Lichen planopilaris

INTRODUCTION — Lichen planopilaris (LPP) is an uncommon inflammatory scalp disorder that is clinically characterized by perifollicular erythema, follicular hyperkeratosis, and permanent hair loss. LPP is considered a follicular form of lichen planus based upon shared pathologic features and the frequent coexistence of clinical findings of these disorders. (See "Lichen planus".)

LPP is divided into three clinical variants:

●Classic LPP

●Frontal fibrosing alopecia (FFA)

●Graham-Little-Piccardi-Lasseur syndrome (Graham-Little syndrome; GLPLS)

The three variants of LPP are distinguished primarily by the clinical pattern of involvement. Whereas patchy scalp involvement is a common presentation of classic LPP (picture 1), band-like alopecia involving the frontal scalp is typical of FFA (picture 2). GLPLS is defined by a triad of features: cicatricial alopecia on the scalp, noncicatricial alopecia in the axillae and groin, and widespread lichenoid follicular papules.

The treatment of LPP is challenging due to a paucity of data on the efficacy of therapies and an inconsistent response to treatment. However, because uncontrolled LPP results in irreversible hair loss, rapid diagnosis and the prompt institution of treatment are important for the management of patients with LPP.

The diagnosis and management of LPP will be reviewed here. Lichen planus is discussed separately. (See "Lichen planus".)

CLASSIFICATION — The participants of a 2001 workshop on cicatricial alopecia sponsored by the North American Hair Research Society proposed a classification scheme for cicatricial alopecias that is primarily based upon the pathologic features of each disorder [1]. Lichen planopilaris (LPP) was classified as a primary lymphocytic cicatricial alopecia, a member of a group of inflammatory scalp disorders that demonstrate a lymphocyte-predominant inflammatory infiltrate, follicular destruction, and permanent hair loss. The classification of the cicatricial alopecias is reviewed separately. (See "Evaluation and diagnosis of hair loss", section on 'Cicatricial alopecia'.)

EPIDEMIOLOGY — Epidemiologic data on lichen planopilaris (LPP) are limited. Although it is accepted that LPP is uncommon, the incidence and prevalence of LPP are unknown. Data from select North American tertiary hair research centers suggest that patients with LPP account for less than 1 percent to 8 percent of new patients who present to such centers for evaluation [2,3].

Adults between the ages of 25 and 70 years are the primary population affected by LPP; however, LPP also is occasionally observed in children [2,4-6]. A retrospective study of 45 patients with classic LPP found a mean age of onset of 52 years [7].

All three variants of LPP appear to be more common in females than in males [2,4,7,8]. In the retrospective study of 45 patients with classic LPP mentioned above, the female-to-male ratio was 4:1 [7]. Other studies have found less dramatic sex differences; in a retrospective study of 25 patients with LPP, the female-to-male ratio was 1.8:1 [2]. Postmenopausal women are the primary population affected by the frontal fibrosing alopecia (FFA) variant of LPP [8-11]. In a retrospective study of 355 patients with FFA (343 women and 12 men), the mean age was 56 years (range 21 to 81 years) [8]. Although Graham-Little-Piccardi-Lasseur syndrome (GLPLS) can occur in males, most of the reported cases have occurred in females between the ages of 30 and 60 years [12].

Patients with LPP may have an increased risk for thyroid disease. In a case-control study of 166 patients with LPP and 81 control patients evaluated in a dermatology clinic, thyroid disease was significantly more frequent among patients with LPP (34 versus 11 percent of patients) [13]. Hypothyroidism was the most common thyroid abnormality in both groups. Further study will be useful for confirming a relationship between LPP and thyroid disease.

PATHOGENESIS — The pathogenesis of lichen planopilaris (LPP) is poorly understood. Similar to cutaneous lichen planus, LPP is postulated to be an immune-mediated disorder characterized by an autoreactive, lymphocytic inflammatory process against an unknown self-antigen. In LPP, follicular antigens may be the target of a cell-mediated cytotoxic immune reaction.

The permanent loss of hair that characterizes LPP is postulated to emanate from the site in which inflammation occurs. Unlike alopecia areata, a nonscarring form of hair loss in which inflammation is most concentrated around the follicular bulb, LPP demonstrates an inflammatory infiltrate concentrated around the follicular infundibulum and isthmus (figure 1 and picture 3). The follicular "bulge," a site of pluripotent stem cells involved in regeneration of the lower portion of the hair follicle during follicular cycling is located within this same region. Damage to the bulge region may account for the development of permanent alopecia [14].

Endogenous or exogenous agents, such as drugs, viruses, or contact sensitizers have been proposed as potential triggers for the autoimmune response observed in LPP [4,15,16]. Binding of components of these agents to keratinocytes could represent an initial trigger for an inflammatory process. However, a role for specific endogenous or exogenous factors remains unclear.

Other observations that may offer insight into the pathogenesis of LPP include the detection of reduced expression of peroxisome proliferator-activated receptor (PPAR)-gamma in specimens of LPP, and the detection of antibodies against the INCENP protein in a patient with Graham-Little-Piccardi-Lasseur syndrome (GLPLS) [17,18]. PPAR-gamma is a transcription factor that may be critical for the maintenance of normal pilosebaceous units and INCENP is a component of the centromere involved in cell mitosis. In addition, the predilection of frontal fibrosing alopecia (FFA) for postmenopausal women and the apparent response of some cases to antiandrogenic treatment has raised questions about whether androgens are involved in the pathogenesis of FFA [9,19]. Further study is necessary to determine the relevance of a retrospective study that found a higher rate of early menopause among women with FFA than in the general population [8].

A genome-wide association study in two European cohorts of females with FFA and female controls identified susceptibility loci for FFA, supporting a genetic predisposition to the development of this condition [20]. The strongest effect on FFA susceptibility was found at 6p21.1 within the major histocompatibility complex (MHC) region, which upon further analysis was attributed to HLA-B*07:02 allele. HLA-B*07:02 is postulated to facilitate hair follicle autoantigen presentation, an event that may contribute to lymphocytic destruction of the follicular bulge. Other susceptibility loci identified in the study include 2p22.2, 8q24.22, and 15q2.1. The findings suggest a pathogenic role for risk alleles in MHC class I molecule-mediated antigen processing and T cell homeostasis and function.

CLINICAL PRESENTATION — Classic lichen planopilaris (LPP), frontal fibrosing alopecia (FFA), and Graham-Little-Piccardi-Lasseur syndrome (GLPLS) have both overlapping and distinct clinical features. Perifollicular inflammation, follicular hyperkeratosis, and cicatricial alopecia occur in all three variants. The distribution of involvement is the most prominent distinguishing clinical feature.

Classic lichen planopilaris — The most common sites for initial involvement in classic lichen planopilaris (LPP) are the vertex and parietal areas of the scalp. The earliest clinical signs are perifollicular erythema and follicular hyperkeratosis manifesting as perifollicular keratotic spines or follicular keratotic plugs. Eventually, patients develop skin-colored or erythematous patches of alopecia that are a few millimeters to a few centimeters in breadth (picture 4) [21]. Close examination will reveal markedly reduced or absent follicular ostia. Occasionally, residual islands of normal or inflamed hair-bearing follicles remain within the patches of alopecia.

Perifollicular erythema and follicular hyperkeratosis often remain evident at the periphery of areas of alopecia in patients with active disease [7]. Tufted hairs similar to those seen in folliculitis decalvans also may be seen [2].

The extent of scalp involvement varies; patients may present with single or multiple scalp lesions and involvement may be focal or extensive (picture 5) [2,22]. Small patches of alopecia can slowly progress and become interconnected, leading to a reticulated pattern of alopecia (picture 1) [23,24]. Associated itching, burning, or scalp tenderness is common. Rarely, linear presentations of LPP on the face or trunk occur [25,26].

Concomitant features of cutaneous, nail, or mucosal lichen planus are not uncommon in patients with LPP. It is estimated at the time of presentation, 17 to 28 percent of patients with LPP have evidence of lichen planus in other body sites [21]. Involvement of other sites may precede or follow the development of LPP [7].

Frontal fibrosing alopecia — FFA is characterized by the development of frontotemporal loss of both terminal and vellus hairs. Hair loss occurs in a band-like distribution that is usually 1 to 8 cm in diameter (picture 2) [21,27]. Often, a small number of isolated hairs are spared within the band of alopecia, a finding that has been referred to as the "lonely hair sign" [8,28]. Similar to classic LPP, erythematous and hyperkeratotic follicles are often found at the periphery of areas of alopecia. Hypopigmentation may also be evident in the affected area [29]. Pruritus or trichodynia may be present [8].

Involvement of other scalp sites, such as the periauricular, parietal, or occipital areas, may accompany the classic distribution of FFA (picture 6) [8,9]. In addition, in a retrospective study of 60 women with FFA, diffuse features of LPP on the scalp were found in 8 percent of patients [9]. Men may have involvement of the sideburns and facial hair [30].

Eyebrow involvement is common in FFA, occurring in 50 to 83 percent of patients [8,9]. Eyebrow involvement may precede or follow scalp disease. Eyelash involvement also may occur, though it is less common. In a retrospective study of 355 patients with FFA in Spain, 14 percent had eyelash involvement [8]. Men with FFA may experience beard involvement [8].

Patients with FFA also may develop hair loss in areas other than the scalp and face. Body, axillary, or pubic hair loss was documented in 24, 21, and 18 percent of patients in the Spanish retrospective study, respectively [8].

In addition, involvement of vellus hair follicles on the face manifesting as facial papules or follicular red dots has been reported [31]. Facial papules were detected in 14 percent of patients in the Spanish retrospective study [8]. Other reported facial manifestations include diffuse erythema resulting from a follicular and interfollicular lichenoid infiltrate and the gradual appearance of pigmented macules [32].

Graham-Little-Piccardi-Lasseur syndrome — GLPLS has three clinical components [33]:

●Cicatricial (scarring) alopecia of the scalp with features of LPP

●Noncicatricial (nonscarring) alopecia involving axillary and pubic hair

●Lichenoid follicular eruption on the trunk, limbs, face, or eyebrows

Cicatricial alopecia usually precedes the other manifestations of GLPLS [12].

Other presentations — Fibrosing alopecia in a pattern distribution (FAPD), a subtype of LPP that presents with hair loss in a pattern similar to androgenetic alopecia, has been described [34]. Histopathologic examination reveals predominant involvement of vellus hair follicles. In contrast, classic LPP primarily involves terminal hair follicles.

Lichen planopilaris diffuse pattern (LPPDP) may be an additional clinical variant of LPP based upon a retrospective study of 40 patients with a histopathologic diagnosis of LPP of the scalp and diffuse hair thinning, scalp pruritus, and scalp erythema [35]. Twenty patients (11 females and 9 males) were given a diagnosis of LPPDP. Features associated with LPPDP included scalp itching or pain, scalp erythema, and widespread, mild hair thinning throughout the scalp. Common dermoscopy findings included follicular erythema, perifollicular hyperkeratosis, and loss of follicular ostia. The lichenoid lymphocytic infiltrate in histopathologic specimens of LPPDP primarily targeted terminal hair follicles but involved fewer hair follicles and was less intense than the infiltrate typically associated with LPP.

The remaining patients had patterned hair loss most consistent with FAPD (18 patients) or a condition termed cicatricial pattern hair loss (2 patients). Whether cicatricial pattern hair loss, which is characterized by features of female pattern hair loss in conjunction with focal atrichia (small areas of scarring), is a variant of LPP or a manifestation of end-stage androgenetic alopecia is debated [35,36].

CLINICAL COURSE — Lichen planopilaris (LPP) is a chronic disorder with an unpredictable course [15]. LPP may progress for months to years before stabilizing or may continue to slowly progress over time. Occasionally, rapid and extensive hair loss occurs [37].

Data on prognostic factors for LPP are limited. The findings of a Spanish retrospective study of 355 patients with frontal fibrosing alopecia (FFA) suggest that patients with eyelash loss, facial papules, or body hair involvement may be at increased risk for severe FFA [8]. Eyebrow loss as the initial clinical presentation was associated with an increased likelihood for mild disease. Additional studies are necessary to confirm these findings.

DIAGNOSIS — The diagnosis of lichen planopilaris (LPP) is made based upon physical examination and scalp biopsy.

Physical examination — The physical examination should include a thorough examination of the scalp as well as the rest of the skin. The scalp examination may help to narrow the differential diagnosis by detecting clinical signs that distinguish cicatricial alopecia (absent follicular ostia) from noncicatricial alopecia (preserved follicular ostia), or by identifying features characteristically associated with LPP (eg, patchy or frontal alopecia, perifollicular inflammation, and follicular hyperkeratosis). The examination may also provide clues about disease activity. (See "Evaluation and diagnosis of hair loss", section on 'Physical examination' and 'Therapeutic approach' below.)

Performance of a full skin examination allows for the detection of cutaneous or mucous membrane findings of lichen planus, which can occur in patients with LPP. In addition, the skin examination may reveal findings that suggest Graham-Little-Piccardi-Lasseur syndrome (GLPLS), rather than classic LPP. (See 'Clinical presentation' above.)

Dermoscopy — Dermoscopy of the scalp (also known as trichoscopy) can yield additional findings to support the diagnosis. Dermoscopic findings of perifollicular scale, white dots, and reduced follicular ostia have been linked to LPP [38]. Common dermoscopic findings in frontal fibrosing alopecia (FFA) include follicular hyperkeratosis and perifollicular erythema [8]. (See "Overview of dermoscopy".)

Biopsy — A scalp biopsy is required to confirm a diagnosis of LPP.

Procedure — The choice of the biopsy site is critical. Inappropriate biopsy sites are unlikely to yield diagnostic findings.

Ideally, the biopsy should be taken from a hair-bearing area with clinical signs of active disease, such as perifollicular inflammation and follicular hyperkeratosis. Some clinicians have found dermoscopy useful for identifying an ideal biopsy site [39]. Areas of complete alopecia should be avoided.

We typically perform two 4 mm punch biopsies in patients who have clinical findings suggestive of LPP. The receipt of two punch biopsies, rather than a single biopsy, is preferred by many dermatopathologists, as it allows for evaluation of the hair follicles in both horizontal and vertical sections. If only one biopsy is performed, the tissue should be sectioned transversely. (See "Evaluation and diagnosis of hair loss", section on 'Scalp biopsies'.)

Findings — Scalp involvement in classic LPP, frontal fibrosing alopecia (FFA), and GLPLS demonstrates similar features. Typical pathology findings include (picture 3) [40,41]:

●Follicular plugging and wedge-shaped hypergranulosis involving the follicular epithelium

●Interface dermatitis involving the follicular infundibulum and isthmus (necrotic keratinocytes, vacuolization of the basal layer, dense band-like lymphocytic infiltrate), often sparing the interfollicular epithelium

●Perifollicular fibrosis surrounding the infundibulum and isthmus of the hair follicle in developed lesions

●Loss of sebaceous glands in long-standing disease

●Vertical fibrous tracts replacing follicles in end-stage lesions

DIFFERENTIAL DIAGNOSIS — The differential diagnosis for lichen planopilaris (LPP) involving the scalp primarily includes other forms of cicatricial alopecia. LPP should also be distinguished from alopecia areata, a nonscarring form of patchy alopecia.

The clinical and pathologic findings of active LPP are useful for distinguishing LPP from other disorders. Inactive, end-stage classic LPP may be difficult or impossible to distinguish from other inactive cicatricial alopecias.

Disorders commonly in the differential diagnosis of LPP include:

●Discoid lupus erythematosus – Discoid lupus erythematosus is one of the most common causes of primary cicatricial alopecia. Patients with scalp involvement typically develop atrophic plaques with follicular plugging and pigmentary alteration (picture 7A-B). Pathologic findings that suggest discoid lupus erythematosus include a superficial and deep lymphocytic infiltrate and thickening of the basement membrane. Direct immunofluorescence demonstrates deposition of IgG and IgM along the basement membrane zone in some cases [40]. (See "Overview of cutaneous lupus erythematosus", section on 'Discoid lupus erythematosus'.)

●Pseudopelade of Brocq – Pseudopelade of Brocq is an idiopathic cicatricial alopecia that is characterized by the presence of small skin-colored patches of alopecia on the scalp. Follicular hyperkeratosis and erythema are minimal or absent. A biopsy reveals replacement of hair follicles by bands of fibrous tissue [42]. Some authors have suggested that pseudopelade of Brocq may actually represent the end stage of other forms of cicatricial alopecia [21].

●Central centrifugal cicatricial alopecia – Central centrifugal cicatricial alopecia is a primary lymphocytic cicatricial alopecia that is primarily diagnosed in women of African descent. Alopecia develops on the crown of the scalp and gradually progresses in a centrifugal manner to the parietal areas (picture 8). Itching or tenderness may be present. Premature desquamation of the inner root sheath is a key pathologic finding [43]. (See "Central centrifugal cicatricial alopecia".)

●Keratosis follicularis spinulosa decalvans – The follicular papules and cicatricial alopecia of keratosis follicularis spinulosa decalvans (KFSD) should be distinguished from Graham-Little-Piccardi-Lasseur syndrome (GLPLS). KFSD is a rare genetic disorder that initially presents in infancy with follicular papules with keratotic spines on the scalp (picture 9A-B). Involvement of eyebrows, eyelashes, and other hair-bearing areas may develop. Photophobia is a common finding that supports the diagnosis of KFSD. (See "Keratosis pilaris atrophicans", section on 'Keratosis follicularis spinulosa decalvans'.)

●Alopecia areata – Alopecia areata is a nonscarring form of alopecia that most commonly presents with the acute development of round patches of alopecia on the scalp (picture 10A-B). Follicular ostia remain within the areas of alopecia, consistent with a nonscarring process. Unlike LPP, which demonstrates a lymphocytic inflammatory infiltrate centered around the follicular infundibulum and isthmus, the lymphocytic infiltrate in alopecia areata is concentrated around the follicular bulb. (See "Alopecia areata: Clinical manifestations and diagnosis".)

Frontal fibrosing alopecia (FFA) must be distinguished from androgenetic alopecia, which presents with alopecia involving the frontal and vertex area of the scalp. The nonscarring nature of androgenetic alopecia and the retention of vellus hairs in this condition are useful for distinguishing androgenetic alopecia from FFA. Of note, the two disorders may be present simultaneously [8]. (See "Female pattern hair loss (androgenetic alopecia in females): Pathogenesis, clinical features, and diagnosis", section on 'Clinical manifestations' and "Male pattern hair loss (androgenetic alopecia in males): Pathogenesis, clinical features, and diagnosis".)

FFA also should be distinguished from traction alopecia, a form of transient or permanent hair loss that results from chronic tension on hair follicles, such as can occur with hairstyles in which the hair is tightly braided or otherwise pulled (picture 11). The frontal and temporal hairlines are common sites of involvement, a feature that may contribute to confusion with FFA [44]. The patient history, physical examination, and biopsy are useful for distinguishing between these disorders. Perifollicular erythema and hyperkeratosis are not typical features of traction alopecia. Biopsies from patients with traction alopecia reveal an increased number of catagen and telogen follicles in early disease and scarring in late stage disease characterized by permanent hair loss [43]. (See "Traction alopecia".)

TREATMENT — Although lichen planopilaris (LPP) is not a life-threatening disorder, the associated symptoms and concern regarding the cosmetic effects of hair loss prompt many patients to pursue treatment. As with other cicatricial alopecias, treatment is unlikely to induce significant hair regrowth in areas of existing alopecia. Thus, the goals of treatment are to improve patient symptoms and to arrest progression of the disease.

Patient selection — Treatment is most beneficial for patients with active LPP because end-stage lesions are unlikely to respond to treatment. Patients often simultaneously exhibit areas of active and inactive disease.

Active LPP on the scalp is suggested by the following findings:

●Perifollicular erythema and hyperkeratosis

●Progressive hair loss

●Symptoms (eg, itching, burning, or tenderness)

●Scalp biopsy demonstrating an inflammatory process consistent with LPP

Once a patient is considered a candidate for treatment, the expectations for treatment should be thoroughly reviewed with him or her prior to initiating treatment. Because hair loss can cause significant psychologic distress, an empathetic approach to communicating this information is needed.

In general, we communicate the following concepts:

●There is no cure for LPP.

●The course of LPP is unpredictable; the condition may continue to slowly progress over time or may become self-limited.

●Treatment is unlikely to induce hair regrowth in areas of existing alopecia.

●The primary goals of treatment are to prevent additional loss of hair and alleviate symptoms.

●The response to treatment is variable and multiple therapeutic trials may be needed to find the most effective treatment.

●There are cosmetic measures that are helpful for camouflaging hair loss that does not improve with treatment. (See 'Cosmetic measures' below.)

Therapeutic approach — The best approach to the treatment of LPP is unclear due to a paucity of high quality data on therapies for this disorder, the unpredictable clinical course of LPP, and a lack of consistency in methods used to assess the response to treatment in the literature. As a result of the uncertainty about treatment efficacy, recommendations for the management of LPP vary. Our approach to the treatment of LPP is reviewed below.

Classic lichen planopilaris — The major treatment options for classic LPP include local and systemic therapies. In most cases, local treatments are the initial therapeutic choice due to the relative safety of these interventions. Systemic therapy is primarily used for patients who fail to respond to local therapy or who initially present with rapidly progressive or extensive disease. (See 'Second-line therapy' below and 'Refractory disease' below.)

First-line therapy — Topical corticosteroids and intralesional corticosteroid injection are commonly utilized as first-line therapy for classic LPP [45]. Data are insufficient to determine the comparative efficacy of these interventions.

We often combine topical corticosteroid and intralesional corticosteroid therapy in an attempt to augment the response to treatment. However, the superiority of combination therapy is unproven.

Topical corticosteroids — Data on the efficacy of topical corticosteroids for LPP are limited to case reports and retrospective case series that document improvement in some patients [45]. A 2013 systematic review of the English language literature identified 79 patients with biopsy-proven LPP who had documentation of their response to topical corticosteroid therapy [45]. The review found author documentation of good, partial, and absent treatment responses in 53, 27, and 15 percent of patients, respectively.

The largest case series identified in the systematic review was a retrospective case series of 30 patients with LPP. Treatment with a topical corticosteroid (twice daily for three weeks, once daily for three weeks, and every other day for approximately six weeks) was associated with clearing of inflammation and inhibition of progression of cicatricial lesions in 20 patients (67 percent) [4]. Six patients (20 percent) had a lesser degree of improvement, and four patients (13 percent) did not appear to respond to therapy.

The best topical corticosteroid regimen for LPP is unknown. Our preference is to prescribe a high potency or super high potency topical corticosteroid (table 1). We instruct patients to apply the topical corticosteroid twice daily to areas of active disease. Once it appears that disease activity has subsided, we slowly taper the frequency of application. If there is no evidence of a response to topical corticosteroid therapy within four months, we consider alternative modes of treatment.

Cutaneous atrophy is a potential adverse effect of topical corticosteroids. However, the scalp is less likely to develop cosmetically significant atrophy from topical corticosteroid use than many other areas. Additional adverse effects of topical corticosteroids are reviewed in detail separately. (See "Topical corticosteroids: Use and adverse effects", section on 'Adverse effects'.)

Intralesional corticosteroids — The goal of intralesional injection of corticosteroids is to inhibit inflammation through the delivery of corticosteroids directly to the site of inflammation in the dermis. Only a few retrospective case series and case reports have evaluated intralesional corticosteroid therapy for LPP [45]. The largest series, a retrospective case series of 20 patients treated with intralesional corticosteroid injections documented good responses in 40 percent of patients [46]. "Good" responders were required to demonstrate stabilization of disease with greater than a minimal response to treatment, greater than minimal hair regrowth, and a greater than minimal reduction in symptoms. Unstable disease with a lesser degree of improvement was observed in 50 percent of patients, and 10 percent of patients worsened.

The authors of a separate retrospective case series that included seven patients treated with intralesional corticosteroid injection did not document improvement in any patients, but also did not report the measures used to assess response [7]. The regimen used for intralesional corticosteroid therapy was not described in either series.

Our experience suggests that intralesional corticosteroid therapy can be beneficial. We find that intralesional corticosteroids reduce clinical signs of inflammation significantly. We have also noticed that symptoms such as tenderness, itching, and burning can improve after one or two sessions of intralesional corticosteroid therapy.

Our typical treatment regimen consists of the injection of 10 mg/mL of triamcinolone acetonide (5 mg/mL for lesions in the frontal hairline) with a 30-gauge needle every four to six weeks into areas of active disease. Active areas are most commonly found at the periphery of patches of alopecia [2,21]. Injections of approximately 0.1 mL are spaced approximately 1 cm apart within the involved area. The target depth of injection into the skin is approximately 1 to 2 mm. The dose of triamcinolone acetonide should not exceed 40 mg per treatment session. If a significant reduction of clinical signs of inflammation and symptoms is not evident within four months, we transition to alternative treatment.

A disadvantage of intralesional corticosteroid therapy compared with topical corticosteroid therapy is the pain associated with treatment. However, most patients tolerate injections without the need for anesthesia; topical anesthetics may be used for those patients who need them.

Intralesional corticosteroid therapy occasionally causes cutaneous atrophy that manifests as indentations in the scalp. When this occurs, we discontinue treating the site of atrophy until it resolves (usually several months). Other adverse effects of intralesional corticosteroid injection are reviewed separately. (See "Intralesional corticosteroid injection", section on 'Adverse effects and pitfalls'.)

Second-line therapy — Systemic therapy is usually reserved for patients who fail to respond sufficiently to local corticosteroid therapy or for patients who initially present with rapidly progressing or extensive disease. Commonly used systemic therapies for LPP include systemic glucocorticoids and hydroxychloroquine. Of note, there is only low quality evidence to support the use of both therapies. Intralesional or topical corticosteroid therapy typically is continued during systemic therapy.

Systemic glucocorticoids — Although systemic glucocorticoids are considered useful for attaining rapid improvement in LPP, published data on the efficacy of systemic glucocorticoids are limited [45]. A retrospective case series that included 11 patients treated with a systemic glucocorticoid documented improvement in 9 patients (82 percent) [7]. The treatment regimen and response criteria were not reported. Case reports have documented mixed results for systemic glucocorticoid treatment [45].

Because of the serious adverse effect profile associated with long-term systemic glucocorticoid treatment, systemic glucocorticoids are preferably used as short-term therapies for attaining disease control. Relapse may be common following cessation of systemic glucocorticoids [7]; thus, transitioning to an alternative topical or systemic therapy prior to discontinuation is prudent.

The optimal systemic glucocorticoid regimen for LPP has not been established. We typically treat adults with oral prednisone at an initial dose of 1 mg/kg per day, with a plan to taper to discontinuation over two to four months [47,48].

The adverse effects of systemic glucocorticoid therapy are reviewed in detail separately. (See "Major adverse effects of systemic glucocorticoids".)

Hydroxychloroquine — Hydroxychloroquine is a non-immunosuppressive agent with immunomodulatory properties. The generally well-tolerated nature of hydroxychloroquine contributes to its frequent use for LPP.

Similar to other therapies for LPP, data on the efficacy of hydroxychloroquine are limited. A 2013 systematic review of the English literature found 71 patients with both biopsy-proven LPP and documentation of their response to hydroxychloroquine [45]. The proportion of hydroxychloroquine-treated patients who had documentation of good, partial, or absent responses to treatment were 23, 30, and 48 percent, respectively.

The rate of response of LPP to hydroxychloroquine has varied widely across studies, a finding likely influenced by differences in patient population and assessment measures. Examples include:

●A retrospective study of adults with LPP that used a novel scoring system (LPP Activity Index [LPPAI]) to assess symptoms and signs of LPP found that the majority of patients appeared to benefit from hydroxychloroquine therapy, though most did not achieve complete remission [49]. At assessments six and twelve months after starting treatment with hydroxychloroquine, patients were classified as responders (>85 percent reduction in LPPAI), partial responders (25 to 85 percent reduction in LPPAI) or nonresponders (<25 percent reduction in LPPAI). Among 27 patients with LPP who were assessed at six months, 0, 70, and 30 percent were responders, partial responders, and nonresponders, respectively. After 12 months of treatment, the number of responders increased. Among 29 patients assessed at 12 months, 14, 72, and 14 percent were responders, partial responders, and nonresponders, respectively.

●A retrospective study that included 22 patients with LPP treated with hydroxychloroquine (6.5 mg/kg per day for 6 to 12 months) as initial treatment or after failure of doxycycline found that 9 patients (41 percent) had documentation of improvement during treatment [50]. Improvement was defined as an absence of symptoms (pruritus, burning, and/or dysesthesia), lack of progression, reduction in erythema and follicular hyperkeratosis, and an ability to discontinue therapy.

Lower rates of response to hydroxychloroquine have been reported in smaller series [7,15].

Hydroxychloroquine is typically prescribed for adults in a dose of 200 mg twice daily. At least two to three months of treatment are often required to achieve initial signs of a response. Because of the slow onset of action, systemic glucocorticoids are sometimes used as interim therapy.

Adverse effects of hydroxychloroquine include gastrointestinal distress, ocular toxicity, and neurologic or hematologic abnormalities. The adverse effects of hydroxychloroquine and recommendations for monitoring for ocular toxicity during hydroxychloroquine therapy are reviewed separately. (See "Antimalarial drugs in the treatment of rheumatic disease", section on 'Adverse effects' and "Antimalarial drugs in the treatment of rheumatic disease", section on 'Routine eye examinations'.)

Refractory disease — Case reports and small series suggest that cyclosporine [4,15,37] and mycophenolate mofetil may be useful for some patients with refractory LPP. These therapies are typically reserved for refractory cases due to concern for their adverse effects and the limited data in support of their efficacy.

Cyclosporine — A beneficial effect of cyclosporine on LPP was suggested in a report in which three patients who failed to respond well to local corticosteroid therapy and hydroxychloroquine had improvement in disease signs and symptoms as well as progression of hair loss with three to five months of cyclosporine treatment (300 mg per day) [37]. Two patients remained symptom-free 12 months after stopping therapy. In a subsequent series, 10 of 13 patients with LPP were reported to have improvements in clinical and hair count assessments after treatment with cyclosporine [15]. The authors observed that doses between 4 and 5 mg/kg per day and treatment courses of four to five months seemed to yield the best responses. In this series, relapse was common within the first year of treatment.

When treating patients with cyclosporine, we typically utilize doses between 3 and 5 mg/kg per day. Our typical duration of treatment is 4 to 8 months, after which we monitor disease progression every 4 weeks for at least 12 months. Side effects of cyclosporine are reviewed separately. (See "Pharmacology of cyclosporine and tacrolimus", section on 'Side effects'.)

Mycophenolate mofetil — Mycophenolate mofetil has a more benign side effect profile than cyclosporine and a few reports suggest that the drug may be useful in some patients with refractory disease. A retrospective case series documented the use of mycophenolate mofetil (0.5 g twice daily for four weeks, then 1 g twice daily for at least 20 weeks) in 16 patients with LPP who had failed one or more other systemic treatments [51]. Among the 12 patients who completed at least 24 weeks of treatment (four patients withdrew due to mild adverse effects), 42 percent were classified as complete responders (>85 percent improvement in LPP Activity Index [LPPAI] score), 42 percent were partial responders (25 to 85 percent improvement in LPPAI score), and 17 percent were treatment failures (<25 percent improvement in LPPAI score).

In a separate series in which 10 patients with LPP were treated with mycophenolate mofetil after failing to respond to hydroxychloroquine, 3 (30 percent) improved after treatment with mycophenolate mofetil (defined by absence of symptoms, lack of progression, reduction in erythema and follicular hyperkeratosis, and ability to discontinue therapy) [50].

Improvement with mycophenolate mofetil is usually apparent within the first six months of therapy [51]. We usually treat adults with 1 g of mycophenolate mofetil twice daily. Adverse effects of mycophenolate mofetil are reviewed separately.

Other therapies — Although improvement in LPP during oral pioglitazone therapy has been reported in a case report, case series, and uncontrolled studies, relatively few of these patients have achieved complete remission and further study is necessary to confirm efficacy of the drug [52-55]. Additional treatments that have been reported to be effective in small numbers of patients with LPP include tetracyclines [46,50], griseofulvin [7], minoxidil [46], naltrexone [56], and the 308 nm excimer laser [57].

Treatment with oral retinoids has been attempted based upon reports of successful use of these drugs for lichen planus [58]. However, there are few data to support their efficacy in LPP [45]. In addition, the additional hair loss that can occur as a side effect of oral retinoids can be distressing for patients who already have hair loss from LPP.

Frontal fibrosing alopecia — The best approach to the treatment of frontal fibrosing alopecia (FFA) remains unclear. The response to topical corticosteroids has been disappointing [45]. The response to intralesional corticosteroids, which are commonly used as first-line treatment, is variable [8,10,45,59]. Systemic therapies that have been associated with at least partial responses include hydroxychloroquine [8,11,49], finasteride [8], finasteride plus minoxidil [19], dutasteride [8,60,61], and oral glucocorticoids [27].

Our typical first-line regimen consists of a combination of intralesional injection of triamcinolone acetonide (2.5 to 5 mg/mL) every four to six weeks into areas of active disease, a mid-potency to high-potency topical corticosteroid applied once daily, and topical minoxidil (5% solution or foam) applied once daily. We instruct patients to apply minoxidil first. Once the site of application of minoxidil is dry, application of the topical corticosteroid can follow.

Graham-Little-Piccardi-Lasseur syndrome — Compared with FFA, there are even fewer data to guide the management of Graham-Little-Piccardi-Lasseur syndrome (GLPLS). Scalp involvement often fails to respond to medical intervention. Responses to topical or intralesional corticosteroids, systemic glucocorticoids, retinoids, and/or psoralen plus ultraviolet A (PUVA) phototherapy are variable [12,62]. Cyclosporine (4 mg/kg per day) was linked to partial improvement in one patient [33].

COSMETIC MEASURES — The cosmetic effects of scalp and eyebrow hair loss from lichen planopilaris (LPP) can be psychologically distressing for patients. Patients who are interested in reducing the visibility of hair loss can benefit from nonsurgical cosmetic interventions and hair transplantation.

Products and techniques — Patients with LPP should be advised about different possibilities of camouflaging hair loss. Options include hair styling techniques and the use of hair pieces, wigs, hair powder, and hair color. A cosmetologist with experience in dealing with patients with hair loss can be a valuable resource. Patients with eyebrow hair loss may benefit from eyebrow tattooing, a form of permanent makeup.

Hair transplantation — Hair transplantation and scalp reduction are surgical techniques that aim to restore hair coverage on the scalp. To achieve the best results, the patient must have a sufficient amount of healthy scalp hair for donation and the inflammatory process must be quiescent and stable prior to treatment. We perform a scalp biopsy from the margin of an alopecic patch to confirm the absence of active inflammation before these procedures. Of note, LPP has been reported to occur after hair transplantation surgery in patients without a history of LPP [63-65].

Case reports suggest that patients with frontal fibrosing alopecia (FFA) are at risk for poor long-term results from hair transplantation [66-68]. A retrospective study of 51 patients with FFA who underwent hair transplantation found that although 42 (82 percent) reported satisfaction with the procedure, mean graft survival rates after one, two, three, and five years were 87 percent (n = 51), 71 percent (n = 51), 60 percent (n = 38), and 41 percent (n = 12), respectively.

PATIENT SUPPORT — The Scarring Alopecia Foundation is a useful resource for patient information and patient support.

SUMMARY AND RECOMMENDATIONS

●Classification – Lichen planopilaris (LPP) is an uncommon hair disorder that is classified as a primary lymphocytic cicatricial alopecia and is considered a follicular variant of lichen planus. There are three major variants of LPP: classic LPP, frontal fibrosing alopecia (FFA), and Graham-Little-Piccardi-Lasseur syndrome (GLPLS). (See 'Introduction' above and 'Classification' above.)

●Epidemiology – LPP most commonly occurs in adults. Women are more likely to be affected than men. Most reported cases of FFA have occurred in postmenopausal women. (See 'Epidemiology' above.)

●Clinical features:

•Classic lichen planopilaris – The major clinical features of classic LPP are perifollicular erythema, perifollicular hyperkeratosis, and skin-colored or erythematous patches of alopecia on the scalp (picture 1). Patients may experience symptoms of itching, burning, or scalp tenderness. In addition, patients may have accompanying cutaneous, mucosal, or nail findings of lichen planus. (See 'Classic lichen planopilaris' above.)

•Frontal fibrosing alopecia – Frontal fibrosing alopecia (FFA) is characterized by progressive, band-like frontotemporal hair loss that results in the appearance of a receding frontal hairline (picture 2). Often, a few spared hairs can be found within the area of alopecia ("lonely hair sign"). Eyebrow involvement is common. Patients may also exhibit hair loss in the axillary, pubic, beard, or limb areas. (See 'Frontal fibrosing alopecia' above.)

•Graham-Little-Piccardi-Lasseur syndrome – Graham-Little-Piccardi-Lasseur syndrome (GLPLS) is a rare variant of LPP that is defined by the presence of three features. Patients exhibit cicatricial alopecia of the scalp, noncicatricial alopecia involving axillary and pubic hair, and a lichenoid follicular eruption. (See 'Graham-Little-Piccardi-Lasseur syndrome' above.)

●Clinical course – The clinical course of LPP is unpredictable. The condition may stabilize or continue to slowly progress over time. (See 'Clinical course' above.)

●Diagnosis – The diagnosis of LPP is based upon the clinical examination and biopsy results (picture 3). A biopsy should always be performed to confirm a diagnosis of LPP. Proper selection of the biopsy site is crucial. (See 'Diagnosis' above.)

●Treatment – There is a paucity of high-quality data on treatments for LPP resulting in uncertainty about the best approach to patient management. For patients with active, slowly progressing classic LPP, we suggest topical or intralesional corticosteroid therapy as initial treatment based upon limited data that suggest efficacy in some patients and the relative safety of these therapies (Grade 2C). (See 'First-line therapy' above.)

We treat classic LPP patients who fail to respond to local corticosteroid therapy or who present with rapidly progressing disease or extensive disease with systemic therapy. Commonly used treatments include systemic glucocorticoids and hydroxychloroquine. Patients with disease that is refractory to these treatments may benefit from cyclosporine or mycophenolate mofetil. Additional studies will be useful for confirming the efficacy of these and other systemic agents. (See 'Second-line therapy' above and 'Refractory disease' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Nina Otberg, MD, who contributed to an earlier version of this topic review.