PATIENT PRESENTATION A 47-year-old female presented with an itchy scalp that had begun 7 months earlier and eventually progressed to regression of her hairline. She noted no other changes in her scalp and reported no other medical problems or skin conditions. No treatments had been attempted for this condition. On exam, perifollicular erythema and slight follicular hyperkeratosis were noted. These changes were mainly isolated to the frontal hairline. What’s Your Diagnosis? Can you describe the histological changes expected?
Diagnosis: Lichen Planopilaris
Lichen planopilaris (LPP), also sometimes called lichen follicularis or follicular lichen planus, was originally described by Pringle in 1895.1 Lichen planopilaris is a cutaneous inflammatory disease that is characterized by a lymphocytic destruction of the hair follicle resulting in scaling, atrophy, and cicatricial alopecia. The prevalence is not known.
Epidemiology
LPP is one of the most common causes of adult primary cicatricial alopecia. It is more common in women, with an average age of onset between 40 and 60 years. 2,3,4 The incidence of LPP in conjunction with lichen planus (LP) is variable, reportedly ranging from 17% to 28%.5 Lichenoid reactions such as LP and LPP have been found to have associations with chronic liver disease, chronic bowel disease, diabetes, thyroiditis, thymoma, malignancy, trauma, and occasionally stress. 4 It is important to note that no large evidence-based studies have established definitive associations with LPP.
Clinical Findings and Differential Diagnosis
Lichen planopilaris can be subdivided into several variants. The three more commonly seen are classic LPP, frontal fibrosing alopecia (FFA), and Lassueur Graham-Little Piccardi syndrome (LGLPS). All three share clinical, histopathologic and immunohistopathologic findings. 4 Classic LPP involves the scalp and may be accompanied with extra-cranial lichen planus lesions. FFA usually affects post-menopausal, middle-aged women and is characterized by progressive, band-like cicatricial alopecia of the frontal hairline. 6 Lassueur Graham-Little Piccardi syndrome, also known as Graham-Little Syndrome, is characterized by a triad of scarring alopecia of the scalp, widespread lichenoid follicular eruption and non-scarring alopecia of axillary and pubic areas. 7 It is not clear why only some of the affected regions in LGLPS scar, nor has the pathoetiology of this disease been well established. The differential diagnosis for LPP includes the other lymphocytic cicatricial alopecias, such as chronic cutaneous lupus erythematosus, pseudopelade of Brocq, central centrifugal cicatricial alopecia, alopecia mucinosa and keratosis follicularis spinulosa decalvans. 8 Distinguishing LPP from other cicatricial alopecias is often difficult, requiring both histopathologic and clinical correlation. There are those who consider pseudopelade of Brocq, originally described in 1885, as end-stage LPP rather than being a distinct entity. 9,10 However, others believe that sufficient clinicopathologic studies of the various stages of lesions have not been carried out, and that the absence of follicular plugging in addition to preserved elastic fibers support the concept of pseudopelade of Brocq as a distinct entity. 11 The clinical findings of early LPP lesions can be identified with the aid of dermoscopy or videomicroscopy. These early lesions include perifollicular violaceous erythema, scaling and groups of keratotic follicular papules. The active lesions are often located in the periphery of the area of alopecia, in contrast to chronic cutaneous lupus erythematosus (CCLE), which has predominantly central activity. 11 A positive pull test of anagen hairs, although subjective, cannot determine the exact diagnosis but it can confirm disease activity. The pull test requires that the patient abstain from shampooing for 24 hours, after which a small clump of hair (approximately 60 strands) are grasped in the thumb, index and middle fingers, and pulled with gentle but firm pressure. Hairs are counted and active shedding is diagnosed if greater than 6 hairs are shed. 12 Violaceous perifollicular erythema can be subtle, and without hair shedding; some islands of hair affected by the inflammatory process can even persist in the center of the bald area.9 The patches of alopecia are often centrifugal and regress from the frontal hair line. The patches may vary in size and can coalesce into a reticulated pattern and progress to involve the entire scalp. 4,13,14 The inflammation often resolves spontaneously, leaving scars without follicular units. The scars can be atrophic. LPP patients often complain of pruritus and dysesthesia. Environmental factors can aggravate this presentation9,15 . The course of LPP varies significantly between patients. Some patients experience very active and widespread disease, while others have lesions that are more isolated and slower growing. 9
Histopathology
The diagnosis of LPP is suggested based on clinical presentation, but a biopsy is recommended to confirm the diagnosis.16 A biopsy should be performed in the hair-bearing margin in the periphery of alopecia in an active, inflammatory lesion. Multiple biopsies are sometimes required to achieve a definitive diagnosis. 3,16 Biopsies from the central, late-stage “burned out” areas may reveal nothing more than a follicular scar, and often are not helpful in specifying the diagnosis. In early active lesions, histopathology reveals a dense perifollicular lymphocytic infiltrate that rarely involves the interfollicular epidermis. 8 The lymphocytic infiltrate involves the upper portion of the hair follicle (the infundibulum and isthmus), unlike that seen in alopecia areata, where the lymphocytic infiltrate is concentrated primarily in the lower aspect of the hair follicle. 11 In contrast to CCLE, in LPP the vascular plexus is not affected and mucin deposits are absent.8 CCLE has a primarily vacuolar interface change, while the interface change in LPP is primarily lichenoid, may have vacuolar change, and often does not involve the interfollicular epidermis. Pseudopelade of Brocq lacks interface change entirely. 11,16 The nonspecific findings of hyperkeratosis, hypergranulosis, acanthosis and degeneration of basal keratinocytes are also seen in LPP. 2,3,4,9 Numerous colloid bodies can be found in close proximity to the follicular epithelium and may be one of the more reliable distinguishing features in LPP.11 The biopsy of an end-stage lesion of LPP will not aid in the diagnosis, as the findings are similar in all late-stage lesions of other primary cicatricial alopecias. The late-phase lesions of LPP may have little-to-no inflammation. 17 The lichenoid changes may no longer be present and may be replaced with perifollicular fibrosis; likewise, the hair follicles may be replaced with fibrous tracts in association with the loss of sebaceous glands. 8,16,18 Elastic tissue stains can help differentiate patients with CCLE from other cicatricial alopecias. In CCLE, there is fibrosis and loss of elastic fibers throughout the reticular dermis, while late stages of LPP have only wedge-shaped elastic fiber destruction in localized perifollicular areas. 19 In contrast, elastic fibers are markedly thickened in pseudopelade of Brocq. 12 Direct immunofluorescence is often nonspecific in LPP; however, 40% of LPP cases show positive staining for IgM, less commonly IgA or C3. 2,20,21 LPP may show globular IgM deposits at the dermoepidermal junction, unlike the linear, granular deposition of immunoreactants at the dermoepidermal junction, as seen in CCLE. 11
Physiopathology
The etiology and pathogenesis of LPP are poorly understood, although it is widely accepted that LPP may have an autoimmune origin. In LPP, T-lymphocytes recognize an unknown antigen expressed on the surface of keratinocytes located in the bulge area of the follicle. The bulge-isthmus area serves as a reservoir for follicular stem cells. Keratinocyte antigen recognition initiates lymphocyte activation and the subsequent destruction of the follicular stem cells, preventing anagen hair follicle regeneration. This may explain the scarring nature of LPP. In contrast, scarring is not classically seen in alopecia areata as lymphocytic involvement primarily involves the lower portion of the follicle and spares the stem cell containing bulge-isthmus area. 4,11,22 Other suggested hypotheses include sebaceous gland disruption23 and/or destruction of the outer root sheath. 11,24 Although not proven, it has been proposed that this cell-mediated reaction may be initiated by some prior sensitization to an exogenous or endogenous agent binding to keratinocytes. 25,26,27 Some have suggested that infection may play a role in development of not only lichen planus but LPP. The proposed infections include hepatitis C virus, human immunodeficiency virus, herpes simplex virus 2, Helicobacter pylori, human papillomavirus and syphilis, although this has not been proven. 4
Treatment
LPP is often difficult to treat, as relapses are common and many patients are treatment-resistant. Long-term follow-up studies comparing the therapeutic effects with biopsies or hair count have not been published. 9 However, it appears that early diagnosis and treatment is important to prevent inflammation and spread.4 For patients with less than 10% scalp involvement, intralesional triamcinolone acetonide injections (10mg/mL) for a total of 2 mL every 4 to 6 weeks are recommended and can be used in conjunction with topical high potency corticosteroids. 5,28 Side effects of corticosteroid use should be monitored and other treatments should be considered if symptoms remain treatment-resistant. 4 Systemic corticosteroids can be used for rapidly progressive disease and in bridging to other agents. 2 However, up to 80% of patients have been shown to relapse after ceasing systemic therapy. 4 It is suggested that patients be offered stepwise therapy with doxycycline or hydroxychloroquine as a first-line systemic agent; data does not suggest that one is superior to the other. Hydroxychloroquine may take up to 6 to 12 months for maximal efficacy, with the first noticeable benefits occurring within 2 to 3 months. 16,29,30 If LPP is recalcitrant, patients may be transitioned to mycophenolate mofetil, with a recommended dosage of 500 mg twice daily for 4 weeks and sustained for 5 to 6 months at a dose of 1g twice daily. 29,31 Retinoids, such as isotretinoin, and acitretin therapy, have shown some benefit in LPP. Isotretinoin can be started at a dose of 1 mg/kg/day and maintained for 8 months. Acitretin can be used at a low dose as well, increasing up to 0.6 mg/kg/day. While the mechanism of action of retinoids in LPP is unknown, it is thought to normalize hair follicular keratinocyte antigen expression or suppression of the inflammatory cellular infiltrate with new options including PPAR receptor modification. 32 The possible benefits of these systemic therapies must be weighed against the potential for adverse effects, and relapses may occur shortly after discontinuation of therapy. Other controversial treatments in LPP patients include topical minoxidil 5% solution, thalidomide, topical tacrolimus and dapsone. 3,33,34,35,36,37 After inflammation has ceased for greater than 2 years, surgical scalp reduction or hair transplantation may be attempted. 38 In the case described here, the patient refused treatment.
Summary and Conclusion
Lichen planopilaris is a rare, chronic lymphocytic cicatricial alopecia occurring predominantly in women. LPP is difficult to distinguish from other cicatricial alopecias. The diagnosis requires a detailed clinical history coupled with histopathology, and oftentimes, direct immunofluorescence. Treatment options depend on the disease severity, often requiring the use of a combination of topical, intralesional and oral medications. LPP is a challenging disease to manage, as there are no curative therapies, and relapses are common. Further research and clinical studies are necessary for insight into the pathophysiology and effective treatment of lichen planopilaris. Dr. Rashid is with MD Anderson Cancer Center, Houston, TX. Ms. Thomassie is a fourth year medical student at the Louisiana State University School of Medicine, New Orleans, LA. Dr. Khachemoune, the Section Editor of Derm Dx, is with Department of Dermatology, State University of New York, Brooklyn, NY. Disclosure: The authors have no conflicts of interest with any material presented in this column.
PATIENT PRESENTATION A 47-year-old female presented with an itchy scalp that had begun 7 months earlier and eventually progressed to regression of her hairline. She noted no other changes in her scalp and reported no other medical problems or skin conditions. No treatments had been attempted for this condition. On exam, perifollicular erythema and slight follicular hyperkeratosis were noted. These changes were mainly isolated to the frontal hairline. What’s Your Diagnosis? Can you describe the histological changes expected?
Diagnosis: Lichen Planopilaris
Lichen planopilaris (LPP), also sometimes called lichen follicularis or follicular lichen planus, was originally described by Pringle in 1895.1 Lichen planopilaris is a cutaneous inflammatory disease that is characterized by a lymphocytic destruction of the hair follicle resulting in scaling, atrophy, and cicatricial alopecia. The prevalence is not known.
Epidemiology
LPP is one of the most common causes of adult primary cicatricial alopecia. It is more common in women, with an average age of onset between 40 and 60 years. 2,3,4 The incidence of LPP in conjunction with lichen planus (LP) is variable, reportedly ranging from 17% to 28%.5 Lichenoid reactions such as LP and LPP have been found to have associations with chronic liver disease, chronic bowel disease, diabetes, thyroiditis, thymoma, malignancy, trauma, and occasionally stress. 4 It is important to note that no large evidence-based studies have established definitive associations with LPP.
Clinical Findings and Differential Diagnosis
Lichen planopilaris can be subdivided into several variants. The three more commonly seen are classic LPP, frontal fibrosing alopecia (FFA), and Lassueur Graham-Little Piccardi syndrome (LGLPS). All three share clinical, histopathologic and immunohistopathologic findings. 4 Classic LPP involves the scalp and may be accompanied with extra-cranial lichen planus lesions. FFA usually affects post-menopausal, middle-aged women and is characterized by progressive, band-like cicatricial alopecia of the frontal hairline. 6 Lassueur Graham-Little Piccardi syndrome, also known as Graham-Little Syndrome, is characterized by a triad of scarring alopecia of the scalp, widespread lichenoid follicular eruption and non-scarring alopecia of axillary and pubic areas. 7 It is not clear why only some of the affected regions in LGLPS scar, nor has the pathoetiology of this disease been well established. The differential diagnosis for LPP includes the other lymphocytic cicatricial alopecias, such as chronic cutaneous lupus erythematosus, pseudopelade of Brocq, central centrifugal cicatricial alopecia, alopecia mucinosa and keratosis follicularis spinulosa decalvans. 8 Distinguishing LPP from other cicatricial alopecias is often difficult, requiring both histopathologic and clinical correlation. There are those who consider pseudopelade of Brocq, originally described in 1885, as end-stage LPP rather than being a distinct entity. 9,10 However, others believe that sufficient clinicopathologic studies of the various stages of lesions have not been carried out, and that the absence of follicular plugging in addition to preserved elastic fibers support the concept of pseudopelade of Brocq as a distinct entity. 11 The clinical findings of early LPP lesions can be identified with the aid of dermoscopy or videomicroscopy. These early lesions include perifollicular violaceous erythema, scaling and groups of keratotic follicular papules. The active lesions are often located in the periphery of the area of alopecia, in contrast to chronic cutaneous lupus erythematosus (CCLE), which has predominantly central activity. 11 A positive pull test of anagen hairs, although subjective, cannot determine the exact diagnosis but it can confirm disease activity. The pull test requires that the patient abstain from shampooing for 24 hours, after which a small clump of hair (approximately 60 strands) are grasped in the thumb, index and middle fingers, and pulled with gentle but firm pressure. Hairs are counted and active shedding is diagnosed if greater than 6 hairs are shed. 12 Violaceous perifollicular erythema can be subtle, and without hair shedding; some islands of hair affected by the inflammatory process can even persist in the center of the bald area.9 The patches of alopecia are often centrifugal and regress from the frontal hair line. The patches may vary in size and can coalesce into a reticulated pattern and progress to involve the entire scalp. 4,13,14 The inflammation often resolves spontaneously, leaving scars without follicular units. The scars can be atrophic. LPP patients often complain of pruritus and dysesthesia. Environmental factors can aggravate this presentation9,15 . The course of LPP varies significantly between patients. Some patients experience very active and widespread disease, while others have lesions that are more isolated and slower growing. 9
Histopathology
The diagnosis of LPP is suggested based on clinical presentation, but a biopsy is recommended to confirm the diagnosis.16 A biopsy should be performed in the hair-bearing margin in the periphery of alopecia in an active, inflammatory lesion. Multiple biopsies are sometimes required to achieve a definitive diagnosis. 3,16 Biopsies from the central, late-stage “burned out” areas may reveal nothing more than a follicular scar, and often are not helpful in specifying the diagnosis. In early active lesions, histopathology reveals a dense perifollicular lymphocytic infiltrate that rarely involves the interfollicular epidermis. 8 The lymphocytic infiltrate involves the upper portion of the hair follicle (the infundibulum and isthmus), unlike that seen in alopecia areata, where the lymphocytic infiltrate is concentrated primarily in the lower aspect of the hair follicle. 11 In contrast to CCLE, in LPP the vascular plexus is not affected and mucin deposits are absent.8 CCLE has a primarily vacuolar interface change, while the interface change in LPP is primarily lichenoid, may have vacuolar change, and often does not involve the interfollicular epidermis. Pseudopelade of Brocq lacks interface change entirely. 11,16 The nonspecific findings of hyperkeratosis, hypergranulosis, acanthosis and degeneration of basal keratinocytes are also seen in LPP. 2,3,4,9 Numerous colloid bodies can be found in close proximity to the follicular epithelium and may be one of the more reliable distinguishing features in LPP.11 The biopsy of an end-stage lesion of LPP will not aid in the diagnosis, as the findings are similar in all late-stage lesions of other primary cicatricial alopecias. The late-phase lesions of LPP may have little-to-no inflammation. 17 The lichenoid changes may no longer be present and may be replaced with perifollicular fibrosis; likewise, the hair follicles may be replaced with fibrous tracts in association with the loss of sebaceous glands. 8,16,18 Elastic tissue stains can help differentiate patients with CCLE from other cicatricial alopecias. In CCLE, there is fibrosis and loss of elastic fibers throughout the reticular dermis, while late stages of LPP have only wedge-shaped elastic fiber destruction in localized perifollicular areas. 19 In contrast, elastic fibers are markedly thickened in pseudopelade of Brocq. 12 Direct immunofluorescence is often nonspecific in LPP; however, 40% of LPP cases show positive staining for IgM, less commonly IgA or C3. 2,20,21 LPP may show globular IgM deposits at the dermoepidermal junction, unlike the linear, granular deposition of immunoreactants at the dermoepidermal junction, as seen in CCLE. 11
Physiopathology
The etiology and pathogenesis of LPP are poorly understood, although it is widely accepted that LPP may have an autoimmune origin. In LPP, T-lymphocytes recognize an unknown antigen expressed on the surface of keratinocytes located in the bulge area of the follicle. The bulge-isthmus area serves as a reservoir for follicular stem cells. Keratinocyte antigen recognition initiates lymphocyte activation and the subsequent destruction of the follicular stem cells, preventing anagen hair follicle regeneration. This may explain the scarring nature of LPP. In contrast, scarring is not classically seen in alopecia areata as lymphocytic involvement primarily involves the lower portion of the follicle and spares the stem cell containing bulge-isthmus area. 4,11,22 Other suggested hypotheses include sebaceous gland disruption23 and/or destruction of the outer root sheath. 11,24 Although not proven, it has been proposed that this cell-mediated reaction may be initiated by some prior sensitization to an exogenous or endogenous agent binding to keratinocytes. 25,26,27 Some have suggested that infection may play a role in development of not only lichen planus but LPP. The proposed infections include hepatitis C virus, human immunodeficiency virus, herpes simplex virus 2, Helicobacter pylori, human papillomavirus and syphilis, although this has not been proven. 4
Treatment
LPP is often difficult to treat, as relapses are common and many patients are treatment-resistant. Long-term follow-up studies comparing the therapeutic effects with biopsies or hair count have not been published. 9 However, it appears that early diagnosis and treatment is important to prevent inflammation and spread.4 For patients with less than 10% scalp involvement, intralesional triamcinolone acetonide injections (10mg/mL) for a total of 2 mL every 4 to 6 weeks are recommended and can be used in conjunction with topical high potency corticosteroids. 5,28 Side effects of corticosteroid use should be monitored and other treatments should be considered if symptoms remain treatment-resistant. 4 Systemic corticosteroids can be used for rapidly progressive disease and in bridging to other agents. 2 However, up to 80% of patients have been shown to relapse after ceasing systemic therapy. 4 It is suggested that patients be offered stepwise therapy with doxycycline or hydroxychloroquine as a first-line systemic agent; data does not suggest that one is superior to the other. Hydroxychloroquine may take up to 6 to 12 months for maximal efficacy, with the first noticeable benefits occurring within 2 to 3 months. 16,29,30 If LPP is recalcitrant, patients may be transitioned to mycophenolate mofetil, with a recommended dosage of 500 mg twice daily for 4 weeks and sustained for 5 to 6 months at a dose of 1g twice daily. 29,31 Retinoids, such as isotretinoin, and acitretin therapy, have shown some benefit in LPP. Isotretinoin can be started at a dose of 1 mg/kg/day and maintained for 8 months. Acitretin can be used at a low dose as well, increasing up to 0.6 mg/kg/day. While the mechanism of action of retinoids in LPP is unknown, it is thought to normalize hair follicular keratinocyte antigen expression or suppression of the inflammatory cellular infiltrate with new options including PPAR receptor modification. 32 The possible benefits of these systemic therapies must be weighed against the potential for adverse effects, and relapses may occur shortly after discontinuation of therapy. Other controversial treatments in LPP patients include topical minoxidil 5% solution, thalidomide, topical tacrolimus and dapsone. 3,33,34,35,36,37 After inflammation has ceased for greater than 2 years, surgical scalp reduction or hair transplantation may be attempted. 38 In the case described here, the patient refused treatment.
Summary and Conclusion
Lichen planopilaris is a rare, chronic lymphocytic cicatricial alopecia occurring predominantly in women. LPP is difficult to distinguish from other cicatricial alopecias. The diagnosis requires a detailed clinical history coupled with histopathology, and oftentimes, direct immunofluorescence. Treatment options depend on the disease severity, often requiring the use of a combination of topical, intralesional and oral medications. LPP is a challenging disease to manage, as there are no curative therapies, and relapses are common. Further research and clinical studies are necessary for insight into the pathophysiology and effective treatment of lichen planopilaris. Dr. Rashid is with MD Anderson Cancer Center, Houston, TX. Ms. Thomassie is a fourth year medical student at the Louisiana State University School of Medicine, New Orleans, LA. Dr. Khachemoune, the Section Editor of Derm Dx, is with Department of Dermatology, State University of New York, Brooklyn, NY. Disclosure: The authors have no conflicts of interest with any material presented in this column.
PATIENT PRESENTATION A 47-year-old female presented with an itchy scalp that had begun 7 months earlier and eventually progressed to regression of her hairline. She noted no other changes in her scalp and reported no other medical problems or skin conditions. No treatments had been attempted for this condition. On exam, perifollicular erythema and slight follicular hyperkeratosis were noted. These changes were mainly isolated to the frontal hairline. What’s Your Diagnosis? Can you describe the histological changes expected?
Diagnosis: Lichen Planopilaris
Lichen planopilaris (LPP), also sometimes called lichen follicularis or follicular lichen planus, was originally described by Pringle in 1895.1 Lichen planopilaris is a cutaneous inflammatory disease that is characterized by a lymphocytic destruction of the hair follicle resulting in scaling, atrophy, and cicatricial alopecia. The prevalence is not known.
Epidemiology
LPP is one of the most common causes of adult primary cicatricial alopecia. It is more common in women, with an average age of onset between 40 and 60 years. 2,3,4 The incidence of LPP in conjunction with lichen planus (LP) is variable, reportedly ranging from 17% to 28%.5 Lichenoid reactions such as LP and LPP have been found to have associations with chronic liver disease, chronic bowel disease, diabetes, thyroiditis, thymoma, malignancy, trauma, and occasionally stress. 4 It is important to note that no large evidence-based studies have established definitive associations with LPP.
Clinical Findings and Differential Diagnosis
Lichen planopilaris can be subdivided into several variants. The three more commonly seen are classic LPP, frontal fibrosing alopecia (FFA), and Lassueur Graham-Little Piccardi syndrome (LGLPS). All three share clinical, histopathologic and immunohistopathologic findings. 4 Classic LPP involves the scalp and may be accompanied with extra-cranial lichen planus lesions. FFA usually affects post-menopausal, middle-aged women and is characterized by progressive, band-like cicatricial alopecia of the frontal hairline. 6 Lassueur Graham-Little Piccardi syndrome, also known as Graham-Little Syndrome, is characterized by a triad of scarring alopecia of the scalp, widespread lichenoid follicular eruption and non-scarring alopecia of axillary and pubic areas. 7 It is not clear why only some of the affected regions in LGLPS scar, nor has the pathoetiology of this disease been well established. The differential diagnosis for LPP includes the other lymphocytic cicatricial alopecias, such as chronic cutaneous lupus erythematosus, pseudopelade of Brocq, central centrifugal cicatricial alopecia, alopecia mucinosa and keratosis follicularis spinulosa decalvans. 8 Distinguishing LPP from other cicatricial alopecias is often difficult, requiring both histopathologic and clinical correlation. There are those who consider pseudopelade of Brocq, originally described in 1885, as end-stage LPP rather than being a distinct entity. 9,10 However, others believe that sufficient clinicopathologic studies of the various stages of lesions have not been carried out, and that the absence of follicular plugging in addition to preserved elastic fibers support the concept of pseudopelade of Brocq as a distinct entity. 11 The clinical findings of early LPP lesions can be identified with the aid of dermoscopy or videomicroscopy. These early lesions include perifollicular violaceous erythema, scaling and groups of keratotic follicular papules. The active lesions are often located in the periphery of the area of alopecia, in contrast to chronic cutaneous lupus erythematosus (CCLE), which has predominantly central activity. 11 A positive pull test of anagen hairs, although subjective, cannot determine the exact diagnosis but it can confirm disease activity. The pull test requires that the patient abstain from shampooing for 24 hours, after which a small clump of hair (approximately 60 strands) are grasped in the thumb, index and middle fingers, and pulled with gentle but firm pressure. Hairs are counted and active shedding is diagnosed if greater than 6 hairs are shed. 12 Violaceous perifollicular erythema can be subtle, and without hair shedding; some islands of hair affected by the inflammatory process can even persist in the center of the bald area.9 The patches of alopecia are often centrifugal and regress from the frontal hair line. The patches may vary in size and can coalesce into a reticulated pattern and progress to involve the entire scalp. 4,13,14 The inflammation often resolves spontaneously, leaving scars without follicular units. The scars can be atrophic. LPP patients often complain of pruritus and dysesthesia. Environmental factors can aggravate this presentation9,15 . The course of LPP varies significantly between patients. Some patients experience very active and widespread disease, while others have lesions that are more isolated and slower growing. 9
Histopathology
The diagnosis of LPP is suggested based on clinical presentation, but a biopsy is recommended to confirm the diagnosis.16 A biopsy should be performed in the hair-bearing margin in the periphery of alopecia in an active, inflammatory lesion. Multiple biopsies are sometimes required to achieve a definitive diagnosis. 3,16 Biopsies from the central, late-stage “burned out” areas may reveal nothing more than a follicular scar, and often are not helpful in specifying the diagnosis. In early active lesions, histopathology reveals a dense perifollicular lymphocytic infiltrate that rarely involves the interfollicular epidermis. 8 The lymphocytic infiltrate involves the upper portion of the hair follicle (the infundibulum and isthmus), unlike that seen in alopecia areata, where the lymphocytic infiltrate is concentrated primarily in the lower aspect of the hair follicle. 11 In contrast to CCLE, in LPP the vascular plexus is not affected and mucin deposits are absent.8 CCLE has a primarily vacuolar interface change, while the interface change in LPP is primarily lichenoid, may have vacuolar change, and often does not involve the interfollicular epidermis. Pseudopelade of Brocq lacks interface change entirely. 11,16 The nonspecific findings of hyperkeratosis, hypergranulosis, acanthosis and degeneration of basal keratinocytes are also seen in LPP. 2,3,4,9 Numerous colloid bodies can be found in close proximity to the follicular epithelium and may be one of the more reliable distinguishing features in LPP.11 The biopsy of an end-stage lesion of LPP will not aid in the diagnosis, as the findings are similar in all late-stage lesions of other primary cicatricial alopecias. The late-phase lesions of LPP may have little-to-no inflammation. 17 The lichenoid changes may no longer be present and may be replaced with perifollicular fibrosis; likewise, the hair follicles may be replaced with fibrous tracts in association with the loss of sebaceous glands. 8,16,18 Elastic tissue stains can help differentiate patients with CCLE from other cicatricial alopecias. In CCLE, there is fibrosis and loss of elastic fibers throughout the reticular dermis, while late stages of LPP have only wedge-shaped elastic fiber destruction in localized perifollicular areas. 19 In contrast, elastic fibers are markedly thickened in pseudopelade of Brocq. 12 Direct immunofluorescence is often nonspecific in LPP; however, 40% of LPP cases show positive staining for IgM, less commonly IgA or C3. 2,20,21 LPP may show globular IgM deposits at the dermoepidermal junction, unlike the linear, granular deposition of immunoreactants at the dermoepidermal junction, as seen in CCLE. 11
Physiopathology
The etiology and pathogenesis of LPP are poorly understood, although it is widely accepted that LPP may have an autoimmune origin. In LPP, T-lymphocytes recognize an unknown antigen expressed on the surface of keratinocytes located in the bulge area of the follicle. The bulge-isthmus area serves as a reservoir for follicular stem cells. Keratinocyte antigen recognition initiates lymphocyte activation and the subsequent destruction of the follicular stem cells, preventing anagen hair follicle regeneration. This may explain the scarring nature of LPP. In contrast, scarring is not classically seen in alopecia areata as lymphocytic involvement primarily involves the lower portion of the follicle and spares the stem cell containing bulge-isthmus area. 4,11,22 Other suggested hypotheses include sebaceous gland disruption23 and/or destruction of the outer root sheath. 11,24 Although not proven, it has been proposed that this cell-mediated reaction may be initiated by some prior sensitization to an exogenous or endogenous agent binding to keratinocytes. 25,26,27 Some have suggested that infection may play a role in development of not only lichen planus but LPP. The proposed infections include hepatitis C virus, human immunodeficiency virus, herpes simplex virus 2, Helicobacter pylori, human papillomavirus and syphilis, although this has not been proven. 4
Treatment
LPP is often difficult to treat, as relapses are common and many patients are treatment-resistant. Long-term follow-up studies comparing the therapeutic effects with biopsies or hair count have not been published. 9 However, it appears that early diagnosis and treatment is important to prevent inflammation and spread.4 For patients with less than 10% scalp involvement, intralesional triamcinolone acetonide injections (10mg/mL) for a total of 2 mL every 4 to 6 weeks are recommended and can be used in conjunction with topical high potency corticosteroids. 5,28 Side effects of corticosteroid use should be monitored and other treatments should be considered if symptoms remain treatment-resistant. 4 Systemic corticosteroids can be used for rapidly progressive disease and in bridging to other agents. 2 However, up to 80% of patients have been shown to relapse after ceasing systemic therapy. 4 It is suggested that patients be offered stepwise therapy with doxycycline or hydroxychloroquine as a first-line systemic agent; data does not suggest that one is superior to the other. Hydroxychloroquine may take up to 6 to 12 months for maximal efficacy, with the first noticeable benefits occurring within 2 to 3 months. 16,29,30 If LPP is recalcitrant, patients may be transitioned to mycophenolate mofetil, with a recommended dosage of 500 mg twice daily for 4 weeks and sustained for 5 to 6 months at a dose of 1g twice daily. 29,31 Retinoids, such as isotretinoin, and acitretin therapy, have shown some benefit in LPP. Isotretinoin can be started at a dose of 1 mg/kg/day and maintained for 8 months. Acitretin can be used at a low dose as well, increasing up to 0.6 mg/kg/day. While the mechanism of action of retinoids in LPP is unknown, it is thought to normalize hair follicular keratinocyte antigen expression or suppression of the inflammatory cellular infiltrate with new options including PPAR receptor modification. 32 The possible benefits of these systemic therapies must be weighed against the potential for adverse effects, and relapses may occur shortly after discontinuation of therapy. Other controversial treatments in LPP patients include topical minoxidil 5% solution, thalidomide, topical tacrolimus and dapsone. 3,33,34,35,36,37 After inflammation has ceased for greater than 2 years, surgical scalp reduction or hair transplantation may be attempted. 38 In the case described here, the patient refused treatment.
Summary and Conclusion
Lichen planopilaris is a rare, chronic lymphocytic cicatricial alopecia occurring predominantly in women. LPP is difficult to distinguish from other cicatricial alopecias. The diagnosis requires a detailed clinical history coupled with histopathology, and oftentimes, direct immunofluorescence. Treatment options depend on the disease severity, often requiring the use of a combination of topical, intralesional and oral medications. LPP is a challenging disease to manage, as there are no curative therapies, and relapses are common. Further research and clinical studies are necessary for insight into the pathophysiology and effective treatment of lichen planopilaris. Dr. Rashid is with MD Anderson Cancer Center, Houston, TX. Ms. Thomassie is a fourth year medical student at the Louisiana State University School of Medicine, New Orleans, LA. Dr. Khachemoune, the Section Editor of Derm Dx, is with Department of Dermatology, State University of New York, Brooklyn, NY. Disclosure: The authors have no conflicts of interest with any material presented in this column.
