JEADV-2015-1010.R1

Title: Towards a consensus on how to diagnose and quantify female pattern hair loss – The “Female Pattern Hair Loss Severity Index (FPHL-SI)”

Authors: Matthew Harries (Manchester), Antonella Tosti (Miami/Bologna), Wilma Bergfeld (Cleveland), Ulrike Blume-Peytavi (Berlin), Jerry Shapiro (Vancouver/New York), Gerhard Lutz (Bonn), Andrew Messenger (Sheffield), Rodney Sinclair (Melbourne), Ralf Paus (Manchester/Münster)

Address for correspondence:

Dr Matthew Harries

Consultant Dermatologist and Honorary Senior Lecturer

The University of Manchester

Salford Royal NHS Foundation Trust

Salford

Greater Manchester

M6 8HD

UK

Tel: +44 (0)161 2061012

Email: matthew.harries@srft.nhs.uk

Word count: 4218

Figures: 6

Tables: 1

Funding sources: The Edinburgh consensus meeting, its transcription, and the generation of the corresponding manuscript were supported by an educational grant from Dr Kurt Wolff, Bielefeld, Germany.

Conflicts of interest: The authors state no conflict of interest. All authors serve as consultants for competing commercial entities with an interest in treating or preventing hair loss and therefore have strived to reach a consensus that has the potential of meeting universal approval among experts in the field. The sponsor had no influence on the contents of this consensus paper, which solely expresses the opinion of its authors.

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Abstract

Background: Female pattern hair loss (FPHL) is a common non-scarring alopecia characterized by widening of the midline hair-part at the crown (vertex). In 1977 Ludwig developed a scale that graded the degree of visible vertex hair thinning from I (least severe) to III (most severe). However, by the time patients exhibit the full manifestations of “Ludwig I” they have already lost a significant volume of hair. Although current therapies may realistically halt progression of hair loss, improvements in hair density is often more limited. Identification and grading of FPHL at an earlier stage is desirable to institute appropriate therapy before significant hair loss has occurred and to enable monitoring over time.

Aim: To generate consensus guidance for the recognition and quantification of FPHL that can be used in the clinic.

Methods: Nine clinicians from Europe, North America and Australia experienced in the management of FPHL developed this scale by consensus.

Results: We propose a three point severity scale (termed the FPHL Severity Index (FPHL-SI)) that combines validated measures of hair shedding, midline hair density and scalp trichoscopy criteria to produce a total FPHL-SI score (maximum score = 20). The score is designed to grade FPHL severity over time, whilst being sufficiently sensitive to identify early disease. A score of 0-4 makes FPHL unlikely; a score of 5 - 9 would indicate early-stage FPHL, with higher scores indicating greater disease severity.

Conclusions: As a starting point for further public debate, we employ criteria already used in clinical practice to generate a pragmatic FPHL grading system (FPHL-SI) of sufficient sensitivity to identify and monitor early FPHL changes. This may have to be further optimized after systematic validation in clinical practice.

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Female pattern hair loss

Female pattern hair loss (FPHL) is a non-scarring, diffuse alopecia that generally occurs in post-pubescent females. It shows a characteristic clinical presentation and distribution pattern of scalp hair loss (for reviews on diagnosis and management of FPHL, see [1-10]) (Fig. 1). These characteristics set FPHL apart from male pattern hair loss (MPHL), and usually allow one to distinguish FPHL clinically from other causes of hair loss in women [2, 7, 8, 11-13]. However, FPHL can also show a phenotypic overlap with classical Hamilton-type MPHL, and may be observed in women with excessive systemic androgen levels, associated with hirsutism and other signs of androgen excess [2, 8, 14, 15]. In some women FPHL presents with diffuse hair thinning involving not only the crown, but also the parietal (and rarely) the occipital region.

Male pattern hair loss (androgenetic alopecia) occurs when intra-cutaneous androgens induce miniaturization, shorten anagen duration and prolong telogen (and kenogen) in genetically susceptible hair follicles. The pathogenesis of FPHL also involves miniaturization, shortened anagen duration and prolongation of telogen (and kenogen) in genetically susceptible hair follicles. While most dermatologists still conceive FPHL as a variant of androgenetic alopecia, there is doubt whether androgens and in particular increased intra-cutaneous dihydrotestosterone production by 5-α-reductase and its effects on terminal scalp hair follicles (HFs)[16] is the sole or even the major culprit in FPHL. A relative lack of intra-cutaneous synthesized oestrogens, e.g. through reduced aromatase activity [17-22], and perhaps abnormalities in prolactin-mediated signaling [23] may also have to be taken into account.

The familial occurrence of FPHL [24] renders linkage to defined susceptibility genes likely, which may well be different from those identified for androgenetic alopecia in males [25-35]. However, convincing genetic loci linked to FPHL remain to be identified, and the potentially important impact of epigenetic factors on FPHL awaits systematic exploration [21, 25, 36-41]. The epidemiology of FPHL remains unclear and partially contradictory (see below), likely as a reflection of major variations in the populations examined, the inherent ethnic diversity of hair, and the techniques by which a diagnosis of FPHL was reached. Thus, in view of these variables, the available epidemiological data on FPHL are overall unsatisfactory and may, in fact, be misleading.

Future therapeutic trials on FPHL management will require the examination of well-defined collectives of patients with emphasis on early-stage FPHL, as these early stages are likely to be most responsive to therapeutic manipulation. Similarly investigations into the pathobiology that focus on patients with early stage FPHL are most likely to reveal pathomechanisms of primary significance. As it is improbable that definitive genetic and other molecular markers of FPHL will become available any time soon, clinical examination along with a patient’s history and familial predisposition to hair loss will remain the essential basis of reaching a correct diagnosis of FPHL in the foreseeable future.

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The problem

This poses two central questions: What clinical pattern and early predictive features exactly support a clinical diagnosis of FPHL; and how can very discrete, early-stage hair loss in FPHL be objectively recognized and quantified? In other words, a patient comes in and says “I have hair loss” but you don’t see it (Fig. 2). In this situation how do we objectively assess whether or not that individual is headed towards a full manifestation of FPHL (i.e. Ludwig I)?

How important it is to answer these questions convincingly is illustrated by the current state of the FPHL epidemiology literature. Frequently reverberated figures are, for example, that FPHL becomes first clinically detectable in 3% of women by age 29 years, in 13% by age 49 years, 19% by age 69 years, and 25% thereafter [42-44] or that about 10% of pre-menopausal women show FPHL / female androgenetic alopecia, as opposed to 20-30% of post-menopausal women [45]. In Chinese and Korean individuals FPHL is reportedly lower than in Caucasians [46]. However, as Olsen rightly points out, “True prevalence of FPHL is difficult to determine given that most authors either (1) have not clearly stated the diagnostic criteria used, including any pertinent screening laboratory tests performed or not performed, or (2) have chosen to focus only on one pattern of FPHL” [9]. Thus, hard data on the true incidence and prevalence of FPHL in well-defined and sufficiently large populations is limited [47].

Based on their own long-standing experience in managing hair loss patients, the authors of this consensus paper are convinced that the true incidence and prevalence of FPHL is greater than the frequently repeated numbers cited above and may well affect the majority of females sooner or later if one includes early stages of a process that will lead to the Ludwig I phenotype [11] and/or to mixed Hamilton/Ludwig phenotypes of FPHL [2, 9, 14]. However, differentiating these early FPHL changes from hair density decline expected with age, and predicting those who will or won’t progress over time, remains to be answered. Interestingly, Venning and Dawber observed that “...when specifically sought, vertical [= vertex hair] thinning is present to some degree in a very high proportion (63-87%) of normal women”, although the hair status assessment used in this study (i.e. by wetting and flattening the hair) may explain to some degree the high rates reported. Also, the same authors found fronto-parietal hair recession (commonly viewed as a marker of pathological virilization) was more common than previously described and present in 13% of premenopausal and 37% of post-menopausal women [14]. Even affected individuals themselves tend to underestimate the degree of loss in hair density they have already gone through [48]. Indeed, it has been suggested that “Every slowly progressive diffuse hair loss in women […] as long as there is no suggestion of scarring, should be considered as androgenetic alopecia until proven otherwise and so treated.” [49].

 

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Problem solving by consensus

Therefore, five dermatologists from Europe, North America and Australia with long-standing clinical experience in the management of FPHL patients (A.T., W.B., R.S., M. H., R.P.) met for a consensus discussion during the World Congress of Hair Research (Edinburgh, May 2013) to explore the problem and to jointly generate a consensus paper on a plausible approach to how FPHL (including early-stage disease) can be recognized and quantified in a standardized and reproducible manner. The lively and productive discussion that ensued was recorded and transcribed. A first manuscript version jointly generated on this basis was then shown to a second group of senior colleagues with special expertise in FPHL (A.M., J. S., U.B.-P., G.L). Their critical comments and suggestions for modifications were subsequently incorporated into the final consensus paper. Therefore, the current paper integrates the expertise of a very diverse and international group of dermatologists specializing in the management of hair growth disorders and represents their shared views.

We publish this proposal in the hope to stimulate further public debate and to invite additional, concrete suggestions for how the pragmatic FPHL grading system outlined below may be further optimized before it is put to rigorous clinical testing. The main purpose of this exercise was not to present a definitive, validated grading system (a lengthy process that requires substantial resources), but to encourage our colleagues to provide constructive critical feedback so that the proposed grading system is further optimized before a corresponding multi-centre trial is organized in order to validate the system.

Premises

Whatever the pathobiology of FPHL , it needs to explain a) how terminal scalp hair follicles (HFs) are progressively miniaturized into small, depigmented vellus HFs in FPHL, b) why this usually is associated with periodic hair shaft shedding on the basis of a shortened anagen phase (telogen effluvium), c) why FPHL shows a characteristic distribution pattern, clinical presentation, and course, and d) why this condition is often familial [5, 6, 8, 9, 14, 15, 50, 51]. This is important to keep in mind, since satisfactory techniques for the clinical assessment of FPHL should take these components of FPHL pathobiology into account.

We suspect that one reason why the Ludwig staging system (I - III) fails to detect early-stage FPHL (Fig. 3) is that is relies mainly on assessing visible hair thinning on the crown [11]. Although the so-called “midline part” and “Christmas tree pattern” undoubtedly are important and valuable clinical criteria in assessing FPHL [2] (Fig. 3 and 4), they reflect advanced stages of FPHL. Thus, scales of this type are less useful for early diagnosis but are helpful in assessment over time and to appreciate the impact of visually appreciable hair thinning on the patient. Conversely, trichoscopy (hair and scalp dermoscopy) has now become the main tool in diagnosing FPHL (see below) even at an early stage, although trichoscopic criteria (in a similar way to scalp biopsy findings) identifies the proportion of

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terminal to (miniaturized) vellus-like hairs, which does not always correlate with visible severity [50]. Another prominent (and not uncommon presenting) symptom in FPHL patients is increased hair shedding, although it is not seen in all cases [5]. Moreover, hair shedding is a highly volatile parameter, and fluctuations in hair shedding are expected [52, 53]. Yet, it remains advisable to estimate hair shedding, particularly if more apparent from the top of the scalp, as this may be an early presenting feature of FPHL. However, excessive shedding should also prompt further investigation to exclude a co-existing telogen effluvium.

In order to make them generally applicable in clinical practice, the employed criteria for recognizing and quantifying early-stage FPHL should facilitate quantification with minimal of effort, require only widely available standard equipment for the evaluation of hair loss patients, and should be assessable in a single session. Thus, we have not considered the use of more sophisticated techniques such as (contrast-enhanced) phototrichogram [54, 55], pluck trichogram, high-magnification video-dermoscopy (as not readily available to most general dermatologists), measurement of scalp hair diameter using optical fibre diameter and image analysis [56], the modified wash test [57] or other more elaborate diagnostic techniques [58, 59]; as desirable as they unquestionably can be in specific settings. Also, while quality of life assessment tools are important for clinical hair trials [60] such questionnaires are dispensable for diagnosing and quantifying FPHL.

Finally, the main reason for promoting the development of a pragmatic, but sufficiently sensitive system to objectively diagnose and quantify FPHL, including early-stage disease, is that while currently available therapies [1, 4-6, 8, 44] can be reasonably efficient in terms of halting FPHL progression, they are often disappointing in terms of inducing hair regrowth. Thus, it is only logical to advocate therapeutic intervention as early as possible in those individuals who complain about hair loss but do not yet display a classical Ludwig I phenotype so as to halt progression before it becomes a psychological burden [61, 62].

Proposal: How to assess FPHL severity and diagnose early-stage FPHL

On this basis, we propose the following simple and relatively fast three-component system (the “FPHL-SI”; Table 1) for diagnosis and grading of suspected FPHL. The FPHL-SI is designed to be used “at the bedside” as part of standard clinical assessment, as a framework for diagnosis and to facilitate monitoring over time, whilst being sufficiently sensitive to diagnose early-stage FPHL in women complaining of hair loss who have little objective reduction in hair density. A clear history or appearance suggesting an alternative diagnosis (e.g. patchy hair loss, significant inflammation with scarring, etc.) should not be scored in this way but assessed appropriately for the condition suspected (see [8, 12, 63, 64]).

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1. Assess hair shedding (effluvium) by (a) asking the patient to identify the subjectively estimated amount of hair shedding over time using a visual scale produced by Sinclair (Fig. 5), and (b) the hair pull test at different scalp locations.

(a) Sinclair hair shedding scale (Fig. 5) [65] . This is used to follow women prospectively while undergoing treatment for hair loss. In women with long straight hair it can also be used as a guide to normal or excessive hair shedding [NB. different photo series are required for short or very curly hair assessments]. A collection of hair from a single patient was counted out into smaller bundles and photographed. Bundle one (=1) contains 10 hair, bundle two (=2) 50 hairs, bundle three (=3) 100 hairs, bundle four (=4) 200 hairs, bundle five (=5) 400 hairs and bundle six (=6) 750 hairs. On presentation women are asked how much hair they shed each day. For women who wash their hair less frequently than every day they should be asked about wash days and non-wash days. 1 - 4 are regarded as normal levels of shedding; 5 or more denoted excessive shedding. Using this scale, excessive shedding was seen in 70% FPHL patients compared with 1% controls [65]. However, some patients may not be able to estimate their degree of shedding if they do not wash their own hair; it may also be unsuitable for those who wash their hair very infrequently.

(b) Hair pull test . This should be performed in a standardized way based on your regular practice. When the patient last washed their hair should be noted and taken into account when interpreting the results (we recommend no hair washing for 2 days before assessment where possible, but as long as the duration remains consistent across your practice the test is valid). Grasp 50-60 hairs close to the scalp and pulled away from the head letting your thumb and finger slide along the hair shaft. This technique is designed to remove any loose telogen hairs. It is normal to remove the odd telogen hair. However, if >10% hairs pulled are removed this suggests excessive shedding. Look for any differences between four scalp locations (i.e. right and left parietal scalp and frontal and occipital areas) [58, 59]. In FPHL, shedding of shorter hairs from the top of the scalp is characteristic.

When the diagnosis of FPHL is established, levels of shedding may be used to monitor treatment response over time [65]. However, excessive shedding should also prompt further investigation and review of the patient’s history to identify (and treat) co-existing telogen effluvium that can sometimes “un-mask” FPHL (see [8, 64]), or identify other rarer causes of increased hair fall (e.g. diffuse alopecia areata).

Scoring the FPHL-SI1. Assess hair shedding (effluvium):Use one or both tests and score the highest reading.(a)Sinclair hair shedding scale1 - 4 score = 0

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5 or 6 score = 2(b) Hair pull testNegative hair pull test score = 0Positive hair pull test (frontal scalp positive; occipital scalp negative) score = 2(Maximum score = 2)

2. Assess midline hair density by employing the Sinclair hair density severity scale for FPHL (fig. 4) [48]. Note the difference in part-width between the vertex and occipital scalp and whether the fronto-parietal hairline is preserved or receding.

Various midline hair density scales have been proposed to grade severity of FPHL (Fig. 3 and 4) [48, 66]. However, it has been shown that among women with ostensibly normal appearing scalp hair density (i.e. Sinclair grade 1) who presented with hair loss, up to 40% will have hair follicle miniaturization on scalp biopsy of sufficient severity to allow a diagnosis of androgenetic alopecia [50]. Further, a significant proportion (up to 50%) of hair may be lost (as evidenced by hair follicle miniaturization on biopsy) without any clinically evident baldness; an observation likely due to preservation of scalp follicular units but a reduction in the number of hairs per follicular unit [67]. Thus, pattern hair loss principally characterised by a widened midline hair part is not a sensitive marker of early-stage FPHL and may only manifest after significant hair loss has already occurred. However, visible reduction in hair density is a validated approach to grading more established cases of FPHL, with changes on visible hair density potentially having the most impact on the patient’s perception of disease severity. Pre-morbid hair density along with variations in the balance between hair shaft diameter and hair follicle density levels may influence the timing of objective scalp density reduction from person to person [38].

Although the Ludwig pattern of hair loss is by far the most common presentation of reduced hair density in FPHL, other presentations, such as the “Christmas tree” pattern [2] or diffuse pattern may be seen. In these presentations the severity can be broadly assessed and scored using the Sinclair scale using maximum area of thinning as the target area for comparison. The less common appearance of male pattern “FPHL” can be separately assessed using the Norwood-Hamilton scale (with appropriate corresponding scores – see Table 1).

Scoring the FPHL-SI2. Assess midline hair density: Sinclair grade 1 score = 0 pointsSinclair grade 2 score = 4 pointsSinclair grade 3 score = 6 pointsSinclair grade 4 score = 8 pointsSinclair grade 5 score = 10 points(Maximum score = 10)

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At this point patients with subjective hair loss (with or without excessive shedding) and Sinclair grade 1 midline hair density may or may not have early-stage FPHL; trichoscopy evaluation is required (see below). Patients with Sinclair grade 2 or more are showing signs of established pattern hair loss, with the higher the grade the greater the confidence in the diagnosis of FPHL (e.g. 97% of women with Sinclair grade 3 or more show histopathological changes diagnostic of FPHL [68]).

3. Trichoscopy can be used both to assess increased hair diameter diversity and the loss of terminal hairs within follicular units, both features of FPHL.

Follicular units (FU) on the scalp contain up to 4 hairs. On a normal scalp one primary and 1-3 secondary hairs will emerge as a tuft from a single pore. Secondary hairs emerge in early childhood. In both FPHL and MPHL the total number of terminal hairs as well as the number of terminal hairs per FU diminish with increased disease severity [38] ; it is proposed that this may reflect a heirarchy of androgen sensitivity in FUs leading to selective minaturisation of (?secondary) terminal hairs within each FU [67]. Loss of terminal hairs leads to a reduction in hair density that precedes the diffuse loss of volume over the crown and the appearance of a bald scalp. Loss of (secondary) hairs can be recognized on trichoscopy as a reduced ratio of double and triple (terminal) hair FU on the mid-frontal scalp compared to the occipital scalp, with a corresponding increase in the proportion of single (terminal) hair FUs. Comparison with the occipital scalp is very important as telogen effluvium cause a reduction of double and triple FU throughout the scalp [69] .

Hair diameter diversity (also termed “anisotrichosis”) is the appearance of hair shafts of different caliber easily seen on trichoscopy that reflect the hair miniaturization that characterizes the disease [70, 71]. Hair diameter diversity should be assessed at a point 2 cm from the frontal hair line in the midline (“frontal area”) and always compared with the occipital scalp. Observation of reduced hair shaft caliber in > 20% hair follicles has traditionally been deemed essential in diagnosing patterned hair loss [72, 73]; although a cut-off of 10% diversity may be more appropriate in females [74].

Other trichoscopic criteria are proposed for FPHL diagnosis. In 2009, Rakowska et al. proposed major and minor diagnostic trichoscopic criteria for the diagnosis of FPHL [69]. One of the major criteria was the presence of more than 10% of thin short regrowing hairs in the frontal area (20X magnification; Fig 6(c)). Herskovitz et al. have recently evaluated the role of this criteria for diagnosis of early-stage FPHL and found that women with early-stage FPHL have more than 6 thin short regrowing hairs in the frontal scalp [75] (20X magnification). Unfortunately, these data were generated using features observed at 20X – 70X magnification. As most dermatologists only have access to a 10X magnification hand-held dermoscope in clinic, the FPHL-SI only uses criteria identifiable with this equipment.

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Thus, trichoscopy has the potential to diagnose FPHL before objective reduction in hair density. However, just as with scalp biopsy findings, correlation with visible severity is less well established [50], although associated (but not specific) trichoscopy signs (e.g. yellow dots; white peri-pilar sign; focal atrichia) may correlate with severity [74]. Yellow dots represent empty follicular ostia filled with keratin and sebum and represent the kenogen (or “latent”) phase of the hair cycle between hair shedding and the initiation of the next anagen phase. Thus, presence of yellow dots can further support the diagnosis of FPHL and may be more prominent in advanced disease [69, 74, 76] . However, yellow dots have not been included in the FPHL-SI as validated diagnostic criteria for this sign in FPHL are only available using x70 magnification [69] and its presence is not specific for FPHL (i.e. also seen in alopecia areata) [71] .

Specifically look for the following trichoscopy criteria (Fig 6):

A) hair diameter diversity in more than 20% of hairs assessed by trichoscopy [72, 73, 76];B) Reduction in proportion of triple hairs and increased proportion of single hairs per follicular unit in the mid-frontal scalp compared with the occipital scalp.

Scoring the FPHL-SI3. trichoscopy (frontal area):Score both trichoscopy criteria A and B.(A) Hair diameter diversity<20% hair diameter diversity. score = 0 points>20% hair diameter diversity. score = 5 points(B) Triple and single hairs per FUNo difference in proportion of multiple / single FUs between the frontal area and occiput. score = 0 points25 – 50 % of FU in the frontal area are single hair FU, or >25% reduction in triple hairs in the frontal area compared with the occiput. score = 1 point50 – 75 % of FU are single hair FU. score = 2 points≥75% of FU are single hair FU. score = 3 points(Maximum score = 8)

At this point you should have generated an “FPHL-SI” score (2 + 10 + 8 = maximum score 20) (Table 1). If your patient scores 0-4 FPHL is unlikely. A score of 5 - 9 would indicate early-stage FPHL, with higher scores indicating greater severity (and certainty) of the diagnosis. For borderline cases always consider the trichoscopic features as the most important criteria for diagnosis. See discussion below for interpretation of results.

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However, if diagnosis is still in doubt consider:

Scalp biopsy. This is generally regarded as the gold standard for the diagnosis of FPHL. However, with increased use of trichoscopy the need for diagnostic scalp biopsy in FPHL has significantly reduced. One or more 4mm scalp punch biopsies are taken under local anaesthetic from the affected areas; biopsies are sectioned horizontally and hair counts performed. However, for optimal diagnosis biopsies should be taken from the midline, potentially resulting in a small visible scar. Diagnosis is made when the terminal to vellus-like hair ratio is <3:1 (cf. normal >7:1) and no other pathology is apparent. Histology will also identify the degree of inflammation, which appears to influence the likely response to minoxidil therapy [77]. For details of how to assess samples in this way, see references [78-81].

Discussion:

We call this score the “Female Pattern Hair Loss Severity Index (FPHL-SI)”. The assigned points are added for each of the three components, producing a score range of 0 to 20 FPHL-SI points (i.e. 2 + 10 + 8).

This scale formalizes criteria already used in clinical practice to generate a pragmatic FPHL grading system (FPHL-SI) of sufficient sensitivity to identify and monitor FPHL, including early changes. This index combines three validated components for hair loss diagnosis and severity assessment, which is easily applicable to all degrees of FPHL severity (Sinclair stages 2-5), and weighted appropriately to identify early-stage (“Sinclair 1”) FPHL. Moreover, it can be executed quickly in a single session using widely available standard hair diagnostics equipment. It is rapidly quantifiable, and permits one to examine patients over time so as to quantitatively compare the results (Table 1).

Although the sub-components of this scale are already validated, evidently, the FPHL-SI as a whole now requires rigorous validation. However, before one engages in this labour-intensive and costly activity, it is important to expose our specific suggestions to public scrutiny and discussion by other experts in the field so as to reach a widely shared consensus on how to diagnose and quantify FPHL, with particular emphasis on early-stage disease. Thus, we urge colleagues to critically and constructively appraise our proposed grading system so as to further optimize the scale before extensive validation, and in doing so maximize engagement in using this clinical and research tool.

Future application of the FPHL-SI for diagnosing and quantifying early-stage FPHL (“Sinclair 1”) in clinical practice will be a valuable and pragmatic tool to elucidate the exact incidence and prevalence of FPHL in defined geographical regions, ethnic groups, families, and other collectives. Moreover, systematic use of the suggested FPHL-SI criteria will facilitate standardized hair loss evaluation in women, and will make published data on FPHL more

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comparable between different investigators, research communities and patient populations. The FPHL-SI will also offer an instructive and sensitive tool for assessing the therapeutic benefit of clinically tested candidate anti-hair loss agents.

Finally, the proposed FPHL-SI encourages early intervention schemes that may help to prevent or at least retard the development of more advanced FPHL phenotypes, namely in females with “Sinclair 1” [24]. In fact, “Sinclair 1” may be considered a normal variant that does not yet meet the full criteria of a clinical hair loss disorder, but is already subjectively experienced as cosmetically undesirable, thus providing sufficient motivation to initiate treatment in individuals bothered by it. An early therapeutic intervention, e.g. on the basis of 5 or more FPHL-SI points, and objective monitoring of therapeutic results with this system, may increase the chance to halt hair loss progression towards Ludwig I-III FPHL.

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Figure legends

Fig. 1: Female pattern hair loss (FPHL): Reduced hair density with widened hair part over the vertex and mid-frontal scalp (“Ludwig I”).

Fig. 2: Early-stage FPHL. Patient presented with subjective hair loss but with normal midline hair-part (“Sinclair grade 1”). Subsequent investigations diagnosed early-stage FPHL.

Fig. 3: Ludwig’s midline hair density scale [11]. Grade I = perceptible thinning of the hair on the crown with preservation of the frontal hair line; Grade II = pronounced rarefaction of the hair on the crown within the area seen in grade I; Grade III = full baldness within the area seen in grades I and II.

Fig 4: Sinclair’s midline hair density scale [48]. Sinclair subdivided Ludwig I into grades 2 and 3, and Ludwig II into grades 4 and 5. As Ludwig III is rarely seen in clinical practice that was not includes in this grading scale.

Fig. 5: Sinclair hair shedding scale [65]. Bundle one contains 10 hair (= grade 1), bundle two 50 hairs (= grade 2), bundle three 100 hairs (= grade 3), bundle four 200 hairs (= grade 4), bundle five 400 hairs (= grade 5) and bundle six 750 hairs (= grade 6). On presentation women are asked how much hair they shed each day. For women who wash their hair less frequently than every day they should be asked about wash days and non-wash days. 1 - 4 are regarded as normal levels of shedding; 5 or 6 denoted excessive shedding.

Fig. 6: Scalp trichoscopy. (a) and (b), diagnosis confirmed by presence of more than 20% hair diameter diversity (i.e. variability and reduction in hair shaft caliber) in the frontal area scalp (appreciable at standard magnification). Fig 6(b) also shows yellow dots, reduction in the number of triple hair FU (<10% all FUs) and increased single hair FU (approx. 50%); (c) diagnosis confirmed by presence of 10% (≥7) short vellus hairs on the frontal area scalp (at 20X magnification); (d) later stage FPHL showing a high proportion of single hair FU; thin short re-growing hairs on the frontal area scalp are also present (appreciable at standard magnification).

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Table 1

FPHL-SI diagnostic criteria

FPHL-SI Scores0 1 2 3 4 5 6 8 10

Increased hair shedding:Sinclair shedding scaleorHair pull test

Sinclair shedding scale 1-4 or negative

pull test

0

Sinclair shedding scale 5 or

6 or positive pull test

2Midline hair density:Sinclair hair density scale

Sinclair 1(NH I-II)

0

Sinclair 2(NH III)

4

Sinclair 3(NH IV)

6

Sinclair 4(NH V)

8

Sinclair 5(NH VI-VII)

10Trichoscopy:(A) Hair diameter diversity

<20% hairs

0

>20% hairs

5Trichoscopy:(B) Triple / Single hairs per follicular unit

No difference between frontal

area and occiput

0

≥25%single hair FU

or≥25%

reduction in triple hair FU

between frontal area and occiput

1

≥50% single hair

FU

2

≥75% single

hair FU

3FPHL-SI Total Score(range 0-20)0-4 FPHL unlikely5-9 Early FPHL≥10 established FPHL

Table 1: Female Pattern Hair Loss Severity Index (FPHL-SI) scoring sheet (maximum score 20). [NH = Norwood-Hamilton alternative scale if “MPHL” pattern]

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What is already known about this topic?

Female pattern hair loss (FPHL) is characterized by a widening of the midline hair-part at the crown (vertex) with preservation of the frontal hairline.

By the time patients exhibit this hair loss pattern they have already lost a significant volume of hair.

What does this study add?

The Female Pattern Hair Loss Severity Index (FPHL-SI) is a three point severity scale that assesses hair shedding, midline hair density and scalp trichoscopic criteria designed to diagnose and grade FPHL; it is sufficiently sensitive to identify early-stage disease.

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References

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