown to have an essential role in the differentiation, growth and regulation of the human hair cycle. The use of both systemic and topical retinoids is implicated in both the pathogenesis and treatment of various hair disorders. Of particular importance is the direct impact that retinoids have in the dynamic hair growth cycle. Retinoic acid has been shown to directly affect the anagen initiation phase of the hair cycle and direct the differentiation of embryonic and induced pluripotent stem cells into keratinocytes to produce normal hair follicles. Retinoids also have a critical role in the up- or down-regulation of protein pathways depending on their mode of transmission. Systemic retinoids have been shown to cause hair disorders including acute telogen effluvium, alopecia areata and acquired progressive kinking of the hair. Conversely, the use of topical retinoid agents has been reported as an effective treatment option for androgenetic alopecia and alopecia areata, whilst systemic retinoid agents have been reported as an effective option for frontal fibrosing alopecia and monilethrix.
Content may be subject to copyright.
Nature of Query Response
Q1 Instead of “Miscellaneous” suggest change to, i.e., “Other
Hair Disorders”.
Q2 Please provide volume and last page details for
Q3 Reference 18, Please check the page number.
Q4 Please provide better quality source for this Figure 22.1.
ISBN No: 9781138314771 Chapter No: C022
The following queries have arisen during the typesetting of your manuscript. Please answer
these queries by marking the required corrections at the appropriate point in the text.
9781138314771_C022.indb 1 09-08-2019 21:16:44
Q1 - We are happy to change this to "Other Hair Disorders"
Q2 - This reference is from an eCollection, and as such, does not have a volume
or page number. It should be referenced as it is currently written.
Q3 - Page number has been amended below to reflect pages 27-66, and chapter
has been included in the title "Chapter 66: Disorders of Hair".
Happy with change
As below
As below
Q4 - Unfortunately, the image provided is the highest quality image that we are able to
Provide, this has been attached to the proof.
As below
Early observations have shown that vitamin A deciency can
induce epidermal hyperkeratosis, squamous metaplasia of
mucous membranes, various keratinization disorders, and cer-
tain precancerous conditions (1). Conversely, vitamin A has been
shown to induce robust immune responses and aids in the dif-
ferentiation and growth of skin, hair, and other tissues (2). These
ndings suggest that vitamin A is implicated in both the patho-
genesis and treatment of various hair disorders.
Retinoids are derivatives of vitamin A, or all-trans retinol,
or synthetic compounds that share structural and/or functional
similarities with the vitamin. Retinoids function by binding to
nuclear receptors, which in turn interact with other transcrip-
tion factors to coordinate gene expression. The regulation of the
retinoid signaling pathway is complex, and retinoids can have
numerous effects on multiple tissues in a dose-dependent manner.
For decades, dermatologists have used vitamin A and related
compounds (retinoids) to treat a wide range of cutaneous disor-
ders, including psoriasis, acne, and cutaneous T-cell lymphoma.
More recently, evidence has emerged for the use of retinoids both
as a causative agent in some hair disorders as well as a therapeu-
tic option for treatment of specic hair disorders.
Retinoids and Hair Cycle
Hair growth involves complex interactions of genes, signal-
ing factors, cell-to-cell interactions, and complex proteins and
hormones. Retinoids have a direct impact on these interactions
by altering the dynamic hair growth cycle. The cycle of hair
growth comprises four main stages, including anagen (growth
and differentiation), catagen (regression and apoptosis), telo-
gen (inactivity), and exogen (the shedding of old hair follicles)
(Figure22.1) (3). This cycle results in the replacement of every
hair on the scalp every 3–5 years, with individual follicles
undergoing 10–30 such cycles in a lifetime (4). On average, a
normal scalp has 100,000 hairs, with approximately 86% being
in anagen, 1% in catagen, and 13% in telogen (5). The variation
in hair cycle length is attributable to the length of the anagen
phase, which is unique to the individual (6). As hair is produced
solely in anagen, this phase also determines the physical length
of the hair.
The regeneration of hair is dependent on the recycling of the
anagen terminal follicle. The primary follicle stem cells are at
the site of contact of the external root sheath and the erector pili
muscle, with a secondary site of regeneration located at the ana-
gen bulb (6). Hair follicle induction and growth is also dependent
on interactions between the external environment, the epider-
mis. and underlying mesenchyme. Several pathways, such as the
Wnt, sonic hedgehog, bone morphogenetic protein, and broblast
growth factor intracellular pathways are essential in these recip-
rocal signaling events necessary for hair follicle morphogenesis
and differentiation (7).
Studies with transgenic mice support a role for retinoic acid
in the hair follicle (8). It was found that blocking of the retinoic
acidsignaling pathways resulted in a delay in anagen initiation
while increasing retinol and all-trans-retinoic acid (tretinoin) (8).
Exogenous tretinoin was also shown to induce catagen in cul-
tured hair follicles (9). In addition, exogenous tretinoin with bone
morphogenetic protein directed the differentiation of embryonic
and induced pluripotent stem cells into keratinocytes that when
grafted into nude mice produced normal epidermis, hair folli-
cles, and sebaceous glands (10). There was upregulation of sig-
naling proteins with the addition of retinoic acid, peaking during
mid-anagen through to early catagen (8). The results suggest that
retinoic acid can alter differentiation and the hair growth cycle to
regulate both the telogen-to-anagen and anagen-to-catagen tran-
sitions and assist in lipid metabolism for maintenance of epider-
mal barrier function.
It has also been shown that retinoic acid plays an impor-
tant role in hair follicle formation and patterning through the
homeobox gene proteins Hox C8 and Hox C6 (11). Retinoic acid
appears to up- and downregulate the homeobox genes, which
consequently inuences hair follicle generation, initiation, dif-
ferentiation, and even inhibition (11). Retinoic acid receptor
(RAR) and retinoid X receptor (RXR) genes have been identi-
ed in almost every portion of the hair follicle. The RARs and
RXRs differ depending on the specic portion of the hair fol-
licle (12). This gene arrangement also provides validation of the
complex interaction that exists between protein synthesis, cell
turnover, and the activation of cellular retinoic acid-binding
protein from retinoic acid within the nucleus (12). The local-
ized components that are involved in the signaling to the hair
follicle by retinoic acid have been hypothesized in many reports
(13–15). There is still much that is unknown regarding the exact
mechanism of retinoic acid’s function within the hair follicle,
Retinoids in Hair Disorders
Brent J. Doolan and Rodney Sinclair
9781138314771_C022.indb 129 09-08-2019 21:16:44
130 Retinoids in Dermatology
and future studies are required to determine the mechanism of
retinoic acid differentiation within the hair follicle.
Retinoid-Induced Hair Disorders
Acute Telogen Effluvium
Acute telogen efuvium (ATE) is a self-limiting, non-scarring,
diffuse loss of club (telogen) hair in disease states of the fol-
licle that usually occurs 3–4 months after a triggering event
(Figure 22.2) (16). The exact prevalence of ATE is not known,
but among those seeking treatment, women are overrepresented,
probably due to unawareness or underreporting in males. It can
occur in people of any age, any gender, and any racial background
and can be triggered by metabolic stress, hormonal changes, or
medications, including retinoids (17). ATE is usually a reactive
and self-limiting condition.
The condition can be assessed and monitored using the hair
pull test (Figure 22.3), where the clinician applies traction to
a bundle of scalp hairs. If more than 10% of the hairs in each
bundle are removed from the scalp area, the hair pull test is con-
sidered positive.
Removal of the inciting factor will usually lead to spontaneous
improvement (16). In general, reassurance about the reversibil-
ity of the hair loss is sufcient to alleviate the patient’s concern.
Dose reduction or cessation of therapy may be necessary in more
severe cases. In some cases, telogen efuvium may not sponta-
neously resolve when the inciting trigger is removed. Chronic
telogen efuvium is a diffuse hair loss of the scalp that persists
longer than 6 months. It is characterized by abrupt, diffuse shed-
ding of hair that runs a uctuating course over several years (18).
Patients receiving systemic treatment with synthetic retinoids
often suffer from substantial retinoid-induced ATE. This is one of
the most frequent and psychologically distressing adverse effects
of retinoid therapy, which results in premature termination of a
clinically desired and often highly effective systemic therapy
with retinoids (19). The risk of ATE due to the systemic retinoids
has been reported to vary over a range of 10%–75% (20). The
risk is greater for acitretin than for etretinate therapy and is much
less common with isotretinoin and bexarotene. Hair loss is a
dose-related effect and is reversible starting 2 months after either
discontinuation of therapy or a signicant dose reduction. Hair
loss may affect body hair also, with mild hair loss involving the
pubic, axillary, and vellus hairs. Increased hair fragility may also
be observed. As with telogen efuvium of other causes, women
report more noticeable hair loss than men, and the condition may
make underlying mild androgenic alopecia more obvious.
The administration of systemic retinoids can induce a large
number of hair follicles in the growing (anagen) phase to shift
to the telogen phase. It is estimated that approximately 7%35%
of the follicles may shift to this state (17). Growth of the telogen
hairs ceases for 16 months (on average 3 months), though this
cessation of growth is not noticed by the patient. When the hairs
FIGURE 22.1 Human ha ir growth cycle dynam ics.
FIGURE 22.2 Acute telogen efuvium.
9781138314771_C022.indb 130 09-08-2019 21:16:45
Updated Figure 22.1 Attached.
131Retinoids in Hair Disorders
re-enter the growth phase (anagen), the hairs that had been sus-
pended in the resting phase (telogen) are extruded from the fol-
licle, and hair shedding is observed. A small proportion of ATE
cases may experience persistent, episodic shedding, as some fol-
licles may not revert to an asynchronous growth pattern (18).
The exact mechanism by which systemic retinoids induce
ATE has not been established, but it has been hypothesized that
it is due to defective anchoring of the hair shaft during telogen
(21). It has also been postulated that ATE may in part be due to
upregulation of transforming growth factor-beta 2, which is a key
inducer of catagen and has been shown to have signicant upreg-
ulation of transcripts with retinoic acid treated hair bulbs (9).
Alopecia Areata
Alopecia areata (AA) is an autoimmune, non-scarring alopecia
that is mediated by CD8+ T-cell attack on the lower cycling
hair follicle and a loss of immune privilege in the hair follicle
(Figure 22.4) (22). Lesions of AA often resolve spontaneously,
but the disease may progress to loss of all scalp hair (alopecia
totalis) or to total loss of scalp and body hair (alopecia univer-
salis). AA is a common disease, affecting about 0.2% of the
population (22). Males and females are affected equally, and
the prevalence is almost the same for all ethnic groups. Studies
suggest AA is a complex polygenetic disease that also involves
exogenous, environmental factors (23). It has been suggested that
vitamin A may play a role in the formation of AA, with vitamin
A toxicity leading to the establishment of AA (24).
It has been reported that the expression of retinoid synthesis
enzymes and binding proteins are increased in human patients
with AA, as well as in rodent models (25). It was noted that
feeding mice high levels of dietary vitamin A combined with
increased retinoic acid synthesis accelerated the onset of AA (25).
Furthermore, in mice with excess retinol and all-trans-retinoic
acid within the basal epidermis and outer root sheath, progressive
cyclical alopecia with accelerated telogen to anagen transition was
noted. In contrast, a severe reduction in dietary vitamin A intake
resulted in a reduction in alopecia-related anagen induction.
Vitamin A also directly regulates the immune response, hav-
ing been shown to increase T-helper 2 and reduce T-helper 1 cyto-
kines (26). Vitamin A also reduces levels of interferon gamma,
which has been shown to play a key role in the etiology of AA
(26). It has been suggested that vitamin A may promote the ini-
tiation of the anagen hair cycle, which likely increases follicle
susceptibility to autoimmune destruction (27). Together, these
reports implicate retinoids in the pathogenesis of AA, although
the precise mechanism behind these effects remains unclear and
requires further investigation.
It has been noted that acquired progressive kinking of the hair
was present in a case series of three patients who were prescribed
FIGURE 22.3 The ha ir pull test—Around 10–20 hairs are grasped rmly at the scalp between the thumb and index nger, and traction is applied as the
hairs a re pulled along their length.
FIGURE 22.4 Alopecia areata with a close-up examination of scalp hair
9781138314771_C022.indb 131 09-08-2019 21:16:46
132 Retinoids in Dermatology
long- term oral etretinate at 50 mg/day or more (28). Kinking of
the hair was noticed 3–12 months after starting treatment and
coincides with the normal anagen cycle of hair growth. This nd-
ing suggests that systemic retinoid treatment at high doses may
have a dynamic effect on the inner root sheath or may represent
a pre-alopecia phase of hair loss.
There have also been case reports that have documented hair
color lightening and darkening while during oral etretinate
treatment for psoriasis (29) and pityriasis rubra pilaris (30).
Repigmentation of white hair and change of hair texture after
6 months of oral acitretin (25 mg/day) for treatment of psoriasis
has also been reported (31).
Retinoids for Treatment of Hair Disorders
Frontal Fibrosing Alopecia
Frontal brosing alopecia (FFA) is a primary lymphocytic
scarring alopecia with a distinctive clinical pattern of pro-
gressive frontotemporal hairline recession and eyebrow loss
that mainly affects postmenopausal women (Figure 22.5) (32).
Histopathology from affected regions shows an immune-medi-
ated inammatory inltrate of lymphocytes surrounding the
bulge region of the hair follicle. Inammation of the bulge area
destroys the hair follicle stem cells, preventing hair regenera-
tion (32). Hair follicles are permanently replaced by a scar-like
brous tissue. It has been hypothesized that loss of the follicu-
lar immune privilege and a peroxisome proliferator-activated
receptor-γ deciency may enable the inammatory process
to attack the stem cells in the bulge region and permanently
destroy them (33).
A recent study assessing the efcacy of oral isotretinoin and
acitretin in treatment of FFA showed success with this treatment
modality (34). The investigators reported an arrest of disease pro-
gression in the majority of patients using oral isotretinoin 20 mg/
day and in those treated with acitretin 20 mg/day. Furthermore,
results were superior to the control group treated with nasteride
5 mg/day. Notably, in contrast to all other drugs used to treat
FFA, this study noted no disease progression after discontinua-
tion of treatment. The mechanism of action of retinoids in FFA
is not fully understood but may represent an anti-inammatory
effect that contributes to normalizing of the antigen expression of
the hair follicle keratinocytes.
Androgenetic Alopecia
Unlike AA, which is caused by an autoimmune reaction at the
hair follicle, androgenetic alopecia (AGA) (commonly referred to
as male- or female-pattern baldness) is caused by the heightened
sensitivity of scalp follicles to dihydrotestosterone. In men, hair
loss typically involves the temporal and vertex region while spar-
ing the occipital region: the characteristic “horseshoe” pattern
(35). AGA features a progressive miniaturization of the hair fol-
licle leading to vellus transformation of terminal hair. This results
from an alteration in hair cycle dynamics: anagen phase duration
gradually decreases and the telogen phase increases. As the ana-
gen phase duration determines hair length, the new anagen hair
becomes shorter, eventually leading to bald appearance (35).
Data on the use of topical retinoids to treat AGA was rst
described in 1986, within a cohort of 56 subjects (36). Results
showed that after 1 year of combination treatment involving the
use of topical tretinoin with 0.5% minoxidil, there was termi-
nal hair regrowth in 66% of the subjects (36). Treatment with
tretinoin monotherapy was also shown to stimulate some hair
regrowth in approximately 58% of patients.
It has been documented that the percutaneous absorption of 2%
minoxidil is increased nearly threefold by the addition of 0.05%
tretinoin, which increases the permeability of the stratum cor-
neum (37). When minoxidil combined with tretinoin is applied
only once daily, the urinary excretion of minoxidil was found to
be signicantly higher than that of minoxidil alone applied twice
daily. Moreover, 0.5% minoxidil plus 0.025% tretinoin (95%
alcohol plus 5% propylene glycol vehicle) applied twice daily to
the affected scalp area was reported to prolong the anagen hair
ratio and induce new hair regrowth (37).
These ndings prompted further studies into the efcacy of
combined retinoids. One study assessed the efcacy of 5% topi-
cal minoxidil solution with the use of 0.01% tretinoin (38). The
efcacy and safety of therapy was compared using a combined
solution of 5% minoxidil and 0.01% tretinoin once daily with
that of conventional 5% topical minoxidil therapy applied twice
daily for treatment of AGA. No statistical differences were found
between the two treatment groups, therefore validating the use of
daily treatment including the use of 0.01% tretinoin, instead of
twice-daily treatment with minoxidil monotherapy.
Alopecia Areata
Although systemic retinoid therapy has been shown to induce
hair loss in some patients, approaches involving the use of topi-
cal retinoids have shown promising results as therapeutic options
for treatment of AA. This difference in mode of administration
most likely represents targeted growth and differentiation from
topical retinoid application versus a complete systemic response
that may recruit a multitude of other biochemical pathways that
possibly result in unwanted side effects such as AA.
In a phase I/II randomized, half-head trial reviewing the ef-
cacy of 1% bexarotene gel for management of treatment refrac-
tory AA, general improvement in hair regrowth was found
FIGURE 22.5 Frontal brosing alopecia.
9781138314771_C022.indb 132 09-08-2019 21:16:47
133Retinoids in Hair Disorders
within a cohort of 42 patients over 24 weeks (39). Five of 42
(12%) had 50% or more partial hair regrowth on the treated side,
and 6 of 42 (14%) on both sides, including 3 complete responders.
Side effects included mild scalp irritation in 31/42 patients, with
4 patients having grade-3 irritation.
Topical tretinoin (0.05%) cream was also compared to topical
betamethasone dipropionate, dithranol paste (0.25%), and white
soft petroleum jelly in a cohort study of 80 patients with AA
(40). Medications were applied to the patients twice daily for 3
months. Assessment at the 3-month time interval showed good
regrowth in 55% of patients using tretinoin versus 70%, 35%, and
20% of those who used topical steroids, dithranol paste, or white
soft petroleum jelly respectively.
In a more recent study, the effectiveness of adapalene in com-
bination with steroids has been assessed for treatment of AA.
The researchers compared the efcacy of topical mometasone
furoate 0.1% cream monotherapy versus mometasone furoate
0.1% cream plus adapalene 0.1% gel in the treatment of AA (41).
Over a 12-week study period, mean regrowth scores were higher
in patients who were exposed to combination therapy. Mean per-
centages of hair regrowth in the combination group were statisti-
cally higher than monotherapy group for the fourth (50.2% vs.
23.5%), eighth (78.5% vs. 50.7%), and twelfth week (90.5% vs.
71%). This new approach has potential as a future therapeutic
modality in the treatment of AA.
Monilethrix presents clinically with hair that tends to be normal
at birth but becomes short, fragile, and brittle within months.
This results in hypotrichosis, particularly on the occipital scalp
(42). It is characterized by regular, periodic thinning of hair
shafts, giving them a beaded appearance. Although the occipital
scalp is most commonly affected, the eyebrows and eyelashes
can be involved, as well as the nails. Three genes have been
associated with monilethrix (KRT81, KRT83, and KRT86),
which are responsible for the autosomal dominant form of the
disease (43).
Systemic retinoids have been reported as potential therapeutic
options for the treatment of monilethrix. A single case of child-
hood monilethrix showed increased hair length with loss of bead-
ing along the hair shaft with a dose of 0.5 mg/kg of etretinate
over 6 months (44). During treatment, the scalp appearance of
keratosis pilaris persisted, suggesting that the beading alone was
inuenced by etretinate. A second case report found cosmetic
and clinical improvement with the use of 0.5 mg/kg of acitretin
in a 7-year-old girl over a 12-month period, but clinical symp-
toms recurred within 4 months of therapy discontinuation (45).
Retinoids are implicated in the pathogenesis and treatment of
various hair disorders. Vitamin A and retinoids play an important
role in hair follicle transformation and the hair cycle. Therefore,
their use may interrupt the normal hair cycle and can cause a dif-
fuse hair loss that presents as a telogen efuvium. They may also
be responsible for changes in hair texture and color. Generally,
hair loss due to retinoids is reversible with the medication’s
withdrawal, and the overall prognosis is favorable. Conversely,
there is emerging evidence that retinoids are effective treatments
for various hair disorders, including frontal brosing alopecia,
alopecia areata, androgenetic alopecia, and monilethrix.
1. Rollman O, Vahlquist A. Cutaneous vitamin A levels in seb-
orrheic keratosis, actinic keratosis, and basal cell carcinoma.
Arch Dermatol Res. 1981;270:193–196.
2. Oliviera LM, Teixeria LME, Sato MN. Impact of retinoic
acid on immune cells and inammatory diseases. Mediators
Inamm. 2018:306712 6.
3. Bergfeld WF. Retinoids and hair growth. J Am Acad Dermatol.
4. Stenn KS, Paus R. Controls of hair follicle cycling. Physiol
Rev. 20 01;81:4 49–494.
5. Grover C, Khurana A. Telogen efuvium. Indian J Dermatol
Venereol Leprol. 2013;79:591– 603.
6. Krause K, Foitzik K. Biology of the hair follicle: The basics.
Semin Cutan Med Surg. 2006;25:2–10.
7. Okano J, Levy C, Lichti U etal. Cutaneous retinoic acid levels
determine hair follicle development and downgrowth. J Biol
Chem. 2012;287:3930 4–39315.
8. Everts HB. Endogenous retinoids in the hair follicle and seba-
ceous gland. Biochim Biophys Acta. 2012;1821:222–229.
9. Foitzik K, Spexard T, Nakamura M etal. Towards dissecting
the pathogenesis of retinoid-induced hair loss: All-trans reti-
noic acid induces premature hair follicle regression (catagen)
by upregulation of transforming growth factor-beta 2 in the
dermal papilla. J Invest Dermatol. 200 5;124:1119–1126.
10. Bilousova G, Chen JA, Roop DR. Differentiation of mouse
induced pluripotent stem cells into a multipotent keratinocyte
lineage. J Invest Dermatol. 2011;131:857–864.
11. Duverger O, Morasso MI. Role of homeobox genes in the
patterning, specication and differentiation of ectodermal
appendages in mammals. J Cell Physiol. 2008;216:337–346.
12. Persaud SD, Lin YW, Wu CY et al. Cellular retinoic acid
binding protein 1 mediates rapid non-canonical activation of
ERK1/2 by all-trans retinoic acid. Cell Signal. 2013;25:19–25.
13. Reichrath J, Mittmann M, Kamradt J et al. Expression of
retinoid-X receptors (-alpha,-beta,-gamma) and retinoic acid
receptors (-alpha,-beta,-gamma) in normal human skin: An
immunoh istologica l eva lu ation. Histochem J. 199 7;29:127–133.
14. Billoni N, Gautier B, Mahe YF et al. Expression of retinoid
nuclear receptor superfamily members in human hair fol-
licles and its implication in hair growth. Acta Derm Venereol.
199 7;77:350 –355.
15. Viallet JP, Dhouailly D. Retinoic acid and mouse skin mor-
phogenesis: Expression pattern of retinoic acid receptor genes
during hair vibrissa follicle, plantar, and nasal gland develop-
ment. J Invest Dermatol. 1994;103:116 –121.
16. Harrison S, Sinclair R. Telogen efuvium. Clin Exp Dermatol.
20 02;27(5 ):389–395.
17. Bergfeld WF. Telogen efuvium. In: McMichael A, Hordinsky
M, editors. Hair and Scalp Diseases: Medical, Surgical and
Cosmetic Treatments. Informa Health Care. 2008. p. 119.
18. Messenger AG, de Berker DA, Sinclair RD. Disorders of hair.
In: Burns T, Breathnach S, Cox N, editors. Rook’s Textbook
of Dermatology. 8th ed. UK: Blackwell Publishing. 2010. p.
9781138314771_C022.indb 133 09-08-2019 21:16:47
134 Retinoids in Dermatology
19. Katz HI, Waalen J, Leach EE. Acitretin in psoriasis: An
overview of adverse effects. J Am Acad Dermatol. 1999;41:
S7–S12 .
20. Murray HE, Anhalt AW, Lessard R et al. A 12-month treat-
ment of severe psoriasis with acitretin: Results of a Canadian
open multicenter study. J Am Acad Dermatol. 1991;24:
598– 602.
21. Berth-Jones J, Hutchinson PE. Novel cycle changes in
scalp hair are caused by etretinate therapy. Br J Dermatol.
22. Pratt CH, King LE, Messenger AG. Alopecia areata. Nat Rev
Dis Primers. 2017;3:17011.
23. Petukhova L, Duvic M, Hordinsky M et al. Genome-wide
association study in alopecia areata implicates both innate and
adaptive immunity. Nature. 2 010 ;466:113–117.
24. Shih MYS, Kane MA, Zhou P etal. Retinol esterication by
DGAT1 is essential for retinoid homeostasis in murine skin. J
Biol Chem. 2009;284:4292–4299.
25. Duncan FJ, Silva KA, Johnson CJ etal. Endogenous retinoids
in the pathogenesis of alopecia areata. J Invest Dermatol.
2013;133:33 4–3 43.
26. Freyschmidt-Paul P, McElwee KJ, Hoffmann R et al.
Interferon-gamma-decient mice are resistant to the develop-
ment of alopecia areata. Br J Dermatol. 20 06;155:515–521.
27. Darwin E, Hirt PA, Fertig R etal. Alopecia areata: Review of
epidemiology, clinical features, pathogenesis, and new treat-
ment options. Int J Trichology. 2018;10:51– 60.
28. Graham RM, James MP, Ferguson DJ etal. Acquired kink-
ing of the hair associated with etretinate therapy. Clin Exp
Dermatol. 1985;10:426– 431.
29. Nanda A, Alsaleh QA. Hair discolouration caused by etreti-
nate. Dermatol. 199 4;18 8:172.
30. Vesper JL, Fenske NA. Hair darkening and new growth
associated with etretinate therapy. J Am Acad Dermatol.
31. Seckin D, Yildiz A. Repigmentation and curling of hair after
acitretin therapy. Australas J Dermatol. 20 09;50:214–216.
32. Iorizzo M, Tosti A. Frontal brosing alopecia: An update on
pathogenesis, diagnosis, and treatment. Am J Clin Dermatol.
33. Karnik P, Tekeste Z, McCormick TS etal. Hair follicle stem
cell-specic PPAR-γ deletion causes scarring alopecia. J
Investig Dermatol. 2009;129:1243–1257.
34. Rakowska A, Gradzinska A, Olszewska M, Rudnika L.
Efcacy of isotretinoin and acitretin in treatment of frontal
brosing alopecia: Retrospective analysis of 54 cases. J Drugs
Dermatol. 2 017;16:98 8–992.
35. Lolli F, Pallotti F, Rossi A et al. Androgenetic alopecia: A
re vi ew. Endocrine. 2017;57:9 –17.
36. Bazzano GS, Terezakis N, Galen W. Topical tretinoin for hair
growth promotion. J Am Acad Dermatol. 1986;15:880–893.
37. Ferry JJ, Forbes KK, VanderLugt JT, Szpunar GJ. Inuence
of tretinoin on the percutaneous absorption of minoxidil
from an aqueous topical solution. Clin Pharmacol Ther.
38. Shin HS, Won CH, Lee SH etal. Efcacy of 5% minoxidil
versus combined 5% minoxidil and 0.01% tretinoin for male
pattern hair loss. Am J Clin Dermatol. 2007;8:2 85 –290.
39. Talpur R, Vu J, Bassett R etal. Phase I/II randomized bilateral
half-head comparison of topical bexarotene 1% gel for alope-
cia areata. J Am Acad Dermatol. 200 9;61:59 2–e1.
40. Das S, Ghorami RC, Chatterjee T, Banerjee G. Comparative
assessment of topical steroids, topical tretinoin (0.05%)
and dithranol paste in alopecia areata. Indian J Dermatol.
41. Unal M. Use of adapalene in alopecia areata: Efcacy and
safety of mometasone furoate 0.1% cream versus combination
of mometasone furoate 0.1% cream and adapalene 0.1% gel in
alopecia areata. Dermatol Ther. 2018;31:e12574.
42. Singh G, Miteva M. Prognosis and management of congenital
hair shaft disorders with fragility—part I. Pediatr Dermatol.
43. Van Steensel M, Vreeburg M, Urbina MT etal. Novel KRT83
and KRT86 mutations associated with monilethrix. Exp
Dermatol. 2015;24:222–224.
44. De Berker D, Dawber RP. Monilethrix treated with oral reti-
noids. Clin Exp Dermatol. 1991;16:226 –228.
45. Karincaoglu Y, Coskun BK, Seyhan ME etal. Monilethrix:
Improvement with acitretin. Am J Clin Dermatol.
20 0 5;6 :4 07 – 410.
9781138314771_C022.indb 134 09-08-2019 21:16:47
ResearchGate has not been able to resolve any citations for this publication.
Full-text available
Alopecia areata (AA) is an autoimmune disease characterized by non-cicatricial hair loss. No definitive therapy currently exists for AA. To compared the efficacy and safety of the mometasone furoate 0.1% cream alone with the mometasone furoate 0.1% cream plus adapalene 0.1% gel in treatment of AA. Twenty patients with AA and with mean age of 27.4 ± 9.2 years were enrolled. Patches with a diameter of < 5 cm were treated with mometasone furate 0.1% cream (M), and patches with a diameter of ≥5 cm were treated with mometasone furate 0.1% cream plus adapalene 0.1% gel (M + D) for a period of 12 weeks. Hair regrowth was evaluated using a Re-growth score (RGS). Mean RGSs of M + D group were higher than M group for 4th week (2.60 vs. 1.45); 8th week (3.85 vs. 2.40) and 12th week (4.40 vs. 3.30). Mean percentages of hair re-growth in M + D group were statistically higher than M group for 4th (50.2% vs. 23.5%), 8th (78.5% vs. 50.7%), and 12th week (90.5% vs. 71%). Study revealed the efficacy and safety of adapalene and mometasone furoate combination in AA. Adapalene can be used as a new therapeutic modality in AA.
Full-text available
Purpose: Androgenetic alopecia, commonly known as male pattern baldness, is the most common type of progressive hair loss disorder in men. The aim of this paper is to review recent advances in understanding the pathophysiology and molecular mechanism of androgenetic alopecia. Methods: Using the PubMed database, we conducted a systematic review of the literature, selecting studies published from 1916 to 2016. Results: The occurrence and development of androgenetic alopecia depends on the interaction of endocrine factors and genetic predisposition. Androgenetic alopecia is characterized by progressive hair follicular miniaturization, caused by the actions of androgens on the epithelial cells of genetically susceptible hair follicles in androgen-dependent areas. Although the exact pathogenesis of androgenetic alopecia remains to be clarified, research has shown that it is a polygenetic condition. Numerous studies have unequivocally identified two major genetic risk loci for androgenetic alopecia, on the X-chromosome AR?EDA2R locus and the chromosome 20p11 locus. Conclusions: Candidate gene and genome-wide association studies have reported that single-nucleotide polymorphisms at different genomic loci are associated with androgenetic alopecia development. A number of genes determine the predisposition for androgenetic alopecia in a polygenic fashion. However, further studies are needed before the specific genetic factors of this polygenic condition can be fully explained.
Full-text available
Retinoic acid (RA) is essential during embryogenesis and for tissue homeostasis, whereas excess RA is well known as a teratogen. In humans, excess RA is associated with hair loss. In the present study, we demonstrate that specific levels of RA, regulated by Cyp26b1, one of the RA-degrading enzymes, are required for hair follicle (hf) morphogenesis. Mice with embryonic ablation of Cyp26b1 (Cyp26b1−/−) have excessive endogenous RA, resulting in arrest of hf growth at the hair germ stage. The altered hf development is rescued by grafting the mutant skin on immunodeficient mice. Our results show that normalization of RA levels is associated with reinitiation of hf development. Conditional deficiency of Cyp26b1 in the dermis (En1Cre;Cyp26b1f/−) results in decreased hair follicle density and specific effect on hair type, indicating that RA levels also influence regulators of hair bending. Our results support the model of RA-dependent dermal signals regulating hf downgrowth and bending. To elucidate target gene pathways of RA, we performed microarray and RNA-Seq profiling of genes differentially expressed in Cyp26b1−/− skin and En1Cre;Cyp26b1f/− tissues. We show specific effects on the Wnt-catenin pathway and on members of the Runx, Fox, and Sox transcription factor families, indicating that RA modulates pathways and factors implicated in hf downgrowth and bending. Our results establish that proper RA distribution is essential for morphogenesis, development, and differentiation of hfs.
Full-text available
Alopecia areata (AA) is an autoimmune disease that attacks anagen hair follicles. Gene array in graft-induced C3H/HeJ mice revealed that genes involved in retinoic acid (RA) synthesis were increased, whereas RA degradation genes were decreased in AA compared with sham controls. This was confirmed by immunohistochemistry in biopsies from patients with AA and both mouse and rat AA models. RA levels were also increased in C3H/HeJ mice with AA. C3H/HeJ mice were fed a purified diet containing one of the four levels of dietary vitamin A or an unpurified diet 2 weeks before grafting and disease progression followed. High vitamin A accelerated AA, whereas mice that were not fed vitamin A had more severe disease by the end of the study. More hair follicles were in anagen in mice fed high vitamin A. Both the number and localization of granzyme B-positive cells were altered by vitamin A. IFNγ was also the lowest and IL13 highest in mice fed high vitamin A. Other cytokines were reduced and chemokines increased as the disease progressed, but no additional effects of vitamin A were seen. Combined, these results suggest that vitamin A regulates both the hair cycle and immune response to alter the progression of AA.Journal of Investigative Dermatology advance online publication, 27 September 2012; doi:10.1038/jid.2012.344.
Frontal fibrosing alopecia (FFA), first described by Kossard in the early 1990s, is a form of primary lymphocytic cicatricial alopecia characterized by selective involvement of the frontotemporal hairline and eyebrows. Since the original description, an increasing number of cases have been reported worldwide and the clinical aspects of the disease have been better characterized. However, the pathogenesis is still unknown and several hypotheses have been made about possible triggering factors, including hormones, neurogenic inflammation, smoking, UV filters, and ingredients in leave-on facial products. A genetic basis has also been hypothesized as the disease can occur in siblings and members of the same family. Besides its pathogenesis, research is also focused on treatment; FFA is a chronic condition and at present there is no validated or approved treatment for this disorder. Commonly prescribed topical treatments include corticosteroids, minoxidil, and calcineurin inhibitors. Systemic treatments include 5α-reductase inhibitors, hydroxychloroquine, and retinoids. Intralesional triamcinolone acetonide is also utilized, especially for the eyebrows. Other possible treatments include pioglitazone, naltrexone, tofacitinib, and lasers.
This study aimed to assess the efficacy of systemic retinoids in treating frontal fibrosing alopecia (FFA). It was based on a retrospective analysis of 54 female patients with FFA treated with: oral isotretinoin at the daily dose of 20 mg (29/54) or acitretin at the daily dose of 20 mg (11/54) or with oral finasteride 5 mg/daily (14/54). The study was conducted between 2007 and 2017. The basic of the study is the measurement of distance between the frontal hairline and the glabellar crease prior to the commencement of treatment and after 6, 12, and 24 months. The treatment with systemic retinoids lasted between 12 and 16 months (the mean duration of treatment was 13.5 months). The primary treatment goal was defined as no further progression of disease after 12 months of treatment, while the secondary treatment goal was defined as no further progression of disease following the discontinuation of systemic retinoids. The primary treatment goal was achieved by 76% (23/29) of patients treated with isotretinoin, 73% (8/11) of patients treated with acitretin, and 43% (6/14) of patients treated with finasteride. The secondary treatment goal was achieved by 72% (21/29) of patients treated with isotretinoin, 73% (8/11) of patients treated with acitretin, and 43% (6/14) of patients treated with finasteride. Thus, the administration of systemic retinoids may be beneficial for the stabilization of frontal hairline in patients with FFA. J Drugs Dermatol. 2017;16(10):988-992. .
Alopecia areata (AA) is a complex autoimmune condition that causes nonscarring hair loss. It typically presents with sharply demarcated round patches of hair loss and may present at any age. In this article, we review the epidemiology, clinical features, pathogenesis, and new treatment options of AA, with a focus on the immunologic mechanism underlying the treatment. While traditional treatment options such as corticosteroids are moderately effective, a better understanding of the disease pathogenesis may lead to the development of new treatments that are more directed and effective against AA. Sources were gathered from PubMed, Embase, and the Cochrane database using the keywords: alopecia, alopecia areata, hair loss, trichoscopy, treatments, pathogenesis, and epidemiology. © 2018 International Journal of Trichology | Published by Wolters Kluwer Medknow.
Alopecia areata is an autoimmune disorder characterized by transient, non-scarring hair loss and preservation of the hair follicle. Hair loss can take many forms ranging from loss in well-defined patches to diffuse or total hair loss, which can affect all hair-bearing sites. Patchy alopecia areata affecting the scalp is the most common type. Alopecia areata affects nearly 2% of the general population at some point during their lifetime. Skin biopsies of affected skin show a lymphocytic infiltrate in and around the bulb or the lower part of the hair follicle in the anagen (hair growth) phase. A breakdown of immune privilege of the hair follicle is thought to be an important driver of alopecia areata. Genetic studies in patients and mouse models have shown that alopecia areata is a complex, polygenic disease. Several genetic susceptibility loci were identified to be associated with signalling pathways that are important to hair follicle cycling and development. Alopecia areata is usually diagnosed based on clinical manifestations, but dermoscopy and histopathology can be helpful. Alopecia areata is difficult to manage medically, but recent advances in understanding the molecular mechanisms have revealed new treatments and the possibility of remission in the near future.
Hair shaft disorders are characterized by congenital or acquired abnormalities of the hair shaft. The objective was to review the literature regarding the prognosis and treatment options of hair shaft disorders. We used keywords in the search engines PubMed and Medline to identify all publications in the English language related to the prognosis and management of hair shaft disorders. Data were extracted from 96 articles that met search criteria. Findings were limited to case reports and small case series, as no studies were found. Disorders that improve in childhood include pili torti, trichorrhexis invaginata, wooly hair, and pili trianguli et canaliculi. Others, such as trichorrhexis nodosa, monilethrix, pili annulati, and pili bifurcati improve with minoxidil. Oral retinoids have improved hair abnormalities in trichorrhexis invaginata and monilethrix. There is no specific treatment for congenital hair shaft abnormalities. Gentle hair care is the mainstay of care for hair shaft disorders associated with fragility. Practices for gentle care include no brushing, backcombing, chemical products, tight braids, heat exposure, or mechanical grooming. Any inherited or congenital disorder requires genetic counseling as part of management.
Monilethrix is an autosomal dominant hair disorder caused by mutations in the hard keratins KRT81, KRT83 and KRT86. The affected hairs are fragile and break easily, leading to scarring alopecia. Follicular hyperkeratosis in the neck and on extensor sides of extremities is a frequently associated finding. The disorder is rare, but probably underreported because its manifestations may be mild. Mutations in KRT81 and KRT86 are the most common. Here we report new cases from Venezuela, the Netherlands, Belgium and France. The Venezuelan kindred is special for having patients with digenic novel nucleotide changes, a KRT86 mutation associated with monilethrix and a KRT81 variant of unknown clinical significance. In the French and Dutch patients we found novel KRT86 and KRT83 mutations. Our findings expand the mutational spectrum associated with monilethrix.