Primary cicatricial alopecias refer to a group of rare, idiopathic, inflammatory scalp disorders that result in permanent hair loss. Primary cicatricial alopecias comprise a diverse group of inflammatory diseases and can be classified via different approaches, such as clinical presentation, histopathologic findings, or both. Primary cicatricial alopecias are rare scalp disorders. Whiting found a prevalence of 7.3% in all patients who sought advice for hair and scalp problems at the Baylor Hair Research and Treatment Center in Dallas between 1989 and 1999.
Key Points
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Primary cicatricial alopecias are defined as idiopathic, inflammatory scalp disorders that result in permanent hair loss.
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Primary cicatricial alopecias can be classified via different approaches, such as clinical presentation, histopathologic findings, or both.
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Primary cicatricial alopecias are rare scalp disorders. Prompt diagnosis and treatment is crucial for a successful management.
Introduction
Primary cicatricial alopecias refer to a group of rare, idiopathic, inflammatory scalp disorders that result in permanent hair loss. The destructive process is characterized by a folliculocentric inflammatory process that ultimately destroys the hair follicle. Primary cicatricial alopecias are probably the most misdiagnosed scalp disorders and frequently cause major distress for the affected patient. These scalp diseases represent trichologic emergencies because hair follicles are permanently destroyed and therefore the patient might experience disfiguration, psychosocial embarrassment, and a lack of self-esteem. A quick and confident proof of diagnosis and aggressive treatment in the case of active disease are crucial in the management of primary scarring alopecias. Diagnosis and therapy are challenging for the treating dermatologist and the dermatopathologist.
Introduction
Primary cicatricial alopecias refer to a group of rare, idiopathic, inflammatory scalp disorders that result in permanent hair loss. The destructive process is characterized by a folliculocentric inflammatory process that ultimately destroys the hair follicle. Primary cicatricial alopecias are probably the most misdiagnosed scalp disorders and frequently cause major distress for the affected patient. These scalp diseases represent trichologic emergencies because hair follicles are permanently destroyed and therefore the patient might experience disfiguration, psychosocial embarrassment, and a lack of self-esteem. A quick and confident proof of diagnosis and aggressive treatment in the case of active disease are crucial in the management of primary scarring alopecias. Diagnosis and therapy are challenging for the treating dermatologist and the dermatopathologist.
Classification
Primary cicatricial alopecias comprise a diverse group of inflammatory diseases and can be classified via different approaches, such as clinical presentation, histopathologic findings, or both. Each disease shows specific clinical and histopathologic characteristics, although the clinical appearance may show overlapping findings and symptoms. To classify this diverse group, a consensus meeting on cicatricial alopecia held at Duke University, Durham, North Carolina, in February 2001 came up with a classification based on the predominant inflammatory cells found in and around the follicular epithelium. According to this consensus meeting primary cicatricial alopecias are classified into 3 main groups: 1, lymphocytic; 2, Neutrophilic; and 3, mixed. However, some cases of primary cicatricial alopecia remain unclassifiable and therefore fall in the category “unspecific” ( Table 1 ).
| Lymphocytic | Neutrophilic | Mixed |
|---|---|---|
|
| Folliculitis (acne) keloidalis Folliculitis (acne) necrotica Erosive pustular dermatosis |
Epidemiology and pathogenesis
Primary cicatricial alopecias are rare scalp disorders. Whiting found a prevalence of 7.3% in all patients who sought advice for hair and scalp problems at the Baylor Hair Research and Treatment Center in Dallas between 1989 and 1999. Tan and colleagues found a prevalence of 3.2% of all patients who visited the UBC Hair Clinic in Vancouver between 1997 and 2001.
Pathogenesis is barely understood. The inflammatory process affects mainly the upper portion of the follicle and is followed by a permanent destruction of the hair follicle and continuous deposition of collagen and a loss of sebaceous glands. The follicle loses its capability to regenerate because pluripotent stem cells located in the bulge area are destroyed by inflammation. These cells are responsible for the renewal of the upper part of the follicle and the sebaceous gland. Additionally, they restore the lower impermanent part of the follicle and start a new growth (anagen) phase. Damage of sebaceous glands and destruction of the outer root sheath are also believed to be possible pathogenetic factors in the development of cicatricial alopecia.
Clinical findings
Primary cicatricial alopecia frequently starts at the central and parietal scalp before progressing to other sites of the scalp. A lack of follicular ostia is the hallmark of scaring alopecia. Isolated alopecic patches showing atrophy and a lack of follicular ostia with inflammatory changes such as diffuse or perifollicular erythema, follicular hyperkeratosis, pigment changes, tufting, and pustules provide hints to the diagnosis. However, clinically visible inflammatory changes may be absent in the affected lesions.
Diagnosis
A quick and confident diagnosis is the key to an effective treatment. A thorough examination of the entire scalp, a detailed clinical history, and 1 or 2 biopsy samples of an active lesion are crucial in the diagnosis of cicatricial alopecia. Time of onset and symptoms such as itching or pain can give information on the activity of the disease. Presents of sun sensitivity can lead to diagnose (eg, discoid lupus erythematosus [DLE]). Diffuse or perifollicular erythema, follicular hyperkeratosis, pigment changes, tufting, pustules, and the general pattern (frontal or central location, patchy or reticulated appearance) provide further hints in direction to the diagnosis.
A 3-fold magnifying lens or a 10-fold magnifying dermatoscope with and without polarized light can be used as a diagnostic tool. Videodermoscopy has been show to be very helpful in the diagnosis of hair and scalp disorders, especially in cicatricial alopecia.
A scalp biopsy is mandatory to confirm the diagnoses and to estimate disease activity. A 4-mm punch biopsy including subcutaneous tissue should be taken from a clinical active area where hair follicles are still present. The punch should be angled according to the growth direction of the hair. The biopsy sample is processed for horizontal sections and stained with hematoxylin and eosin. A second 4-mm punch biopsy sample can be cut vertically into 2 equal pieces. One half provides tissue for direct immunofluorescence studies; the other half can be use for transversal routine histologic sections. Elastin (acid alcoholic orcein), mucin, and periodic acid–Schiff stains may provide additional information.
Patient management
Cicatricial alopecia, especially advanced stages, can cause disfiguration and major distress for the patient. The management and treatment of patients with scarring hair loss require an exceptionally empathetic interaction with the patient. The physician should carefully clarify that hair regrowth is not expected and that the goal of any therapy is the arrest of further loss. Concomitant hair growth problems such as telogen effluvium and androgenetic alopecia should also be addressed and treated. Cicatricial patches can be camouflaged easier when the remaining hair is thick and healthy, even if regrowth is impossible in the lesions. Furthermore, the patient should be advised about different possibilities of camouflage techniques, including hair style, hair pieces, wigs, hair powder, and color. Hair transplantation and scalp reduction surgery are possible once the lesions are burnt out and stable. A scalp biopsy should confirm the absence of inflammatory cells before the surgery. For hair transplantation, the patient needs to have a suitable donor area. Graft survival may not be as good as in androgenetic alopecia and disease reactivation is possible at any time after surgery.
Lymphocytic primary cicatricial alopecia
Chronic Cutaneous Lupus Erythematosus (DLE)
DLE and lichen planopilaris represent the most common primary cicatricial alopecia. DLE is a form of chronic lupus erythematosus that can affect the scalp and result in cicatricial alopecia. The typical age of onset is between 20 and 40 years of age. Women are more often affected than men and the disease is more common in adults than in children.
Clinical presentation
DLE frequently starts at the occipital and parietal scalp. It presents with 1 or more erythematous patches of alopecia. Early in the process, follicular ostia can still be present in the margin of the lesion. Follicular hyperkeratosis, hyperpigmentation, depigmentation, and teleangiektasia can often be found in or around the lesions. The affected patient may report a worsening after ultraviolet exposure, pruritus, or dyesthesia. The clinical features can be very similar those of to lichen planopilaris ( Fig. 1 ).
Pathologic examination
Two 4-mm punch biopsies should be taken from a hair-baring margin of an alopecic patch: one for standard histologic horizontal sections and a second for longitudinal sections and direct immunofluorescence.
A lymphocyte-mediated interface dermatitis that shows basilar vacuolar degeneration with necrotic keratinocytes and a thickening of the basement membrane are characteristic for an active DLE lesion. The lymphocytic infiltrate is predominantly found in the upper permanent part of the follicle. However, perivascular lymphozytic infiltrate around the periadnexal vessel and the superficial and deep vascular plexus can be found. Plasma cells are seen occasionally. Sebaceous glands can already be destroyed in early lesions. The infundubula are filled with laminated keratin, which corresponds to the clinically observed follicular plugging. Older lesions are characterized by a complete loss of follicular units and a perifollicular and interstitial fibrosis.
Direct immunofluorescence shows a linear granular deposition of IgG and C3 at the dermoepidermal junction. IgM, C1q, and, rarely, IgA can also be found.
Additional stains, such as periodic acid–Schiff stain, can be used to identify the characteristic thickening of the basement membrane; elastic stains, such as Verhoeff–van Gieson stain, may help to identify a loss of elastic fibers throughout the reticular dermis. Dermal mucin can be increased in older lesions and can be highlighted by Alcian blue and colloidal iron stains.
Risk factors
Patient diagnosed with DLE may develop systemic lupus erythematosus; the risk is higher in children (26%–31% opposed to 5%–10% in adults). Therefore, a thorough medical history and physical examination, as well as serum antinuclear antibody titer, complete blood count, and urinalysis should be performed in every patient with DLE.
The incidence of alopecia areata is higher in patients with DLE ; a close examination of every alopecic area is mandatory to distinguish between different forms of alopecia.
DLE has also been associated with veruciform xanthoma and papulonodular dermal mucinosis. Longstanding DLE lesions are prone to develop squamous cell carcinoma with a high occurrence of metastasis ; therefore, every hyperkeratotic or ulcerated lesion in a DLE patch should be biopsied early.
Management and treatment
For rapidly progressive DLE, hydroxychloroqine has been shown to be highly effective. It should be started at a dosage of 200 to 400 mg daily in adults or 4 to 6 mg/kg in children. A baseline ophthalmologic examination and complete blood count are required before the therapy is started. Bridge therapy with oral prednisone (1 mg/kg) tapered during the first 8 weeks of treatment might be helpful in patients with very rapid progressive disease. For patients with slowly progressive, limited DLE first-line therapy should be intralesional triamcinolone acetonide at a concentration of ideally 10 mg/mL every 4 to 6 weeks 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. Oral retinoids have also shown to be effective: acitretin at a dosage of 50 mg daily and isotretinoin at a dosage of 40 mg twice daily.
Oral immunosuppressive therapies such as mycophenolate mofetil, methotrexate, or azathioprine should only be considered when these therapies failed.
Lichen Planopilaris
Lichen planopilaris (LPP) can be subdivided into 3 groups based on clinical presentation: (1) classic LPP, (2) frontal fibrosing alopecia (FFA), and (3) Graham-Little syndrome. The typical age of onset in classic LPP is around 50 years, and women are more often affected than men. Frontal fibrosing alopecia (FFA) predominantly affects postmenopausal women.
Clinical presentation
LPP most commonly starts at the parietal scalp. Patients may report itching, burning, and sensitivity of the scalp. The clinical features of classic LPP overlap with those of DLE. The alopecic plaques are often smaller and interconnected, which can lead to a reticulated pattern. The typical LPP lesion presents with follicular hyperkeratosis and perifollicular erythema ( Figs. 2 and 3 ).
FFA is characterized by a frontal or, in some cases, a circumferential recession of the hair line. The cicatricial hair loss appears as a bandlike area of variable width of 1 to 8 cm and typically spares a few hairs. Clinical features of classic LPP, such as follicular hyperkeratosis and perifollicular erythema, can often be found in the first rows of hairs in the hair line. Alopecia of the eyebrows is an additional typical finding in FFA ( Fig. 4 ).
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.
Pathologic examination
All 3 subgroups show more or less the same histopathologic features. Similar to DLE lymphocyte-mediated interface, dermatitis can be found especially in the permanent part of the follicle. The interfollicular epidermis is often spared, and often nonaffected hair follicles can be found next to affected follicles in the biopsy sample. Unlike DLE, the vascular plexus is not affected by inflammation and mucin deposits are absent. The lymphocytic infiltrate is predominantly found in the upper permanent part of the follicle, mostly at the bottom of the dilated, keratin-filled, infundibulum. Sebaceous glands are already destroyed in early lesions.
Direct immunofluorescence may show globular cytoid depositions of IgM, and rarely IgA, IgG, or C3, in the dermis around the infundibulum.
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 be found with a loss of elastic fibers only in that area. Elastic stains can be useful to distinguish between DLE and LPP.
Risk factors
Extracranial lichen planus can be found in 17% to 28% of patients with LPP. A higher incidence of hepatitis C in patients with lichen planus had been described. Patients with extensive lesions should undergo hepatitis C virus testing.
Management and treatment
A thorough review of the patient’s medications is necessary to identify possible triggering drugs.
Literature on the treatment of LPP is limited. Oral cyclosporine of 300 mg daily for 3 to 5 months and low-dose tretinoin at a dosage of 10 mg daily have been reported to be effective in a small number of patients with LPP. Oral acitretin at a dosage of 30 mg daily has been shown to be most effective in lichen planus. Antimalarias and griseofulvine showed also a positive outcome. Oral corticosteroids in the first weeks of treatment as bridge therapy should be considered in very active, rapidly progressive cases.
First-line treatment of moderately active LPP lesions is intralesional triamcinolone acetonide at a concentration of ideally 10 mg/mL every 4 to 6 weeks optional in combination with topical class I or class II corticosteroids. In frontal fibrosing alopecia, a lower dose of intralesional triamcinolone acetonide (2.5–5 mg/mL) and topical application of corticosteroids and minoxidil can be considered. The treatment of Graham-Little syndrome equals the management of classic LPP. Alopecia of the eyebrows may be treated with intralesional triamcinolone acetonide (2.5 mg/mL) and topical minoxidil, although an effective treatment has not yet been reported in literature.
Classic Pseudopelade of Brocq
Pseudopelade of Brocq (PPB) is the second most common cause of primary cicatricial alopecia. Women between 30 and 50 years of age are most frequently affected.
Clinical presentation
PPB frequently starts on the parietal scalp and presents with small flesh-toned alopecic patches with irregular margins. This particular pattern has been described as “foot prints in the snow.” Follicular hyperkeratosis and perifollicular or diffuse erythema are mostly absent. However, clinical overlap with DLE and LPP is possible ( Figs. 5 and 6 ).
Pathologic examination
A sparse or moderate lymphocytic infiltrate around the infundibulum and the absence of sebaceous glands are pathologic hallmarks for an early PPB lesion. In later lesions, the follicular epithelium becomes more and more atrophic and follicles are often surrounded by concentric lamellar fibroplasias until finally the follicle is replaced by fibrous tracts. Unlike in DLE and LPP, the elastic fiber network is preserved and elastin stain might show markedly thickened elastic fibers. Occasionally, granular deposits of IgM can be found on direct immunofluorescence.
Management and treatment
Disease activity in patients with no clinical signs and symptoms of inflammation can be difficult to track. Measurements and photographs of the lesion may help to document progression.
Topical and intralesional triamcinolone acetonide at a concentration of ideally 10 mg/mL every 4 to 6 weeks, hydroxychloroquine, oral prednisone, and isotretinoin have shown some effectiveness.
Central Centrifugal Cicatricial Alopecia
Central centrifugal cicatricial alopecia (CCCA) primarily affects African American women but can also rarely been seen in whites (“central elliptical pseudopelade”) and African American men. It remains unclear exactly which role hair care practices such as chemical processing, heat, traction, or other traumas play in the pathogenesis of this cicatricial alopecia.
Clinical presentation
CCCA presents with a patch of scarring alopecia similar to PPB on the central scalp that slowly progresses centrifugally. It remains unclear if chemical processing, heat, traction, or other traumas contribute to the development of this condition ( Fig. 7 ).
