Cicatricial (Scarring) Alopecias
Salient
features
·
Scarring
alopecia occurs in a heterogeneous etiologic group of various disorders.
·
The
inflammatory process leads to permanent destruction of hair follicular stem
cell structure and subsequent replacement with fibrous tissue.
·
The
destructive process can occur as a primary or secondary cicatricial alopecia.
·
Loss
of hair-producing attribute finalizes this process and results clinically in
permanent alopecia.
·
No
evidence-based treatment is available.
Introduction
“Cicatricial”
or “scarring” implies that follicular epithelium has been replaced by
connective tissue. The broadest definition of scarring alopecia might include
all forms of alopecia in which hair follicles are permanently lost. In most
cases, it is assumed that permanent injury of the follicular stem cell
region in the outer root sheath at the level of insertion of the
arrectorpili muscle (the bulge) destroys any potential for hair regrowth. Histologically,
the follicles ultimately disappear and are replaced by fibrous stelae. Scar
tissue is not seen on histology. In contrast, non-scarring alopecia is
potentially reversible. Unlike patients with non‐scarring
alopecia who are generally asymptomatic, patients with cicatricial alopecia may
complain of itching, burning, soreness, scaling or discharge. A few hair diseases demonstrate a biphasic pattern, where non-scarring hair loss is
seen early in the course of the disease, and permanent
hair loss becomes apparent in the later stages of
the disease. Examples include androgenetic alopecia, alopecia areata, and
traction alopecia where after many years or decades of continuous active
disease, permanent dropout of follicles may occur.
In
primary scarring alopecia, the target of inflammation appears to be the
follicle. In secondary scarring alopecia, the follicle is merely an
“innocent bystander” in the disease process. Examples
of secondary cicatricial alopecia include deep burns, radiation dermatitis,
cutaneous malignancies, cutaneous sarcoidosis, morphea, necrobiosis lipoidica,
and certain chronic infections such as cutaneous tuberculosis. The various
forms of secondary cicatricial alopecia should have distinctive clinical and
histologic features typical of the underlying disease.
Performing a scalp biopsy may be helpful not only in establishing
a diagnosis but also in assessing the degree of inflammation and injury to the
stem cell region. Specimens should be at least 4 mm in diameter and extend into
the fat. Ideally, two should be obtained – one for vertical sectioning, the
other for horizontal sectioning. In the HoVert technique, a 4 mm punch biopsy
is transected ~1 mm below the skin surface in order to create an epidermal disc
(for vertical sections) and a lower portion (for horizontal sections).
In
2001, a North American Hair Research Society workshop developed a provisional
classification to facilitate future discussion and research. This scheme
divides the entities into “lymphocytic”, “neutrophilic”, and “mixed lymphocytic
and neutrophilic” forms.
Cicatricial
alopecia refers to patchy hair loss that follows the permanent destruction of
hair follicles, either by a disease affecting the follicles themselves (primary
cicatricial alopecia) or by an external process (secondary cicatricial
alopecia). Any hair‐bearing skin may be affected although cicatricial alopecia
most commonly presents on the scalp. Primary cicatricial alopecia tends to run
a chronic and progressive course.
The most common identifiable causes are lichen planopilaris (LPP), discoid lupus erythematosus and folliculitis decalvans.
Investigations
Once
the preliminary diagnosis of cicatricial alopecia has been made, the scalp
should be examined for other clues as to the cause of the hair loss such as
folliculitis, follicular plugging or broken hairs. Dermoscopy reveals a loss of
follicular ostia. These signs may help to establish the cause of a cicatricial
alopecia, but no single sign is pathognomonic for a particular disease, and
clinicopathological correlation is usually needed to make a specific diagnosis.
In most cases, a diagnostic biopsy is indicated. The site
for biopsy must be carefully selected: early lesions are likely to yield more
information.
Management
The
aim of treatment is to reduce symptoms and to slow or stop the progression of
hair loss – it is not possible to restore hair growth where hair follicles have
been lost. Early treatment is the key to minimizing the extent of permanent
alopecia.
Surgical
correction with a combination of scalp reduction and hair transplantation is
generally recommended for secondary cicatricial alopecia. Hair transplantation
and scalp reduction surgery for primary cicatricial alopecia is more
complicated due to the often progressive nature of the condition, lack of
adequate donor population and the potential for graft rejection due to
persisting inflammation in the recipient skin.
Attention
to any associated hair loss disorders such as androgenetic alopecia is
important, as the surrounding hair is required to conceal the patches of
cicatricial alopecia. Camouflage powders and sprays as well as wigs are useful.
Despite multiple investigations a
specific diagnosis is not always possible and a generic diagnosis of
cicatricial alopecia is the best that can be offered. In such cases, a trial of
oral steroids or antimalarials may be considered to assess the potential for
regrowth. Surgical correction of small areas can be considered once the
underlying disorder has burned out. This can be done either by follicle
transplantation or excision of the area. Larger areas may require the prior use
of tissue expanders.
Lichen Planopilaris
Introduction
Lichen planopilaris (LPP) is a relatively uncommon cutaneous
disorder characterized by a chronic lymphocytic inflammation that leads to the
selective destruction of hair follicles, thus resulting in scarring
alopecia. Some authors consider LPP as a follicular form of lichen planus,
although only about 30% of patients develop lesions of lichen
planus on the glabrous skin and mucous membranes or nail changes characteristic
of lichen planus. Like lichen planus, the aetiology of LPP is not known, but is
presumably related to the cause(s) of lichen planus.
LPP is more common in women than in men (ratio varying from
1.8:1 to 9:1), and the peak age of onset is observed between 30 and 60 years.
Although pathogenesis of LPP is still poorly understood,
many authors regard such a condition as a hair-specific autoimmune disorder in
which T-lymphocytes target follicular antigens with the consequent destruction
of the hair follicle stem cells. Possible involved inflammatory mediators
include b-FGF and TGF-β, which would be responsible for fibroblast
activation. Interestingly, recent evidence has pointed out a possible role
of PPAR-γ in the destruction of the pilosebaceous unit typical of LPP.
LPP classically presents as follicular keratotic plugs
and/or perifollicular scaling along with perifollicular erythema. Later stage show patchy areas of scarring alopecia with loss of
follicular openings, but significantly less erythema. Of note, in acute phases, LPP patients may experience
pruritus, pain, and/or burning sensation, differently from other primary
scarring alopecias. Besides classic LPP, there are two main clinical variants,
viz. frontal fibrosing alopecia and Graham-Little–Piccardi–Lasseur syndrome. A
good physical assessment, along with dermoscopic and histological examination,
is important to distinguish LPP from such conditions.
Clinical Presentations
of classic LPP
Classic LPP typically
starts at the crown and vertex area. Recent
scalp lesions may show violaceous papules, erythema and scaling. These papules
are replaced quickly by follicular plugs and scarring. Eventually, the plugs
are shed from the scarred area, which remains white, smooth and atrophic.
Follicular orifices are absent within the area of alopecia. If the patch is
extending, horny follicles plugs may still be present around its margins, and
the hair pull will be positive at the margins, with twisted anagen hairs being
easily extracted by gentle traction. The alopecic areas of LPP are often
smaller, irregularly shaped and interconnected, which can lead to a reticulated
clinical pattern as compared to DLE.
Histopathology
From a histological point of view, active lesions show a
band-like subepidermal lymphocytic infiltrate, “hugging” the upper hair
follicle (isthmus and infundibulum), with no involvement of the deeper portion
of the follicle (differently from alopecia areata), while late lesions are
mainly characterized by the reduction/loss of sebaceous glands and of
arrectorpili muscles, concentric perifollicular fibrosis, and irreversible
destruction of the follicle with perifollicular hyalinization in both
upper/lower dermis and follicular tract. In 40% of cases, direct
immunofluorescence shows colloid bodies and/or positive staining for
immunoglobulin M (IgM) and, less commonly, IgA or C3; a linear band of fibrin
and/or fibrinogen at the dermoepidermal junction may also be present.
Trichoscopy
The dermoscopy of LPP displays several features, with the
most specific finding of active lesions being perifollicular scaling forming a
sort of “collar” on the proximal portion of the hair shaft. Late lesions may
show discrete white dots due to loss of melanin over scarred fibrotic tracts
and perifollicular fibrosis, acquired pilitorti, loss of follicular openings,
white areas, honeycomb/scattered hyperpigmentation, milky red areas, and hair
tufts.
Lichen planopilaris, loss of
follicles and peripilar blue grey pigmentation (yellow circle)
Lichen planopilaris, Trichoscopy
done without contact medium showing prominent peripilar scaling (yellow arrow)
Lichen planopilaris, follicular
plugging (blue arrow)
Lichen planopilaris, Amorphous
white areas (red arrow)
Treatment
LPP
can be difficult to treat. Therapeutic recommendations include oral
antimalarial drugs (e.g. hydroxychloroquine) and corticosteroids (topical,
intralesional, and oral).A
short course of systemic corticosteroid may be desirable initially to stabilize
the disease. In other cases, intralesional corticosteroids are helpful, but
only at a stage when active inflammatory changes are still present. Potent
topical steroids such as clobetasol propionate ointment once daily usually
relieve associated symptoms such as itch or pain, and may slightly inhibit the
process. Acitretin and low-dose weekly methotrexate may
be effective in some patients.
Clobetasol bd for 1 month, then od
for 3 months, then A/D for 3 months. If no response at 1-3 months, then add I
/L steroid (10mg/ml) monthly, HCQS (6mg/kg /day) + Doxy 100 mg bd for 6-12
months (all combination). For severe, refractory, progressive disease: oral steroid
+ MTX.
Frontal fibrosing alopecia
FFA
predominantly affects postmenopausal women.An
association with environmental exposure to leave-on cosmetics and sunscreens
has been suggested.
Clinical
features
Recession
of the frontal hairline is the cardinal feature of frontal fibrosing alopecia
and is characterised by progressive symmetric, band-like, scarring
alopecia on the frontal and temporal hairline of the scalp. In contrast to androgenetic alopecia, the frontal hairline
recedes in a straight line rather than bitemporally and sideburns are commonly
lost. However, because the entire fringe of the scalp, including the
occipital region, may be affected, “marginal fibrosing alopecia” might be a more
accurate designation. Skin
is pale and shiny in contrast to chronically sun exposed skin of the upper
forehead as well as the presence of isolated “lonely” hairs on the
upper forehead. Loss of
eyebrows is an early and near universal finding. On close inspection there is a
loss of follicular orifices, and perifollicular erythema and follicular
hyperkeratosis may be
found at the marginal hairline. The
eyelashes appear normal.
Histopathology
The histopathologic features are similar to those found in LPP. Common microscopic findings
for both FFA and LPP included an inflammatory lymphocytic infiltrate involving
the isthmus and infundibulum of the hair follicles, the presence of apoptotic
cells in the external root sheath, and a concentric fibrosis surrounding the
hair follicles that resulted in their destruction with subsequent scarring
alopecia. Biopsies taken from FFA patients showed less follicular inflammation
and more apoptotic cells than those from LPP patients. In some cases of LPP,
the inflammatory infiltrate involved the interfollicular epidermis, a finding
never present in FFA.
While frontal fibrosing alopecia
appears to be just one of several clinical patterns of hair loss that can be
seen in LPP, lesions of lichen planus are usually not found elsewhere in these
patients.
Dermatoscopic
findings
Trichoscopy
shows perifollicular scales, perifollicular erythema and branching capillaries.
In contrast to classic LPP, where the background may be milky-red, in the early
fibrotic phase of the disease, the background in patients with FFA is always
ivory-white.
Treatment
A variety of treatments are used, including topical and
intralesional corticosteroids, hydroxychloroquine, doxycycline and finasteride,
but there is no convincing evidence that any is effective.
Graham‐Little syndrome
Clinical
features
Most
patients are women between the ages of 30 and 70 years. The essential features
of the syndrome are progressive patchy cicatricial alopecia of the scalp,
non scarring alopecia of axillae, pubic area, and eyebrows as well as grouped
spinous follicular papules resembling lichen spinulosus or keratosis pilaris on
the trunk and extremities.
Treatment
No treatment is universally
effective. A short course of oral prednisolone is used to stabilize rapidly
progressive disease. Ciclosporin was reported as useful in a single case.
Potent topical steroids, hydroxychloroquine and thalidomide have also been
used.
Chronic cutaneous lupus erythematosus
Introduction
Lupus erythematosus is an autoimmune, connective tissue
disease characterized by the presence of circulating non‐organ‐specific
autoantibodies to cell nuclear antigens. Three different forms are described:
systemic lupus erythematosus (SLE), subacute cutaneous lupus erythematosus
(SCLE) and chronic cutaneous lupus erythematosus (CCLE). However, only CCLE
regularly produces cicatricial alopecia. Inflammation of the infundibular
region of the hair follicle that contains the stem cells is thought to be the
basis of the scarring alopecia that occurs in CCLE.
Lesions
of discoid lupus erythematosus (LE) can be the sole manifestation of LE or they
can occur in conjunction with other forms of cutaneous LE (e.g. lupus
panniculitis) and in the setting of systemic LE. Although DLE is seen in
patients with systemic LE, the majority of patients do not have systemic
disease. Discoid LE (DLE) usually occurs in adults with a peak age of onset is around 40 yearsand
is more common in women. Among patients with skin disease only, about 50% will
have scalp lesions, and very few of the patients with DLE confined to the scalp
will ever develop systemic LE.
Clinical
features
The diagnosis of DLE requires
histologic confirmation and cannot be based solely on the clinical appearance
of scalp lesions. They may resemble classic discoid lesions elsewhere. Scarring alopecia occurs in 20% of men and 50% of women
affected with CCLE, and the scalp is the only area affected in a significant
number of patients. DLE usually presents with one or more erythematous,
atrophic, and alopecic patches on the scalp. Telengiectasis and dilated,
plugged follicular ostia and adherent scale are present. Carpet tag sign may be elicited. Central hypopigmentation and
peripheral hyperpigmentation are commonly seen in dark-skinned individuals. Inflammatory activity is most pronounced centrally within
the area of alopecia. Although pruritus or tenderness
is common, the condition may be asymptomatic.
Histopathology
The
histology of CCLE, in common with SLE, shows hyperkeratosis with follicular
plugging, superficial and deep perivascular and periadnexal lymphocytic
infiltrate – which may be sparse, moderate or heavy – and the essential feature
of focal basal layer vacuolar degeneration. This may be associated with colloid
body formation, pigmentary incontinence, papillary dermal oedema, thickening of
the basement‐membrane zone and exocytosis of lymphocytes into the
epidermis and follicular epithelium. The lymphocytic infiltrate is
predominantly found in the upper part of the follicle. Mucin can be seen in the dermis as a faint blue tinge
between widely separated collagen bundles. Scarring occurs only in CCLE and
manifests as homogenized collagen fibres running parallel to the surface with
loss of appendages. Staining for elastin shows that elastic fibres are absent throughout
the reticular dermis.
Hypergranulosis,
saw‐toothed rete ridges, perifollicular fibrosis and clefts are
not seen in lupus, and this helps to distinguish it from lichen planus.
However, it is frequently not possible to separate these two conditions on
routine histological examination and in such cases immunofluorescence may be
decisive. There is linear staining of deposits of complement (C3), IgM and IgG
on the basement membrane in more than 80% of cases of lupus erythematosus, but
not in lichen planus (the lupus band test).
Trichoscopy
Follicular red dots are a
characteristic sign and they correspond histologically to dilated vessels,
extravasated erythrocytes and keratin plugs.
Discoid lupus erythematosus,
Follicular plugging (red arrows)
Discoid lupus erythematosus,
hyper pigmentation around the follicle (yellow arrow)
Discoid lupus erythematosus,
amorphous white and brown areas are seen
Discoid lupus erythematosus, hypo
pigmentation, background erythema with simple red lines and red loops. (Blue
arrows)
Comparative analysis between
different types of alopecia
Treatment
As
CCLE is often made worse by exposure to UV radiation, photo protection with a
hat or a broad‐spectrum sunscreen should be used daily. Discoid
lesions usually respond to oral antimalarial drugs (e.g. hydroxychloroquine)
and corticosteroids (topical, intralesional and oral). If initiated early, a
surprising amount of re-growth can occur. Potent topical corticosteroids, intralesional triamcinolone
and oral prednisolone (1 mg/kg) may halt the progression of active CCLE.
Antimalarials form the mainstay of treatment in chronic cases refractory to
topical steroids. Hydroxychloroquine in a regimen of 200–400 mg/day produces a
remission within 3 months in the majority and the dosage can then be tapered
gradually. Oral retinoids such as acitretin have been found to have similar
efficacy to antimalarial treatment. Dapsone, vitamin E, clofazamine, topical
pimecrolimus or a combination of these medications may be useful in refractory
cases. Drugs like mycophenolate mofetil, azathioprine, low-dose
weekly methotrexate, cyclosporine, and TNF-α inhibitors have also been used in severe, rapidly progressive cases
where all other treatments have failed.
Classic Pseudopelade of Brocq
Introduction
Pseudopelade of Brocq is an idiopathic,
chronic, slowly progressive, patchy lymphocytic primary cicatricial alopecia
that occurs without any evidence of inflammation. It is primarily an atrophic
rather than an inflammatory folliculitis (primary PB). It is the second most common cause of primary
cicatricial alopecia. Women between 30 and 50 years of age are most frequently
affected.
PB can also be
considered as the final atrophic stage of several scarring disorders such as
lichen planus pilaris (LPP) and discoid lupus erythematosus (DLE) (secondary
PB). If a definitive diagnosis of
another form of cicatricial alopecia can be made, the term “Brocq’s alopecia” cannot
be used.
Pathology
Early lesions may have a light lymphocytic
infiltrate around the upper two‐thirds
of the hair follicle (including the hair bulge). This infiltrate invades the
walls of the follicles and sebaceous glands and eventually destroys the entire
pilosebaceous unit.
In later disease stages, hair follicles are
completely replaced by fibrous tracts. Unlike DLE and LPP, interface dermatitis
is usually absent and the elastic fibres are preserved and thickened in PPB.
Clinical Presentation
Pseudopelade
of Brocq (PB) is a permanent progressive scarring alopecia characterized by
numerous alopecic patches that tend to coalesce into larger, irregular patches
with polycyclic borders. The alopecia is asymptomatic
and is often discovered by chance. It always remains confined to the scalp. The
initial patch is often on the vertex but may occur anywhere. On examination,
the affected patches are smooth, soft and slightly depressed and devoid of hair
and hair follicles. At an early stage in
the development of any individual patch there may be some erythema. The patches
tend to be small and round or oval, but irregular shaped bald patches may be
formed by the confluence of many lesions producing finger like projections.
This pattern has been described as “footprints in the snow.” The hair in the
uninvolved scalp is normal, but if the process is active the hairs at the edges
of each patch are very easily extracted. Follicular hyperkeratosis and
perifollicular erythema is mostly absent. The
term pseudopelade implies that the lesions resemble alopecia areata.
Diagnostic
criteria for pseudopelade of Brocq
Clinical
criteria
·
Irregularly defined and confluent patches of
alopecia
·
Moderate atrophy (late stage)
·
Mild perifollicular erythema (early stage)
·
Female : male ratio 3 : 1
·
Long course (more than 2 years)
·
Slow progression with spontaneous termination
possible
Histological
criteria
·
Absence of marked inflammation
·
Absence of widespread scarring (best seen
with elastin stain)
·
Absence of significant follicular plugging
·
Absence, or at least a decrease, of sebaceous
glands
·
Presence of normal epidermis (only occasional
atrophy)
·
Fibrotic streams into the dermis
Direct
immunofluorescence
·
Negative (or only weak IgM on sun‐exposed
skin)
Treatment
The
alopecia is irreversible and does not respond to topical or intralesional
corticosteroids. No treatment is known to arrest progression. If the
disfigurement is considerable and no active inflammatory changes are present, auto
grafting from unaffected to scarred scalp may be considered or surgical
‘expansion’ techniques in severe cases.
Folliculitis decalvans
Introduction
Approximately, 11% of
all primary cicatricial alopecia cases are diagnosed with folliculitis
decalvans (FD). FD predominantly occurs in young and middle-aged adults (average 30 years) with a slight preference of the male
gender. Folliculitis decalvans is an
uncommon, progressive purulent folliculitis that may involve any hair‐bearing
site, although it is most common on the vertex of the scalp.
“Usually, it is
applied to highly inflammatory forms of cicatricial alopecia, where
inflammatory, follicular papules and pustules dominate the clinical picture. A
bacterial infection involving S. aureus, in combination with hypersensitivity
reaction to “superantigens” and defect in host cell-mediated immunity have all
been suspected as possible pathogenetic factors causing follicular destruction.
Pathology
Histologically,
folliculitis decalvans presents as dense, perifollicular inflammation of the
upper portion of follicles, with partial or complete epithelial destruction.
Usually, both acute and chronic inflammation is present. In acute stage, histology reveals follicular abscesses, with a dense
perifollicular polymorphonuclear infiltrate, and scattered eosinophils and
plasma cells. In later stage, foreign‐body granulomas occur in response to follicular disruption,
which is succeeded by scarring. Eventually all that remains of the follicle is
extensive fibrosis.
Clinical Presentation
It
is characterized initially by crops of painful follicular pustules that
become crusted. A patch of alopecia then develops from an expanding zone of
folliculitis, eventually resulting in a central area of scarring. Unlike CCLE
and LPP the scar is indurated and boggy rather than atrophic, at least in the
early stages. Multiple tufts of up to 15 hairs found emerging from a common
dilated follicular opening, giving the appearance of doll's hair. Tufting occurs when the infundibular epithelia of damaged
follicles heal with the formation of a large, common infundibulum. A zone of
fibrosis separates individual clusters of damaged follicles.
In
advanced cases there is usually one, but occasionally more, rounded patches of
alopecia over the vertex of the scalp surrounded by honey-coloured crusting and a few follicular pustules. Successive crops of
pustules appear and are followed by progressive destruction of the affected
follicles and lateral expansion of the alopecia patches.
Patients frequently
complain about pain, itching and/or burning sensations.
Trichoscopic features
·
The characteristic trichoscopic finding is tufting
of hairs that include 6 or more hairs emerging together from single ostia.
·
Perifollicular pustules are seen in active FD.
·
Thick white scales are present both in inter- and
perifollicular area.
·
Coiled and dilated capillary loops are suggestive of
diagnosis of FD.
·
At the base of the hair shafts, a starburst pattern
is formed which is known as starburst sign. This is formed by a band of
yellowish scales and perifollicular epidermal hyperplasia.
Treatment
Treatment
is mainly aimed at eradicating S. aureus from the scalp. Antiseptic
shampoos and topical clindamycin are sufficient for mild cases. The only
treatment shown to induce prolonged remission is rifampicin in a dosage of 300
mg twice daily. This should be given in combination with other antibiotics to
prevent the emergence of resistant organisms. Drugs commonly used in
combination include clindamycin 300 mg twice daily, ciprofloxacin, doxycycline
or clarithromycin. Oral therapy should be combined with
topical antibiotics such as mupirocin
or fusidic acid.
Intranasal eradication of S. aureus with topical antibacterial agents has been
described to be useful. Other
measures tried include oral dapsone, oral zinc, laser depilation and surgical
excision.
Summary of characteristics of lesions
Lesions
in chronic cutaneous lupus erythematosus show maximal activity in the centre,
with perifollicular inflammation, follicular plugging, atrophy and
dyspigmentation, whereas in lichen planopilaris and folliculitis decalvans,
disease activity is most pronounced at the hair-bearing periphery.
Perifollicular
erythematous and violaceous papules, spinous follicular hyperkeratosis and
multifocal disease support the diagnosis of lichen planopilaris. The pattern
described as “footprints in the snow” with lack of inflammation is suggestive
of Brocq pseudopelade
In late-stage
disease, an important distinguishing feature is that the scar of folliculitis
decalvans is thickened, whereas that of lichen planopilaris, chronic cutaneous
lupus erythematosus and Brocq pseudopelade is atrophic.
