Histologically, cicatricial alopecia of the scalp is characterized by an interface dermatitis and a lichenoid lymphocytic infiltrate of the isthmus and infundibulum of the hair follicle sparing the bulb (Figure). A follicular plug is present in the active border. The increased pressure from the keratinous plug from above and the pressure from the infiltrate from the sides has been proposed to decrease the blood supply to the follicle and result in its death.2 Late-stage disease is notable for fibrotic longitudinal tracks of the hair follicle, perifollicular lamellar fibrosis, and adjacent epidermal atrophy.20 Direct immunofluorescence in GLPL generally is negative. A trichogram performed in a 29-year-old woman with GLPL was normal, with 84% anagen, 2% catagen, and 14% telogen hairs. It was noted that 10% of the sampled hairs were classified as dystrophical dysplastic hairs.12 Despite the lack of fibrosis on physical examination in patients with GLPL, nonscarring alopecia of the axilla and groin may show follicular destruction on microscopic examination.1 The pathology of the papules present on the trunk and extremities—whether that of keratosis pilaris or lichen spinulosus—demonstrates similar hyperkeratosis, hypergranulosis, and follicular plugging with a possible superficial, perivascular, lymphocytic infiltrate.
A and B, Mild scarring alopecia with isthmic fibroplasia consistent with early lichen planopilaris in a patient with Graham-Little-Piccardi- Lassueur syndrome (H&E, original magnifications ×10 and ×40).
The differential diagnosis of GLPL includes other variants of LPP as well as discoid lupus erythematous (DLE), pseudopelade of Brocq, pityriasis rubra pilaris, sarcoidosis, acne keloidalis, central centrifugal scarring alopecia, follicular mucinosis, and folliculitis decalvans.14 Differentiation of LPP from DLE is difficult. Clinical clues include lack of central erythema and telangiectases within the lesions. Histologically, the lymphocytic dermatitis and folliculitis can be indistinguishable, but subtle findings suggesting DLE may be present, such as increased mucin in the reticular dermis, a focally thinned epidermis, and less severe dermal sclerosis when compared to cases of LPP.2 Direct immunofluorescence with IgG and C3 revealing linear granular deposits at the dermoepidermal junction is characteristic of DLE.20 Pseudopelade of Brocq is best thought of as an end-stage clinical pattern of hair loss in LPP rather than a separate condition. It is considered to be the end point of GLPL as well as DLE and others when the inflammation has subsided and the cicatricial alopecia is stable. For the duration of active disease, GLPL is classified as an unstable cicatricial alopecia that has a tendency to progress and recur periodically.20 Folliculitis decalvans also can mimic GLPL during a period when the pustules have resolved; however, a neutrophilic infiltrate will be present.
The goal of treatment in GLPL as well as other scarring alopecias is to stop the progression of hair loss. Early diagnosis is imperative if control is to be gained before considerable hair loss has occurred. Once follicular destruction has occurred as a result of the inflammation, there is minimal potential for hair rejuvenation.21 To date, treatment has been mostly fruitless, except in the management of keratosis pilaris that accompanies GLPL. First-line therapy often includes topical corticosteroids with or without intralesional corticosteroids. Systemic corticosteroids, retinoids, and psoralen plus UVA therapy also are frequently employed.1,2 Success in treating GLPL with cyclosporine A at a dosage of 4 mg/kg daily was described in several studies.1,2,15 Treatment resulted in reduction of perifollicular erythema and follicular hyperkeratotic papules as well as mild hair regrowth within the scarring patches.15 Nonetheless, cyclosporine A may prove useful in the initial inflammatory phase of GLPL. Consequently, cyclosporine A also is associated with a high relapse rate.1,2
Because the number of patients with GLPL is so few, therapy should mirror advances being made in treatments for other variants of LPP. More recent studies of LPP treatment with hydroxychloroquine showed opposing results, though the safety profile of this agent makes it an enticing treatment option.22,23 Tetracyclines showed improvement in 4 of 15 (26.7%) patients in a retrospective study by Spencer et al.24 Another retrospective study showed promising results with the potent 5-alpha reductase inhibitor dutasteride with 7 of 10 (70%) postmenopausal patients reporting stabilization over a mean duration of 28 months with no reported side effects.25 Antimalarial medications also have been implemented as adjunct therapies with mixed results.5 A case of a 26-year-old man with GLPL from South India showed systemic disease improvement following treatment with pulsed systemic steroids, isotretinoin, and anxiolytics.7 Chloroquine phosphate at a daily dose of 150 mg for 3 to 9 months yielded a transient response in one postmenopausal patient with frontal fibrosing alopecia.6 Stabilization of hair loss was achieved with a combination of hydroxychloroquine and doxycycline in a woman with GLPL who was previously unresponsive to tacrolimus ointment.10 Thalidomide showed early promise in an isolated report claiming successful treatment of LPP,26 but there is contradictory evidence, as thalidomide showed no benefit in a series of 4 patients with LPP.27
Peroxisome proliferator–activated receptor gamma (PPAR-γ), a transcription factor that regulates genes, is downregulated in LPP.28 Deletion of PPAR-γ within follicular stem cells in mice results in a phenotype similar to cicatricial alopecia. Data have supported the role of PPAR-γ in maintaining the pilosebaceous unit. A case report of pioglitazone (PPAR-γ agonist) therapy used at 15 mg daily for 8 months was successful in treating a patient with LPP.28 Further investigation must be conducted to evaluate these treatments since early attenuation of the disease process is crucial to the reduction of permanent hair loss.
Advances in the early recognition and successful treatment of GLPL are dependent on continued research in all variants of LPP. Randomized controlled trials are necessary to establish standard of care. Further studies should target the association of GLPL and other autoimmune phenomena. Moreover, research into the etiology will provide direction in understanding disease progression and outcome.