Cicatricial (Scarring) Alopecias

Cicatricial (Scarring) AlopeciasAn Overview of Pathogenesis, Classification, Diagnosis, and Treatment

Franco Rongioletti and Konstantina Christana

Section of Dermatology, Dissal, University of Genoa, Genoa, Italy

Contents

Abstract. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 247

1. Prevalence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 248

2. Primary Cicatricial Alopecias . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 248

2.1 Diagnosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 248

2.2 Hypotheses on the Pathogenesis of Cicatricial Alopecia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 249

2.2.1 Autoimmune-Mediated Hypothesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 249

2.2.2 Immune Privilege Breakdown and Langerhans Cell Distribution Hypothesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 249

2.2.3 Bulge Stem Cell Destruction Hypothesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 249

2.2.4 Hair Follicle Epithelial-Mesenchymal Communication Inhibition Hypothesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 250

2.2.5 Peroxisome Proliferator-Activated Receptor-g Deletion Hypothesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 250

2.2.6 Sebaceous Gland Dysfunction Hypothesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 250

2.2.7 ‘No Danger’ Signal CD200 Deletion Hypothesis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 250

2.2.8 Genetic Mutation of Keratin Hypothesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 250

2.3 Classification of Primary Cicatricial Alopecias. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 250

2.4 Inflammatory Primary Cicatricial Alopecias. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 251

2.4.1 Lymphocyte-Predominant Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 251

2.4.2 Neutrophil-Predominant Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 253

3. Secondary Cicatricial Alopecias . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 254

3.1 Genodermatoses and Other Congenital Defects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 254

3.2 Inflammatory Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 255

3.3 Physical and Chemical Injuries . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 255

3.4 Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 255

3.5 Neoplasms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 255

3.6 Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 255

4. Biphasic Alopecias . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 255

5. Management of Cicatricial Alopecias . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 255

6. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 259

Abstract Cicatricial (scarring) alopecia forms a group of disorders in which the common final pathway is the

destruction of the hair follicle unit that is replaced by fibrous tissue. Hair loss may occur as a primary event

when the follicle is the main target of the disease process (primary cicatricial alopecias) or as a secondary

event when the follicle act as an ‘innocent bystander’ in the course of a disease occurring outside of the

follicular unit (secondary cicatricial alopecias). Permanent hair lossmay also occur in the late phases of some

nonscarring alopecias that are called ‘biphasic alopecias.’ Primary cicatricial alopecia accounts for 5% of all

trichologic consultations at the Section of Dermatology, University of Genoa, Genoa, Italy. Considering

that hair loss has a strong impact on patients’ psychology and quality of life, and that cicatricial alopecias

REVIEWARTICLEAm J Clin Dermatol 2012; 13 (4): 247-260

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can be associated with underlying systemic implications, it is extremely important that every clinician is

familiar with the diagnosis and treatment of the different types of cicatricial alopecia.

An accurate clinical assessment integrated with (video) dermatoscopy and histopathologic studies per-

mits a high standard performance of correct diagnoses. A brief review of our current knowledge of disease

pathogenesis and the hypothetical disease mechanisms is presented. Some practical considerations for

improving the 2001 North American Hair Research Society working classification of the primary cicatricial

alopecias are suggested. The aim of treatment is to slow or stop the progression of the inflammatory waves

and the scarring process at the earliest phase of involvement. Recommendations for therapy are based upon

a literature review, personal experience, expected adverse effects, and some pragmatic considerations such as

the cost and patient compliance.

Cicatricial (scarring) alopecias form a group of disorders in

which the common final pathway is the destruction of the hair

follicle unit that is replaced by fibrous tissue. They are one of

the most difficult challenges for dermatologists.[1] Because the

condition is uncommon, we know little about etiopathogenesis

and the best therapy approaches. In fact, there are no ran-

domized controlled trials in evidence-based medicine about the

treatment of scarring alopecias. Scarring alopecia may be di-

vided into a ‘primary’ condition when the follicle is the main

target of the disease process or a ‘secondary’ event when the

follicle act as an ‘innocent bystander’ in the course of a disease

occurring outside of the follicular unit.[1,2] Permanent hair loss

may also occur in the late phases of some nonscarring alopecias

that are called ‘biphasic alopecias.’[3]

We review the classification, etiopathogenesis, diagnostic

features, and treatment options based upon our personal ex-

perience and a literature search using the PubMed database and

the keywords ‘cicatricial alopecia,’ ‘scarring alopecia,’ ‘preva-

lence,’ ‘etiology,’ ‘pathogenesis,’ ‘classification,’ ‘pathology,’

and ‘treatment.’

1. Prevalence

Cicatricial forms of alopecia account for 3.2% of all tricho-

logic consultations in Vancouver, BC, Canada.[1] In a tricho-

logic outpatient consultation center in Dallas, TX, USA,

cicatricial alopecias accounted for 7.3% of all the cases over a

10-year period.[2] In our trichologic consultation room at the

University of Genoa, Genoa, Italy, cicatricial alopecia has been

diagnosed in 5% out of 475 patients with hair loss (329 females

and 146 males) seen from January 2007 to March 2009.

2. Primary Cicatricial Alopecias

In primary cicatricial alopecia, the inflammatory infiltrate

involves the permanent region of the follicle, i.e. the in-

fundibulum and the isthmus that incorporates the so-called

‘bulge region’ (at its lower end). The ‘bulge region’ is thought to

contain the follicular stem cell reservoir and its destruction

might permanently destroy the hair follicle.

2.1 Diagnosis

It is extremely important that every clinician is familiar with

this diagnosis, considering the strong impact of this condition

on patients’ quality of life. Sometimes, only an appropriate

clinical assessment permits one to reach the right diagnosis, but

more often a clinico-pathologic correlation is mandatory.[4]

First of all, an adequate clinical approach consists of taking a

careful history about the presence of other disorders, especially

those of autoimmune pathogenesis, and about hair-care prac-

tices. This is followed by a careful examination of the scalp and

the rest of the body, enquiry as to scalp symptoms such as

itching or trichodynia, and the performance of a hair pull test.

The extraction of anagen hairs with thickened root sheaths

could be suspicious for scarring alopecia.[4]

(Video) dermatoscopy can further improve not only our

diagnostic skills by observing a loss of visible follicular ostia

(figure 1), but also allow us to have an objective assessment of

the progression or the improvement of the disease.

Histopathology is often very helpful, and sometimes man-

datory formaking a correct diagnosis because it permits evalua-

tion of the type of the inflammatory infiltrate and performance

of special stains (elastic tissue, Gram, periodic acid-Schiff

colloidal iron for mucin), cultures, or immunofluorescence stud-

ies.[3,4] Sometimes, multiple biopsies are necessary to achieve

a definitive diagnosis for the highly variable clinical course.

Two 4–6mm punch biopsies should be taken from the edge of

an active lesion where there are still a reasonable number of

follicles. The punch should be oriented parallel to the direc-

tion of hair growth. One biopsy should be processed for hori-

zontal sectioning while the other one is processed for vertical

248 Rongioletti & Christana

Adis ª 2012 Springer International Publishing AG. All rights reserved. Am J Clin Dermatol 2012; 13 (4)

sectioning.[5] Vertical sections allow us to examine the overall

reaction pattern and the dermoepidermal junction but the

chance of finding a lot of follicles is small. Horizontal sections

permit examination of most of the follicular units contained in

the sample of tissue at multiple levels,[6] but is more time con-

suming and requires a dermatopathologist with expertise in

trichology.

2.2 Hypotheses on the Pathogenesis of Cicatricial Alopecia

The pathogeneses of scarring alopecias remain an un-

resolved conundrum; however, if we want to improve our di-

agnostic and therapeutic tools for these very difficult disorders,

we will need greater insight into their etiopathogenesis.[7] At

present, various nonmutually exclusive hypotheses have been

taken into consideration (see sections 3.1–3.8).

2.2.1 Autoimmune-Mediated Hypothesis

An autoimmune mechanism in which particular self-reactive

lymphocytes are activated towards hair follicle antigens[7]

has been suggested for lymphocyte-mediated cicatricial alope-

cias. Itmakes sense that target autoantigens/epitopes that couldelicit this immune response are located in the permanent region

of the follicle including the stem cells in the bulge area, differ-

ently from alopecia areata where the autoreactive T lympho-

cytes are predominantly present in the peribulbar, transient area

of the follicle.[8,9] However, neither autoantibodies to follicular

components in the blood of patients with autoimmune scarring

alopecia such as lichen planopilaris (LPP) and discoid lupus

erythematosus (DLE) have been identified nor have studies

about oligoclonal and autoreactive lymphocytes directed to

specific follicular epitopes been published. Accepting an auto-

immune disease mechanism as the main hypothesis implies that

the immune system is predisposed towards developing scarring

alopecia or that some endogenous or exogenous factors such as

traumatic events or inflammatory diseases of the scalp can

produce an exposure of masked antigens.

2.2.2 Immune Privilege Breakdown and Langerhans

Cell Distribution Hypothesis

The lower transient portion of anagen hair follicle and more

recently the permanent region with the hair-follicle bulge have

been identified as areas of relative immune privilege in which a

combination of immunosuppressive mechanisms are present

to protect these structures from immune-mediated injury.[10]

A collapse of the bulge immune privilege could expose the stem

cells to immune autoaggressive responses. In fact, MHC class I,

b2-microglobulin, and MHC class II immune reactivity is sig-

nificantly up-regulated in the bulge region of skin affected by

scarring alopecia, compared with un-involved skin.[11] It is un-

clear whether bulge immune privilege collapse occurs early in

the disease process of cicatricial alopecia or develops only later

as a secondary phenomenon.[7] A high concentration of Lan-

gerhans cells in the permanent region of the hair follicle, includ-

ing the bulge, has been described and this resident population of

Langerhans cells may be inappropriately activated by unknown

stimuli leading to a loss of any immune privilege.[12,13] This

distribution of Langerhans cells correspondswith the pattern of

follicular inflammation in scarring alopecias of lupus erythe-

matosus and LPP and suggests a role for CD1a+ Langerhans

cells as a trigger for immune attack.

2.2.3 Bulge Stem Cell Destruction Hypothesis

In inflammatory scarring alopecias, the inflammatory in-

filtrate is predominantly focused on the permanent non-cycling

region of the pilosebaceous unit close to the bulge stem cells.

Potentially, destruction of this bulge stem cell region might per-

manently destroy the hair follicle.[14] Once this area is damaged

or destroyed, the hair loses its potential for regrowth, with re-

sultant scarring alopecia. This is in contrast with inflammatory

non-scarring alopecias such as alopecia areata, where the lower

cycling region of the hair follicle is targeted by a peribulbar

infiltrate, sparing the stem cells. One of the most useful dis-

tinctive markers of the stem cells is cytokeratin 15 and this has

been used in some studies to demonstrate the disappearance of

the bulge region in primary cicatricial alopecia.[14] Moreover,

evidence of hair follicle destruction using a keratin 15 targeted

suicide gene has been demonstrated in a mouse model.[15]

Fig. 1. Dermatoscopy of cicatricial alopecia showing a loss of visible fol-

licular ostia in lichen planopilaris.

Cicatricial (Scarring) Alopecias 249


2.2.4 Hair Follicle Epithelial-Mesenchymal Communication

Inhibition Hypothesis

The lower follicle recreates itself after each cycle and the

regeneration is regulated by intimate interactions between the

follicular papilla and the very special regenerative epithelium of

the lower resting follicle. Thus, epithelial-mesenchymal inter-

actions play a crucial role in the induction of life-long cyclic

transformations of hair follicles. Interference in communica-

tion between the epithelial stem cells and the hair follicle mes-

enchyme may lead to damage of the hair follicle.[7] This

hypothesis is not in total disagreement with the bulge destruc-

tion theory, as differential follicular localization of stem cells

with follicular progenitor cell heterogeneity has been suggested.

Thus, the inflammatory infiltrate does not necessarily target the

bulge stem cells, but could also target any other component of

the hair.[16]

2.2.5 Peroxisome Proliferator-Activated Receptor-c

Deletion Hypothesis

Peroxisome proliferator-activated receptor (PPAR)-g is

a transcription factor that is essential for healthy pilosebaceous

units, as it plays an important role in regulating both inflamma-

tory and lipid metabolism. In particular, a loss of PPAR-gfunction leads to decreased peroxisome biogenesis and lipid

homeostasis. This causes damage to the pilosebaceous unit by

creating a lipotoxic effect due to an abnormal build-up of lipids

within the follicle and abnormal sebum production with sub-

sequent inflammatory response. Some data supporting this

concept are a down-regulation of PPAR-g in LPP, the devel-

opment of a form of cicatricial alopecia in mice after targeted

deletion of PPAR-g in their follicular stem cells, and the efficacy

of pioglitazone, an antidiabetic drug agonist of PPAR-g in a

patient with LPP.[17-20]

2.2.6 Sebaceous Gland Dysfunction Hypothesis

Recent work with the mouse mutant, Asebia, seems to

provide a model for scarring alopecia.[20] In this model the

perifollicular inflammation, sebaceous gland ‘destruction,’ hair

shaft granuloma, and cicatricial follicle drop-out result from

the mutation of one very important sebaceous gland gene. In

the absence of this gene, the sebaceous gland is hypoplastic and

normal sebum production is minimal to absent. However, a

normal amount of sebum is a prerequisite for normal desqua-

mation of the inner root sheath and unhindered hair shaft

progression. In the absence of properly constituted sebum, the

follicle shaft experiences a mechanical resistance in its outward

course so that instead of moving distally it moves proximally.

Evidence for this reversed movement is the shaft perforation of

the inferior, bulb portion with resultant granulomatous foreign

body reaction leading to scarring alopecia. These findings sug-

gest that a sebaceous gland dysfunction could be relevant to one

or more of the human primary scarring alopecias. This is fur-

ther supported by the observation that sebaceous glands are

characteristically ablated in the early stages of the primary

cicatricial alopecias.[21]

2.2.7 ‘No Danger’ Signal CD200 Deletion Hypothesis

The ‘danger signal’ mechanism proposes that the immune

system does not distinguish between self- and non-self-antigens

when it mounts a response, but instead discerns betweenwhat is

dangerous or not to the host. Danger signals stimulate an in-

flammatory response, which can lead to the induction of tissue-

specific autoimmunity. Immunosuppressive molecules expressed

on selected cells have the potential to regulate tissue-specific

inflammation, and consequently, autoimmunity. Recent stud-

ies have revealed that CD200, a potent immunoregulatory

protein, is expressed on keratinocytes of the outer root sheath

of murine hair follicles. The deletion of CD200 makes the fol-

licle more susceptible to an inflammatory response in the set-

ting of immune-mediated alopecia. In fact, recent studies on

CD200 and its inhibitory receptor (CD200R) have provided

evidence that CD200-CD200R interaction attenuates peri-

follicular inflammation, prevents specific autoimmunity against

the hair follicle, and may protect epidermal stem cells from

autoimmune destruction.[22]

2.2.8 Genetic Mutation of Keratin Hypothesis

Mutant K6 gene transgenic mice develop a progressive scar-

ring alopecia due to the destruction of the outer root sheath,[23]

and many other rodent models exhibit scarring alopecia in-

dependent of sebaceous gland defects.[24] It could be interesting

to study these models and compare themwith humanmodels in

which genetically determined disorders of keratin may induce

inflammatory scarring alopecias secondary to the primary keratin

defect, such as keratosis follicularis spinulosa decalvans.[25]

2.3 Classification of Primary Cicatricial Alopecias

In 2001, theNorthAmericanHairResearch Society (NAHRS)

put forward a ‘‘proposed working classification of the primary

cicatricial alopecias’’ based on the predominant type of in-

flammatory cell component.[26]

Four groups have been considered as follows: lymphocytic,

neutrophilic, mixed, and non-specific (table I). This classifica-

tion is not devoid of criticisms and deserves some comments.

First of all, classic pseudopelade of Brocq should not be included



in the group of inflammatory lymphocytic scarring alopecias

strictu sensu but rather should be considered as a non-

inflammatory cicatricial form because histopathology is charac-

terized by fibrotic changes with absent or minimal infiltrate.[4]

Moreover, the microscopic observation that in pseudopelade of

Brocq the elastic fibers are retained and are markedly thickened

seems to support the concept that this entity may represent an

atrophic process rather than a true scarring condition since elastic

fibers should be lost and totally destroyed in the latter.[3]

Secondly, primary follicular mucinosis (alopecia mucinosa)

is a self-healing disease, as most lesions spontaneously resolve

between 2 months and 2 years with normal hair re-growth and

cannot be considered a form of cicatricial alopecia.[27] It is

difficult to consider keratosis follicularis spinulosa decalvans

a lymphocytic cicatricial alopecia. In fact, it is an X-linked dis-

order of cornification in which the main alteration is an ab-

normal hyperkeratosis involving the infundibulum and isthmus

followed by a reactive inflammatory infiltrate with neutrophils

replaced only later by a lymphocytic/mixed infiltrate.[3] It is

characterized by acuminate keratotic follicular papules and

pustules on the scalp with loss of eyebrows and eyelashes. It is

associated with palmoplantar keratoderma, atopy, photo-

phobia, and corneal dystrophy. Alopecia starts in childhood.[25]

Folliculitis (acne) necrotica is a controversial, idiopathic

entity characterized by a necrotizing folliculitis, which is itching

and painful, involving mainly the face, neck, and chest and

healing with varioliform scars.[28] The scalp is not a classic site

of involvement. Histology shows an early follicular dilatation,

lymphocyte exocytosis, follicular spongiosis, and perifollicular

edema. Characteristic is the single cell necrosis progressing to

confluent cell necrosis throughout the follicle.[5] Thus, its in-

clusion in the cicatricial alopecia with mixed infiltrate category

does not seem to be appropriate, either. Furthermore, erosive

pustular dermatosis is another condition that is difficult to

classify into the group of cicatricial alopecias. In fact, it affects

elderly patients, especially men with bald scalps and actinic

damage reporting a history of scalp trauma.[29] It manifests

with a thick crust overlying erosions and pustules on the vertex.

Histopathology is not specific, showing epidermal atrophy with

erosion and a mixed infiltrate of lymphocytes, neutrophils, his-

tiocytes, and plasma cells throughout the dermis.[5] Perifolliculitis

or folliculitis is not a feature, especially because patients are

often bald.

Finally, the fourth group includes non-specific cicatricial

alopecia whose significance is far from clear. It is likely that this

section represents a waste basket where all the cases with in-

conclusive clinical and histopathologic findings are stored wait-

ing for a better diagnosis.[4] In fact, we have all seen patients

with cicatricial alopecia that cannot be confidently assigned to

one specific group and ‘cicatricial alopecia, unclassified’ would

be a more appropriate label than non-specific for such cases.

Although the NAHRS classification has some shortcomings, it

remains a consensus classification that attempts to cover all

conditions that result in primary follicular destruction with

scarring. It is likely that significant advances in our under-

standing of the pathogenesis of scarring alopecias and the dis-

covery of underlying disease mechanisms/metabolic markers

could lead to improvement and updating of this classification.

2.4 Inflammatory Primary Cicatricial Alopecias

2.4.1 Lymphocyte-Predominant Disorders

Discoid (Chronic Cutaneous) Lupus Erythematosus

DLE is responsible for 32% of all cases of cicatricial alopecia

seen at the Section of Dermatology, University of Genoa. It has

a predilection for young women. Clinical features include alo-

pecia characterized by erythematous and scaling plaques pro-

gressing to atrophy, telangiectasia, and dyspigmentation with

central hypopigmentation and peripheral hyperpigmentation

(figure 2). Patients may complain of scalp tenderness and

pruritus. Positive antinuclear antibodies (ANAs) are seen in

20% of individuals although Fabbri et al.[30] found a positivity

of ANAs in 43% of patients with scalp DLE. However, full

Table I. Primary cicatricial alopecia according to North American Hair

Research Society classification (reproduced from Olsen et al.,[26] with

permission)

Group 1: Lymphocytic

Chronic cutaneous lupus erythematosus

Lichen planopilaris

Classic lichen planopilaris

Frontal fibrosing alopecia

Graham-Little syndrome

Classic pseudopelade (Brocq)

Central centrifugal alopecia

Alopecia mucinosa

Keratosis follicularis spinulosa decalvans

Group 2: Neutrophilic

Folliculitis decalvans

Dissecting cellulitis

Group 3: Mixed

Folliculitis (acne) keloidalis

Folliculitis (acne) necrotica

Erosive pustular dermatosis

Group 4: Non-specific



blood count, urinalysis, ANAs, and extractable nuclear anti-

gens should be performed in all affected individuals.

Dermatoscopy of the active lesions shows absent follicular

openings, follicular keratin plugs, erythema around follicles,

arborizing red lines, and pigmentary changes.[31] Histologically,

both the follicle and the epidermis show basilar vacuolar de-

generation with scattered necrotic keratinocytes, thickening of

the basement membrane, and a lymphocytic infiltrate at the

dermal-epidermal interface and arranged in a perivascular and

periadnexal pattern.[32] Mucin deposition in the reticular der-

mis is an additional clue to the diagnosis. In the late stages there

is a reduction in follicular units and perifollicular and inter-

stitial fibrosis. Elastic tissue stain shows a broad dermal loss of

elastic fibers including the elastic follicular sheath. Direct

immunofluorescence (DIF) shows a granular or linear pattern

of IgG, IgM, and C3 along the dermal-epidermal junction.

Lichen Planopilaris

LPP is themost frequent cicatricial alopecia diagnosed at the

Section ofDermatology at theUniversity ofGenoa, accounting

for 52% of all cases. It is a follicular disease without any age

predilection, characterized by perifollicular erythematous papules

that progress to scarring alopecia. The disease is more active

peripherally. The scalp lesionsmay be single ormultiple, patchy

or extensive and involvemostly the vertex and parietal areas.[33]

Acuminate keratotic plugs at the margins of the expanding

area of alopecia are a good diagnostic clue (figure 3). Up to 50%of patients may develop lesions of the glabrous skin and mu-

cous membranes or nail changes. Liver function tests and

hepatitis B virus or hepatitis C virus markers should be per-

formed to rule out an associated chronic hepatopathy, a rela-

tively infrequent association. Dermatoscopic features of LPP

include follicular plugging, hair casts, peripilar white dots, in-

terfollicular simple red loops, and arborizing red lines. Fol-

licular openings are absent while honeycomb and patchy deep

pigmentation is present.[5] Histopathology exhibits a predomi-

nantly perifollicular lymphocytic infiltrate with an interface

lichenoid pattern and minimal perivascular involvement.[2,3]

Root sheaths of the hair follicles are destroyed and the follicular

structure is progressively replaced by extensive perifollicular

lamellar fibrosis. DIF shows the presence of colloid bodies

demonstrating IgM, C3, and IgG along the upper hair follicle

with a band of fibrinogen at the basal membrane zone.

In addition to the classic type of LPP, there are two variants:

frontal fibrosing alopecia (FFA) and Lassueur-Graham-Little-

Piccardi syndrome. FFA[34] involves predominantly postmen-

opausal women. Clinically, it is characterized by a progressive

recession of the frontal and temporal hair lines with follicular

hyperkeratosis, perifollicular erythema, and loss of follicular

ostia (figure 4). Fifty-two percent of FFA patients also have

eyebrow hair loss.[35] Histopathology shows a lichenoid reaction

against miniaturized hair follicles. Dermatoscopic examination

shows features similar to LPP, i.e. a decrease of follicular ostia

with follicular hyperkeratosis and perifollicular erythema in the

absence of miniaturization and yellow dots.[36] Histopathology

shows a lymphocytic infiltrate in a lichenoid pattern around the

infundibular isthmus and bulge portions of the terminal fol-

licles,[37] also involving the intermediate and miniaturized hair

follicles with a prominent perifollicular fibrosis.[38] The diag-

nosis of Lassueur-Graham-Little-Piccardi syndrome is based

on the clinical triad of patchy, progressive scarring alopecia of

Fig. 2. Cicatricial alopecia with erythema and scaling due to discoid lupus

erythematosus.

Fig. 3. Cicatricial alopecia due to lichen planopilaris. Note the follicular

hyperkeratosis.



the scalp, nonscarring alopecia of axillary and pubic hair, and

the presence of widespread horny follicular papules on the

trunk and limbs.[39]

Central Centrifugal Cicatricial Alopecia

Central centrifugal cicatricial alopecia (CCCA) is commonly

seen in young to middle-aged women of African-American

descent. It usually starts at the vertex or mid-top of the scalp

and gradually spreads centrifugally. It is often associated with a

history of traumatic hairstyling involving heat, traction, and

chemicals. The active phase can last for years although it seems

to be self-limiting. It can give mild pruritus, pain, or tender-

ness.[2,40] Histologically, there is a perifollicular lymphocytic

infiltrate and fibroplasia. Eccentric atrophy of the outer root

sheath epithelium, concentric lamellar fibroplasias, and hair fiber

granulomas within fibrous tract remnants are also features.[1]

Pseudopelade of Brocq

Classic pseudopelade of Brocq (PPB) is a rare, slowly pro-

gressive hair disorder of adult Caucasians, mostly women,

characterized by small, smooth, and slightly depressed alopecic,

atrophic patches resembling ‘‘footprints in the snow’’[41] with

irregular outlines over the vertex (figure 5). It has been diag-

nosed in 10% of all the cases of cicatricial alopecia seen at the

Section of Dermatology, University of Genoa. There are con-

troversial opinions whether PPB is a single entity or the end

stage of several cicatricial alopecic disorders such as DLE or

LPP.[1,41] Recently, the degree of similarity between LPP and

PPB gene expression associated with cicatricial alopecia de-

velopment, such as the genes that influence cellular adhesion,

apoptosis, proliferation, development, and transcriptional reg-

ulation patterns, and the potential for common and unique

gene pathways and gene activity in LPP and PPB using mi-

croarrays has been explored. The gene expression data from

LPP and PPB exhibit relatively little similarity and consid-

erably more differences both at the individual gene level and

when genes were categorized by function. These data suggest

that LPP and PPB are distinct biologic entities and that PPB is

unlikely to be part of the LPP disease spectrum.[42]

Histologically, there is no inflammatory infiltrate at the

dermo-epidermal junction or follicular plugging, while wide

fibrous hyalinized tracts, as well as thickened elastic fibers in

hyalinized dermis stained by elastic tissue stains are present.[3]

DIF is negative. It is debatable whether PPB is a non-inflam-

matory disease as suggested by some authors or an atrophic

form of alopecia[3] or a lymphocytic-related alopecia. In the

histopathologic study by Mirmirani et al.,[43] blinded derma-

topathologists were unable to distinguish between PPB and

other lymphocytic cicatricial alopecias (excluding DLE).

2.4.2 Neutrophil-Predominant Disorders

Folliculitis Decalvans

Folliculitis decalvas is more frequent in men and starts on

the vertex with a single focus of alopecic patch characterized by

an advancing border studded with pustules and perifollicular

papules (figure 6) resulting in central scarring.[44] Additional

foci occur over the years. In the evolving disease, multiple hairs

emerge from a single follicular orifice in a pattern known as

‘‘tufted hair folliculitis’’ (figure 7). The etiology is unknown

although Staphylococcus aureus is commonly isolated from

primary lesions and is thought to be implicated in disease patho-

genesis. Histologically, in the early phase, the inflammatory

Fig. 4. Frontal fibrosing alopecia.

Fig. 5. Pseudopelade of Brocq with small, smooth, and slightly depressed

alopecic atrophic patches on the vertex.



infiltrate is composed of neutrophils, replaced later by lym-

phocytes and plasma cells. There is a perifollicular and intra-

follicular inflammation with abscess formation in the absence

of sinus tract formation. Gram-positive bacteriamay be stained

in the infundibulum. Dermal fibrosis and follicular remnants

are seen in the late stage.[45] Dermoscopic findings include low

hair density and loss of follicular ostia, with thinned shafts of

the remaining hairs.[44] The main differential diagnosis is with

inflammatory tinea capitis (kerion). Histopathology and fungal

cultures are crucial for correct diagnosis and therapy.[44,45]

DissectingCellulitis or Perifolliculitis Capitis Abscedens et Suffodiens

This disease is not infrequent in young African American

men aged between 20 and 40 years but can occasionally affect

other races such as Caucasians and women, too.[46] The disease

presents with painful, fluctuant nodules, abscesses, and inter-

connecting sinus tracts that begin on the occiput or vertex

and may involve the entire scalp (figure 8). Acne conglobata, hi-

dradenitis suppurativa, and arthritis are associated.[47] Histologi-

cally, there is an early perifollicular and interfollicular neutrophilic

infiltrate becoming mixed later. Neutrophilic accumulation

around a squamous epithelium (sinus tract) and granulomatous

reaction due to follicular rupture with fibrosis are seen.[3]

All the main clinical, dermoscopic, and histologic features of

primary cicatricial alopecias are summarized in table II.

3. Secondary Cicatricial Alopecias

In secondary cicatricial alopecias, the follicle is not the main

target of the disease process but only an innocent bystander

in the course of a disease. The causes of secondary scarring

alopecias, including congenital and inflammatory diseases,

chemical and physical, infections, neoplasms, and drugs, are

shown in table III with a list of the main forms. In some cases it

is better to use the term secondary permanent alopecias because

not all conditions cause true fibrosis.[48]

3.1 Genodermatoses and Other Congenital Defects

In early infancy, a congenital area of alopecia of the scalp

may be the clinical presentation of various diseases, with the

two most common being aplasia cutis congenita and sebaceous

nevus. Aplasia cutis congenita is characterized by a focal or

diffuse defect of the skin that in most cases is limited to the

epidermis, dermis, and sometimes the subcutis. Clinically, it

may present at birth as an erosion, ulcer, or area of atrophy

with a smooth or papyraceus appearance. Histopathology

shows epidermal atrophy, thickened sclerotic collagen bundles

with reduction of follicles and loss of elastic fibers. Intrauterine

and perinatal trauma, defective neural tube closure, drugs, and

ischemia have been implicated as etiologic agents.[49]

Organoid nevi, especially of sebaceous type (Jadassohn), are

usually localized on the scalp as a yellowish, waxy, verrucous

plaque, often following the lines of Blaschko and resulting in

permanent alopecia.[50] Surgical excision, preferably before

puberty, is suggested because of the risk of developing benign

and malignant adnexal tumors such as syringocystadenoma

papilliferum, trichoblastoma, and basal cell carcinoma, which,

however, is relatively low.[50]

Fig. 6. Folliculitis decalvans with cicatricial alopecia and pustules.

Fig. 7. Tufted hair folliculitis with groups of follicular shafts emerging from

a single ostium.



Rudimentary meningoencephaloceles may present with a

nodule or a patch of annular alopecia in the midline of the

scalp.[51]

Triangular alopecia is a circumscribed, non-cicatricial con-

genital form of permanent alopecia confined to the fronto-

temporal region of the scalp.[52]

3.2 Inflammatory Disorders

Rarely, psoriasis can cause scarring alopecia.[53] Chronic

inflammation and hyperkeratosis can be more severe in HIV-

positive patients.[54]

Linear morphea affecting the frontoparietal scalp and/or theparamedian forehead can cause cicatricial alopecia (scle-

roderma en coupe de sabre).

Cicatricial pemphigoid is a subepidermal blistering disease

that involves both the mucous membranes and the skin. In the

Brunsting-Perry variant, only the skin is affected. When it in-

volves the scalp, tense or flaccid bullae, erosions, atrophy, and

scarring produce cicatricial alopecia.[55]

Sarcoidosis may affect the scalp resulting in scarring alope-

cia, sometimes as the presenting sign of the disease, mostly in

African American women.[56]

3.3 Physical and Chemical Injuries

Mechanical trauma such as prolonged traction due to hair-

styling techniques, scalp injuries, long-lasting pressure, burns,

chemical injuries, radiation therapy with x-rays and ionizing

rays used to treat intracranial or scalp neoplasms, or meso-

therapy used for the treatment of androgenetic alopecia[57] may

be the cause of scarring alopecia.

3.4 Infections

Tinea capitis is a common skin infection that should be con-

sidered in any type of scalp lesion. It requires systemic treatment,

and inappropriate and delayed treatment can result in the devel-

opment of kerion celsi, an inflammatory deep infection due to

zoophilic fungi such as Trichophyton verrucosum and Trichophy-

ton mentagrophytes that can lead to scarring alopecia.

3.5 Neoplasms

Neoplastic cells, bothmalignant andbenign, local occurring and

metastatic, can cause alopecia of the scalp (alopecia neoplastica).

Themost commonneoplasm leading to scalp alopecia ismetastatic

breast carcinoma. Other causes include squamous and basal cell

carcinomas, angiosarcoma, gastric carcinoma, placental site tro-

phoblastic tumor, renal cell carcinoma, and cutaneous T-cell lym-

phoma. Syringoma-like proliferations can underlie alopecia.[58]

3.6 Drugs

Drugs that could irreversibly destroy hair follicles include

cytostatic drugs from polychemotherapy, retinoids, gold, and

busulfan.[48,59,60]

4. Biphasic Alopecias

The term ‘biphasic alopecia’ includes some conditions where

cicatricial alopecia becomes apparent in the late stages of an

otherwise nonscarring form of alopecia.[3] Alopecia areata,

androgenetic alopecia, and traction alopecia may belong to this

setting.[1] Alopecia areata can result in fibrosis in 10% of cases

while in advanced stages of androgenetic alopecia, vellus hairs

also disappear and the alopecia becomes permanent. Perma-

nent traction of hairs caused by traumatic styling, including

chemical and physical straighteners, traction, braiding, hair

extensions, hair gluing, and chemical curls, especially but not

exclusively in African American women, may lead to perma-

nent (end-stage) alopecia.[61]

Secondary follicular mucinosis associated with mycosis

fungoides and psoriasis could also be considered as biphasic

forms of alopecia considering that in late stages hair follicles

can be destroyed permanently.

5. Management of Cicatricial Alopecias

The treatment of cicatricial alopecia is one of the most dif-

ficult tasks in dermatology. The aim is to slow or stop the

Fig. 8. Dissecting cellulitis of the scalp with nodules and sinus tract.



Table

II.Clinical,derm

atoscopic,andhistopathologicfeaturesofthemain

primary

cicatriciala

lopecia

entitie

sandtheirtherapeuticmanagement

Entity

Clinicalfeatures

Derm

atoscopy

Histopathology

Management

Lichenplanopilaris

(LPP)

Single

ormultiple,patchyorextensive

scarringalopecia

onthevertexand

parietala

reaswithperifollicular

erythematouspapulesand

hyperkeratosisatthemarginsofthe

expandingarea.Predominantactivityat

theperiphery

ofalopecicpatches.Lichen

planusmaycoexist.Frontalfibrosing

alopecia

andLassueur-Graham-Little-

Picca

rdisyndromepattern

Follicularplugging,haircasts,

peripilarwhitedots,

interfollicularsim

ple

redloops,

andarborizingredlineswith

absentfollicularopenings

Predominantly

perifollicularlymphocytic

infiltrate

withinterfacelichenoid

pattern

andminim

alp

erivascularinvolvement.

Destroyedrootsheathswithreplacement

ofthefolliclesbyextensiveperifollicular

lamellarfibrosis.DIF:colloid

bodieswith

IgM,C3,andIgG

alongtheupperhair

follicle

withabandoffibrinogenatthe

basalm

embranezone

Firstline:

Topicalcorticosteroids(clobetaso

l,

betamethaso

ne),intralesional

corticosteroids(triamcinoloneacetonide

3–10mg/m

L),topicaltacrolim

us,

antimalarials(hydroxychloroquine

200mgbid)

Secondline:

Prednisone,oralcyclosporine,oral

retinoids,

Thirdline:

Mycophenolate

mofetil,griseofulvin,

tetracyclines

Discoid

(chronic

cutaneous)lupus

erythematosus

(DLE)

Erythematousandscalingplaques

progressingto

atrophy,telangiectasia

withcentralh

ypopigmentation,and

peripheralh

yperpigmentationonthe

vertexofyoungwomen.Predominant

activityin

thecentreofalopecia

patch.

Non-scalplesionsmaycoexistontheface

Absentfollicularopenings,

follicularkeratinplugs,

erythemaaroundfollicles,

arborizingredlines,

and

pigmentary

changes

Superficiala

nddeepperivascularand

periadnexallymphocyticinfiltrate

with

follicularandepiderm

alinterface

changes.Thickenedbasement

membrane.Mucin.Fibrosis.Broad

derm

allossofelasticfibers

includingthe

elasticfollicularsheath.DIF:granularor

linearpattern

ofIgG,IgM,andC3along

thederm

al-epiderm

aljunction

Firstline:


l,

betamethaso

ne),intralesional


3–10mg/m

L),antimalarials

(hydroxychloroquine),sunscreen

Secondline:

Oralp

rednisone,topicaltacrolim

us

Thirdline:

Thalidomide,isotretinoin,dapso

ne,

methotrexate

Pseudopeladeof

Brocq(PPB)

Small,smooth,andslightlydepressed

alopecicatrophicpatchesresembling

‘‘footprints

inthesnow’’withirregular

outlinesoverthevertexofmiddle-aged

Caucasianwomen.Novisible

inflammatio

n

Absentfollicularopenings

Noinflammatory

infiltrate

atthe

derm

o-epiderm

aljunctionorfollicular

plugging.Fibroushyalinizedtracts,

thickenedelasticfibers

inhyalinized

derm

is.DIF:negative

Firstline:


l,

betamethaso

ne),intralesional


3–10mg/ m

L),antimalarials

(hydrox ychloroquine200mgbid)

Secondline:

Prednisone,oralretinoids,topical

tacrolim

us

Centralcentrifugal

cicatricialalopecia

(CCCA)

Progressivealopeciaatthevertexormid-

topofthescalp

inyoungto

middle-aged

womenofAfrican-Americandescentthat

gradually

spreadscentrifu

gally

without

evidentinflammation.Single

orgrouped

hairsmaysurvivewithinzonesofscarring

Notwelldefined

Eccentricatrophyoftheouterrootsheath

epithelium,concentriclamellar

fibroplasias.Hairfibergranulomaswithin

fibroustractremnants.Perifollicular

lymphocyticinfiltrate

Firstline:

Avoid

physicala

ndchemicaltraumas,

topicalcorticosteroids,

topicaltacrolim

us,

intralesionalcorticosteroids,

antibacterials(tetracyclines),oral

corticosteroids

Continuednextpage



progression of the inflammatory waves and the scarring process

at the earliest phase of involvement. Patients should always be

informed that hair re-growth cannot be expected in the scarring

areas and the primary goal of the treatment is just to arrest any

further hair loss. It is important to monitor the disease activity

through frequent clinical evaluation, (video) dermatoscopy,

and photos. Actually, dermatoscopy with hair counting (tri-

choscan) is probably the best method available of assessing

response to treatment.[62] However, no fully satisfactory, evi-

dence-basedmedicine regimen for treating cicatricial alopecia is

available and the recommendations for therapy are still based

upon the literature review, expert opinion, personal experience,

expected adverse effects, and some pragmatic considerations

such as the cost and the patient’s compliance (table II). There-

fore, the treatment of cicatricial alopecias is selected in the

absence of precise information on the expected outcome and

treatment failure is common.

First-line therapies for patients with DLE include potent

topical corticosteroids (or intralesional triamcinolone aceto-

nide) and antimalarials, which are our favorite treatments,

associated with photoprotection. Oral retinoids, topical im-

munomodulators such as tacrolimus, thalidomide, dapsone,

and oral vitamin B may be considered in the case of failure.[63]

As for LPP, first we have to rule out a drug-induced li-

chenoid eruption.[64] Potent topical corticosteroids and topical

tacrolimus are our first-line therapies. Oral corticosteroids (in

the case of rapidly progressive, extensive disease and resistance

to topical corticosteroids), antimalarials, oral cyclosporine,

and oral retinoids may also be taken into consideration. The

same drugs should be used for FFA and Lassueur-Graham-

Little-Piccardi syndrome. Although classic lichen planus may

heal spontaneously over a mean period of 18 months,[64] the

course of LPP is more chronic and unpredictable. There is no

long-term study that provides answers about the duration of

the disease.[65] An effective treatment for alopecia of the eye-

brows has not yet been identified, although intralesional cor-

ticosteroids in a small series of patients with FFA were of

benefit.[66]

PPB is a very difficult challenge and no clear treatment

consensus has been established. The treatment approach is

quite similar to LPP and potent topical and intralesional cor-

ticosteroids and/or antimalarials are considered as the first

line of therapy. Topical tacrolimus, isotretinoin, mycopheno-

late mofetil, and thalidomide can be tried but the results are

variable and sometimes disappointing.[67] Indeed, many au-

thors consider the condition intractable.[1] Spontaneous reso-

lutions may occur in a period ranging from 2 to 18 years.

Minoxidil 5% and finasteride can be evaluated as adjunctiveTable

II.Contd

Entity

Clinicalfeatures

Derm

atoscopy

Histopathology

Management

Folliculitis

decalvans(FD)

Single

focusofalopecicpatch

characterizedbyanadvancing

borderstuddedwithpustulesand

perifollicularpapulesonthevertexof

youngandadultmenresultingin

central

scarring.‘Tuftedhairfolliculitis’in

theevolvingdisease

Lowhairdensityandlossof

follicularostia,withthinned

shaftsoftheremaininghairs

Intheearlyphase

,perifollicularand

intrafollicularneutrophils,replacedby

lymphocytesandplasm

acells.Abscess

intheabsenceofsinustractform

ation.

Gram-positivebacteriain

the

infundibulum.Derm

alfibrosisand

follicularremnants

(late

stage)

Firstline:

Orala

ndtopical

antibacterial–

corticosteroid

Secondline:

Isotretin

oin,zincsulfate,dapsone

Dissecting

cellulitisofthe

scalp

(DCS)

Painful,fluctuantnodules,abscesses,

andinterconnectingsinustracts

that

begin

ontheocciputorvertexin

young

AfricanAmericanmenagedbetween20

and40years.Acn

econglobata

and

hidradenitissuppurativa

Notwelldefined

Earlyperifollicularandinterfollicular

neutrophilicinfiltrate

becomingmixed

later.Follicularocclusion.Neutrophilic

accumulationaroundsquamous

epithelium

(sinustract)and

granulomatousreactiondueto

follicular

rupture

withfibrosis.DIF:negative

Firstline:

Oralisotretinoin–orala

ndtopical

antibacterials,intralesional

corticosteroids

Secondline:

Oralp

rednisone,zincsulfate,dapsone

bid

=twicedaily;DIF

=directim

munofluorescence.



treatments in all cases associated with concomitant andro-

genetic alopecia.

Topical corticosteroids and tetracyclines have been reported

to be helpful in active, progressive cases of CCCA but our

experience with these cases is limited.

Topical and oral antibacterials (based on organism cultures

and antibacterial sensitivity tests) and oral isotretinoin are the

mainstays of therapy for neutrophilic scarring alopecias. If

culture and antibacterial sensitivity tests are not available,

tetracyclines are our preferred choice. Oral rifampicin and oral

clindamycin together for 10 weeks has been suggested as a good

antibacterial regimen for folliculitis decalvans.[68] A short cycle

of oral corticosteroids is used in cases of severe and disabling

clinical inflammation, especially in dissecting cellulitis of the

scalp. Oral zinc and dapsone have also been used with variable

results.

Treatment for secondary cicatricial alopecias depends on the

disease that has caused it and can vary from simple keratolytics

to surgical corrections. The aim is always to limit the extension

of the alopecia and achieve a good result with minimal adverse

effects.

Surgical correction of primary and secondary or permanent

cicatricial alopecia such as hair transplantation, scalp reduc-

tion, tissue expansion, flap surgery, and hair transplantation

after carbon dioxide laser-assisted scar tissue remodeling can be

a successful option.[69,70]

Two categories of cicatricial alopecia have been proposed in

order to decide which corrective therapy is the most suitable

one: ‘unstable’ cicatricial alopecia and ‘stable’ cicatricial alo-

pecia.[71] Unstable alopecia includes those forms that have a

tendency to progress with an intermittent chronic course such

as LPP, DLE, and PPB while stable alopecia refers to fixed

permanent scarring in the setting of trauma, burns, infection,

etc. Before considering any surgical procedure, it is mandatory

to identify the type of alopecia and to evaluate if the alopecia is

still active or is quiescent. Finally, a 2-year disease-free period is

recommended to achieve acceptable results and tominimize the

risk of relapse.[72]

Table III. Main causes of secondary scarring (permanent) alopecias (the

conditions discussed in the text are shown in italics)

1. Infections

Bacterial

Fungal

Viral

2. Inflammatory dermatoses

Papulosquamous

Psoriasis

Pityriasis amiantacea

Bullous disorders

Cicatricial pemphigoid

Epidermolysis bullosa

Granulomatous

Sarcoidosis

Necrobiosis lipoidica

Autoimmune disorders

Graft vs host disease

Morphea (en coup de sabre)

3. Physical and chemical injuries

Ischemia/pressure

Thermal injury

Corrosive injury/toxic injury

Traction alopecia/trichotillomania

Radiation

4. Drugs

Cytostatic drugs, busulfan, retinoids, gold

5. Neoplasms

Benign

Cysts

Syringoma-like proliferations

Malignant

Primary (basal cell carcinoma)

Metastatic (breast carcinoma)

Atypical lymphoproliferative disorders

6. Developmental/hereditary

Fibrodysplasia

Darier disease

Ectodermal dysplasias

Ichthyosis

Porokeratosis

Incontinentia pigmenti

Continued

Table III. Contd

Ichthyosis

Meningoencephalocele

Aplasia cutis congenita

Temporal triangular alopecia

Organoid nevus (sebaceous)

7. Miscellaneous

Lipedematous alopecia



6. Conclusions

Cicatricial alopecias are one of the most difficult challenges

for the dermatologist and the pathologist. The reasons for this

difficulty are varied. First of all, the clinical and pathologic

findings may overlap among the different forms or may change

over time. They may appear quite similar in the advanced fi-

brotic stage, making specific alopecia classification a very hard

task. Second, no clinical or histopathologic feature appears to

be specific or diagnostic for a particular form of primary cica-

tricial alopecia and no conclusive molecular diagnostic marker

is available. Moreover, often biopsies are performed incorrectly;

the cutaneous specimens obtained are too superficial or too

small and are sent to the laboratory with inaccurate clinico-

pathologic correlation. Physicians have to take under consid-

eration that cicatricial alopecia has a negative impact on a

patient’s quality of life and therefore they should follow an

organized diagnostic strategy in order to render a specific diag-

nosis. Finally, because these conditions are uncommon, we know

little about etiopathogenesis and the best therapy approaches,

which are poorly defined and not sufficiently evidence based. It

is crucial that much larger cohort, multicenter, prospective

studies with a double-blinded design and optimally chosen con-

trols, documentation, and classification standards, as well as

quantitative methodology, are performed in order to provide

more stringent treatment recommendations.

Acknowledgments

We thank Prof. Bruce R. Smoller for his advice and suggestions. The

authors declare that they have no conflicts of interest related to the con-

tents of this article.

References1. Ross EK, Tan E, Shapiro J. Update on primary cicatricial alopecias. J Am

Acad Dermatol 2005; 53: 1-37

2. Whiting DA. Cicatricial alopecia: clinico-pathological findings and treatment.

Clin Dermatol 2001; 19: 211-25

3. Somani N, Bergfeld WF. Cicatricial alopecia: classification and histopathol-

ogy. Dermatol Ther 2008; 21: 221-37

4. Sperling LC, Cowper SE. The histopathology of primary cicatricial alopecia.

Semin Cutan Med Surg 2006 Mar; 25: 41-50

5. Harries MJ, Trueb RM, Tosti A, et al. How not to get scar(r)ed: pointers to

the correct diagnosis in patients with suspected primary cicatricial alopecia.

Br J Dermatol 2009 Mar; 160: 482-501

6. Sellheyer K, Bergfeld WF. Histopathologic evaluation of alopecias. Am J

Dermatopathol 2006; 28: 236-59

7. McElwee KJ. Etiology of cicatricial alopecias: a basic science point of view.

Dermatol Ther 2008; 21: 212-20

8. McElwee KJ, Yu M, Park SW, et al. What can we learn from animal models

of alopecia areata? Dermatology 2005; 211: 47-53

9. Tobin DJ. Characterization of hair follicle antigens targeted by the anti-hair

follicle immune response. J Investig Dermatol Symp Proc 2003; 8: 176-81

10. Meyer KC, Klatte JE, Dinh HV, et al. Evidence that the bulge region is a site

of relative immune privilege in human hair follicles. Br J Dermatol 2008;

159: 1077-85

11. Harries MJ,Meyer KC, Chaudhry IH, et al. Does collapse of immune privilege

in the hair-follicle bulge play a role in the pathogenesis of primary cicatricial

alopecia? Clin Exp Dermatol 2010; 35: 637-44

12. Moresi JM, Horn TD. Distribution of Langerhans cells in human hair follicle.

J Cutan Pathol 1997; 24: 636-40

13. HutchensKA, Balfour EM, Smoller BR. Comparison between Langerhans cell

concentration in lichen planopilaris and traction alopecia with possible im-

munologic implications. Am J Dermatopathol 2011; 33: 277-80

14. Pozdnyakova O, Mahalingam M. Involvement of the bulge region in primary

scarring alopecia. J Cutan Pathol 2008; 35: 922-5

15. Ito M, Liu Y, Yang Z, et al. Stem cells in the hair follicle bulge contribute

to wound repair but not to homeostasis of the epidermis. Nat Med 2005;

11: 1351-4

16. Hoang MP, Keady M, Mahalingam M. Stem cell markers (cytokeratin 15,

CD34 and nestin) in primary scarring and nonscarring alopecia. Br J Der-

matol 2009; 160: 609-15

17. Karnik P, Tekeste Z, McCormick TS, et al. Hair follicle stem cell-specific

PPARgamma deletion causes scarring alopecia. J Invest Dermatol 2009; 129:

1243-57

18. Harries MJ, Paus R. Scarring alopecia and the PPAR-gamma connection.

J Invest Dermatol 2009; 129: 1066-70

19. Mirmirani P, Karnik P. Lichen planopilaris treated with a peroxisome pro-

liferator-activated receptor gamma agonist. Arch Dermatol 2009; 145: 1363-6

20. Harries MJ, Paus R. The pathogenesis of primary cicatricial alopecias. Am J

Pathol 2010; 177: 2152-62

21. Sundberg JP, Boggess D, Sundberg BA, et al. Asebia-2J (Scd1) (ab2J): a new

allele and a model for scarring alopecia. Am J Pathol 2000; 156: 2067-75

22. RosenblumMD, Yancey KB, Olasz EB, et al. CD200, a ‘‘no danger’’ signal for

hair follicles. Dermatol Sci 2006; 41: 165-74

23. Sundberg JP, King Jr LE. Mouse models for the study of human hair loss.

Dermatol Clin 1996; 14: 619-32

24. Rothnagel JA, LongleyMA,Holder RA, et al. Genetic disorders of keratin: are

scarring alopecias a sub-set? J Dermatol Sci 1994; 7 Suppl.: S164-9

25. Romine KA, Rothschild JG, Hansen RC. Cicatricial alopecia and keratosis pilaris:

keratosis follicularis spinulosa decalvans. Arch Dermatol 1997; 133: 381, 384

26. Olsen EA, Bergfeld WF, Cotsarelis G, et al. Workshop on cicatricial alopecia:

summary of North American Hair Research Society sponsored workshop on

cicatricial alopecia. J Am Acad Dermatol 2003; 48: 103-10

27. Rongioletti F, De Lucchi S, Meyes D, et al. Follicular mucinosis: a clin-

icopathologic, histochemical, immunohistochemical and molecular study

comparing the primary benign form and the mycosis fungoides associated

follicular mucinosis. J Cutan Pathol 2010; 37: 15-9

28. Kossard S, Collins A, McCrossin I. Necrotizing lymphocytic folliculitis: the early

lesion of acne necrotica (varioliformis). J Am Acad Dermatol 1987; 16: 1007-14

29. Rongioletti F, Delmonte S, Rossi ME, et al. Erosive pustular dermatosis fol-

lowing cryotherapy and topical tretinoin for actinic keratoses. Clin Exp

Dermatol 1999; 24: 499-500

30. Fabbri P, Amato L, Chiarini C, et al. Scarring alopecia in discoid lupus

erythematosus: a clinical, histopathologic and immunopathologic study.

Lupus 2004; 13: 455-62

31. Lopez-Tintos BO, Garcia-Hidalgo L, Orozco-Topete R. Dermoscopy in active

discoid lupus. Arch Dermatol 2009; 145: 358

32. Hordinsky M. Cicatricial alopecia: discoid lupus erythematosus. Dermatol

Ther 2008; 21: 245-8

33. Kang H, Alzolibani AA, Otberg N, et al. Lichen planopilaris. Dermatol Ther

2008; 21: 249-56



34. Tan KT, Messenger AG. Frontal fibrosing alopecia: clinical presentations and

prognosis. Br J Dermatol 2009; 160: 75-9

35. Moreno-Ramırez D, Camacho Martınez F. Frontal fibrosing alopecia: a sur-

vey in 16 patients. J Eur Acad Dermatol Venereol 2005; 19: 700-5

36. Rubegni P, Mandato F, Fimiani M. Frontal fibrosing alopecia: role of der-

moscopy in differential diagnosis. Case Rep Dermatol 2010; 2: 40-5

37. Poblet E, Jimenez F, Pascual A, et al. Frontal fibrosing alopecia versus lichen

planopilaris: a clinicopathological study. Int J Dermatol 2006; 45: 375-80

38. Tosti A, Piraccini BM, Iorizzo M, et al. Frontal fibrosing alopecia in post-

menopausal women. J Am Acad Dermatol 2005; 52: 55-60

39. Viglizzo G, Verrini AM, Rongioletti F. Familial Lassueur-Graham-Little-

Piccardi syndrome. Dermatology 2004; 208: 142-4

40. WhitingDA, Olsen EA. Central centrifugal cicatricial alopecia. Dermatol Ther

2008; 21: 268-78

41. Alzolibani AA, Kang H, Otberg N, et al. Pseudopelade of Brocq. Dermatol

Ther 2008; 21: 257-63

42. YuM, Bell RH,Ross EK, et al. Lichen planopilaris and pseudopelade of Brocq

involve distinct disease associated gene expression patterns by microarray.

J Dermatol Sci 2010; 57: 27-36

43. Mirmirani P, Willey A, Headington JT, et al. Primary cicatricial alopecia:

histopathologic findings do not distinguish clinical variants. J Am Acad

Dermatol 2005; 52: 637-43

44. Otberg N, Kang H, Alzolibani A, et al. Folliculitis decalvans. Dermatol Ther

2008; 21: 238-44

45. Stefanato C. Histopathology of alopecia: a clinicopathological approach to

diagnosis. Histopathology 2010; 54: 24-38

46. Scheinfeld NS. A case of dissecting cellulitis and a review of the literature.

Dermatol Online J 2003; 9 (1): 8

47. Kierland RR. Unusual pyodermas (hidrosadenitis suppurativa, acne con-

globata, dissecting cellulitis of the scalp). Min Med 1951; 34: 319-25

48. Finner AM, Otberg N, Shapiro J. Secondary cicatricial and other permanent

alopecias. Dermatol Ther 2008; 21: 279-94

49. Frieden IJ. Aplasia cutis congenita: a clinical review and proposal for classi-

fication. J Am Acad Dermatol 1986; 14: 646-60

50. Cribier B, Scrivener Y, Grosshans E. Tumors arising in nevus sebaceus: a study

of 596 cases. J Am Acad Dermatol 2000; 42: 263-8

51. Kishimoto H, Kishimoto H, Nagata S, et al. Rudimentary meningocele pre-

senting with an annular alopecia. Eur J Dermatol 2000; 10: 215-6

52. Silva CY, Lenzy YM, Goldberg LJ. Temporal triangular alopecia with

decreased follicular density. J Cutan Pathol 2010; 37: 597-9

53. Wright AL, Messenger AG. Scarring alopecia in psoriasis. Acta Derm Vene-

reol 1990; 70: 156-9

54. Schon MP, Reifenberger J, Gantke B, et al. Progressive cicatricial psoriatic

alopecia in AIDS [in German]. Hautarzt 2000; 51: 935-8

55. Martın JM, Pinazo I, Molina I, et al. Cicatricial pemphigoid of the Brunsting-

Perry type. Int J Dermatol 2009; 48: 293-4

56. Katta R, Nelson B, Chen D, et al. Sarcoidosis of the scalp: a case series and

review of the literature. J Am Acad Dermatol 2000; 42: 690-2

57. Duque-Estrada B, Vincenzi C, Misciali C, et al. Alopecia secondary to meso-

therapy. J Am Acad Dermatol 2009; 61: 707-9

58. Cohen PR. Primary alopecia neoplastica versus secondary alopecia neo-

plastica: a new classification for neoplasm-associated scalp hair loss. J Cutan

Pathol 2009; 36: 917-8

59. Tran D, Sinclair RD, Schwarer AP, et al. Permanent alopecia following che-

motherapy and bone marrow transplantation. Australas J Dermatol 2000;

41: 106-8

60. Tosti A, Piraccini BM, Vincenzi C, et al. Permanent alopecia after busulfan

chemotherapy. Br J Dermatol 2005 May; 152: 1056-8

61. Scott DA. Disorders of the hair and scalp in blacks. Dermatol Clin 1988; 6: 387-95

62. Tosti A, Duque-Estrada B. Treatment strategies for alopecia. Expert Opin

Pharmacother 2009; 10: 1017-26

63. Harries MJ, Sinclair RD, Macdonald-Hull S, et al. Management of primary

cicatricial alopecias: options for treatment. Br J Dermatol 2008; 159: 1-22

64. Otberg N,WuWY,McElwee KJ, et al. Diagnosis and management of primary

cicatricial alopecia: part I. Skinmed 2008; 7: 19-26

65. Assouly P, Reygagne P. Lichen planopilaris: update on diagnosis and treat-

ment. Sem Cutan Med Surg 2009; 28: 3-10

66. Donovan JC, Samrao A, Ruben BS, et al. Eyebrow regrowth in patients with

frontal fibrosing alopecia treated with intralesional triamcinolone acetonide.

Br J Dermatol 2010; 163: 1142-4

67. Jouanique C, Reygagne P, Bachelez H, et al. Thalidomide is ineffective in the

treatment of lichen planopilaris. J Am Acad Dermatol 2004; 51: 480-1

68. Powell JJ, Dawber RP, Gatter K. Folliculitis decalvans including tufted folli-

culitis: clinical, histological and therapeutic findings. Br JDermatol 1999; 140:

328-33

69. Rose P, Shapiro R. Transplanting into scar tissue and areas of cicatricial

alopecia. In: Unger WP, Shapiro R, editors. Hair transplantation. 4th ed.

New York (NY): Marcel Dekker, 2004: 606-9

70. Kwon OS, Kim MH, Park SH, et al. Staged hair transplantation in cicatricial

alopecia after carbon dioxide laser-assisted scar tissue remodeling. Arch

Dermatol 2007; 143: 457-6

71. Unger W, Unger R, Wesley C. The surgical treatment of cicatricial alopecia.

Dermatol Ther. 2008; 21: 295-311

72. Ross EK, Shapiro J. Management of hair loss. Dermatol Clin 2005; 23: 227-43

Correspondence: Prof. Franco Rongioletti, Clinica Dermatologica, Universita

di Genova, Viale Benedetto XV, 7, 16132 Genova, Italy.

E-mail: [email protected]



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Cicatricial (Scarring) Alopecias