Absence of HLA-DR1 positivity in 2 familial cases of frontal fibrosing alopecia
Authors: Derek V. Chan, Francisca Kartono, Rebecca Ziegler, Nebila Abdulwahab, Nicholas DiPaola, Joseph Flynn, Henry K. Wong
Journal: Journal of the American Academy of Dermatology (2014)

To the Editor: Frontal fibrosing alopecia (FFA) is a variant of lichen planopilaris (LPP), a specific presentation of lichen planus involving the hair follicles.1Kossard S. Lee M.S. Wilkinson B. Postmenopausal frontal fibrosing alopecia: a frontal variant of lichen planopilaris.J Am Acad Dermatol. 1997; 36: 59-66Abstract Full Text Full Text PDF PubMed Scopus (294) Google Scholar, 2Chew A.L. Bashir S.J. Wain E.M. Fenton D.A. Stefanato C.M. Expanding the spectrum of frontal fibrosing alopecia: a unifying concept.J Am Acad Dermatol. 2010; 63: 653-660Abstract Full Text Full Text PDF PubMed Scopus (126) Google Scholar HLA-DR1 positivity has already been linked to cases of lichen planus and another variant of LPP, Lassueur-Graham-Little–Piccardi syndrome, in 2 related family members.3Viglizzo G. Verrini A. Rongioletti F. Familial Lassueur-Graham-Little-Piccardi syndrome.Dermatology. 2004; 208: 142-144Crossref PubMed Scopus (48) Google Scholar, 4Powell F.C. Rogers R.S. Dickson E.R. Moore S.B. An association between HLA DRI and lichen planus.Br J Dermatol. 1986; 114: 473-478Crossref PubMed Scopus (50) Google Scholar To our knowledge, only 1 reported case of familial FFA, another variant of LPP, has been reported, and HLA-DR1 status in that case was unknown, raising the question of whether HLA-DR1 positivity correlates with FFA.5Junqueira Ribeiro Pereira A.F. Vincenzi C. Tosti A. Frontal fibrosing alopecia in two sisters.Br J Dermatol. 2010; 162: 1154-1155Crossref PubMed Scopus (35) Google Scholar We present 2 cases of familial FFA with negative HLA-DR1 status. Patient 1 was a 49-year-old Caucasian woman who presented with an approximately 1.5 year–history of hair loss (Fig 1, left) refractory to topical steroids. Physical examination was notable for frontal and temporal scarring alopecia with perifollicular erythema with fine scales on her frontal and temporal hairline. Thinning on the lateral eyebrows was appreciated, but the eyelashes were intact. The remainder of her scalp was unaffected. A hair-pull test produced negative findings. Vellus hair growth on bilateral axilla was noted. A scalp biopsy specimen revealed perivascular and perifollicular dermatitis with associated folliculitis (Fig 2). It was notable for immunoglobulin heavy chain monoclonality. T-cell receptor gene rearrangement studies produced unremarkable results. An antinuclear antibody multiplex screen and serum protein electrophoresis revealed negative findings. A complete blood count was notable for elevated monocytes (8.7%), and a comprehensive metabolic panel produced unremarkable results, although a slightly elevated aspartate aminotransferase was noted (37 U/L [5-34]). An immunoglobulin panel workup revealed a slightly elevated IgM (237 mg/dL [40-230]). A bone-marrow biopsy specimen and positron emission tomography/computed tomography revealed unremarkable findings. HLA-DRB typing revealed DRB1*04:XX,11:XX, DRB3: positive, DRB4: positive, and DRB5: negative.Fig 2Familial frontal fibrosing alopecia. Case 1. Perifollicular inflammation and lymphocytes within follicle. (Hematoxylin-eosin stain; original magnification: ×20.)View Large Image Figure ViewerDownload Hi-res image Download (PPT) She had been scheduled to receive systemic chemotherapy by her previous oncologist because of the finding of monoclonality in the immunoglobulin heavy chain rearrangement, but chemotherapy plans were stopped after the diagnosis of LPP. Patient 2 was the 63-year-old Caucasian sister of patient 1 with an approximately 2- to 3-year history of hair loss involving her left temple and frontal hairline (Fig 1, right) that had been refractory to intralesional steroid injection and daily doxycycline. Physical examination revealed scarring alopecia and follicular erythema on the forehead and temporal areas. She maintained terminal hair growth on the axilla and groin areas. A scalp biopsy specimen was compatible with LPP. A metabolic panel, serum immunoglobulin panel, and serum protein electrophoresis revealed unremarkable findings. Her complete blood cell count was notable for elevated monocytes (8.3%), and an antinuclear antibody multiplex screen produced positive results. HLA-DRB typing revealed the same findings as in patient 1. To date, only 1 other case of familial FFA has been reported to our knowledge.5Junqueira Ribeiro Pereira A.F. Vincenzi C. Tosti A. Frontal fibrosing alopecia in two sisters.Br J Dermatol. 2010; 162: 1154-1155Crossref PubMed Scopus (35) Google Scholar We now report, to our knowledge, the first case of familial FFA in the United States and demonstrate that although HLA-DR1 positivity has been correlated with LPP and the variant of LPP known as Lassueur-Graham-Little–Piccardi syndrome, it does not appear to correlate with the presence of FFA in our 2 familial patients. Our case therefore raises the possibility that other alleles may correspond with FFA. Familial frontal fibrosing alopeciaJournal of the American Academy of DermatologyVol. 73Issue 1PreviewTo the Editor: We read the article by Chan and colleagues1 on frontal fibrosing alopecia (FFA) with interest. The authors report that, to their knowledge, "to date, only 1 other case of familial FFA has been reported." We would like to bring to the authors' attention an article published by Dlova and colleagues reporting 4 previously unreported and 3 previously reported families with frontal fibrosing alopecia.2 Moreover, 7 further families with highly consistent clinical features of FFA are currently under our care and 5 more have been referred to us for genetic exploration. Full-Text PDF