Diagnosis and Management of Primary Cicatricial Alopecia: Part I

Authors


Nina Otberg, MD, Department of Dermatology and Skin Science, University of British Columbia, 835 West 10th Avenue, Vancouver, BC, V5Z4E8 Canada
E-mail: ninaotberg@gmx.com

Abstract

In this 2-part article, the authors review the primary cicatricial alopecias. Primary cicatricial alopecia can be defined as predominantly lymphocytic, neutrophilic, or mixed based on the nature of the follicular infiltrate that is present around affected hair follicles. Lymphocytic primary cicatricial alopecias include chronic cutaneous lupus erythematosus (discoid lupus erythematosus), lichen planopilaris, classic pseudopelade of Brocq, central centrifugal cicatricial alopecia, alopecia mucinosa, and keratosis follicularis spinulosa decalvans. In this first part, the authors summarize the classification, epidemiology, diagnostic approach, and patient management of lymphocytic cicatricial alopecias. In part II, the authors will focus on neutrophilic cicatricial alopecias and mixed cicatricial alopecias.

Cicatricial alopecia, also called scarring alopecia, represents a “trichologic emergency” because hair follicles are permanently destroyed. Consequently, a patient affected by cicatricial alopecia might experience overt disfiguration, leading to psychosocial embarrassment and a significant lack of self-esteem. A fast and confident confirmation of diagnosis, as well as aggressive treatment in the case of active disease, is crucial in the management of scarring alopecia. A swift response increases the chances of success with treatment, and successful treatment is the most effective approach in combating psychosocial hair loss issues.

The category of primary cicatricial alopecias includes a diverse group of inflammatory diseases of the hair follicles. In primary cicatricial alopecia, the hair follicle is the prime target of the destruction as opposed to secondary cicatricial alopecia, which is caused by a cutaneous, but not specifically folliculocentric, inflammatory process that eventually encroaches on the follicle and ultimately destroys it. Regardless of whether a cicatricial alopecia is primary or secondary in nature, all scarring alopecias are characterized by permanent destruction of the hair follicles clinically indicated by a loss of follicular ostia and histomorphologically by an eventual replacement of hair follicles with fibrous tissue.

Classification

Primary cicatricial alopecias can be classified using different approaches. The scalp disorders can be characterized by clinical presentation, histopathologic findings, or a combination of both. Each disease diagnosis has specific clinical and histopathologic characteristics, although the clinical presentation of scarring alopecia in a patient can show overlapping findings and symptoms of more than one diagnosis. According to a consensus meeting on cicatricial alopecia held at Duke University in North Carolina in February 2001, primary cicatricial alopecia was classified into 3 main groups: (1) lymphocytic, (2) neutrophilic, and (3) mixed, based on the nature of the inflammatory cells observed histologically in and around affected hair follicles. Some cases of scarring hair loss remain unclassifiable, however, and fall into the category of “unspecific.”1,2

Lymphocytic Primary Cicatricial Alopecia.

Figure 1.

Patient with chronic discoid lupus erythematosus. Note the hyperpigmentation.

Figure 2.

Patient with classic lichen planopilaris in a reticulated pattern.

Figure 3.

Patient with frontal fibrosing alopecia. Note the receding of the hairline in the frontal and temporal area.

Figure 4.

Patient with a small patch of pseudopelade of Brocq.

Figure 5.

Patient with central centrifugal cicatricial alopecia.

Neutrophilic Primary Cicatricial Alopecia.

  • Folliculitis decalvans
  • Dissecting cellulites/folliculitis (perifolliculitis abscedens et suffodiens)

Mixed Cicatricial Alopecia.

  • Folliculitis (acne) keloidalis
  • Folliculitis (acne) necrotica
  • Erosive pustular dermatosis

Epidemiology

Very few data on the epidemiology of cicatricial alopecia can be found in the literature. Whiting3 found a cicatricial alopecia frequency of 7.3% in all patients who sought advice for hair and scalp problems at the Baylor Hair Research and Treatment Center in Dallas, Texas, between 1989 and 1999. Tan and colleagues4 found a prevalence of 3.2%of all patients who visited the University of British Columbia Hair Clinic in Vancouver, Canada, between 1997 and 2001 had some form of cicatricial alopecia.

Pathogenesis

Primary cicatricial alopecia is characterized by a permanent destruction of hair follicles related to progressive deposition of collagen and is frequently associated with a loss of sebaceous glands.5 In scarring alopecia, inflammatory infiltrates primarily affect the upper, permanent portion of the follicles. The bulge region, the morphologic structure where the arrector pili muscle attaches to the outer root sheath, is the approximate location of pluripotent hair follicle stem cells.6 These cells are responsible for the renewal of the upper part of the hair follicle and sebaceous glands. In addition, they restore the lower cyclical component of the follicles at the onset of a new anagen growth period.7 It has been suggested that the development of scarring hair loss is a consequence of damage to the hair follicle stem cell region.3,5,8,9 Other hypotheses suggest disruption of the sebaceous glands10 or destruction of the outer root sheath as possible mechanisms of scarring alopecia development.5,11

Diagnostic Approach

Clinical history, thorough examination of the entire scalp, and skin biopsies can be crucial in the correct diagnosis of cicatricial alopecia. Time of onset and degree of patient-reported symptoms such as itching or pain can be used as approximate indicators of disease activity. Clinical findings such as diffuse or perifollicular erythema, follicular hyperkeratosis, pigment changes, tufting, pustules, and the general alopecic pattern (frontal or central location, patchy or reticulated appearance) provide further hints as to the diagnosis.12,13 Diagnostic tools such as a 3-fold magnifying lens or a 10-fold magnifying dermatoscope with and without polarized light can help to identify the presence or absence of follicular ostia in the affected areas. Presence of other indirectly related symptoms, such as sun sensitivity, may also help support a particular diagnosis (eg, DLE).

A scalp biopsy is often necessary to confirm a scarring alopecia diagnosis. The following recommendations were developed at the consensus meeting on cicatricial alopecia1 in February 2001: one 4-mm punch biopsy including subcutaneous tissue should be taken from a clinically active area, processed for horizontal sections, and stained with hematoxylin and eosin. Elastin (acid alcoholic orcein), mucin, and periodic acid-Schiff stains may provide additional diagnosis-defining information. A second 4-mm punch biopsy from a clinically active disease affected area should be cut vertically into two equal pieces. One-half provides tissue for transverse cut routine histological sections, the other half can be used for direct immunofluorescence (DIF) studies.14

Patient Management

Cicatricial alopecia is psychologically a highly distressing disease that requires an exceptionally empathetic interaction with the patient. It is the physician's task to enable the patient to comprehend that hair regrowth cannot be expected and the primary goal of any drug therapy is the arrest of further hair loss. The patient should be advised about different cosmetic camouflage techniques including hair pieces and wigs. Hair transplant surgery is possible when the patient has a suitable occipital donor area and the scarring alopecia has reached a “burnt out” stage, which means the lesions show no signs of inflammation or progression without any kind of therapy for at least 2 years (J. Shapiro, MD, FRCPC, oral communication, March 2007).

Lymphocytic Primary Cicatricial Alopecia Chronic Cutaneous Lupus Erythematosus (DLE).

Clinical Features. DLE is a form of chronic lupus erythematosus that can affect the scalp and result in cicatricial alopecia.12 Women are more often affected than men and the disease is more common in adults (with first onset typically at the age of 20–40 years) than in children.15–17 DLE usually presents with one or more erythematous atrophic plaques of alopecia. Follicular hyperkeratosis, hyperpigmentation, depigmentation, and telangiectasia might also be present.3,8 Active lesions can be sensitive and pruritic, the patient might report a worsening after UV exposure. The clinical features can be very similar to LPP, therefore 2 biopsies, one for standard histological horizontal sections and a second for longitudinal sections, as well as direct immunofluorescence staining, are often needed to confidently confirm the diagnosis.

Primary cicatricial alopecias represent trichologic emergencies. Immediate diagnosis including careful examination and scalp biopsies as well as prompt, aggressive treatment is necessary to stop further progression of the disease.

The incidence of concurrent alopecia areata is higher in patients with DLE18; a close examination of every alopecic area is mandatory to distinguish between different forms of alopecia. DLE has also been associated with verruciform xanthoma19 and papulonodular dermal mucinosis. Longstanding DLE lesions are prone to develop squamous cell carcinomas20 with a high occurrence of metastasis21; therefore every hyperkeratotic or ulcerated lesion in a DLE patch should be biopsied early.12

Histology. Characteristic of an early, active DLE lesion of the scalp is a lymphocyte-mediated interface dermatitis that shows basilar vacuolar degeneration with necrotic keratinocytes and a thickening of the basement membrane. The lymphocytic infiltrate is predominantly found in the upper, permanent part of the follicle.22–25 The lower cycling part of the follicle and the interfollicular epidermis, however, are also commonly involved. Sebaceous glands can be destroyed even in early lesions.8,16 The hair follicle infundibula are filled with laminated keratin, which corresponds with the clinically observed follicular plugging. A perivascular lymphocytic infiltrate around the periadnexal vessel as well as the superficial and deep vascular plexus can be found. Plasma cells can also be seen occasionally. Older lesions are characterized by a complete loss of pilosebaceous units associated with a perifollicular and interstitial fibrosis.

The characteristic thickening of the basement membrane can be identified with periodic acid-Schiff staining; an elastic stain such as Verhoeff-van Gieson stain may help to identify a loss of elastic fibers throughout the reticular dermis.5,14 Dermal mucin can be increased in older lesions and highlighted by Alcian blue and colloidal iron stains.

Direct immunofluorescent studies show a linear granular deposition of IgG and C3 at the dermoepidermal junction. IgM, C1q, and rarely IgA, can also be found.

Management and Treatment. Approximately 26% to 31% of children with DLE and 5% to 10% of adult patients will develop systemic lupus erythematosus.17,26 Therefore, a thorough medical history and physical examination, as well as serum antinuclear antibody titer, complete blood cell count, and urine analysis, should be carried out in every patient with DLE.12,27

First-line therapy for patients with slowly progressive, limited DLE should be intralesional triamcinolone acetonide at a concentration of ideally 10 mg/cc every 4 to 6 weeks12 with or without topical class I or class II corticosteroids. Topical corticosteroids alone have also been shown to be effective in milder forms of DLE.13,14,17,23 For rapidly progressive DLE, hydroxychloroquine has been shown to be highly effective. It should be started at a dose of 200 to 400 mg daily in adults or 4 to 6 mg/kg in children.15,17 A baseline ophthalmologic examination and complete blood cell count is required before the therapy is started. Bridge therapy with oral prednisone (1 mg/kg) tapered over the first 8 weeks of treatment might be helpful in patients with very rapid progressive disease.12,13 Oral retinoids have also been shown to be effective; acitretin at a dose of 50 mg daily28 and isotretinoin at a dose of 40 mg twice daily29 have been suggested. Oral immunosuppressive therapies such as mycophenolate mofetil, methotrexate, or azathioprine should only be considered if the above therapies fail.

Lichen Planopilaris.

Clinical Features. LPP can be subdivided into 3 main subgroups: (1) classic LPP, (2) FFA, and (3) Graham Little syndrome. A typical patient with classic LPP is around 50 years of age, and women are more often affected compared with men.30 Patients may report itching, burning sensations, and sensitivity of the scalp. The clinical features of classic LPP overlap with those of DLE, necessitating careful differential diagnosis. The alopecic plaques of LPP are often smaller and interconnected, which can lead to a reticulated clinical pattern as compared with DLE. Lesions usually present most commonly with follicular hyperkeratosis and perifollicular erythema.23

FFA predominantly affects postmenopausal women. FFA is characterized by a frontal or in some cases circumferential recession of the hairline caused by scarring alopecia.5 The hair loss can appear as a band-like area of alopecia, with a variable width of 1 to 8 cm,12,31 that spares few hairs. Clinical features of classic LPP, such as follicular hyperkeratosis and perifollicular erythema can often be found in the first hairs of the hair line. Alopecia of the eyebrows is also frequently seen in FFA.

Graham Little syndrome presents with lesions of classic LPP on the scalp, nonscarring alopecia of axillary and pubic hair, and keratosis pilaris on the trunk and extremities. In some cases, alopecia of the eyebrows can be found.32

Histology. All 3 subgroups of LPP show more or less the same essential histopathologic features. Similar to DLE, lymphocyte-mediated interface dermatitis can be found, especially in the permanent part of the hair follicle. The interfollicular epidermis is often spared, and often nonaffected hair follicles can be found adjacent to affected follicles in the same scalp biopsy. The lymphocytic infiltrate is predominantly found in and around the upper permanent part of the hair follicle, often with the greatest focus at the bottom of the dilated, keratin-filled infundibulum. This phenomenon is described as “hugging.”33,34 Sebaceous glands are often destroyed early in disease development. Unlike DLE, the vascular plexus is not affected by inflammation and mucin deposits are absent.5

Elastic stain can be useful to distinguish between DLE and LPP. Whereas in DLE the lack of elastic fibers can be found throughout the entire reticular dermis, in LPP a wedge-shaped scar in the area of the infundibulum can often be found with a loss of elastic fibers only in that area.35 Direct immunofluorescence might show globular cytoid depositions of IgM and rarely IgA, IgG, or C3 in the dermis around the infundibulum.36

Management and Treatment. A systematic medical history with thorough review of the patient's medications is necessary to identify possible drug-induced LPP. Many drugs can rarely cause lichenoid eruptions but the most common are gold, antimalarials, and captopril. Actinic lichenoid drug eruption is confined to sun-exposed sites. The most likely drugs to cause this are quinine, taken for leg cramps, and thiazide diuretics, used for hypertension and heart failure.37,38

A close physical examination can reveal extracranial lichen planus, which occurs in 17% to 28% of patients with LPP.4,39 A higher incidence of hepatitis C in patients with lichen planus has also been described.40 Patients with extensive LPP lesions should undergo hepatitis C testing.

Published literature on the treatment of LPP is limited. As with DLE, the first-line treatment for moderately active LPP lesions is intralesional triamcinolone acetonide at a suggested concentration of 10 mg/cc every 4 to 6 weeks optionally in combination with topical class I or class II corticosteroids.12,29 Oral cyclosporine of 300 mg daily over 3 to 5 months and low-dose tretinoin at a dose of 10 mg daily have been reported to be effective in small numbers of patients with LPP.41,42 Oral acitretin at a dose of 30 mg daily has been shown to be effective in lichen planus.43 Use of antimalarials3,8 and griseofulvine44 have also promoted a positive response in the treatment of patients with lichen planus. Oral corticosteroids in the first weeks of treatment as bridge therapy might be considered in very active cases. In FFA, a lower dose of intralesional triamcinolone acetonide (2.5–5 mg/cc) as well as topical application of minoxidil can be considered, although no effective treatment has yet been reported. The treatment of Graham Little syndrome is typically similar to the management of classic LPP. An effective treatment for alopecia of the eyebrows has not yet been identified.

Classic PPB.

Clinical Features. Classic PPB most commonly affects women between the ages of 30 and 50 years. It usually presents with small flesh-toned alopecic patches with irregular margins. This pattern has been described as “foot prints in the snow.”45 Unlike DLE and LPP, follicular hyperkeratosis and perifollicular or diffuse erythema are mostly absent.8 A clinical overlap in presenting features between DLE and LPP, however, is possible.

Histology. Early PPB lesions show a sparse or moderate lymphocytic infiltrate around the infundibulum; sebaceous glands are usually completely destroyed.46 In later lesions, the follicular epithelium becomes progressively more atrophic and affected hair follicles are often surrounded by concentric lamellar fibroplasias3,24,25 until the follicle is finally replaced by fibrous tracts. Unlike DLE and LPP, the elastic fiber network is preserved in PPB, and elastin staining can show markedly thickened elastic fibers.35 Occasionally, granular deposits of IgM can be found in direct immunofluorescence staining of scalp biopsies.46

Management and Treatment. Without clinical signs and symptoms of inflammation, activity of the disease is sometimes difficult to appreciate. A patient's history, a hair pull test, and measurements of the size of the lesions can help to identify active areas of disease. Topical and intralesional triamcinolone acetonide at a concentration of 10 mg/cc every 4 to 6 weeks, hydroxychloroquine, oral prednisone, and isotretinoin have shown some effectiveness in treating PPB.4,8,47

Central Centrifugal Cicatricial Alopecia.

Clinical Features. CCCA primarily affects African American women but can also rarely be seen in Caucasians (sometimes called central elliptical pseudopelade) and African American men. CCCA presents with a patch of scarring alopecia similar to PPB on the central scalp that slowly progresses centrifugally. It remains unclear whether chemical processing, heat, traction, or other traumas contribute to the development of this condition.2,23

Histology. Limited studies suggest that histopathologic features of CCCA seem to be similar to those of PPB.3,23

Management and Treatment. Since a multifactorial etiology is debated for CCCA, some dermatologists recommend a switch to more natural, less traumatizing, hair care practices.8,14,48 Topical corticosteroids and tetracycline have been shown to be effective in active progressive cases.23

Alopecia Mucinosa.

Clinical Features. AM can occur as an expression of mycosis fungoides or without an underlying disease.49 AM can lead to scarring alopecia but, strictly speaking, it is not a primary cicatricial alopecia since the hair follicle is not replaced by a true scar.5 AM can present as indurated, wellmargined erythematosus patches of scarring or nonscarring alopecia that can be accompanied by diffuse hair loss50 and alopecia of the eyebrows.51 Therefore, AM can be mistaken for alopecia areata or other cicatricial hair loss conditions. Grouped follicular papules, follicular cysts, and follicular hyperkeratosis can also be found in some cases. Lesions can occur on the neck, trunk, and extremities.51

Histology. Histology in AM is characterized by mucin deposition in the outer root sheath and later by a replacement of the entire pilosebaceous unit by pools of mucin.5,51 A lymphocytic infiltrate can be found in and around the follicular epithelium and with variable expression around the superficial and/or deep vascular plexus and also diffusely in the dermis. Cell atypia and monoclonal populations of T lymphocytes can be present in the idiopathic form of AM as well as in the mycoides fugoides-related form.49 Mucin staining is mandatory to confirm the diagnosis.

Management and Treatment. A complete work-up to rule out an underlying malignancy such as mycosis fungoides and Sézary syndrome is necessary. No effective standard therapy for AM is currently available. Oral corticosteroids,52 minocycline,53 and isotretoin54 have been shown to be effective. Topical and intralesional corticosteroids,55 dapsone,56 indomethacin,57 and light therapy58 have also been used with variable outcomes.

Keratosis Follicularis Spinulosa Decalvans.

Clinical Features. KFSD is an X-linked keratinizing disorder located in the Xp22 region.59 It is closely related to keratosis atrophicans faciei (also called ulerythema ophryogenes) and atrophodermia vermiculata, which mostly affects the face. KFSD usually develops during adolescence and mostly presents with scarring alopecic patches, follicular hyperkeratosis, and rarely pustules.5 Eyebrow and eyelash involvement can also be present.

Histology. KFSD is characterized by follicular plugging and hypergranulosis.60 An inflammatory infiltrate consisting of lymphocytes and neutrophils can be seen in the infundibular epithelium at an early stage of disease development. Later, the infiltrate is predominantly lymphocytic, and the follicle is eventually replaced by fibrous tissue.

Management and Treatment. Since KFSD is a disease of adolescence, careful calculation of risks and benefits of any treatment is important. Topical and intralesional corticosteroids60 and oral retionids61 have shown some effectiveness.

Conclusions

Lymphocytic primary cicatricial alopecias are a diverse group of permanent hair loss that show a predominantly lymphocytic inflammatory infiltrate as a common feature. Lymphocytic primary cicatricial alopecias can be a sign of underlying diseases such as lupus erythematosus, lichen planus, or mycosis fungoides. More research in etiology and treatment is necessary to provide more sufficient patient care.

Part II of this article will summarize clinical features, histology, and treatment options of neutrophilic cicatricial alopecias and mixed cicatricial alopecias.