Perifollicular inflammation and follicular spongiosis in androgenetic alopecia

To the Editor: Androgenetic alopecia (AGA) is typically classified as a noninflammatory, nonscarring form of hair loss, but inflammation at the level of the pilosebaceous unit has previously been reported.1Mahé Y.F. Michelet J.F. Billoni N. et al.Androgenetic alopecia and microinflammation.Int J Dermatol. 2000; 39: 576-584https://doi.org/10.1046/j.1365-4362.2000.00612.xCrossref PubMed Scopus (132) Google Scholar,2Whiting D.A. Chronic telogen effluvium: increased scalp hair shedding in middle-aged women.J Am Acad Dermatol. 1996; 35: 899-906https://doi.org/10.1016/s0190-9622(96)90113-9Abstract Full Text PDF PubMed Scopus (0) Google Scholar One prior study suggested inflammation did not differ significantly from normal controls, leading to uncertainty regarding its role in pathogenesis.3Valdebran M. Mo J. Elston D.M. Doan L. Pattern hair loss: assessment of inflammation and fibrosis on histologic sections.J Am Acad Dermatol. 2020; 82: 757-758https://doi.org/10.1016/j.jaad.2019.09.013Abstract Full Text Full Text PDF PubMed Scopus (5) Google Scholar We sought to confirm these findings and characterize follicular spongiosis in association with lymphoid inflammation. A retrospective slide review was conducted of all AGA and alopecia areata (AA) scalp biopsy specimens from 2014 to 2019 at the Medical University of South Carolina. Of 96 total specimens (58 AGA and 38 AA), 92 (95.8%) had both vertical and horizontal sections available for review. Perifollicular inflammation was evaluated for its presence, location, and degree of involvement (Table I). Follicular spongiosis was characterized by its presence and location within the follicle. One investigator (MV) assessed each variable. This study was approved by the Institutional Review Board at the Medical University of South Carolina.Table IDemographics and histopathologic featuresCharacteristicAndrogenetic alopeciaAlopecia areataP valuen (%)n (%)Sex.041 Male5 (8.6)9 (23.7) Female53 (91.4)29 (76.3)Age at biopsy, y- <357 (12.1)18 (47.4).0001 35-7037 (63.8)15 (39.5).019 >7014 (24.1)5 (13.2).187Perifollicular inflammation.388 Yes51 (87.9)31 (81.6) No7 (12.1)7 (18.4)Location of inflammation∗Percentages exceed 100 since these features were identified in multiple locations within some biopsy specimens.- Infundibulum34 (58.6)14 (36.8).037 Isthmus46 (79.3)21 (55.3).012 Bulb0 (0.0)24 (63.2)<.0001 None7 (12.1)7 (18.4).388Degree of inflammation.724 Mild34 (58.6)20 (52.6) Moderate13 (22.4)7 (18.4) Severe4 (6.9)4 (10.5) None7 (12.1)7 (18.4)Follicular spongiosis.197 Yes17 (29.3)16 (42.1) No41 (70.7)22 (57.9)Location of spongiosis∗Percentages exceed 100 since these features were identified in multiple locations within some biopsy specimens..128 Infundibulum7 (12.1)11 (28.9) Isthmus12 (20.7)10 (26.3) None41 (70.7)22 (57.9)∗ Percentages exceed 100 since these features were identified in multiple locations within some biopsy specimens. Open table in a new tab Our cohort was predominantly female, and AA patients were younger at the time of biopsy. We identified perifollicular lymphocytic infiltrates in most specimens (87.9% AGA, 81.6% AA), with no significant difference in incidence. AGA specimens were more likely to exhibit infundibular (58.6% vs 36.8%) and isthmic (79.3% vs 55.3%) infiltrates and less likely to demonstrate peribulbar infiltrates (0.0% vs 63.2%). The degree of inflammation did not differ significantly between the 2 groups, with most cases exhibiting mild inflammation (58.6% AGA, 52.6% AA). Isthmic infiltrates were moderate in 10 AGA and 5 AA samples and severe in 4 AGA and 1 AA samples. Follicular miniaturization was present in all specimens, and inflammation adjacent to miniaturized follicles was observed in 50 AGA (86.2%) and 30 AA (78.9%) cases (Fig 1). Follicular spongiosis was observed in 17 AGA (29.3%) and 16 AA (42.1%) cases, usually on vertical sections because it tended to involve upper regions of the follicle. Bulbar spongiosis was not identified. Inflammation was adjacent to spongiosis in 10 AGA (58.8%) and 14 AA (87.5%) cases. A prior study demonstrated perifollicular infiltrates in 73% of AGA and 84% of control specimens.3Valdebran M. Mo J. Elston D.M. Doan L. Pattern hair loss: assessment of inflammation and fibrosis on histologic sections.J Am Acad Dermatol. 2020; 82: 757-758https://doi.org/10.1016/j.jaad.2019.09.013Abstract Full Text Full Text PDF PubMed Scopus (5) Google Scholar Our current AGA cases had similar overall rates of inflammation. However, isthmic involvement was more common in our present study. More cases of moderate and severe inflammation were also observed. In the current study, AGA samples exhibited similar overall rates of inflammation as AA controls, and there were no significant differences in severity. However, infundibular and isthmic involvement was significantly more common in AGA (P = .037 and P = .012, respectively). A previous series of 17 women with AGA and 5 normal controls demonstrated a significant association between infiltrate severity and the extent of miniaturization.4Ramos P.M. Brianezi G. Martins A.C. da Silva M.G. Marques M.E. Miot H.A. Apoptosis in follicles of individuals with female pattern hair loss is associated with perifollicular microinflammation.Int J Cosmet Sci. 2016; 38: 651-654https://doi.org/10.1111/ics.12341Crossref PubMed Scopus (31) Google Scholar,5Merlotto M.R. Ramos P.M. Miot H.A. Pattern hair loss: assessment of microinflammation in miniaturized and terminal hair follicles through horizontal histologic sections.J Am Acad Dermatol. 2020; 83: e145-e146https://doi.org/10.1016/j.jaad.2020.03.119Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar In our study, inflammation was noted adjacent to miniaturized follicles in most cases. Several highly miniaturized follicles were also surrounded by severe inflammation. The isthmic predilection and association of inflammation with miniaturized follicles potentially suggest a possible mechanistic relationship. Larger, sex-matched studies examining this relationship are needed.5Merlotto M.R. Ramos P.M. Miot H.A. Pattern hair loss: assessment of microinflammation in miniaturized and terminal hair follicles through horizontal histologic sections.J Am Acad Dermatol. 2020; 83: e145-e146https://doi.org/10.1016/j.jaad.2020.03.119Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar None disclosed.