New Histopathological Findings in Scarring Alopecias.

CONTEXT.­: Clinical, dermoscopic, and histological diagnostic criteria may overlap in cases with scarring and nonscarring alopecia, making diagnosis difficult for clinicians and pathologists. New histopathological discoveries indicate that the cutaneous adnexal structural and homeostatic unit made up of the pilosebaceous unit, eccrine sweat gland coils (ESGCs), and dermal white adipose tissue may have a role in hair follicle renewal. OBJECTIVE.­: To verify the presence of adipose tissue in the dermis at the level of the isthmus, infiltrating the bundles of the arrector pili muscle in biopsies from the scalp of 3 scarring alopecias: frontal fibrosing alopecia (FFA), fibrosing alopecia in a pattern distribution (FAPD), and lichen planopilaris (LPP). DESIGN.­: We performed a retrospective and descriptive survey of 71 female scalp biopsies from 2016 to 2022 diagnosed at the Dermatopathology Laboratory at Fluminense Federal University of Rio de Janeiro. Two pathologists reviewed and diagnosed the cases correlating pathological features with clinical and dermoscopic findings. RESULTS.­: The histopathological findings of adipose tissue infiltration in the dermis at the level of the isthmus and in the bundles of the arrector pili muscle, and the displacement of ESGCs were more frequently identified in FFA, followed by FAPD and less frequently found in LPP. CONCLUSIONS.­: According to our research, adipose tissue infiltration in the dermis at the level of the isthmus and in the bundles of the arrector pili muscle, and the displacement of ESGCs were observed in 3 scarring alopecias (FFA, FAPD, and LPP) and seems to be involved in the development of scarring alopecia.

Case Series of Frontal Fibrosing Alopecia and Fibrosing Alopecia in a Pattern Distribution: Is There a Familial Correlation?

Introduction: Frontal Fibrosing Alopecia (FFA) and Fibrosing Alopecia in a Pattern Distribution (FAPD) are two distinct entities of cicatricial pattern hair loss that share histological features of perifollicular lichenoid inflammation associated with concentric fibrosis. Although the pathophysiology of FFA and FAPD are still unknown, recently published reports of familial cases indicate a possible genetic correlation. Case Presentation: We report 6 cases of familial alopecia composed of mothers and daughters: five with FFA and one with FAPD. We describe clinical, trichoscopy and histological correlation in cases of familial alopecia. Conclusions: These cases of mother and daughter disease association suggest a potential benefit of and role for performing systematic scalp examinations of all first-degree relatives of patients with pattern cicatricial alopecia.

The Association of Frontal Alopecia with a History of Facial and Scalp Surgical Procedures.

INTRODUCTION: The prevalence of frontal fibrosing alopecia (FFA) is increasing worldwide, though the pathogenesis remains unknown. Anecdotal reports describe alopecia occurring in an FFA pattern following facial surgical procedures, but this potential link remains unexplored. OBJECTIVE: The objective of this study is to determine if a significant association exists between the diagnosis of FFA and a history of facial and scalp surgical procedures. METHODS: This retrospective study comparing data from frontal alopecia patients to controls was conducted at a tertiary medical center. Additionally, a literature review was conducted on scarring alopecias occurring from scalp procedures. RESULTS: Fifty percent of frontal alopecia patients (n = 54) reported a history of facial surgical procedures compared to 9.8% of controls (n = 51) (OR: 7.8 [95% CI: 2.77-25.98, p < 0.001]). Although no significant differences were observed in current daily facial sunscreen use, sunscreen use prior to alopecia onset was significantly higher in frontal alopecia (p = 0.295; p = 0.021). Sunscreen use was not a significant modifier in the association between frontal alopecia and facial surgical procedures (p = 0.89). CONCLUSIONS: A significant association exists between frontal alopecia clinically consistent with FFA and a history of facial surgery, the nature of which is unclear. The role of sunscreen use and frontal alopecia development in this setting needs to be better elucidated.

Reflectance Confocal Microscopy, Optical Coherence Tomography, and Multiphoton Microscopy in Inflammatory Skin Disease Diagnosis.

BACKGROUND AND OBJECTIVES: Technological advances in medicine have brought about many novel skin imaging devices. This review aims to evaluate the scientific evidence supporting the use of noninvasive optical imaging techniques to aid in the diagnosis and prognosis of inflammatory skin diseases. STUDY DESIGN/MATERIALS AND METHODS: PubMed and Scopus were searched in September 2020 according to PRISMA guidelines for articles using reflectance confocal microscopy (RCM), optical coherence tomography (OCT), and multiphoton microscopy (MPM) in inflammatory skin diseases, excluding studies monitoring treatment efficacy. RESULTS: At the time of the study, there were 66 articles that addressed the utilization of noninvasive imaging in interface, spongiotic, psoriasiform, vesiculobullous, and fibrosing/sclerosing inflammatory skin dermatoses: RCM was utilized in 46, OCT in 16, and MPM in 5 articles. RCM was most investigated in psoriasiform dermatoses, whereas OCT and MPM were both most investigated in spongiotic dermatoses, including atopic dermatitis and allergic contact dermatitis. CONCLUSIONS: There is preliminary evidence to support the diagnostic potential of noninvasive optical imaging techniques in inflammatory skin diseases. Improvements in the devices and further correlation with histology will help broaden their utility. Additional studies are needed to determine the parameters for diagnostic features, disease differentiation, and staging of inflammatory skin conditions. Lasers Surg. Med. © 2021 Wiley Periodicals LLC.

Combining Deep Learning With Optical Coherence Tomography Imaging to Determine Scalp Hair and Follicle Counts.

BACKGROUND AND OBJECTIVES: One of the challenges in developing effective hair loss therapies is the lack of reliable methods to monitor treatment response or alopecia progression. In this study, we propose the use of optical coherence tomography (OCT) and automated deep learning to non-invasively evaluate hair and follicle counts that may be used to monitor the success of hair growth therapy more accurately and efficiently. STUDY DESIGN/MATERIALS AND METHODS: We collected 70 OCT scans from 14 patients with alopecia and trained a convolutional neural network (CNN) to automatically count all follicles present in the scans. The model is based on a dual approach of both detecting hair follicles and estimating the local hair density in order to give accurate counts even for cases where two or more adjacent hairs are in close proximity to each other. RESULTS: We evaluate our system on 70 OCT manually labeled scans taken at different scalp locations from 14 patients, with 20 of those redundantly labeled by two human expert OCT operators. When comparing the individual human predictions and considering the exact locations of hair and follicle predictions, we find that the two human raters disagree with each other on approximately 22% of hairs and follicles. Overall, the deep learning (DL) system predicts the number of follicles with an error rate of 11.8% and the number of hairs with an error rate of 18.7% on average on the 70 scans. The OCT system can capture one scalp location in three seconds, and the DL model can make all predictions in less than a second after processing the scan, which takes half a minute using an unoptimized implementation. CONCLUSION: This approach is well-positioned to become the standard for non-invasive evaluation of hair growth treatment progress in patients, saving significant amounts of time and effort compared with manual evaluation. Lasers Surg. Med. © 2020 Wiley Periodicals, Inc.

Optical Coherence Tomography in the Evaluation of the Scalp and Hair: Common Features and Clinical Utility.

BACKGROUND AND OBJECTIVE: Early diagnosis and treatment of hair loss disorders is vital in providing patients with improved psychological outcomes. Non-invasive imaging with optical coherence tomography (OCT) may be useful in characterizing and managing alopecia. Despite expanding clinical applications of OCT in dermatology, guidelines demonstrating in vivo features of normal and alopecic scalp images remain scant. This pilot study aims to provide an atlas of OCT findings of healthy and alopecia subjects, explore diagnostic quantitative endpoints of alopecia, and compare epidermal thickness and follicular density between scalp regions. STUDY DESIGN/MATERIALS AND METHODS: A total of 32 patients (19-76 years old) were enrolled in the study, including healthy patients (n = 6), and patients with scarring alopecia (n = 12) or non-scarring alopecia (n = 14). An in-line fiber-based swept source OCT was used to image five scalp locations at baseline and 6-month visits. Three investigators evaluated each image for gross features, epidermal thickness, and follicular density. RESULTS: Only data from baseline imaging analysis is discussed in this manuscript. Qualitative differences of OCT images are identified in sample images from healthy scalp and each subtype of alopecia studied. Scarring alopecia is characterized by significantly increased epidermal thickness (average Image J pixel units 32 ± 2 compared with non-scarring alopecia [average 28 ± 3] and control [average 27 ± 3]) (P = 0.022) and decreased follicle count (average 35 ± 5 in a 5 × 7 mm2 area compared with control (50 ± 3) and non-scarring patients (47 ± 6)) (P = 0.0052). Scalp location had no impact on epidermal thickness (P = 0.861) or follicular density (P = 0.15). CONCLUSION: OCT holds promise as a non-invasive technique to further characterize and objectively measure alopecia. Larger sample sizes and longitudinal data are needed to improve reliability and determine if additional distinction between alopecia subtypes and treatment monitoring is possible. Lasers Surg. Med. © 2020 Wiley Periodicals, Inc.

Hair Cosmetics for the Hair Loss Patient.

Medical professionals that treat patients with alopecia usually lack knowledge about hair cosmetics. Trichologists focus on hair cycling and growth problems and not on the hair shaft integrity. This may lead to abandon of the use of the prescribed treatment, such as topical minoxidil or to inadequate traumatic grooming habits that may jeopardize hair follicle health. Shampoos, hair dyes, and hair-straightening products may alter hair fiber structure, remove lipids, and elude protein. Hair procedures such as hair dying and straightening have side effects and health concerns, especially for pregnant women or sensitive hair and scalp patients. Hair breakage, follicle traction, frizz, contact dermatitis, and mutagenicity are possible side effects of hair cosmetics misuse. The proper use of hair care products may help to increase patients' adherence to alopecia treatments and avoid health problems related to inadequate application of hair cosmetics and procedures.

Oral isotretinoin for the treatment of dermatologic conditions other than acne: a systematic review and discussion of future directions.

While isotretinoin has been the gold-standard of therapy for severe acne since its approval in 1982, its anti-inflammatory properties makes it a potentially applicable and versatile therapy for a wide variety of dermatologic conditions yet to be explored. This systematic review comprehensively recounts the success of oral isotretinoin in non-acne cutaneous diseases and provide insight into future directions of isotretinoin utility. A systematic literature review was performed using PubMed. Search terms included "isotretinoin" OR "accutane" AND "skin" OR "dermatology" OR "hair" OR "nails" OR "rosacea" OR "psoriasis" OR "pityriasis rubra pilaris" OR "condyloma acuminata" OR "granuloma annulare" OR "darier's disease" OR "non-melanoma skin cancer" OR "frontal fibrosing alopecia" OR "cutaneous lupus erythematosus" OR "hidradenitis suppurativa" OR "photodamaged skin" OR "skin aging" OR "wart" OR "flat warts" OR "plane warts" OR "lichen planus" OR "dissecting cellulitis" OR "folliculitis decalvans" OR "sebaceous hyperplasia" OR "cutaneous t-cell lymphoma" OR "mycosis fungoides." A total of 169 studies discuss the use of oral isotretinoin for 16 non-acne dermatologic conditions, the most common being non-melanoma skin cancers (0.2-8.2 mg/kg/day), cutaneous T-cell lymphomas (0.5-2 mg/kg/day), and rosacea (0.22-1 mg/kg/day). Inflammatory conditions such as rosacea, granuloma annulare, and hidradenitis suppurativa benefit from lower oral isotretinoin dosage of 0.3-1 mg/kg/day, whereas, hyperkeratotic diseases such as psoriasis and pityriasis rubra pilaris, consistently respond better to higher dosages of up to 2-4 mg/kg/day for lesion clearance. Recurrence of disease following discontinuation of isotretinoin have been reported for rosacea, psoriasis, granuloma annulare, Darier's disease, dissecting cellulitis, and non-melanoma skin cancers. Disease exacerbation was reported in some patients with hidradenitis suppurativa. Off-label isotretinoin is an effective treatment choice for dermatological conditions beyond acne. Further prospective, randomized human trials are needed to clarify when and how to prescribe off-label isotretinoin for maximum efficacy and safety.

Treatments of Periorbital Hyperpigmentation: A Systematic Review.

BACKGROUND: Periorbital hyperpigmentation (POH) is an aesthetic concern for patients. Etiologies of the condition include pigmentary, structural, vascular, and mixed causes. OBJECTIVE: To systematically review the current literature for treatment of POH. METHODS: A systematic literature review was performed on PubMed. Search terms included "infraorbital dark circles," "dark circles," "periorbital hyperpigmentation," "idiopathic hyperchromia AND orbital," "under-eye circles," "ICHOR (idiopathic cutaneous hyperchromia of the orbital region)," "dark circles" AND "treatment," and "filler" AND "dark circles." RESULTS: A total of 39 studies were included. Effective treatments for POH include lasers, topical creams and serums, fillers, chemical peels, carboxytherapy, plasma-rich platelet injections, blepharoplasty, and normobaric oxygen. CONCLUSION: Soft tissue fillers and autologous fat grafting are most effective in treating dark circles due to volume loss. Blepharoplasty surgery is best when excessive skin laxity is the underlying cause. Various topical creams and chemical peels are useful in treating pigment-based POH, whereas lasers are mildly to moderately beneficial for both vascular and pigment types. Given the scarcity of high-quality evidence supporting these results, recommendations should be interpreted selectively. Additional randomized clinical trials studying POH will be helpful.

Monitoring Response to Platelet-Rich Plasma in Patients with Alopecia Areata with Optical Coherence Tomography: A Case Series.

Alopecia areata (AA) is an autoimmune hair loss condition that is difficult to treat and frequently disruptive to the psychosocial well-being of patients. Platelet-rich plasma (PRP) is an innovative therapy that provides concentrated GFs that impart anti-inflammatory effects. Optical coherence tomography (OCT) is a noninvasive imaging modality with the potential for providing quantitative monitoring of AA response to PRP. Our objective is to share our experience using OCT to monitor the therapeutic progress of patients with AA treated with PRP. Two patients with patchy AA and one with alopecia universalis were treated with PRP three times at 6-week intervals as part of a larger clinical trial. Patients were followed from baseline to week 24 with OCT imaging. OCT demonstrates an increase in hair density associated with improvement in inflammation at week 24. Conversely, the patient with alopecia universalis did not experience any significant change in follicular activity. This case series exemplifies the potential of PRP in inflammatory regulation as well as hair regrowth in patchy AA, whereas there is no notable advantage in alopecia universalis. Our findings add evidence on the possible value of OCT in quantitatively assessing hair growth progress throughout a treatment course.

Psoriatic Disease in the US Latino Population: A Comprehensive Review.

Current evidence suggests that there are notable differences in the severity of psoriasis between racial and ethnic groups. While the US Latino population is growing rapidly, there is little research on the various factors impacting disease severity in this minority population. This review evaluates the current evidence on psoriasis in Latinos within the US. Psoriasis affects the US Latino population at a lower prevalence, with more severe disease and a greater quality-of-life impact than their White counterparts. In addition, Latinos with psoriasis experience higher rates of comorbidities, such as depression, obesity, and diabetes compared with Whites. There is evidence showing non-inferior or better response to systemic treatments, such as etanercept, secukinumab, and brodalumab, in this population. The combination of barriers to care and lack of involvement in research limit the current understanding of the mechanisms responsible for the pathologic outcomes and the environmental and social disparities observed. Future studies that reflect the growing proportion of minorities in the US may help close these knowledge gaps and improve care.

Dietary and metabolic factors in the pathogenesis of hidradenitis suppurativa: a systematic review.

Hidradenitis suppurativa (HS) is a systemic recalcitrant inflammatory condition characterized by debilitating lesions with high morbidity. Its known association with obesity and smoking indicate correlation with other environmental factors, such as diet, suggesting a larger role for lifestyle modifications in disease treatment. This study seeks to assess the contribution of weight loss and dietary intake in HS management. A primary literature search was conducted using PubMed, Web of Science, and CINAHL in November 2018 to include association and intervention studies on the influence of diet and weight on HS. Twenty-five articles were included. Meta-analysis of nine case-control studies across Asia, Europe, and the United States showed that HS patients are four times more likely to be obese compared to the general population; random effects pooled odds ratio 4.022 (2.667-6.065), P < 0.001. Five articles assessed weight-loss interventions and revealed mixed findings. The remaining articles included three association studies on micronutrient levels, eight dietary intervention studies, and one article analyzing both micronutrient association and dietary intervention. Included articles in this systematic review reveal that low serum zinc and vitamin D levels are associated with increased lesion count in HS. Supplementation of zinc, vitamin D, vitamin B12, or exclusion of dairy or brewer's yeast can be effective in partial or complete lesion resolution. Reviewed data show that weight loss from bariatric surgery may lead to HS improvement but often results in more severe malnutrition that worsens or even leads to new onset HS post bariatric surgery. Future reporting is needed to conclusively determine the role of diet in HS.

A Systematic Review of the Outcome of Hair Transplantation in Primary Scarring Alopecia.

IMPORTANCE: Hair loss, or alopecia, is one of the most commonly presented problems in dermatology. Scarring alopecias are considered particularly damaging due to limited success in slowing permanent disease progression, and current treatment methods, such as intralesional and topical steroids and topical minoxidil, are largely ineffective. OBJECTIVE: Hair transplantation is a debated treatment option for advanced cases of primary scarring alopecia. This study reviews the efficacy of hair transplantation as a treatment option for primary scarring alopecia. EVIDENCE REVIEW: A primary literature search was conducted using PubMed to identify articles in scarring alopecia and hair transplants published from 1960 to the present time. FINDINGS: Fifteen reports with 34 patients were included in this review. Twenty six patients experienced moderate to positive results, while 8 patients experienced negative results or recurrence of disease. Positive hair transplantation results have been reported in patients with central centrifugal cicatricial alopecia, en coup de sabre, discoid lupus erythematous, pseudopelade de brocq, and folliculitis decalvans. Positive and -negative results were observed in patients with lichen planopilaris and frontal fibrosing alopecia. CONCLUSION AND RELEVANCE: Findings show that hair transplant surgery can be considered as a treatment option for certain primary scarring alopecias. However, data must be interpreted with caution due to concern for positive-result publication bias.

Radiofrequency Therapy and Noncosmetic Cutaneous Conditions.

BACKGROUND: The need for noninvasive methods in treatment of cutaneous disease has continued to evolve exponentially. Amidst the search for technologies, radiofrequency (RF) has proven efficacious in numerous skin disease processes. Although RF is well known for its cosmetic utility, its mechanism is valued in the treatment of many noncosmetic cutaneous conditions of various etiologies. OBJECTIVE: To identify and describe studies in which RF was used to treat noncosmetic skin conditions and to explore the potential of this modality for further application in dermatologic diseases. MATERIALS AND METHODS: The PubMed database was used to find relevant articles. RESULTS: This search strategy yielded 54 articles that met the eligibility criteria. Noncosmetic indications discussed in these articles include varicose veins (n = 10,550), lymphangioma circumscriptum (n = 72), cutaneous neoplasms (n = 42), cutaneous leishmaniasis (n = 743), acne and acne scarring (n = 158), non-acne scarring (n = 43), primary axillary hyperhidrosis (n = 76), and acute and chronic wounds (n = 94). CONCLUSION: Treatment with RF is an effective, generally noninvasive modality with a relatively short postprocedure recovery time and little potential for severe adverse effects in the treatment of several cutaneous conditions. Further clinical studies would prove useful to assess the efficacy and cost-effectiveness of this treatment.

The effect of melanin on in vivo optical coherence tomography of the skin in a multiethnic cohort.

BACKGROUND: Noninvasive real-time assessment of living tissue is quickly becoming invaluable for bolstering histologic and dermatoscopic measures of cutaneous conditions. While many skin researchers have explored the utility of noninvasive imaging in inflammatory and malignant skin conditions, there is yet to be a definitive and direct assessment of the effects of melanin on the quality of optical coherence tomography (OCT) imaging and its accuracy in multiethnic patient populations. We conducted a study to evaluate the effects of melanin on the quality of in vivo OCT imaging. METHODS: Volunteers of all Fitzpatrick skin types were imaged once in five skin regions. Images were analyzed for quality, defined quantitatively as depreciation of light as it passes through the depth of skin, and qualitatively as depth and contrast ranked by blinded clinicians. RESULTS: Our analysis of sixteen subjects shows that there is a significant difference in quantitative OCT image quality between light (Fitzpatrick I-III) and dark (IV-VI) skin types for both epidermal (p 0.0328) and dermal levels (p 0.0021). However, there was no significant difference in qualitative blinded rater measures of image clarity (p 0.11) or perceived depth (p 0.13). CONCLUSION: Based on our definition of image quality, our study shows that OCT images taken from darker skin types have slightly lower quality than those taken from lighter skin. However, because blinded rater assessment showed no differences in clarity or perceived depth, we conclude that OCT may be used without hesitation for manual visualization of skin and its appendages in all Fitzpatrick skin types. Further studies are required to more extensively characterize the effects of melanin on OCT imaging. Lasers Surg. Med. 51:407-411, 2019. © 2019 Wiley Periodicals, Inc.

Utility of Naltrexone Treatment for Chronic Inflammatory Dermatologic Conditions: A Systematic Review.

Importance: Dermatology is encountering increasing rates of autoimmune disease manifesting in primary skin conditions that are difficult to treat without a risk of immunosuppression. Naltrexone is an orally active opioid antagonist that influences a variety of systemic pathways, including the immune system, in low doses of 1.5 to 4.0 mg/d. This phenomenon has piqued the interest of researchers and practitioners in regard to low-dose naltrexone's potential in the treatment of several autoimmune conditions. Objective: To review the existing literature on naltrexone treatment for dermatologic conditions. Evidence Review: A primary literature search was conducted using PubMed in April 2018 for all articles published from 1971 to April 2018. Search terms consisted of naltrexone or low dose naltrexone or low-dose naltrexone and dermatology or skin or hair or nails. Reviews, animal studies, and nondermatologic and pharmacologic studies were excluded. Findings: From 1037 articles, 22 were deemed to be appropriate for inclusion in this review for a qualitative synthesis. The 22 articles included randomized clinical trials, case reports, and series. There were 7 articles on low-dose naltexone, 1 on topical naltrexone, and 14 on high-dose naltrexone use in dermatology. In high, low, and topical doses, naltrexone was effective in treating pruritus attributable to atopic dermatitis, prurigo nodularis, cholestatsis, burn injury, systemic sclerosis, Hailey-Hailey disease, and lichen planopilaris. High-dose naltrexone was ineffective in treating flushing and uremic pruritus most likely because of the lack of opioid involvement in the pathophysiologic mechanisms of these conditions. Conclusions and Relevance: The findings suggest that low-dose naltrexone is safe and effective in the treatment of Hailey-Hailey disease and lichen planopilaris and both low- and high-dose naltrexone successfully treat pruritus attributable to various pathologic conditions; however, more adverse effects occurred in those taking high doses. Low-dose naltrexone has the potential for the treatment of chronic inflammatory skin conditions; however, additional evidence is needed for dosing and long-term treatment guidelines.

A Systematic Review of Topical Finasteride in the Treatment of Androgenetic Alopecia in Men and Women.

INTRODUCTION: Currently, only topical minoxidil (MNX) and oral finasteride (FNS) are approved by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of androgenetic alopecia. Although FNS is efficacious for hair regrowth, its systemic use is associated with side effects limiting long-term utilization. Exploring topical FNS as an alternative treatment regimen may prove promising. METHODS: A search was conducted to identify studies regarding human in vivo topical FNS treatment efficacy including clinically relevant case reports, randomized controlled trials (RCTs), and prospective studies. RESULTS: Seven articles were included in this systematic review. In all studies, there was significant decrease in the rate of hair loss, increase in total and terminal hair counts, and positive hair growth assessment with topical FNS. Both scalp and plasma DHT significantly decreased with application of topical FNS; no changes in serum testosterone were noted. CONCLUSION: Preliminary results on the use of topical FNS are limited, but safe and promising. Continued research into drug-delivery, ideal topical concentration and application frequency, side effects, and use for other alopecias will help to elucidate the full extent of topical FNS' use.

J Drugs Dermatol. 2018;17(4):457-463.