Abstract
Introduction
Lichen planopilaris (LPP) and frontal fibrosing alopecia (FFA) share histopathology but differ in clinical presentation, disease course, and treatment patterns. This study aimed to compare clinical characteristics, treatments, outcomes, and prognostic factors between LPP and FFA.
Methods
A retrospective cohort study was conducted at Sheba Medical Center, Israel (2010–2023). Patients with LPP or FFA followed for ≥1 year were included. Remission was categorized as early (≤12 months) or late (>12 months).
Results
A total of 141 patients were included (81 LPP, 60 FFA). FFA showed greater female predominance (96.7% vs. 80.2%, p = 0.004), older age at presentation (56.9 ± 12.2 vs. 49.1 ± 14.1 years, p = 0.0008) and higher postmenopausal proportion (81.8% vs. 44.4%, p = 0.004). LPP patients more frequently reported pain (50.6% vs. 6.7%) and pruritus (82.7% vs. 36.7%) (both p < 0.00001). Cumulative remission was higher in FFA than in LPP (68.3% vs. 45.7%, p = 0.022), whereas early remission rates and time to remission were similar (22.8 ± 17.6 vs. 22.9 ± 20.5 months, p = 0.98). Relapse rates were similar during treatment (22.0% vs. 16.2%, p = 0.59) and after discontinuation (29.3% vs. 27.0%, p = 0.83). Early remission was predicted by mild baseline severity in LPP (OR: 4.24), and by rural residence (OR: 7.00) and statin use (OR: 3.85) in FFA; tetracycline treatment was inversely associated (OR: 0.21). For late remission in LPP, older age at first visit was positively associated (OR: 1.06/year), whereas Ashkenazi Jewish ethnicity was inversely associated (OR: 0.33).
Conclusion
FFA had higher cumulative remission than LPP despite similar time to remission and relapse rates, with distinct remission predictors.
Keywords: Lichen planopilaris, Frontal fibrosing alopecia, Cicatricial alopecia, Remission, Prognostic factors, Comparative study
Plain Language Summary
Lichen planopilaris and frontal fibrosing alopecia are 2 scalp diseases that can cause permanent hair loss. This happens because inflammation damages the hair follicles, the small structures in the skin from which hair grows. Although these 2 diseases may look similar when a skin sample is examined under a microscope, they can affect patients in different ways. This study compared people with lichen planopilaris and frontal fibrosing alopecia who were treated and followed at Sheba Medical Center in Israel between 2010 and 2023. The study looked at symptoms, areas of hair loss, treatments, disease control over time, and factors that might be linked with better outcomes. The study included 141 patients: 81 with lichen planopilaris and 60 with frontal fibrosing alopecia. Patients with frontal fibrosing alopecia were more often women, were older when the disease began, and were mostly after menopause. Patients with lichen planopilaris more often reported pain, itching, and burning. Frontal fibrosing alopecia usually affected the front and sides of the scalp and the eyebrows, while lichen planopilaris more often affected wider areas of the scalp. Overall remission, meaning stable disease without further hair loss, inflammation, or symptoms, was more common in frontal fibrosing alopecia. However, the time needed to achieve remission and the chance of relapse were similar in both groups. In lichen planopilaris, milder disease at the first visit was the most consistent factor linked with earlier disease control. Other possible links became less certain after stricter statistical testing and should be interpreted with caution.
Introduction
Lichen planopilaris (LPP) and frontal fibrosing alopecia (FFA) are chronic primary lymphocytic cicatricial alopecias (PCAs) characterized by perifollicular inflammation leading to irreversible hair loss [1, 2]. Histopathologically, both conditions are largely indistinguishable, showing a lichenoid lymphocytic infiltrate and perifollicular fibrosis targeting the upper follicle; however, the inflammation is often less pronounced in FFA. [3–5]. Pathogenesis is thought to involve a T-cell-mediated autoimmune response against follicular antigens, influenced by genetic, hormonal, and environmental factors [1–5]. Although the North American Hair Research Society classifies FFA within the LPP spectrum, its nosological status remains debated as accumulating clinical and epidemiologic evidence supports meaningful distinctions between the two entities [5–7].
LPP typically affects women aged 30–60 years and presents with perifollicular erythema, papules, scaling, and progressive scarring alopecia, most commonly involving the vertex [1, 2]. Patchy scalp involvement is most common, although solitary patches or diffuse patterns may occur, and other hair-bearing areas may be affected [1, 2, 5]. Symptoms are usually prominent, with pruritus, burning, or pain reflecting marked inflammatory activity [1, 2, 5]. Trichoscopy shows perifollicular erythema and tubular scaling, violaceous papules, tufting, milky-red or whitish areas, loss of follicular openings, and elongated perifollicular vessels [5, 8–10]. Diagnosis relies on clinical and trichoscopic features supported by histopathology showing lichenoid lymphocytic infiltrate targeting the infundibulum and isthmus, interface changes, perifollicular fibrosis, sebaceous gland loss, and follicle destruction in advanced disease [5]. Management of LPP is challenging because of its chronic, relapsing course and treatment resistance [1, 8–12]. Available evidence is largely derived from retrospective studies, with few controlled trials [12–16]. Mild disease is usually managed with topical or intralesional corticosteroids or calcineurin inhibitors, while moderate-to-severe or refractory cases often require systemic therapies such as hydroxychloroquine, tetracyclines, retinoids, or immunosuppressants [2, 8–16]. Additional options, including PPAR-γ agonists, low-dose naltrexone, biologics, and Janus kinase inhibitors, have shown benefit in selected cases [2, 12, 16]. Hair growth stimulants, such as minoxidil and 5-alpha-reductase inhibitors, are often used as adjuncts [2, 9, 16]. Reported remission rates vary widely (8%–88%), likely reflecting heterogenecity in disease severity, treatment strategies, and follow-up duration. Earlier diagnosis, milder disease, and coexisting lichen planus have been associated with better outcomes, whereas delayed diagnosis, higher inflammatory activity, and vitamin D deficiency have been linked to poorer prognosis [8, 17–20].
FFA is characterized by frontotemporal hairline recession and frequent eyebrow loss. Since its first description in 1994, FFA has become one of the most common PCAs, with a markedly increasing incidence over recent decades [21–24]. It predominantly affects postmenopausal women, although premenopausal women and men may also be affected. Eyebrow loss, reported in up to 80–90% of patients, often precedes scalp involvement [21–23]. The typical onset age and strong female predominance suggest hormonal influence, while the rising incidence points to environmental factors. Disease extension may become circumferential and involve additional hair-bearing sites, making the term “frontal” somewhat misleading. Despite generally slow progression, FFA may result in extensive alopecia. Most patients are asymptomatic or minimally symptomatic [21]. Trichoscopy shared features with LPP (perifollicular erythema and tubular scaling), alongside with findings more suggestive of FFA, including loss of vellus hair, “lonely hairs,” and red and gray eyebrow dots. Clinically, FFA may also be associated with facial papules and prominent facial veins [1, 2, 21–23].
Diagnosis is primarily clinical, supported by trichoscopy and confirmed by biopsy when required [5, 10, 22–24]. While FFA shares pathogenic pathway overlaps with LPP, hormonal and environmental factors likely play a more prominent role [21, 22, 25]. Management parallels LPP but more often includes 5-alpha-reductase inhibitors, which may slow disease progression and enhance regrowth [26]. Reported remission rates range from 44% to 83%, with proposed prognostic factors including the pattern and extent of hairline recession, degree of eyebrow and body hair involvement, rate of disease progression, presence of facial papules or symptoms, and comorbidities such as hypothyroidism and lichen planus pigmentosus [26–31].
Most previous studies have investigated LPP or FFA separately or analyzed combined cohorts limiting direct comparison. Consequently, evidence distinguishing their clinical profiles and prognostic factors remains limited. The primary aim of this study was to directly compare FFA and LPP in a tertiary care setting with respect to epidemiological and clinical characteristics, treatment patterns, remission rates, prognostic factors for early and late remission, and relapse rates during follow-up.
Materials and Methods
Study Design
This retrospective comparative cohort study was conducted at the Dermatology Department of Sheba Medical Center, Tel Hashomer, Israel. Data were extracted from the institutional electronic medical record system and included demographic information, medical history, clinical features, treatments, disease course, and outcomes.
Study Population
All patients diagnosed with LPP or FFA who were evaluated at the dermatology outpatient clinic between January 2010 and December 2023 were screened. Patients of any age or sex were eligible if they were diagnosed and followed for ≥1 year. LPP was diagnosed based on characteristic clinical and trichoscopic findings and confirmed by biopsy in all cases. FFA was diagnosed clinically and trichoscopically, with biopsy performed when necessary [32]. Exclusion criteria included inconclusive diagnosis, coexistence of LPP and FFA, concomitant inflammatory scalp disorders, incomplete records, or follow-up shorter than 1 year.
Research Variables
Collected demographic variables included sex, age at disease onset (patient-reported), age at the first visit to our clinic, residential area, ethnicity, and Fitzpatrick skin type. Medical history encompassed hormonal factors (menopausal status, prior oral contraceptive therapy [OCT] or hormone replacement therapy [HRT], parity, breastfeeding), comorbidities, family history of LPP/FFA, and medication use. Temporal variables (age at onset, time to diagnosis, follow-up duration) were also recorded. Clinical variables included scalp involvement pattern (frontal, temporal, parietal, occipital, vertex, or diffuse), extra-scalp involvement, trichoscopic features (perifollicular erythema, diffuse erythema, tubular scaling), and symptoms (pain, pruritus, burning, or asymptomatic). LPP severity was graded using the Severity of Alopecia Tool (SALT): mild (<20%), moderate (20–50%), or severe (>50%) [13]. Severe symptoms upgraded severity by one level. FFA severity was defined by frontal hairline regression: <1 cm mild, 1–3 cm moderate, and >3 cm severe, upgraded by symptom severity [26]. Treatments were recorded. Disease course was assessed through outcome categories: remission, partial improvement, or no response/worsening. Remission was defined as disease stabilization without further hair loss, inflammatory signs, or symptoms, acknowledging that regrowth is not expected. Remission was classified as early (≤12 months from diagnosis and treatment initiation) or late (>12 months) and as maintained on or off treatment. The distinction between early and late remission was set to reflect differences between initial treatment response and long-term disease stabilization. Cumulative remission rate was defined as the overall proportion of patients who achieved remission, whether early or late. Partial improvement reflected reduced disease extent or symptoms, while no response/worsening indicated lack of improvement or disease progression. Relapses were documented and classified based on whether they occurred during maintenance therapy or after treatment discontinuation. The study protocol was approved by the Sheba Medical Center Research Ethics Committee (Helsinki), Approval No. SMC-7592-20.
Statistical Analysis
Continuous variables were summarized as mean ± standard deviation and compared between groups using the Student’s t test. Categorical variables were compared using the chi-square test or Fisher’s exact test, as appropriate. Clinical outcomes within 12 months and during follow-up were compared with categorical variables using the chi-square test and with continuous variables using the t test or one-way ANOVA, as applicable. Univariate logistic regression analyses were performed to evaluate associations between demographic, clinical, and treatment-related variables and remission outcomes, separately for early (≤12 months) and late (>12 months) remission. Variables with a p value ≤0.10 in univariate analyses were considered for inclusion in multivariable logistic regression models. Separate multivariable models were constructed for LPP and FFA to identify independent predictors of remission. All statistical tests were two-sided, and a p value <0.05 was considered statistically significant. Statistical analyses were performed using SPSS software (IBM SPSS Statistics, Version 28; IBM Corp., Armonk, NY, USA).
Results
Patient Population
During the study period, 68 patients with FFA and 182 with LPP were identified. After exclusion of 109 patients (74 due to insufficient follow-up, 14 due to concurrent inflammatory scalp disorders, and 21 due to incomplete data), the final cohort comprised 141 patients: 60 with FFA and 81 with LPP.
Demographics
Demographic characteristics are summarized in Table 1. As expected, patients with FFA were older at disease onset than those with LPP (56.9 ± 12.2 vs. 49.1 ± 14.1 years, p < 0.001) and the female predominance was more marked in FFA (96.7% vs. 80.2%, p = 0.004). Other demographic variables were comparable between groups, including time to diagnosis, Fitzpatrick skin type distribution, ethnicity, residential area, and follow-up duration (all p > 0.05).
Table 1.
Demographic characteristics of patients with FFA and LPP
| Variable | FFA (n = 60) | LPP (n = 81) | p value |
|---|---|---|---|
| Age at onset, years | |||
| Range | 20-81 | 15–73 | |
| Mean±SD | 56.9±12.2 | 49.1±14.1 | <0.001 |
| Gender, n (%) | |||
| Female | 58 (96.7) | 65 (80.2) | 0.004 |
| Time to diagnosis, months, n (%) | |||
| Range | 3–210 | 6–138 | |
| Mean±SD | 34.6±37.3 | 34.1±29.9 | 0.930 |
| Fitzpatrick skin type | | | 0.940 |
| 1 | 5 (8.3) | 8 (9.9) | |
| 2 | 11 (18.3) | 11 (13.6) | |
| 3 | 22 (36.7) | 28 (34.6) | |
| 4 | 18 (30.0) | 28 (34.6) | |
| 5 | 4 (6.7) | 6 (7.4) | |
| 6 | 0 (0.0) | 0 (0.0) | |
| Ethnicity, n (%) | | | 0.560 |
| Ashkenazi Jews | 38 (63.3) | 44 (54.3) | |
| Sephardic Jews | 21 (35.0) | 35 (43.2) | |
| Arabs | 1 (1.7) | 2 (2.5) | |
| Residential area, n (%) | | | 0.590 |
| Urban | 54 (90.0) | 75 (92.6) | |
| Rural | 6 (10.0) | 6 (7.4) | |
| Follow-up, months | | | 0.940 |
| Range | 14–133 | 12–128 | |
| Mean±SD | 48.7±28.4 | 49.1±32.3 | |
This table compares baseline demographic characteristics between patients with FFA (n = 60) and LPP (n = 81). Data are presented as n (%) or mean ± SD. p values represent between-group comparisons; statistically significant values are highlighted in bold.
Medical Backgrounds
Medical background characteristics are presented in online supplementary Table S1 (for all online suppl. material, see https://doi.org/10.1159/000553195). FFA patients were more frequently postmenopausal than LPP patients (81.8% vs. 44.4%, p = 0.004), whereas other hormonal factors, including prior OCT and HRT, did not differ between groups (both p > 0.05). Most systemic comorbidities were similarly distributed. Among dermatologic comorbidities, seborrheic dermatitis was more common in LPP (22.2% vs. 8.3%, p = 0.03), and a family history of FFA/LPP was reported only in LPP (9.9% vs. 0%, p = 0.02). Regarding medications, SSRI use was higher in FFA (18.3% vs. 4.9%, p = 0.01), whereas the prevalence of documented psychiatric diagnoses did not differ between groups. Other medication classes showed no significant differences.
Clinical Characteristics
Clinically meaningful trichoscopic, symptomatic, and severity differences are presented in Table 2, whereas expected phenotypic distribution features (scalp and extra-scalp involvement) are provided in online supplementary Table S2. As expected, FFA showed predominantly frontal and temporal involvement with frequent eyebrow/eyelash involvement, whereas LPP more often affected the vertex and broader scalp areas (online suppl. Table S2). In Table 2, perifollicular erythema was more common in FFA (p = 0.03), whereas diffuse erythema predominated in LPP (p < 0.0001). Tubular scaling tended to be more frequent in LPP but did not reach statistical significance (p = 0.09). LPP patients reported substantially higher rates of pain, pruritus, and burning, while most FFA patients were asymptomatic (all p < 0.0001). Disease severity distribution was similar between groups (p = 0.13).
Table 2.
Trichoscopic findings, symptoms, and severity in FFA and LPP
| Variable | FFA (n = 60) | LPP (n = 81) | p value |
|---|---|---|---|
| Trichoscopic signs, n (%) | |||
| Perifollicular erythema | 52 (86.7) | 58 (71.6) | 0.03 |
| Diffuse erythema | 4 (6.7) | 47 (58.0) | <0.0001 |
| Tubular scaling | 47 (78.3) | 72 (88.9) | 0.09 |
| Symptoms, n (%) | |||
| Pain | 4 (6.7) | 41 (50.6) | <0.0001 |
| Pruritus | 22 (36.7) | 67 (82.7) | <0.0001 |
| Burning | 2 (3.3) | 57 (70.4) | <0.0001 |
| Asymptomatic | 35 (58.3) | 10 (12.3) | <0.0001 |
| Severity, n (%) | | | 0.13 |
| Mild | 10 (16.7) | 14 (17.3) | |
| Moderate | 25 (41.7) | 22 (27.2) | |
| Severe | 25 (41.7) | 45 (55.6) | |
This table compares clinically meaningful inflammatory and symptomatic features between patients with FFA (n = 60) and LPP (n = 81). LPP severity was graded by SALT (mild <20%, moderate 20–50%, severe >50%); FFA severity was graded by frontal hairline regression (<1 cm mild, 1–3 cm moderate, >3 cm severe). Data are presented as n (%). p values represent between-group comparisons; statistically significant values are shown in bold.
Treatments
Treatment patterns are presented in online supplementary Table S3. Several therapies differed significantly between groups. Topical corticosteroids were used more frequently in LPP (100% vs. 78.3%, p < 0.0001), whereas topical calcineurin inhibitors (91.7% vs. 23.5%, p < 0.0001) and topical minoxidil (80.0% vs. 11.1%, p < 0.0001) were markedly more common in FFA. Systemic corticosteroids were used only in LPP (16.0% vs. 0%, p = 0.0006), whereas 5-α-reductase inhibitors (30.0% vs. 6.2%, p = 0.0001) and oral minoxidil (18.3% vs. 4.9%, p = 0.01) were more frequently prescribed in FFA. Use of intralesional corticosteroids and most other systemic therapies did not differ significantly between groups (all p > 0.05).
Outcomes
Outcome measures are presented in Table 3. Early remission rates and time to remission were comparable between FFA and LPP, suggesting similar initial treatment response. Late remission rates were also comparable, indicating that the main between-group differences were not driven by remission timing. Instead, FFA demonstrated a significantly higher cumulative remission rate than LPP (68.3% vs. 45.7%, p = 0.022). Consistently, at the last follow-up, remission maintained on treatment was more common in FFA (53.3% vs. 21.0%, p = 0.0001), whereas partial remission was more common in LPP (6.7% vs. 44.4%, p < 0.0001). Relapse rates during treatment and after treatment discontinuation were similar between groups (all p > 0.05).
Table 3.
Comparison of outcomes in patients with FFA and LPP
| Outcome category | FFA (n = 60) | LPP (n = 81) | p value |
|---|---|---|---|
| Early remission (achieved within 12 months), n (%) | |||
| Remission maintained on treatment | 16 (26.7) | 15 (18.5) | 0.25 |
| Remission maintained off treatment | 0 (0.0) | 2 (2.5) | 0.51 |
| Late remission (achieved after 12 months), n (%) | |||
| Remission maintained on treatment | 23 (38.3) | 19 (23.5) | 0.09 |
| Remission maintained off treatment | 2 (3.3) | 1 (1.2) | 0.39 |
| Cumulative remission rate (early+late), n (%) | 41 (68.3) | 37 (45.7) | 0.02 |
| Time to remission, mean±SD, months | 22.8±17.6 | 22.9±20.5 | 0.98 |
| Partial remission only during follow-up, n (%) | 2 (3.3) | 30 (37.0) | <0.001 |
| No remission during follow-up, n (%) | 17 (28.3) | 14 (17.3) | 0.17 |
| Outcome at the last follow-up, n (%) | |||
| Remission maintained on treatment | 32 (53.3) | 17 (21.0) | 0.001 |
| Remission maintained off treatment | 2 (3.3) | 6 (7.4) | 0.30 |
| Partial remission | 4 (6.7) | 36 (44.4) | <0.001 |
| No remission | 22 (36.7) | 17 (21.0) | 0.062 |
| Relapse, n (%) | |||
| Relapse during treatment | 9 (22.0) | 6 (16.2) | 0.59 |
| Relapse after treatment discontinuation | 12 (29.3) | 10 (27.0) | 0.83 |
This table summarizes and compares treatment outcomes between FFA (n = 60) and LPP (n = 81). Relapse outcomes are reported among patients who achieved remission (FFA: n = 41; LPP: n = 37), and are categorized as relapse during treatment or after treatment discontinuation. Data are presented as n (%) unless otherwise specified. p values represent between-group comparisons; statistically significant values are shown in bold.
Prognostic Factors for Remission
Univariate logistic regression was used to evaluate demographic, clinical, and treatment-related predictors of early remission and late remission in LPP and FFA (Table 4), and variables significant in univariate analyses were entered into multivariable models (Table 5). In LPP, early remission was most strongly associated with mild baseline disease severity (OR: 8.59, p < 0.001). Additional univariate associations included PPI use (OR: 6.64, p = 0.048) and inverse associations with intralesional corticosteroids (OR: 0.15, p = 0.003), hydroxychloroquine (OR: 0.26, p = 0.034), tetracyclines (OR: 0.25, p = 0.015), and prior OCT exposure (OR: 0.12, p = 0.046), likely reflecting confounding by indication. For late remission in LPP, older age at the first visit (p = 0.041), older age at onset (p = 0.035), and Ashkenazi Jewish ethnicity were associated with remission in univariate analysis (Table 4). In FFA, early remission was associated with rural residence (OR 7.00, p = 0.036) and statin use (OR: 3.85, p = 0.028), and inversely associated with tetracycline treatment (OR: 0.21, p = 0.017) (Table 4); no significant predictors of late remission were identified.
Table 4.
Univariate logistic regression: variables associated with early and late remission in LPP and FFA
| Prognostic factor | OR | 95% CI | p value |
|---|---|---|---|
| LPP – early remission | |||
| History of OCT | 0.12 | (0.01–0.96) | 0.046 |
| Proton pump inhibitor use | 6.64 | (1.01–43.57) | 0.048 |
| Mild disease severity | 8.59 | (2.41–30.6) | <0.001 |
| Intralesional corticosteroid therapy | 0.15 | (0.04–0.52) | 0.003 |
| Hydroxychloroquine therapy | 0.26 | (0.08–0.91) | 0.034 |
| Tetracycline therapy | 0.25 | (0.08–0.76) | 0.015 |
| LPP – late remission | |||
| Age at the first visit (per year) | 1.05 | (1.00–1.10) | 0.041 |
| Age at disease onset (per year) | 1.05 | (1.00–1.09) | 0.035 |
| Ashkenazi Jewish ethnicity | 0.34 | (0.13–0.88) | 0.037 |
| FFA – early remission | |||
| Rural residence | 7.00 | (1.14–42.96) | 0.036 |
| Statin use | 3.85 | (1.16–12.81) | 0.028 |
| Tetracycline treatment | 0.21 | (0.06–0.76) | 0.017 |
| FFA – late remission | No variables reached statistical significance in univariate analysis | ||
This table presents univariate logistic regression results assessing associations between candidate predictors and remission outcomes, analyzed separately for LPP and FFA. Early remission was defined as remission achieved within 12 months from diagnosis and treatment initiation; late remission was defined as remission achieved thereafter during follow-up. Results are reported as odds ratios (ORs) with 95% confidence intervals (CIs) and p values. Only variables reaching statistical significance in univariate analysis are displayed.
Table 5.
Multivariable logistic regression models for predictors of remission in LPP and FFA
| Variable | OR | 95% CI | p value |
|---|---|---|---|
| LPP – early remission | |||
| History of OCT | 0.36 | 0.06–2.07 | 0.25 |
| Proton pump inhibitor use | 5.55 | 0.52–59.73 | 0.16 |
| Mild disease severity | 4.24 | 1.00–17.96 | 0.04 |
| Intralesional corticosteroid therapy | 0.28 | 0.07–1.16 | 0.08 |
| Hydroxychloroquine therapy | 0.40 | 0.09–1.79 | 0.23 |
| Tetracycline therapy | 0.36 | 0.10–1.34 | 0.13 |
| LPP – late remission | |||
| Age at the first visit (per year) | 1.06 | 1.01–1.12 | 0.018 |
| Ashkenazi Jewish ethnicity | 0.33 | 0.12–0.87 | 0.025 |
| FFA – early remission | |||
| Rural residence | 7.00 | 1.14–42.96 | 0.036 |
| Statin use | 3.85 | 1.16–12.81 | 0.028 |
| Tetracycline treatment | 0.21 | 0.06–0.78 | 0.017 |
| FFA – late remission | No variables qualified for entry into the multivariable model | ||
This table shows multivariable logistic regression models identifying independent predictors of remission outcomes, constructed separately for LPP and FFA. Odds ratios (ORs) with 95% confidence intervals (CIs) and p values are provided. Variables included in each model were selected based on statistical signal in univariate analyses using a prespecified threshold. A multivariable model for late remission in FFA was not fitted because no candidate variables qualified for entry.
In multivariable analysis, mild disease severity remained the only independent predictor of early remission in LPP (OR: 4.24, p = 0.040). For late remission in LPP, older age at first visit remained independently associated with remission (OR: 1.06 per year, p = 0.018), whereas Ashkenazi Jewish ethnicity was inversely associated (OR: 0.33, p = 0.025). In FFA, rural residence (OR: 7.00, p = 0.036) and statin use (OR: 3.85, p = 0.028), were independently associated with increased odds of early remission, whereas tetracycline treatment was independently associated with a reduced likelihood of remission (OR: 0.21, p = 0.017). No variables qualified for multivariate modeling of late remission in FFA (Table 5).
Discussion
FFA and LPP are PCAs with overlapping histopathological features, yet our findings suggest that their disease course and remission patterns are not identical. To emphasize observations that extend or differ from prior/expected data, the key results are summarized in Table 6 and discussed below. Although established phenotypic differences between FFA and LPP were confirmed, the most clinically relevant findings concern remission dynamics, predictors of remission, treatment-pattern differences, and selected background-related observations.
Table 6.
Key findings that extend or differ from prior/expected data in FFA and LPP
| Category | Prior/expected | What we found (this cohort) | Interpretation/clinical relevance |
|---|---|---|---|
| Hormonal therapy exposure (OCT/HRT) | Proposed as a differentiator | OCT/HRT exposure: no group difference (p > 0.05) | Points to endogenous hormonal milieu/age-related effects over prior OCT/HRT history |
| Seborrheic dermatitis | Not emphasized as a distinguishing feature | Higher in LPP (22.2% vs. 8.3%, p = 0.03) | May reflect sebaceous activity/inflammation; mechanistic interpretation speculative |
| Psychiatric diagnoses vs. SSRI use | Variably reported | Psychiatric diagnoses similar (p = 0.83); SSRI use was higher in FFA (18.3% vs. 4.9%, p = 0.01) | Prescribing patterns/symptom perception; serotonin-pathway hypothesis (exploratory) |
| Remission dynamics (timing vs. likelihood) | Limited direct comparisons | Cumulative remission higher in FFA (68.3% vs. 45.7%, p = 0.022); time to remission similar (22.8 vs. 22.9 months, p = 0.98) | Differences in remission attainment/maintenance, rather than speed of response |
| Outcome at the last follow-up | Often not separated by maintenance vs. partial response | Remission on treatment higher in FFA (53.3% vs. 21.0%, p = 0.001); partial remission higher in LPP (6.7% vs. 44.4%, p < 0.001) | Supports counseling on long-term control/maintenance needs |
| Treatment patterns | Reflect phenotype/inflammation | LPP: more topical CS (100% vs. 78.3%, p < 0.0001), systemic CS (16.0% vs. 0%, p = 0.0006). FFA: more topical calcineurin inhibitors (91.7% vs. 23.5%, p < 0.0001), topical minoxidil (80.0% vs. 11.1%, p < 0.0001), 5-ARI (30.0% vs. 6.2%, p = 0.0001), oral minoxidil (18.3% vs. 4.9%, p = 0.01) | Provides context for outcome differences; descriptive only (no causality) |
| Relapse (among remitters) | Variable | Similar: during treatment (22.0% vs. 16.2%, p = 0.59), after discontinuation (29.3% vs. 27.0%, p = 0.83) | Differences mainly in remission attainment/maintenance, not relapse rate |
| Predictors of remission (LPP, multivariable) | Inconsistent | Early: mild severity (OR: 4.24, p = 0.04). Late: older age at the first visit (OR: 1.06/year, p = 0.018); Ashkenazi Jewish ethnicity inversely associated (OR: 0.33, p = 0.025) | Emphasizes early diagnosis; ethnicity signal should be interpreted cautiously (confounding/collinearity) |
| Predictors of remission (FFA, multivariable) | Inconsistent | Early: rural residence (OR: 7.00, p = 0.036), statin use (OR: 3.85, p = 0.028); tetracycline treatment inversely associated (OR: 0.21, p = 0.017). Late: none identified | Hypothesis-generating; inverse tetracycline association likely reflects confounding by indication |
Summary of findings that extend prior reports and guide the Discussion. FFA, frontal fibrosing alopecia; LPP, lichen planopilaris; OCT, oral contraceptive therapy; HRT, hormone replacement therapy; SSRI, selective serotonin reuptake inhibitor; 5-ARI, 5-alpha reductase inhibitor; CS, corticosteroids.
Background-related observations included hormonal and comorbidity signals. Although FFA patients were older and more often postmenopausal, OCT and HRT exposure did not differ between groups, contrasting with prior suggestions of an association with exogenous hormonal exposure and supporting a potentially greater role of endogenous hormonal milieu and age-related changes [23]. While hormonal influences appear more prominent in FFA, the role of hormonal factors in LPP remains less clear and likely interacts with non-hormonal immune-mediated mechanisms [8, 9, 20, 31–33]. Seborrheic dermatitis was more prevalent in LPP, potentially reflecting differences in sebaceous activity and/or inflammatory burden. Prior hypotheses linking LPP to relative androgen excess and FFA to androgen deficiency with early sebaceous gland loss may contribute to differing scalp microenvironments, including Malassezia-related factors, but require further study [32–34]. Systemic comorbidities were otherwise comparable between groups despite prior reports suggesting possible differences [35, 36]. Although documented psychiatric diagnoses were similar, SSRI use was higher in FFA; this may reflect prescribing patterns or symptom perception, although serotonin-related pathways have been proposed to contribute to neurogenic inflammation, immune privilege collapse, and fibrotic remodeling, warranting further investigation in FFA [22, 34].
Treatment-pattern differences likely reflected phenotype and inflammatory burden. LPP patients more frequently received topical and systemic corticosteroids, consistent with greater inflammatory activity, whereas FFA patients more often received topical calcineurin inhibitors and hair growth-oriented therapies, including topical/oral minoxidil and 5-α-reductase inhibitors. Greater use of topical calcineurin inhibitors in FFA may reflect a preference for steroid-sparing therapy in thinner or more sensitive skin and the typically less overt inflammatory presentation. These differences may have contributed to the more favorable long-term remission pattern observed in FFA, although causality cannot be established in this retrospective analysis.
Remission dynamics were the most clinically informative finding. Early remission rates were comparable, and mean time to remission was similar (∼23 months), but FFA demonstrated a higher cumulative remission rate.
At the last follow-up, remission maintained on treatment was more common in FFA, whereas partial response was more common in LPP, suggesting that LPP may follow a more persistently active course despite similar initial response. Relapse rates were similar between groups, indicating that the main group differences relate to remission attainment and maintenance. The more frequent use of minoxidil and 5-α-reductase inhibitors in FFA may have contributed to improved long-term stabilization, supporting further evaluation of their role in FFA and their therapeutic significance in LPP [8, 37].
Predictors of remission differed by disease entity. In LPP, multivariable analysis identified mild baseline disease severity as the only independent predictor of early remission, emphasizing the value of early diagnosis and intervention before more extensive inflammatory damage develops [17, 38]. For late remission in LPP, older age at the first visit remained independently associated with remission; whereas Ashkenazi Jewish ethnicity showed an inverse association after adjustment; these findings should be interpreted cautiously given potential residual confounding or collinearity. In FFA, early remission was independently associated with rural residence and statin use, whereas tetracycline treatment was inversely associated.
Statins may exert pleiotropic anti-inflammatory/immunomodulatory and anti-fibrotic effects relevant to PCA. Although not recommended as primary therapy, statins warrant further evaluation as adjunctive treatment [39]. Rural residence may capture environmental or lifestyle factors (e.g., reduced exposure to urban pollutants or cosmetic products, and differences in stress or health-seeking behavior), although these hypotheses remain speculative [21, 31]. The inverse association with tetracyclines likely reflects confounding by indication as these agents are preferentially used in more inflammatory disease. No independent predictors of late remission were identified in FFA.
Strengths of this study include direct comparison of LPP and FFA within a single tertiary center, long-term follow-up, standardized outcome definitions, and diagnostic confirmation by hair specialists. Limitations include the retrospective design, potential information and selection bias, limited generalizability due to the single-center setting (which may have influenced treatment selection and management approach), and inability to establish causality from treatment associations. Wide confidence intervals for some regression estimates reflect limited event numbers, underscoring the need for prospective multicenter studies.
Conclusions
Despite shared histopathology, FFA and LPP differ in remission dynamics, in addition to their known phenotypic distinctions. While early remission rates were similar, FFA showed a higher cumulative remission rate, suggesting more sustained disease control, whereas LPP more frequently exhibited partial response. Mild baseline disease severity predicted early remission in LPP, highlighting the value of early diagnosis. In FFA, early remission was associated with statin use and rural residence, findings that warrant cautious interpretation. Prospective multicenter studies are needed to clarify causality, validate prognostic factors, and optimize personalized treatment strategies.
Statement of Ethics
The study protocol was approved by the Sheba Medical Center Research Ethics Committee (Helsinki), Approval No. SMC-7592-20. The committee waived the requirement for written informed consent due to the retrospective nature of the study, on long period, using medical patient files, data were coded. The study was conducted in accordance with the Declaration of Helsinki.
Conflict of Interest Statement
The authors declare that they have no conflicts of interest regarding this study.
Funding Sources
This study was not supported by any sponsor or funder.
Author Contributions
Lyakhovitsky A., MD: conceptualization, methodology, data curation, writing – original draft and edited draft, supervision, and project administration. Zilbermintz T., MD: investigation, formal analysis, data curation, visualization, and writing – edited draft. Jaworowski B., MD: investigation, formal analysis, data curation, visualization, and writing – critical review and edited draft. Baum S., MD: investigation, data curation, and writing – critical review and edited draft. Galili E., MD: conceptualization, methodology, formal analysis, writing – critical review and edited draft, and supervision. Barzilai A., MD: conceptualization, methodology, validation, writing – edited draft, and supervision.
Funding Statement
This study was not supported by any sponsor or funder.
Data Availability Statement
The data supporting the findings of this study are available from the corresponding author upon request owing to privacy/ethical restrictions.
Supplementary Material.
Supplementary Material.
Supplementary Material.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
The data supporting the findings of this study are available from the corresponding author upon request owing to privacy/ethical restrictions.
