Clinicopathologic lessons in distinguishing cicatricial alopecia: 7 Cases of lichen planopilaris misdiagnosed as discoid lupus
Authors: Vinod E. Nambudiri, Ruth Ann Vleugels, Alvaro C. Laga, Lynne J. Goldberg
Journal: Journal of the American Academy of Dermatology (2014)

To the Editor: Cicatricial alopecia represents a complex set of scarring hair loss conditions. They present challenges in initial diagnostic evaluation, histopathological analysis, and long-term management.1Nayar M. Shomberg K. Dawber R.P.R. Millard P.R. A clinicopathologic study of scarring alopecia.Br J Dermatol. 1993; 128: 533-536Crossref PubMed Scopus (41) Google Scholar, 2Fabbri P. Amato L. Chiarini C. Moretti S. Massi D. Scarring alopecia in discoid lupus erythematosus: a clinical, histopathologic and immunopathologic study.Lupus. 2004; 13: 455-462Crossref PubMed Scopus (43) Google Scholar Clinically, the hallmark of cicatricial alopecia is obliteration of follicular ostia, reflecting follicular destruction, secondary to inflammation. The common cicatricial alopecias marked by lymphocytic inflammation include discoid lupus erythematosus (DLE), lichen planopilaris (LPP), frontal fibrosing alopecia (a clinical variant of LPP), and central centrifugal cicatricial alopecia. Because both clinical and histologic features of lymphocytic scarring alopecia overlap, distinguishing between them can be difficult, especially the distinction between DLE and LPP.3Inalöz H.S. Chowdhury M.M. Motley R.J. Lupus erythematosus/lichen planus overlap syndrome with scarring alopecia.J Eur Acad Dermatol Venereol. 2001; 15: 171-174Crossref PubMed Scopus (39) Google Scholar, 4Annessi G. Lombardo G. Gobello T. Puddu P. A clinicopathologic study of scarring alopecia due to lichen planus: comparison with scarring alopecia in discoid lupus erythematosus and pseudopelade.Am J Dermatopathol. 1999; 21: 324-331Crossref PubMed Scopus (61) Google ScholarSeven patients with scarring alopecia were referred by dermatologists to 1 of 2 specialty clinics in Boston (focused on connective tissue diseases or alopecia). All patients were diagnosed with DLE based on clinical and histopathologic findings, however, upon our evaluation, these cases of cicatricial alopecia were most consistent with LPP. This study was approved by the institutional review boards of Partners Healthcare and Boston Medical Center, both located in Boston, Massachusetts.Patient demographics, clinical examination, and biopsy findings are summarized in Table I. Representative clinical and pathologic images are presented in Fig 1. Five individuals exhibited similar hair loss patterns with numerous small alopecic foci throughout the scalp with less than 25% involvement. Five of the 7 individuals also exhibited perifollicular scaling. All exhibited some perifollicular erythema. None exhibited follicular plugging or central depigmentation.Table IDemographic, clinical, and pathologic features of 7 cases of lichen planopilaris initially misdiagnosed as discoid lupus erythematosusCaseAge, ySexInitial clinical impressionInitial biopsy diagnosisTreatments triedHistory of LPOverall scalp involvementScalp findingsANA titerCPC diagnosis161MSA; DLE; LPP; FDDLETS, ILS, HCQ, MTXNoneDiffuse patches ∼40%PF erythema, PF scaleNegativeLPP266FTender bald patchesDLETS, ILS, HCQNoneSeveral foci <25%PF scale; PF erythemaNegativeLPP362FSA; LPP; DLEDLETSOral LPSeveral foci <25%PF erythema, PF scaleNegativeLPP444MDLE; scalp erythemaDLETS, ILS, HCQ, CQ, finasteride, IVIG, MMFNoneSeveral foci <25%HK follicles, PF scale, PF erythemaNegativeLPP543MDLE; scalp erythemaDLETS, ILS, HCQNoneDiffuse patches <25%Atrophy, PF scale, PF erythemaNegativeLPP647MDLE; LPP; SADLETS, ILS, HCQNoneSeveral foci <25%Atrophy, PF scale, doll hairs; PF erythema1:160, speckledLPP777FFPHLDLETS, ILS, MTXNoneFrontal hairline; crownPF erythema, loss of eyebrows1:640FFA (LPP variant)ANA, Antinuclear antibody; CPC, clinicopathologic correlation; CQ, chloroquine; DLE, discoid lupus erythematosus; F, female; FD, folliculitis decalvans; FFA, frontal fibrosing alopecia; FPHL, female pattern hair loss; HCQ, hydroxychloroquine; HK, hyperkeratotic; ILS, intralesional steroids; IVIG, intravenous immune globulin; LP, lichen planus; LPP, lichen planopilaris; M, male; MMF, mycophenolate mofetil; MTX, methotrexate; PF, perifollicular; SA, scarring alopecia; TS, topical steroids. Open table in a new tab Upon histopathology review, all patients were considered to have LPP given the presence of primarily perifollicular inflammation and clinicopathologic correlation. Features that can lead to misdiagnosis because of their occurrence in both conditions include interface dermatitis, perivascular inflammation, increased mucin, and focal basement membrane zone thickening. Although interface dermatitis is a hallmark of DLE, interfollicular involvement in LPP occurs uncommonly. Any accompanying thickening of the basement membrane zone in LPP is mild, unlike the striking thickening seen in DLE. In LPP, the inflammation is predominantly perifollicular, unlike in DLE. The increased dermal mucin in LPP is admixed with fibrosis in a perifollicular location (Fig 1, F), unlike the mucin in DLE that is interstitial in the dermis.Our experience reinforces that LPP and DLE have distinct, yet overlapping, clinical and histologic features and present diagnostic challenges for dermatologists.4Annessi G. Lombardo G. Gobello T. Puddu P. A clinicopathologic study of scarring alopecia due to lichen planus: comparison with scarring alopecia in discoid lupus erythematosus and pseudopelade.Am J Dermatopathol. 1999; 21: 324-331Crossref PubMed Scopus (61) Google Scholar The presence of perifollicular erythema and scale, combined with a lack of follicular plugging or central depigmentation, favors LPP over DLE. Histopathologically, perivascular inflammation should not favor DLE unless it is deep and dense. Similarly, the presence of mucin does not favor DLE when it is in a perifollicular location. Interface dermatitis can be seen in LPP, and DLE should not be favored when it is present, especially if the inflammation is primarily perifollicular. Finally, the basement membrane thickening in DLE is prominent, and mild thickening should not favor DLE. Identification of factors leading to misdiagnosis–including the rarity of these conditions, the limited clinical experience with scarring alopecia, and the frequently subtle and overlapping histologic features of these entities–is the first step in making the correct diagnosis. Clinicians must recognize that clinicopathologic correlation, albeit challenging, is essential in distinguishing these diseases. To the Editor: Cicatricial alopecia represents a complex set of scarring hair loss conditions. They present challenges in initial diagnostic evaluation, histopathological analysis, and long-term management.1Nayar M. Shomberg K. Dawber R.P.R. Millard P.R. A clinicopathologic study of scarring alopecia.Br J Dermatol. 1993; 128: 533-536Crossref PubMed Scopus (41) Google Scholar, 2Fabbri P. Amato L. Chiarini C. Moretti S. Massi D. Scarring alopecia in discoid lupus erythematosus: a clinical, histopathologic and immunopathologic study.Lupus. 2004; 13: 455-462Crossref PubMed Scopus (43) Google Scholar Clinically, the hallmark of cicatricial alopecia is obliteration of follicular ostia, reflecting follicular destruction, secondary to inflammation. The common cicatricial alopecias marked by lymphocytic inflammation include discoid lupus erythematosus (DLE), lichen planopilaris (LPP), frontal fibrosing alopecia (a clinical variant of LPP), and central centrifugal cicatricial alopecia. Because both clinical and histologic features of lymphocytic scarring alopecia overlap, distinguishing between them can be difficult, especially the distinction between DLE and LPP.3Inalöz H.S. Chowdhury M.M. Motley R.J. Lupus erythematosus/lichen planus overlap syndrome with scarring alopecia.J Eur Acad Dermatol Venereol. 2001; 15: 171-174Crossref PubMed Scopus (39) Google Scholar, 4Annessi G. Lombardo G. Gobello T. Puddu P. A clinicopathologic study of scarring alopecia due to lichen planus: comparison with scarring alopecia in discoid lupus erythematosus and pseudopelade.Am J Dermatopathol. 1999; 21: 324-331Crossref PubMed Scopus (61) Google Scholar Seven patients with scarring alopecia were referred by dermatologists to 1 of 2 specialty clinics in Boston (focused on connective tissue diseases or alopecia). All patients were diagnosed with DLE based on clinical and histopathologic findings, however, upon our evaluation, these cases of cicatricial alopecia were most consistent with LPP. This study was approved by the institutional review boards of Partners Healthcare and Boston Medical Center, both located in Boston, Massachusetts. Patient demographics, clinical examination, and biopsy findings are summarized in Table I. Representative clinical and pathologic images are presented in Fig 1. Five individuals exhibited similar hair loss patterns with numerous small alopecic foci throughout the scalp with less than 25% involvement. Five of the 7 individuals also exhibited perifollicular scaling. All exhibited some perifollicular erythema. None exhibited follicular plugging or central depigmentation. ANA, Antinuclear antibody; CPC, clinicopathologic correlation; CQ, chloroquine; DLE, discoid lupus erythematosus; F, female; FD, folliculitis decalvans; FFA, frontal fibrosing alopecia; FPHL, female pattern hair loss; HCQ, hydroxychloroquine; HK, hyperkeratotic; ILS, intralesional steroids; IVIG, intravenous immune globulin; LP, lichen planus; LPP, lichen planopilaris; M, male; MMF, mycophenolate mofetil; MTX, methotrexate; PF, perifollicular; SA, scarring alopecia; TS, topical steroids. Upon histopathology review, all patients were considered to have LPP given the presence of primarily perifollicular inflammation and clinicopathologic correlation. Features that can lead to misdiagnosis because of their occurrence in both conditions include interface dermatitis, perivascular inflammation, increased mucin, and focal basement membrane zone thickening. Although interface dermatitis is a hallmark of DLE, interfollicular involvement in LPP occurs uncommonly. Any accompanying thickening of the basement membrane zone in LPP is mild, unlike the striking thickening seen in DLE. In LPP, the inflammation is predominantly perifollicular, unlike in DLE. The increased dermal mucin in LPP is admixed with fibrosis in a perifollicular location (Fig 1, F), unlike the mucin in DLE that is interstitial in the dermis. Our experience reinforces that LPP and DLE have distinct, yet overlapping, clinical and histologic features and present diagnostic challenges for dermatologists.4Annessi G. Lombardo G. Gobello T. Puddu P. A clinicopathologic study of scarring alopecia due to lichen planus: comparison with scarring alopecia in discoid lupus erythematosus and pseudopelade.Am J Dermatopathol. 1999; 21: 324-331Crossref PubMed Scopus (61) Google Scholar The presence of perifollicular erythema and scale, combined with a lack of follicular plugging or central depigmentation, favors LPP over DLE. Histopathologically, perivascular inflammation should not favor DLE unless it is deep and dense. Similarly, the presence of mucin does not favor DLE when it is in a perifollicular location. Interface dermatitis can be seen in LPP, and DLE should not be favored when it is present, especially if the inflammation is primarily perifollicular. Finally, the basement membrane thickening in DLE is prominent, and mild thickening should not favor DLE. Identification of factors leading to misdiagnosis–including the rarity of these conditions, the limited clinical experience with scarring alopecia, and the frequently subtle and overlapping histologic features of these entities–is the first step in making the correct diagnosis. Clinicians must recognize that clinicopathologic correlation, albeit challenging, is essential in distinguishing these diseases.