Female pattern hair loss: clinico-laboratory findings and trichoscopy depending on disease severity.

BACKGROUND: Female pattern hair loss (FPHL) is a progressive hair loss disorder with unclear triggering and supporting factors. Trichoscopic features of each stage of FPHL have not been specifically elaborated previously. AIMS: To analyze characteristics and investigate associations of clinico-laboratory and trichoscopic features of female patients in regard to the severity of hair loss in FPHL and to facilitate its diagnosis using noninvasive scalp dermoscopy (trichoscopy) in Fitzpatrick skin type III patients.
MATERIALS AND METHODS: Clinico-laboratory and trichoscopic data from 60 patients with FPHL were analyzed using Spearman's correlation test.
RESULTS: Patients had mean age of 34.4±10.6 years and mean duration of hair loss of 4.49±3.76 years. Of all, 45% (27/60) had a family history of pattern hair loss (PHL) and had an earlier onset of hair loss. Stage of hair loss positively correlated with duration and age at presentation. No association was found between the severity of FPHL and laboratory values including anemic and gonadal hormone profiles. Characteristic trichoscopic features (at 10-fold magnification) of FPHL were peripilar signs (PPS) (brown, BPPS and white, WPPS), white dots, scalp pigmentation, and focal atrichia. WPPS, scalp pigmentation, and focal atrichia positively correlated with the stage and duration of hair loss.
CONCLUSIONS: Family history of PHL causes an earlier onset of hair loss but does not influence its course or severity. The latter is also not affected by abnormal anemic profile or hormonal levels. PPS, scalp pigmentation, focal atrichia, and white dots are characteristic of PHL. WPPS, scalp pigmentation, and focal atrichia reflect advanced PHL.

INTRODUCTION

Female pattern hair loss (FPHL) is a form of non-scarring diffuse hair loss and hair thinning in a pattern fashion as described by Ludwig which mainly affects females as early as in their teen years.[1] To date, some factors considered as etiopathogenetic for FPHL including genetic predisposition, iron deficiency and hormonal imbalances have already been established in certain populations. A recent study excluded iron deficiency as being a causative factor of FPHL in Caucasians and a low estrogen to androgen ratio in the presence of genetic susceptibility has been found to be of significance in the same population.[23] However, despite these new findings in this research arena, its underlying cause is still puzzling as once, triggered this type of hair loss is slowly progressive and may be resistant to the few known therapies. Past studies are mainly directed toward investigating its etiological factors; however, though quite common in the Chinese population, pattern hair loss (PHL) studies in China are scarce.

Recently, trichoscopy (scalp dermoscopy), being a hot-spot in the field of trichology has led to the establishment of diagnostic features of some hair disorders like alopecia areata, trichotillomania, tinea capitis among others. However, literature investigating features of PHL in females are few. Peripilar signs (PPS) and yellow dots have been reported to be specific features observed in 20% to 86% and 10% of FPHL patients, respectively.[45] But trichoscopic features of each stage of FPHL and its possible association with other clinico-laboratory factors have not been specifically elaborated previously.

In this study, we aimed to analyze characteristics and investigate associations of clinico-laboratory and trichoscopic features of female patients in regard to the severity of hair loss in FPHL and to facilitate its diagnosis using noninvasive trichoscopic method.

MATERIALS AND METHODS

Sixty patients with signs and symptoms of FPHL who referred to the hair clinic of the First Affiliated Hospital of Sun Yat-sen University for investigation and treatment of hair loss were enrolled in this study. Patients were of Fitzpatrick skin type III. None of these patients followed any food and drug administration - approved treatment for FPHL in the past. The diagnosis of FPHL was made on the basis of anamnesis, clinical findings including hair thinning and miniaturization in a pattern fashion.[67] These patients were divided into subgroups based on stage and type of hair loss as per Ludwig scale into Ludwig I (LW I), Ludwig II (LW II), and Ludwig III (LW III) and in male type frontotemporal recession (MT).[89] Clinically suspicious patients with possible hair diagnoses mimicking FPHL such as chronic telogen effluvium (CTE) were excluded from this study.

Laboratory investigations including complete blood count, anemic profile (serum ferritin, serum folate, and serum vitamin B12), gonadal steroid hormones (total testosterone-T, estradiol-E2, follicle-stimulating hormone-FSH, luteinizing hormone-LH), thyroid function tests (TFTs including T3, T4, and TSH), and thyroid autoantibodies levels (thyroid peroxidase antibody-TPO-Ab, thyroglobulin antibody- TG-Ab) were carried out. The E2/T ratio was calculated for each patient.

Trichoscopy with a non-contact polarized dermoscope (Dermlite, DL3 model, 3Gen US Company) at 10-fold magnification was performed at hair loss areas in all patients as well as at vertex areas of control subjects who consisted of 20 age-matched female patients with CTE whose diagnosis was made on the basis of detailed anamnesis, chronology of events, increased hair shedding for more than 6 months, and clinical presentation with a normal-looking head full of hair with/without a positive hair pull test (>6 hairs/pull) with no hair miniaturization. Clinically suspicious patients with coexistent FPHL and CTE were excluded from this study. Trichoscopic photographs of each patient and control obtained from four different fields of visualization were assessed for typical differentiating features by two independent observers.

SPSS 13.0 software was used for statistical analysis. Mann Whitney, t tests, and one-way analysis of variance were used to evaluate clinical and laboratory values in FPHL age and stage subgroups. Chi-Square test was used to compare the incidences of abnormal laboratory findings among the subgroups as well as to compare incidences of trichoscopic features between patients with FPHL and control group. Correlations were run to determine relationships between trichoscopic features observed and stage of hair loss using Spearman's rank correlation test. Statistical significance was set at P value of < 0.05.

RESULTS

Clinico-laboratory result

Overall demographic result

The 60 patients, all of Chinese ethnic background, had a mean age of 34.4±10.6 years with a mean duration of hair loss of 4.49±3.76 years. The age of onset of hair loss corresponded to a mean age of 29.8±9.47 years. Of all, 45% (27/60) of the patients had a family history of PHL, these patients had an earlier age of onset of hair loss (23.5±6.50 years) than those with no family history of PHL (35.3±8.08 years) (P< 0.001). However, a family history of PHL did not correlate to a more severe hair loss condition at presentation (R=0.167, P=0.221). 14.8% (9/60) of the patients were peri- or post-menopausal.

Stage and type of hair loss

40% (24/60), 23.3% (14/60), 26.7% (16/60), and 10% (6/60) of patients had hair loss as per Ludwig type I, II, II and male-type frontotemporal recession, respectively, with corresponding mean age of onset of 29.3±9.32 years, 27.1±7.43 years, 34.3±11.6 years, and 26.3±2.65 years which were not statistically different from each other (P=0.133). However, duration of hair loss condition among the four groups were different (LW I = 3.0±3.4 years; LW II = 5.0±3.4 years; LW III = 7.0±3.7 years; MT = 3.0±3.5 years). Stage of hair loss positively correlated with duration and age at presentation (R=0.531, P<0.001; R=0.278, P=0.042), but not with age of onset (R=0.165, P=0.233).

Laboratory results

Slight deviations were found in TSH (3.33%, 2/60) but corresponding T3 and T4 thyroid hormone levels were within normal limits. Remarkable elevations in thyroid autoantibodies were found in 11.6% (7/60) of the patients. These patients were referred to endocrinology department for treatment and follow-up. Anemic profile revealed iron deficiency (serum ferritin <12 μg/l) in 6.7% (4/60); iron depletion (12 μg/l < serum ferritin <20 μg/l) in 3.3% (2/60), and serum ferritin level lower than required for normal hair cycle (20 μg/l patients. The incidences of iron deficiency, iron depletion as well as a serum ferritin level of below 70 μg/l did not differ among the stages of hair loss (Ps>0.05). Overall mean serum ferritin level was 58.8±57.3 μg/l. 8.3% (5/60) of patients had hemoglobin level below 120 mg/l.

Gonadal hormones levels tested on the first day of their menstrual cycle showed hormonal alterations in two patients (aged 14 and 31 years) who were referred to the gynecological department of our hospital for further evaluation and pelvic ultrasound. Both patients had LW II hair loss. The older patient was a known case of polycystic ovarian syndrome (PCOS), while the younger one was newly diagnosed as PCOS after gynecological diagnostic work-up. Correlation tests did not reveal any association between the severity of FPHL and the changes in laboratory results including E2/T ratio and different serum ferritin levels.

Trichoscopic features

Observed trichoscopic features in the patients were PPS [brown, BPPS, (19/60) 31.7% and white, WPPS, (16/60) 26.7%]; pinpoint white dots, (13/60) 21.7%; yellow dots, (1/60) 1.67%; scalp pigmentation, (37/60) 61.7%; focal atrichia, (34/60) 56.7%. In the control group, only yellow dot sign was found in one patient. On comparison of FPHL and control group, apart from the incidence of yellow dots (P>0.05), the incidence of all other trichoscopic features including BPPS [Figure 1], WPPS [Figure 2], white dots [Figure 3], scalp pigmentation, and focal atrichia [Figure 4] were higher in the FPHL group (P=0.002; 0.008; 0.031; <0.001; <0.001, respectively). Scalp pigmentation varied from mildly pigmented in early stages to patchy honeycomb and diffuse honeycomb pattern of pigmentation in late stages. An observation was made regarding a difference in the miniaturization process in Ludwig type hair loss and male-type frontotemporal recession. In advanced stages of FPHL, even though some pilosebaceous unit ended up in complete atrophy manifesting as atrichia, most of them had at least one residual terminal hair fiber; in contrast, in male type frontotemporal recession, most of hair fibers had vellus transformation and no focal atrichia was noted.

Figure 1

Brown peripilar signs in Ludwig type I hair loss patients (Scale bar = 1 mm)

Figure 2

White peripilar signs in Ludwig type II hair loss patients (Scale bar = 1 mm)

Figure 3

White dots evenly scattered on the scalp in Ludwig type II hair loss patient. White peripilar signs of larger diameter can also be noted around follicular units (Scale bar = 1 mm)

Figure 4

Focal atrichia seen as pencil-erased areas of hair loss (Scale bar = 1 mm)

We further sought to investigate any association between the trichoscopic findings and the stages of hair loss (LW I-III) as well as clinico-laboratory features. Table 1 shows the incidence of each trichoscopic signs in each stage of hair loss.

Table 1

Incidence of trichoscopic signs found in each stage of female pattern hair loss patients

Spearman's rank correlation revealed that WPPS, scalp pigmentation, and focal atrichia positively correlated with the stage of hair loss (R=0.400, P=0.003; R=0.433, P=0.001; R=0.591, P<0.001) as well as with duration of hair loss condition (R=0.322, P=0.018; R=0.454, P=0.001; R=0.571, P<0.001). Scalp pigmentation also positively correlated with both age of onset and age at presentation (R=0.298, P=0.029; R=0.435, P=0.001) as well as with WPPS (R=0.459, P<0.001).

No associations were found between trichoscopic signs and laboratory values.

DISCUSSION

In this study involving patients from the Chinese ethnic group, the incidence of family history of PHL (45%) was remarkably higher than previous studies from other regions in China where the incidence varied from 19.2% to 32.4%.[110] By comparison of age of patients with and without family PHL history, we confirmed that genetic predisposition increases susceptibility of developing FPHL at an earlier age which is in concordance with the high incidence of a positive family history in adolescents with PHL.[1] However, family history of PHL does not affect course of hair loss. Severity of hair loss is only influenced by the duration of the condition.

The association of low ferritin level and hair loss has been a debate over the years worsened by the confusion over serum ferritin cut-off levels below which it can be defined as nutritional deficiency to be a trigger for hair loss.[11-15] We investigated different levels of serum ferritin corresponding to iron deficiency (<12 μg/l), iron depletion (<20 μg/l) as well as the level (70 μg/l) which preserves the hair follicle in the normal anagen phase[16] within each stages of FPHL. However, their incidences within each group were not significantly different, which concludes that the course of FPHL is also not affected by low serum ferritin levels.

Normal gonadal hormonal levels in our patients are in concordance with many previous studies.[1718] However, in a previous study, it was found that FPHL patients had a relatively lower estrogen to androgen ratio.[3] In this study, severity of hair loss did not correlate with estrogen and androgen ratio. According to the recently published S1 guideline for diagnostic evaluation of PHL,[19] estimation of the free androgen index test is more appropriate to evaluate any hormonal dysregulation if suspected. 3.3% (2/60) of our FPHL patients had PCOS, among whom one was as young as 14 years and was firstly diagnosed during diagnostic work-up for hair loss. We therefore strongly recommend that young patients presenting with advanced stage of FPHL should have a thorough gynecological work-up including pelvic ultrasound to rule out PCOS.

Previous studies investigating dermatoscopic features of FPHL included subjects with Fitzpatrick I and II skin type; our observations are from Fitzpatrick skin type III subjects. In past studies, features observed in female androgenetic alopecia were PPS and yellow dots observed in 61.5% and 2.6% of patients, respectively. In this study, brown peripilar signs (BPPS), white peripilar signs (WPPS), white dots, different pigmentation patterns of the scalp, and focal atrichia were features observed in FPHL patients. Peripilar sign in androgenetic alopecia is defined as the presence of a brown halo, roughly 1 mm in diameter at the follicular ostium. The histopathological origin of PPS has been associated with perifollicular infiltrate[5] and melanogenesis.[20-22] However, we found that the peripilar halo varied from brown (BPPS) to white (WPPS) color. Although there was no particular relationship observed in the incidence of BPPS and stage of hair loss, WPPS positively correlated with advancing stage of FPHL as well as its duration. We do not exclude the fact that WPPS require a contrast background to be easily detected; it is therefore more prominent in advanced stages of hair loss where the scalp is more pigmented due to increased sun exposure. Interestingly, similar WPPS named as “white dots” have been found in a few patients with lichen planopilaris and folliculitis decalvans,[23] histologically representing focal loss of melanin overlying scarred fibrous tracts.[24] We presume that WPPS in advance stages, which is a novel trichoscopic feature in PHL, may be a sign of discreet atrophy which can be present in long-standing FPHL and can be a poor prognostic finding in regard to therapy.

Focal atrichia and scalp pigmentation besides being characteristic for FPHL also positively correlated with advancing stage. Focal atrichia which is usually referred to as “pencil-erased” focal loss of hair was already present as early as LW I and in LW III, it was seen in almost all the patients. Scalp pigmentation can easily be assessed by comparison of the hair loss region with the occipital region of the same patient. As expected, scalp pigmentation which changed from mildly pigmented to patchy honeycomb and eventually to an evenly diffuse honeycomb pattern was more pronounced with increasing FPHL stages where scalp skin is more prone to sun-exposure.

We here define white dots as being white spots with diameter ranging from 0.2 to 0.3 mm distributed uniformly between the follicular ostia and not around the follicular ostia [Figure 3]. This does not include the white perifollicular signs which are larger in size and may also not coexist with white dots. Histologically, white dots correspond to eccrine sweat glands pores in the scalp.[25] White dots were found to be characteristic of FPHL, though they did not correlate with the stage. Sweat glands are skin organelles with the highest 5-alpha-reductase activity which are subject to hypertrophy in hyperandrogenic states.[26] This suggests that patients with PHL, under the influence of androgens besides hair miniaturization, may also have sweat gland hypertrophy manifesting trichoscopically as white dots. However, sebaceous glands are also organelles that are targeted in hyperandrogenic states; but the incidence of yellow dots which correspond to dilated follicular infundibulum filled with sebum and keratinous matter was not different from healthy controls. The presence of yellow dots was categorized as one of the major criterias in the diagnosis of FPHL in a recent study by Rakowska et al.[27] This disparity in findings can be explained by the difference in ethnic group enrolled in both studies which implies variation in sebaceous gland activity as well as in the degree of pigmentation of the scalp in late stages that allows easy perception of white dots but not yellow dots.

In short, from this study, we support that genetic predisposition favor an earlier onset of FPHL but does not influence the course of hair loss. Anemic and gonadal hormone profiles, though probably implicated as triggering factors, are not dominant on severity of FPHL. PPS, scalp pigmentation, focal atrichia, and white dots are characteristic of PHL. PPS, focal atrichia, and white dots can be used as differentiating diagnostic features of FPHL with CTE. Scalp pigmentation and perhaps white dots as well are secondary to hair loss with resultant increased sun-exposure. WPPS, scalp pigmentation, and focal atrichia are features associated with advanced PHL condition, while WPPS may be a poor prognostic marker of treatment.