Invention of automated numerical algorithm adopting binarization for the evaluation of scalp hair coverage: An image analysis providing a substitute for phototrichogram and global photography assessment for hair diseases.

BACKGROUND: The efficacy of therapeutic modalities for hair disease can be evaluated globally by photo assessment and more precisely by phototrichogram (PTG). However, the latter procedure is laborious, time consuming, subject to inter-observer variation, and requires hair clipping. OBJECTIVE: To establish an automated and patient/investigator friendly methodology enabling quantitative hair amount evaluation for daily clinical practice. METHODS: A novel automated numerical algorithm (aNA) adopting digital image binarization (i.e., black and white color conversion) was invented to evaluate hair coverage and measure PTG parameters in scalp images. Step-by-step improvement of aNA was attempted through comparative analyses of the data obtained respectively by the novel approach and conventional PTG/global photography assessment (GPA). RESULTS: For measuring scalp hair coverage, the initial version of aNA generally agreed with the cumulative hair diameter as assessed using PTG, showing a coefficient of 0.60. However, these outcomes were influenced by the angle of hair near the parting line. By integrating an angle compensation formula, the standard deviation of aNA data decreased from 5.7% to 1.2%. Consequently, the coefficient of determination for hair coverage calculated using the modified aNA and cumulative hair diameter assessed by PTG increased to 0.90. Furthermore, the change in hair coverage as determined by the modified aNA protocol correlated well with changes in the GPA score of images obtained using clinical trials. CONCLUSION: The novel aNA method provides a valuable tool for enabling simple and accurate evaluation of hair growth and volume for clinical trials and for treatment of hair disease.

Efficacy of autologous dermal sheath cup cell transplantation in male and female pattern hair loss: A Single-Arm, Multi-Center, phase III equivalent clinical study.

A previous, proof-of-concept clinical study suggested that dermal sheath cup cell injections into the affected areas of male/female pattern hair loss (PHL) may have some amelioratory effects, the clinical efficacy of which needs further examination. A phase III equivalent clinical study was conducted to further probe the therapeutic potential of this novel approach and verify its safety and efficacy in improving the appearance of PHL. Thirty-six participants with PHL were injected with dermal sheath cup cell harvested from non-affected occipital hair follicles twice in quarterly intervals. Global photographic assessment and phototrichogram were performed in a blinded manner. Patient-reported outcomes were assessed for 12 months. On global photographic assessment, 30% of the participants showed improvement. The analysis of phototricogram data detected the increases in the cumulative hair diameter, hair cross-sectional area, and mean hair diameter of 107.6 ± 152.6 µm/cm2 , 13069.1 ± 10960.7 µm2 /cm2 , and 0.9 ± 0.9 µm (ratios vs. baseline: +1.4%, +3.4%, and +2.2%), respectively. The female and high terminal hair ratio groups achieved better improvement. Of the total participants, 62.9% noted some degree of improvement. No serious adverse events were detected. This novel approach exhibited visible effects while ensuring safety and patient satisfaction. Therefore, it holds promise as a possible therapeutic option for treating PHL, especially in women.

Recent Advances in Understanding of the Etiopathogenesis, Diagnosis, and Management of Hair Loss Diseases.

Hair-loss diseases comprise heterogenous conditions with respective pathophysiology and clinicopathological characteristics. Major breakthroughs in hair follicle biology and immunology have led to the elucidation of etiopathogenesis of non-scarring alopecia (e.g., alopecia areata, AA) and cicatricial alopecia (e.g., lichen planopilaris, LPP). High-throughput genetic analyses revealed molecular mechanism underlying the disease susceptibility of hair loss conditions, such as androgenetic alopecia (AGA) and female pattern hair loss (FPHL). Hair loss attracted public interest during the COVID-19 pandemic. The knowledge of hair loss diseases is robustly expanding and thus requires timely updates. In this review, the diagnostic and measurement methodologies applied to hair loss diseases are updated. Of note, novel criteria and classification/scoring systems published in the last decade are reviewed, highlighting their advantages over conventional ones. Emerging diagnostic techniques are itemized with clinical pearls enabling efficient utilization. Recent advances in understanding the etiopathogenesis and management for representative hair diseases, namely AGA, FPHL, AA, and major primary cicatricial alopecia, including LPP, are comprehensively summarized, focusing on causative factors, genetic predisposition, new disease entity, and novel therapeutic options. Lastly, the association between COVID-19 and hair loss is discussed to delineate telogen effluvium as the predominating pathomechanism accounting for this sequela.

Distinctive age distribution and hair loss pattern putatively highlighting uniqueness of Japanese cases of fibrosing alopecia in a pattern distribution.

Fibrosing alopecia in a pattern distribution (FAPD) is a unique entity which presents clinicopathological characteristics of both male/female pattern androgenetic alopecia (AGA) and lichen planopilaris (LPP). This entity was first reported in 2000 and its criteria was recently proposed. Etiopathogenesis of FAPD has been speculated to be immunological destruction involving miniaturized hair follicles but still remains elusive. To date, few Asian FAPD cases have been reported in the literature. In this study, Japanese FAPD cases were identified based on the aforementioned criteria and analyzed to delineate clinicopathological characteristics. By retrospectively revisiting medical records and clinical photographs, 24 Japanese cases comprising 17 women and seven men were diagnosed as FAPD. All male patients had disease onset by their early 30s, whereas most female patients had developed the condition in middle age or later. Their initial diagnoses prior to the diagnostic confirmation of FAPD were mostly LPP. Based on the clinical phenotypes, the cases were categorized into AGA and LPP types. These subtypes were characterized by foremost trichoscopic and histopathological findings of AGA or LPP, respectively. Unlike previously reported cases, our patients tended to manifest hair loss in both vertex and frontal to mid-scalp with minimal regression of anterior hairline, manifesting unique "parachute" pattern, which has been reported as a representative characteristic of East Asian AGA in the literature. Anti-inflammatory therapies seemed to be effective to deter hair loss but insufficient to achieve improvement. Further accumulation of the cases is necessary; however, these findings may provide additional pathophysiological insights into FAPD and highlight uniqueness of the etiology and clinical phenotype of Japanese FAPD putatively influenced by racial predispositions.

Update on trichoscopy: Integration of the terminology by systematic approach and a proposal of a diagnostic flowchart.

Trichoscopy represents a non-invasive diagnostic modality widely used in daily practice. Despite the common perception that this technique has been fairly established, some key issues remain to be addressed. Complexity and inconsistency in terminology in past literature are likely to confuse investigators when they are recording, reporting, and retrieving the findings. In addition, a diagnostic algorithm adopting sufficiently integrated and updated findings is not readily available. By adopting a systematic review approach, this review attempted to redefine major trichoscopic findings and integrate their synonyms individually into the most frequently used terms besides identifying and discussing terms which potentially cause confusion. The findings are categorized into five subgroups: hair shaft, follicular, perifollicular, scalp findings, and hair distribution pattern abnormalities. The calculation of sensitivities and positive predictive values of such redefined findings was conducted by reviewing the descriptions in the past literature on major hair diseases, including alopecia areata, androgenetic alopecia/female pattern hair loss, telogen effluvium, trichotillomania, lichen planopilaris, frontal fibrosing alopecia, central centrifugal cicatricial alopecia, discoid lupus erythematosus, folliculitis decalvans, tinea capitis, and dissecting cellulitis, to confirm the diagnostically meaningful findings for representative diseases. This attempt redefined, for instance, yellow dots, short vellus hairs, exclamation mark hairs, black dots, and broken hairs as the findings of diagnostic significance for alopecia areata and hair diameter diversity, peripilar sign, and focal atrichia for androgenetic alopecia/female pattern hair loss. An updated diagnostic flowchart is proposed with the instructions to maximize its usefulness. Current limitations and future perspectives of trichoscopy as well as other emerging non-invasive diagnostic modalities for hair diseases are also discussed.

Clinicopathological insight into self-reported hair loss with no findings: How do we manage this enigmatic condition?

Patients who complain of hair loss without any supportive findings can be encountered in daily practice. To provide insight into this embarrassing condition, we retrospectively reviewed medical charts of eight cases with self-reported hair loss with no findings (SHLNOF). High frequency in middle aged women and concomitance of thyroid and gynecological problems were revealed. Four patients reported scalp dysesthesia/trichodynia. Two patients underwent scalp biopsy, both of which demonstrated increase in indeterminate hairs, suggesting mild hair miniaturization. Supportive medical consultation coupled with the presentation of clinical and trichoscopic images reassured the majority of the patients. These findings suggested that SHLNOF should not be disregarded simply as a misconception. A non-biased and diligent workup should be conducted to better manage this enigmatic condition.

Ultra high-frequency ultrasound with seventy-MHz transducer in hair disorders: Development of a novel noninvasive diagnostic methodology.

BACKGROUND: Ultra high-frequency ultrasound (uHFUS) is a recently developed diagnostic technology. Despite its potential usefulness, no study has assessed its advantage in diagnosis and evaluation of hair disorders in comparison with other diagnostic methods. OBJECTIVES: To assess the practicability of uHFUS in diagnosing hair disorders and propose a diagnostic methodology. METHODS: Ultrasonographic images of scalp and forehead from patients with hair disorders (n = 103) and healthy controls (n = 40) were obtained by uHFUS and analyzed by both descriptive and numerical parameters. Furthermore, the data were compared with trichoscopic and histopathological findings. RESULTS: The pattern of inflammation and fibrosis, hair cycle abnormality, and the findings in subcutis were detected by uHFUS. Significant differences were noted in the numerical parameters associated with the number of hair shafts and follicles, hair diameters and their diversity, and dermal echogenicity in both cicatricial and non-cicatricial hair disorders. Findings in uHFUS were associated with those observed in trichoscopy and scalp biopsy but uHFUS was able to detect pathological findings associated with hair cycle, inflammation, fibrosis, and subcutaneous abnormalities, which are hardly assessable by trichoscopy. CONCLUSION: The findings of this study highlighted usefulness of uHFUS in diagnosing hair disorders, while overcoming the weaknesses and limitations of other diagnostic tools.

Oral Methotrexate Monotherapy for Severe Alopecia Areata: A Single Center Retrospective Case Series.

BACKGROUND: Although several therapeutic options have been suggested for alopecia areata (AA), none of them are consistently effective, thus making the management of severe or refractory cases challenging. Several studies have recently reported the usage of methotrexate (MTX) in AA; however, the pure effect of MTX monotherapy remains elusive. OBJECTIVE: To evaluate efficacy and safety of oral methotrexate monotherapy for AA. METHODS: We retrospectively reviewed the clinical course of AA patients including pediatric cases treated with MTX monotherapy. Their detailed clinical data including original severity of AA, final treatment outcome, the duration until the maximum response, and side effects, were assessed. Statistical analysis was performed to evaluate if the clinical factors including the duration of current alopecia, age, the presence of body hair loss, and sex were associated with treatment response. RESULTS: All included patients had severe AA and failed standard therapies. Thirteen out of 15 cases demonstrated improvement during the monotherapy, and all responders demonstrated the maximum response within 1 year. Female patients had significantly better outcomes than male patients. Other factors did not significantly influence on the treatment outcome. None of the patients experienced side effects that were severe enough to terminate the treatment. CONCLUSIONS: Our results support MTX monotherapy as a feasible option for severe AA patients who fail other standard therapies or for whom systemic corticosteroids are contraindicated.

Overview of Ultrasound Imaging Applications in Dermatology [Formula: see text].

Complete visualization of lesions is critical for the accurate diagnosis and management of dermatological diseases. Currently, the most readily available technologies used by dermatologists include dermoscopy and photography. Nevertheless, ultrasound has emerged as a useful non-invasive modality in dermatology, which can be added to the clinical examination supporting an early and more accurate diagnosis. Moreover, there are significant technological advances in recent years, such as the development of handheld devices and ultra-high frequency probes that have expanded the integration of ultrasound into daily dermatology practice. In this article, we reviewed the most common applications of ultrasound in the field of dermatology.

Development of a scoring system to predict outcomes of i.v. corticosteroid pulse therapy in rapidly progressive alopecia areata adopting digital image analysis of hair recovery.

Alopecia areata (AA) is a common autoimmune disease manifesting varying degrees of hair loss. Rapidly progressive AA (RP-AA) is a severe subtype of AA and often resistant to skin-directed treatments. i.v. corticosteroid pulse therapy has been applied for RP-AA; however, the treatment outcome can only become evaluable several months after the intervention, discomposing the patients. In this study, we attempted to develop a scoring system to predict treatment outcomes based on statistical correlations between newly identified predictors and the recovery rates calculated by digital image analysis. Thirty RP-AA patients (15 men and 15 women) who underwent pulse therapy and demonstrated total hair loss during the clinical course were included. The percentages of hair regrowth (%HR) at 6 months after the treatment were quantitatively calculated by image analysis software. The correlation between %HR and clinicopathological and immunological variables were statistically assessed. The analysis identified four confirmatory contributors including female sex (P = 0.015), absence of previous AA history (P = 0.02), lower peripheral blood eosinophil count (P = 0.02) and mild to moderate cell infiltration around the hair bulb (P = 0.034), together with a potential contributor, namely absence of atopic dermatitis in their medical history (P = 0.08). The scoring system was developed by double counting confirmatory variables and single counting a potential variable. Importantly, the scores obtained by this system demonstrated significant correlation with %HR (r = 0.61, P < 0.001). The usefulness of this scoring system was further validated by assessing additional 20 cases of RP-AA. When combined with a recently published algorithm for early detection of self-healing subset, the current scoring system may help strategize the therapeutic approach for RP-AA.

Altered FGF expression profile in human scalp-derived fibroblasts upon WNT activation: implication of their role to provide folliculogenetic microenvironment.

BACKGROUND: Hair follicle (HF) formation and growth are sustained by epithelial-mesenchymal interaction via growth factors and cytokines. Pivotal roles of FGFs on HF regeneration and neogenesis have been reported mainly in rodent models. FGF expression is regulated by upstream pathways, represented by canonical WNT signaling; however, how FGFs influence on human folliculogenesis remains elusive. The aim of this study is to assess if human scalp-derived fibroblasts (sFBs) are able to modulate their FGF expression profile in response to WNT activation and to evaluate the influence of WNT-activated or suppressed FGFs on folliculogenesis. METHODS: Dermal papilla cells (DPCs), dermal sheath cells (DSCs), and sFBs were isolated from the human scalp and cultured independently. The gene expression profile of FGFs in DPCs, DSCs, and sFBs and the influence of WNT activator, CHIR99021, on FGF expression pattern in sFBs were evaluated by reverse transcription polymerase chain reaction, which were confirmed at protein level by western blotting analysis. The changes in the expression of DPC or keratinocyte (KC) biomarkers under the presence of FGF7 or 9 were examined in both single and co-culture assay of DPCs and/or KCs. The influence of FGF 7 and FGF 9 on hair morphogenesis and growth was analyzed in vivo using mouse chamber assay. RESULTS: In single culture, sFBs were distinguished from DPCs and DSCs by relatively high expression of FGF5 and FGF 18, potential inducers of hair cycle retardation or catagen phase. In WNT-activated state, sFBs downregulated FGF7 while upregulating FGF9, a positive regulator of HF morphogenesis, FGF16 and FGF 20 belonging to the same FGF subfamily. In addition, CHIR99021, a WNT activator, dose-dependently modulated FGF7 and 9 expression to be folliculogenic. Altered expressions of FGF7 and FGF9 by CHIR99021 were confirmed at protein level. Supplementation of FGF9 to cultured DPCs resulted in upregulation of representative DP biomarkers and this tendency was sustained, when DPCs were co-cultured with KCs. In mouse chamber assay, FGF9 increased both the number and the diameter of newly formed HFs, while FGF7 decreased HF diameter. CONCLUSION: The results implied that sFBs support HF formation by modulating regional FGF expression profile responding to WNT activation.

Elucidation of demographic, clinical and trichoscopic features for early diagnosis of self-healing acute diffuse and total alopecia.

The term "acute diffuse and total alopecia" (ADTA) has been often used as a synonym for self-regressing severe alopecia areata (AA). However, ADTA is originally defined as a rapidly-progressive subtype of AA (RP-AA) with short recovery time and favorable prognosis irrespective of interventions. Indeed, a subpopulation of ADTA recovers spontaneously. We focused on this unique subset of AA, which we coined as "self-healing ADTA" (sADTA). Prompt and accurate differentiation of sADTA from other RP-AA is important to avoid unnecessary treatments, which is still challenging due to the lack of predictive diagnostic hallmarks. In this study, 18 sADTA patients were retrospectively analyzed to delineate their demographics and clinical features, including gentle hair pull test and trichoscopic findings, followed by statistical comparison with those of RP-AA. All sADTA cases were female and the average age was 38.1 ± 15.9 years. The progression of hair loss areas peaked at 3.6 ± 1.5 months, and complete hair regrowth was achieved in 7.9 ± 1.7 months. The identified factors supporting the diagnosis of sADTA included being female; the absence of scalp pain and itch; the absence of extra-scalp hair loss; club hair predominance in hair pull test; predominant short vellus hairs; and increase in vacant follicular ostia on trichoscopy. Subsequently, a scoring system for early diagnosis of sADTA was developed by counting the number of six identified factors present in a tested case. When analyzed by the developed system, all sADTA cases, including an additional four cases, had scores of 4 or above, while all RP-AA cases had scores below 3 except one case. Therefore, the system successfully differentiated sADTA from RP-AA (P < 0.01). Despite some technical limitations, the current study suggested that sADTA is a distinctive entity with unique pathophysiology and that early diagnosis before intervention is feasible based on the characteristics.

Chronological association between alopecia areata and autoimmune thyroid diseases: A systematic review and meta-analysis.

The association between alopecia areata (AA) and autoimmune thyroid diseases (AITD) has been suggested; however, the chronological relationship between AA and AITD remains elusive. A systematic review and meta-analysis were conducted to assess the association between AA and AITD focusing on the prevalence of thyroid antibodies, thyroid diseases and serological thyroid dysfunctions, respectively. Data collection was performed in October 2018 by searching for articles in two electronic databases: Medline and Embase. Case-control, cohort and cross-sectional studies were included. Meta-analysis of studies eligible for quantitative synthesis was performed to estimate pooled odds ratios of thyroid antibodies; thyroid peroxidase antibody (TPO-Ab) and thyroglobulin antibody (TG-Ab), diagnosed thyroid diseases and serological thyroid dysfunctions. Four hundred and eighty nine research papers were identified and 17 studies with 262 581 patients and 1 302 655 control subjects were included for quantitative synthesis. AA was significantly associated with both TPO-Ab and TG-Ab. In comparison, there was no significant association between AA and diagnosed hypothyroidism or hyperthyroidism and serological hypothyroidism or hyperthyroidism. In conclusion, AA is significantly associated with the existence of thyroid antibodies rather than with clinical or laboratory thyroid abnormality. Lack of long-term follow-up data is a limitation of the existing published work. Our findings do not support routine screening of thyroid diseases for asymptomatic AA patients but highlight the potential future risk of AITD particularly in severe and refractory AA.

Diagnostic and therapeutic approach to scalp dysesthesia: A case series and published work review.

Scalp dysesthesia may be underrecognized but is an important condition which requires special management strategies. Through our case series of four patients, we have noted that patients were frequently misdiagnosed with seborrheic dermatitis and failed standard treatment. However, patients did benefit from low doses of oral pregabalin and a topical compound of amitriptyline, lidocaine and ketamine. Oral antihistamines and topical corticosteroids did not work sufficiently on their own but added value when used in conjunction with analgesic agents. Our experience and published work also suggest the association of cervical spinal changes, psychiatric disorders, and other environmental and habitual factors.

Chronological clinicopathological characterization of rapidly progressive alopecia areata resistant to multiple i.v. corticosteroid pulse therapies: An implication for improving the efficacy.

Intravenous corticosteroid pulse therapy (pulse therapy) has been reported to be effective for rapidly progressive alopecia areata (RP-AA). Mostly, a single 3-day administration of corticosteroid (methylprednisolone 500 mg/day) has been performed in Japan; however, to what extent additional administrations improve the outcome has not been fully elucidated. To assess the advantage of repeating the pulse therapy to RP-AA cases refractory to the initial intervention, retrospective clinicopathological analysis was performed. Detailed chronological analysis was conducted in eight cases (one man and seven women; average age, 38.3 ± 10.4 years) demonstrating total scalp hair loss 3 months after the first pulse therapy and treated with additional rounds of the pulse therapy. All cases manifested total hair loss, scalp edema, itch or pain on the scalp after the initial intervention. Histopathological analyses of affected lesions prior to additional pulse therapies revealed persisting dense perifollicular lymphocytic inflammation in all cases. Interestingly, such inflammatory change tended to be severer when compared with previously reported pulse therapy good responders. Extra pulse therapy resulted in partial regrowth of terminal hairs in three out of eight cases, but all of them experienced relapse in the long run. The literature review also suggested limited efficacy of repeating pulse therapy to severe AA cases. These findings suggested that the efficacy of currently conducted repetitive pulse therapy is limited in RP-AA cases with extensive perifollicular inflammation and resistant to the initial pulse therapy. Modulation of the dose and the interval of intervention, in combination with alternative approaches, may be required to achieve a successful outcome.