Treatment for central centrifugal cicatricial alopecia-Delphi consensus recommendations.

BACKGROUND: There is no established standard of care for treating central centrifugal cicatricial alopecia (CCCA), and treatment approaches vary widely. OBJECTIVE: To develop consensus statements regarding the use of various pharmacological therapies in treating adults with CCCA. METHODS: We invited 27 dermatologists with expertise in hair and scalp disorders to participate in a 3-round modified Delphi study between January and March 2023. Statements met strong consensus if 75% of respondents agreed or disagreed. Statements met moderate consensus if 55% or more but less than 75% agreed or disagreed. RESULTS: In round 1, 5 of 33 (15.2%) statements met strong consensus, followed by 9 of 28 (32.1%) in round 2. After the final round 3 meeting, strong consensus was reached for 20 of 70 (28.6%) overall statements. Two statements achieved moderate consensus. LIMITATIONS: This study included only English-speaking, US-based dermatologists and did not consider nonpharmacological therapies. CONCLUSION: Despite varying opinions among dermatologists, consensus was reached for several statements to help clinicians manage CCCA. We also highlight areas that lack expert consensus with the goal of advancing research and therapeutic options for CCCA.

Fibroadenoma of the vulva with pseudoangiomatous stromal hyperplasia: A common neoplasm in uncommon site.

Mammary-type tissue in the vulva was first described in 1872 but has been rarely reported in the literature. This tissue was previously considered as ectopic breast tissue that occurs as a result of incomplete regression of the milk line. Similar to native breast tissue, ectopic mammary tissue is hormone-sensitive and can develop benign changes, such as fibroadenoma, as well as malignant changes. A more recent theory suggests that these benign and malignant mammary-type entities arise from mammary-like anogenital glands, which constitute normal vulvar components. We report a case of a 41-year-old woman who presented with a chronic asymptomatic cyst on the left vulva that eventually became uncomfortable, especially on standing. The cyst was located on the labium minus, measuring 1.0 × 0.5 cm, with no identified erythema or other skin abnormalities. Excision of the lesion and subsequent microscopic examination showed a circumscribed mass with a nodular overgrowth of epithelial and stromal components, resembling a mammary fibroadenoma with pseudoangiomatous stromal hyperplasia. We bring to attention this rare diagnosis and the importance of considering it in the presence of a vulvar lesion. The malignant and recurrence potential of mammary-type tissue necessitates excision with clear margins and close monitoring of these patients.

Approach to the patient with hair loss.

Hair loss is a common complaint among both men and women and is associated with significant psychologic distress. Due to the varied causes, it is important to correctly diagnose the type of alopecia a patient is experiencing to ensure tailoring of treatment. This continuing medical education article describes the approach to diagnose alopecia based on current clinical practice and standards.

Development of the alopecia areata scale for clinical use: Results of an academic-industry collaborative effort.

BACKGROUND: The current classification for alopecia areata (AA) does not provide a consistent assessment of disease severity. OBJECTIVE: To develop an AA severity scale based on expert experience. METHODS: A modified Delphi process was utilized. An advisory group of 22 AA clinical experts from the United States was formed to develop this AA scale. Representatives from the pharmaceutical industry provided feedback during its development. RESULTS: Survey responses were used to draft severity criteria, aspiring to develop a simple scale that may be easily applied in clinical practice. A consensus vote was held to determine the final AA severity statement, with all AA experts agreeing to adopt the proposed scale. LIMITATIONS: The scale is a static assessment intended to be used in clinical practice and not clinical trials. CONCLUSION: The final AA disease severity scale, anchored in the extent of hair loss, captures key features commonly used by AA experts in clinical practice. This scale will better aid clinicians in appropriately assessing severity in patients with this common disease.

Preferentially expressed antigen in melanoma and p16 expression in acral melanocytic neoplasms.

Acral melanocytic neoplasms often pose diagnostic difficulty. Preferentially expressed antigen in melanoma (PRAME) expression and loss of p16 expression have diagnostic utility in melanocytic tumors. We examined PRAME and p16 expression in 30 acral melanocytic neoplasms (n = 11 nevi; n = 2 dysplastic nevi; n = 7 Spitz nevi; n = 10 acral melanomas). PRAME was scored as % positive nuclei: negative = 0%; 1% to 25% = 1+; 25% to 50% = 2+; 50% to 75% = 3+, or positive: 75% to 100% = 4+. p16 expression was defined as retained (homogeneous or checkerboard) or lost (complete or partial/regionally). PRAME expression was negative in all benign, dysplastic, and Spitz nevi. Conversely, all acral melanomas were diffusely (4+) positive for PRAME expression. p16 expression was retained in all benign acral nevi (8/11 homogeneous, 3/11 checkerboard), completely lost in one dysplastic nevus, and retained in all acral Spitz nevi (3/7 homogeneous, 4/7 checkerboard). p16 was retained in five of 10 acral melanomas (3/10 homogeneous; 2/10 checkerboard), and negative in five of 10 acral melanomas (absent in 3/10, partially lost in 2/10). Our data suggest that 4+ PRAME expression is highly sensitive and specific in the setting of acral melanomas and is a more predictive diagnostic tool compared with p16 immunohistochemistry.

Impact of clinical photographs on the accuracy and confidence in the histopathological diagnosis of mycosis fungoides.

BACKGROUND: The histopathological diagnosis of MF is challenging, and there is significant overlap with benign inflammatory processes. Clinical features may be relevant in the assessment of skin biopsies. METHODS: We provided photomicrographs to board-certified dermatopathologists and one hematopathologist with and without accompanying clinical photographs and assessed accuracy and confidence in diagnosing MF. RESULTS: We found that access to clinical photographs improved diagnostic accuracy in both MF and non-MF (distractors); the degree of improvement was significantly higher in the non-MF/distractor category. Across all categories, diagnostic confidence level was higher when clinical images were available. CONCLUSION: These findings suggest that clinical images are useful in making an accurate diagnosis of MF, and may be particularly helpful in ruling it out when an inflammatory disorder is clinically suspected.

Scalp application of the antioxidant piroctone olamine reduces hair shedding in an 8-week randomized, double-blind, placebo-controlled clinical study.

OBJECTIVE: Increasing scalp hair fullness is a global unmet consumer need. An approach to decrease hair shedding by reducing scalp stratum corneum oxidation via a combination of antioxidant and barrier-enhancing technologies has been previously demonstrated. The purpose of this study was to test the effectiveness of the individual antioxidant piroctone olamine in two different product forms (shampoo or leave-on product) for activity to improve hair retention. METHODS: Female subjects with self-perceived hair thinning participated in an 8-week, double-blind, placebo-controlled, randomized clinical study to evaluate either a piroctone olamine (PO) containing shampoo or a PO containing leave on treatment, each relative to their corresponding placebo formulation Too many periods. Results for phototrichograms, TEWL, and biomarker analysis of scalp condition for the shampoo treatments are discussed. Phototrichogram results are shared for the assessment of the leave on treatment. RESULTS: Statistically significant increases in hair amount were observed by phototrichogram after use of both PO-containing products versus placebo formulations. The PO shampoo treatment also significantly decreased oxidative stress on the hair and scalp, and improved scalp condition as assessed by TEWL and scalp biomarker values. CONCLUSION: These results illustrate the effectiveness of a cosmetic antioxidant to improve scalp condition thereby improving hair retention. The observed improvements in scalp condition are consistent with previous reports with other antioxidant technologies and suggest that the hair retention effect was achieved by preventing oxidative damage to the scalp.

Scalp application of antioxidants improves scalp condition and reduces hair shedding in a 24-week randomized, double-blind, placebo-controlled clinical trial.

OBJECTIVE: Increasing hair fullness is a global unmet need for many men and women. An approach to the problem is to decrease hair fall or shedding by reducing scalp stratum corneum oxidation and barrier damage to increase hair retention. This study evaluated a combination of functional antioxidants and barrier-enhancing cosmetic ingredients to improve scalp condition thereby enabling stronger hair anchorage and longer retention. METHODS: Male and female subjects with normal scalp condition and self-perceived hair thinning participated in a 24-week, double-blind, placebo-controlled, randomized clinical study assessing either a regimen of treatment shampoo and leave-on treatment containing functional antioxidant and barrier-enhancing agents or an identical placebo chassis shampoo control. The functional ingredients were piroctone olamine, zinc pyrithione, zinc carbonate, niacinamide, panthenol and caffeine. At baseline and after 8, 16 and 24 weeks of product use, several measurements were taken: hair shedding, total hair count (by phototrichogram), hair samples, TEWL and evaluation of biomarkers of scalp and hair conditions. Subjects also completed self-assessment questionnaires. RESULTS: Statistically significant effects for functional ingredient-containing treatment regimen versus a placebo control shampoo formulation were observed for reduced hair shedding, increased total hair count, reduced TEWL and improvement in scalp biomarker values. Subjects also noticed these improvements assessed via self-assessment questionnaires. CONCLUSIONS: These results establish that the use of functional antioxidant and barrier-enhancing agents to further improve scalp condition can enable a reduction in hair shedding and thus an increase in perceived hair fullness. The underlying improvements in scalp condition suggest the hair benefits were achieved as a result of improved scalp skin barrier and scalp condition leading to a viable preventative approach for hair thinning.

Development and qualification of a machine learning algorithm for automated hair counting.

OBJECTIVE: Determining the amount of hair on the scalp has always been an important metric of patient satisfaction for hair growth and hair retention technologies. While simple in concept, this measurement is a difficult, resource intensive task for the dermatologist and the research scientist. Specifically, counting and measuring hair in phototrichogram images is very time consuming and labour intensive. Due to cost, often only a fraction of available images is manually analysed. There is a need for an automated method that can significantly increase speed and throughput while reducing the cost of counting and measuring hair in phototrichogram images. METHODS: Recent advances in machine learning and deep convolutional neural networks (deep learning) have led to a revolution in the analysis of image, video, speech, text and other sensor data. Image diagnostics have seen remarkable improvements with completely automated methods outperforming both human experts and human-engineered analysis methods. Deep learning methods can also provide speed and cost benefits. To enable use of a deep learning, we created a data set of 288 manually annotated phototrichogram images with marked location and length of each hair (the training dataset). We designed a custom neural network architecture and custom image processing algorithms to best utilize the available training data and to maximize performance for hair counting and length measurement. The performance of the algorithm was qualified by comparing hair count and length measurements to an independent ground truth method, the semi-manual Canfield's Hair Metrix method. RESULTS: Leveraging deep neural networks, we have developed capability to apply machine learning to reduce the time needed to acquire data from phototrichograms of patients' scalp from months to seconds. Our algorithm enables fast and fully automated hair counting and length measurement. The algorithm shows high agreement with human manually assisted analysis (ground truth). CONCLUSIONS: We have trained and deployed an algorithm utilizing this technology and have demonstrated the reproducibility, accuracy and speed of this algorithm that, once deployed, requires little to no recurring cost or manual intervention for its operation. The method allows fast analysis of large number of images, reducing study cost and significantly reducing study analysis time.

Diagnosis of Mycobacterium abscessus/chelonae complex cutaneous infection: Correlation of tissue culture and skin biopsy.

Mycobacterium abscessus and M. chelonae belong to the rapid-growing nontuberculous mycobacteria (NTM) group, which are defined by their ability to form visible colonies on agar within 7 days of subculture. Cutaneous infections by this complex show a heterogeneous clinical presentation with varied histopathologic findings. However, the presence of vacuoles in many specimens has been reported as a specific histologic finding. Herein, we correlate the histopathology of patients with tissue-culture positive M. abscessus/M. chelonae complex in order to identify features that may prompt a rapid categorization of the infectious etiology. The cohort includes 33 skin punch biopsy specimens from 28 patients who had associated positive tissue cultures. The most frequent clinical presentation was a single or multiple nodule. Twenty-seven specimens (81.81%) were found to have vacuoles. The observation of certain histologic features (ie, polymorphonuclear microabscesses and epithelioid granuloma formation) should raise the possibility of infection by NTM. In addition to these findings, we believe the presence of vacuoles in the dermal and subcutaneous inflammation should raise suspicion for NTM.

Diagnoses of hospitalized patients with skin abnormalities prompting biopsy by consulting dermatologists: A 3-year review from a tertiary care center.

BACKGROUND: Dermatologists play an important role in diagnosing and managing hospitalized patients with cutaneous abnormalities. Skin biopsies remain an indispensable tool for aiding dermatologists in accurate diagnosis and treatment. We aimed to determine the range of conditions, and the most common conditions, prompting skin biopsy by dermatology hospital consultation (HCON) services to aid in evaluation of hospitalized patients. METHODS: All hospitalized patients seen by a single tertiary care center dermatology HCON service between 2015 and 2018 who had associated skin biopsies were identified. Histologic features and clinical diagnoses of each patient were classified into 13 histologic reaction pattern categories. RESULTS: Eight hundred and thirty one inpatients evaluated by our dermatology HCON service had 914 skin biopsies. The most frequent diagnostic categories prompting biopsy were vasculopathic (17.6%), interface dermatitis (16.5%), infectious (12.6%), and spongiotic dermatitis (10.9%). The most frequent diagnostic categories included drug reaction (13.2%), leukocytoclastic vasculitis (8.5%), skin cancer (5.4%), graft-vs-host disease (3.5%), connective tissue disease (3.3%), and calciphylaxis (3.0%). CONCLUSION: Our study suggests a variety of serious diseases affecting inpatients prompts biopsy by dermatology consultation services. Educational curricula for dermatology and pathology residents, fellows, and staff designed with these data may enhance knowledge that improves the quality of inpatient dermatology care.

Evaluating the Utility of Routine Imaging in Squamous Cell Carcinoma of the Nail Unit.

BACKGROUND: Squamous cell carcinoma (SCC) is the most common malignant tumor of the nail unit. No guidelines currently exist regarding the role of imaging in this specific location. OBJECTIVE: To investigate the utility of routine imaging in SCC of the nail apparatus. METHODS: A multi-institutional retrospective review of patients treated for nail unit SCC was performed. Data were collected on patient characteristics, tumor qualities, treatment, and radiographic imaging. A change in treatment was defined as more aggressive treatment (amputation) rather than local excision or Mohs micrographic surgery (MMS). RESULTS: One hundred seven patients with nail unit SCC were identified. Approximately 44/107 (41.1%) of patients were imaged and 63/107 (58.9%) were not. Mohs micrographic surgery was the most common primary treatment (66.4%). Mohs micrographic surgery was more commonly performed in nonimaged patients, and amputation was more commonly performed in imaged patients (p < .001). Bony changes were identified in 13/44 (29.5%) of imaged patients. In 8/44 (18.2%), imaging findings caused a change in treatment. In 99/107 (92.5%) of the cohort, imaging was either not performed or did not change management. CONCLUSION: In select cases, imaging may help guide patient management. Sufficient evidence does not yet exist to support routine imaging for patients with nail unit SCC.

Erythema elevatum diutinum a rare and poorly understood cutaneous vasculitis: A single institution experience.

BACKGROUND: Erythema elevatum diutinum (EED) is a rare vasculitis with variable clinical presentation which diagnosis can be challenging. Herein we want to describe the clinicopathological spectrum of findings in five cases of EED. METHODS: We retrospectively analyzed five cases in a single institution collected over a period of 27 years. The clinical history was collected and all the slides were examined to determine the histopathological characteristics of the lesions. RESULTS: The mean age of our patients is 56.6 years. Two of five patients were females and with lesions showing predilection for the upper-extremities. The most common presentation was of an erythematous plaque on the extensor surfaces. Three patients had a history of neoplasm. All cases showed leukocytoclastic damage consistent with EED. CONCLUSION: Our findings suggest that EED shows a heterogeneous clinical and pathological presentation, which can show an overlap with granulomatous dermatoses and mixed connective tissue diseases. Scalp lesions can occur and can mimic granulomatous dermatoses. The finding of EED in benign and malignant solid tumors in three of our patients begs the question whether there is an association between EED and such solid neoplasms.

Differential expression of phospho-S6 in hair follicle tumors: Evidence of mammalian target of rapamycin pathway activation.

BACKGROUND: The role of the mammalian target of rapamycin (mTOR) in hair follicle tumorigenesis is unclear. mTOR controls cell growth and can be activated through ribosomal S6 kinase. Herein, we sought to evaluate the expression of phospho-S6 in six different benign and malignant follicular tumor types. METHODS: 76 cases were selected (17 fibrofolliculomas, 20 trichoepitheliomas, 10 tricholemmomas, 19 pilomatricomas, 1 malignant proliferating tricholemmal tumor, 8 tricholemmal carcinomas, and 1 trichoblastic carcinoma) and collected over 16 years. Immunohistochemistry with monoclonal antibody for phospho-S6 was performed and analyzed semi-quantitatively; statistical analysis using the χ2 test was performed, with P < 0.05 considered significant. RESULTS: All malignant neoplasms in our series (8/8 [100%] cases of tricholemmal carcinoma, 1/1 [100%] trichoblastic carcinoma, and 1/1 [100%] malignant proliferating tricholemmal tumor) showed a strong and diffuse pattern of staining for phospho-S6 involving 70% to 90% of tumor cells. By contrast, a minority of benign tumors were positive for phospho-S6 and most stained in a patchy pattern including 12/17 (71%) fibrofolliculomas, 9/20 (45%) trichoepitheliomas and 1/10 (10%) tricholemmomas, involving 30% to 50%, 5% to 20%, and 40% to 50% of tumor cells, respectively. Most pilomatricomas (17/19 [89%]) exhibited a stronger, but distinctive staining pattern, staining mostly the basaloid cells with a multifocal distribution, involving 70% to 90% of tumor cells. CONCLUSIONS: Phospho-S6 is differentially expressed among benign and malignant hair follicle tumors (P = 0.0044). While malignant tumors show diffuse expression, only a small subset of benign neoplasms were positive, primarily in a patchy distribution.

Collagenoma of the Eyelid.

The rare case of an eyelid lesion comprised of hamartomatous dermal collagen, known as a collagenoma, is presented. Collagenomas may be sporadically acquired, or inherited as part of numerous autosomal dominant syndromes. In the appropriate clinical context, their diagnosis should prompt a thorough review of systems, systemic examination, and inquiry into family history, to assess for underlying autosomal dominant syndromes. Recognition of collagenomas may thus allow diagnosis of inherited syndromes, allowing patients to obtain appropriate genetic counseling, as well as screening and treatment of associated systemic pathology.

Direct immunofluorescence testing in vasculitis-A single institution experience with Henoch-Schönlein purpura.

BACKGROUND: Direct immunofluorescence (DIF) panels (IgG, IgA, IgM, C3 and fibrinogen) are ordered for clinically suspected vasculitis, with frequently negative results. METHODS: Cases submitted for DIF and histology (2010-2014) with "vasculitis" in the clinical data were examined, and the electronic medical record reviewed for clinical suspicion of Henoch-Schönlein purpura (HSP). Peri/intravascular IgA was considered positive, other reactants non-specific and no immunoreactivity negative. RESULTS: Vasculitis was the given indication for 20% (258/1318) of DIF studies. HSP was clinically suspected in 36% (95/258). In this setting, leukocytoclastic vasculitis (LCV) was common (66%, 63/95) and DIF was positive in 43% (27/63). One hundred percentage of DIF+ had LCV+. In cases without HSP suspicion, 26% (42/163) were LCV+ and <1% DIF+. Of the 258 cases, LCV+ greatly enriched for DIF+ (105/258 LCV+ with 28/105 [27%] DIF+), captured 100% of HSP and included cases with non-specific DIF/etiologic findings. In LCV cases, DIF positivity was not seen, HSP was not diagnosed and non-specific DIF findings were common. CONCLUSIONS: LCV is an H&E-based histopathologic diagnosis that can have positive, negative and non-specific DIF results that are rarely contributory except in the setting of HSP, where DIF is best utilized with IgA as the sole immunoreactant. H&E-based triage of DIF orders is recommended.

Role of family history in patchy alopecia areata.

BACKGROUND: Family history of alopecia areata has been associated with more severe clinical presentations, but its specific prognostic implications in patchy alopecia remains unclear. OBJECTIVE: To evaluate the relationship of family history of alopecia areata with demographics, triggers, comorbidities, disease course, and relapse rate in patchy alopecia. METHODS: The medical records of 256 patients seen over a 17-year period was examined. Data collected included demographics, comorbidities, disease severity, and response to treatment. Comparisons were drawn using Pearson chi-square tests, Fisher exact tests, Wilcoxon rank sum tests, and t-tests as appropriate. RESULTS: Family history of alopecia areata was associated with reduced hair regrowth after relapses, more severe symptoms, and earlier age of onset. Stress/fatigue, illnesses, thyroid disorders, and season changes were the most common relapse triggers. Dermatologic disorders were the most common comorbidities, followed by atopy and autoimmune disease. LIMITATIONS: Given the retrospective nature of data collection, most measures have some missing data, which may impact findings. CONCLUSION: Patchy alopecia patients with a family history of alopecia areata experienced worse outcomes. Concomitant autoimmunity may also adversely affect alopecia areata disease course. Identification of a positive family history of alopecia areata and control of autoimmune comorbidities may aid alopecia areata management.

Prevalence of hormonal and endocrine dysfunction in patients with lichen planopilaris (LPP): A retrospective data analysis of 168 patients.

BACKGROUND: Studies on the pathophysiology and comorbidities associated with lichen planopilaris (LPP) and frontal fibrosing alopecia (FFA) are limited. OBJECTIVE: The purpose of this study was to determine the prevalence of androgen excess in the postmenopausal LPP population, in relation to demographics and comorbidities. METHODS: A retrospective data analysis of 413 patients with LPP, FFA, and LPP/FFA seen in the Department of Dermatology at the Cleveland Clinic Foundation in Ohio between 2005 and 2015 was conducted. Of this cohort, 168 patients met the inclusion criteria. RESULTS: Androgen excess was identified in 31.5% (n = 53) of the 168 patients with LPP and all subtypes (P < .001). Androgen deficiency was identified in 32.1% (n = 17) of the 53 patients with FFA (P < .001). The androgen excess group was significantly more likely to present with hirsutism, seborrheic dermatitis, polycystic ovary syndrome, ovarian cysts, or a combination of these (P < .001). LIMITATIONS: This study was limited by being retrospective. CONCLUSION: Our study demonstrated that LPP is associated with androgen excess, and FFA is associated with androgen deficiency.

The role of immunosuppression in squamous cell carcinomas arising in seborrheic keratosis.

BACKGROUND: Seborrheic keratoses (SK) are common skin neoplasms considered to be benign. Reports of associated squamous cell carcinoma arising within seborrheic keratosis (SCC-SK) have been described. OBJECTIVE: To describe the histopathologic characteristics of SCC-SK and identify predisposing factors in formation of these rare lesions. METHODS: There were 162 cases of SCC-SK in a span of a decade (2003-2014). All of the histopathologic specimens and medical records were reviewed. Data from these patients were compared to a control group with seborrheic keratosis who were matched by age, sex, and location of lesion from the same time period (n = 162). RESULTS: SCC-SK has the classic histopathologic features of SK, such as hyperkeratosis, parakeratosis, papillomatosis, and pseudohorn cysts. The areas of squamous cell carcinoma were characterized by areas of squamous dysplasia (100%), hypogranulosis (79.6%), squamous eddies (79.6%), solar elastosis (80.9%), and brown pigmentation (59.9%). Patients with a history of immunosuppression had an increased risk for developing SCC-SK (19% vs 3%; P < .01), particularly when inhibition was transplant-associated (10% vs 0%; P < .01). LIMITATIONS: This was a single center, retrospective study. CONCLUSION: SCC-SK occurs more often in elderly men with a history of immunosuppression associated with organ transplants.