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.

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.

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.

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.

Acral and digital angioleiomyomata: 14-year experience at the Cleveland Clinic and review of the literature.

BACKGROUND: Angioleiomyoma is a benign neoplasm thought to derive from the tunica media of small venous vessels. Angioleiomyomata most frequently occur in the lower extremities with less common occurrences on the trunk, head and upper extremities. Few cases of acral and digital angioleiomyoma have been described in the literature. METHODS: We add a series of 21 patients with acral angioleiomyoma including 6 cases of digital angioleiomyoma to the body of clinical and histological findings along with a review of the literature of digital angioleiomyomata. RESULTS: Digital angioleiomyoma are equally distributed between male and female patients and are more often painful than the angioleiomyoma of all body sites. Acral angioleiomyomata favor the feet over hands at a ratio of 2.5:1, while digital angioleiomyoma favor the fingers over toes at a ratio of 4.3:1. CONCLUSIONS: We suggest that vascular leiomyoma be included in the differential diagnosis of smooth muscle tumors with particular regard to the digits of both the hands and the feet. Digital angioleiomyomata differ from acral angioleiomyomata in their equal gender distribution, increased tendency to cause pain and preponderance for the fingers over the toes.

Histological pattern of Merkel cell carcinoma sentinel lymph node metastasis improves stratification of Stage III patients.

Sentinel lymph node biopsy is used to stage Merkel cell carcinoma, but its prognostic value has been questioned. Furthermore, predictors of outcome in sentinel lymph node positive Merkel cell carcinoma patients are poorly defined. In breast carcinoma, isolated immunohistochemically positive tumor cells have no impact, but in melanoma they are considered significant. The significance of sentinel lymph node metastasis tumor burden (including isolated tumor cells) and pattern of involvement in Merkel cell carcinoma are unknown. In this study, 64 Merkel cell carcinomas involving sentinel lymph nodes and corresponding immunohistochemical stains were reviewed and clinicopathological predictors of outcome were sought. Five metastatic patterns were identified: (1) sheet-like (n=38, 59%); (2) non-solid parafollicular (n=4, 6%); (3) sinusoidal, (n=11, 17%); (4) perivascular hilar (n=1, 2%); and (5) rare scattered parenchymal cells (n=10, 16%). At the time of follow-up, 30/63 (48%) patients had died with 21 (33%) attributable to Merkel cell carcinoma. Patients with pattern 1 metastases had poorer overall survival compared with patients with patterns 2-5 metastases (P=0.03), with 22/30 (73%) deaths occurring in pattern 1 patients. Three (10%) deaths occurred in patients showing pattern 5, all of whom were immunosuppressed. Four (13%) deaths occurred in pattern 3 patients and 1 (3%) death occurred in a pattern 2 patient. In multivariable analysis, the number of positive sentinel lymph nodes (1 or 2 versus >2, P<0.0001), age (<70 versus ≥70, P=0.01), sentinel lymph node metastasis pattern (patterns 2-5 versus 1, P=0.02), and immune status (immunocompetent versus suppressed, P=0.03) were independent predictors of outcome, and could be used to stratify Stage III patients into three groups with markedly different outcomes. In Merkel cell carcinoma, the pattern of sentinel lymph node involvement provides important prognostic information and utilizing this data with other clinicopathological features facilitates risk stratification of Merkel cell carcinoma patients who may have management implications.

Epidermal multinucleated keratinocytes: a histopathologic clue to dermatitis artefacta.

Dermatitis artefacta is a psycho-cutaneous disorder characterized by self-inflicted cutaneous injuries, often in association with an underlying psychiatric disorder or as a response to external stressors. Cutaneous lesions suggestive of dermatitis artefacta are dependent on the means of injury and thus may be morphologically variable, but typically have geometric shapes, spare hard-to-reach anatomic areas, and are present in variable stages of evolution at any specific time. Although a dermatologist may be suspicious of dermatitis artefacta in a given patient, making a definitive diagnosis is extremely challenging. Patients often clinically evade questioning and deny creating skin lesions, and histopathologic evaluation of lesional biopsies usually reveals non-specific epidermal and dermal changes and inflammation. Thus, identification of clues that lend support to a diagnosis of dermatitis artefacta would be welcomed by both clinicians and pathologists. Here we present a case of dermatitis artefacta with a unique, yet previously reported, histopathological finding of multinucleated keratinocytes within the epidermis. Although probably uncommon and dependent on the etiology of cutaneous injury, we believe this finding is important for dermatopathologists to be aware of as a potential diagnostic clue when evaluating biopsies in patients suspected to have dermatitis artefacta.

Secondary syphilis in HIV positive individuals: correlation with histopathologic findings, CD4 counts, and quantity of treponemes in microscopic sections.

BACKGROUND: Although syphilis is uncommon, infection rates are much higher in HIV-infected individuals than the general population. A proposed explanation is impaired cellular immunity with HIV infection. METHODS: A search of one institution yielded 10 patients with a diagnosis of secondary syphilis on skin biopsy, positive syphilis serology and available CD4 counts. We evaluated 11 biopsies from the 10 patients. We correlated the patients' CD4 counts with the histologic findings and with the number of treponemes on skin biopsies, highlighted by immunohistochemistry (IHC). We also compared the detection of spirochetes in silver stained sections (e.g. Warthin-Starry) with T. pallidum IHC. All biopsies were assessed for various histologic features. RESULTS: The sensitivity of IHC to detect treponemes was 64% and of silver stain was 9% (p-value 0.04). The number of treponemes on the biopsies was determined by IHC. High numbers of spirochetes (i.e. >100 per 10 hpf) were only seen in patients with CD4 counts less than 250 cells/ml. CONCLUSION: The most consistent histologic finding was a moderate to severe lymphoplasmacytic infiltrate. Although the study is small, it appears that a higher number of spirochetes is associated with CD4 counts less than 250 cell/ml. The T. pallidum IHC stain was vastly superior to the Warthin-Starry stain.

Pagetoid Spitz nevi: clinicopathologic characterization of a series of 12 cases.

BACKGROUND: Pagetoid Spitz nevus is an uncommon Spitz nevus variant characterized by a predominantly intraepidermal proliferation of single epithelioid melanocytes. Recognition of this variant is important to avoid misdiagnosis as melanoma. METHODS: We reviewed and characterized 12 pagetoid Spitz nevi diagnosed at a tertiary care institution over the past 25 years. RESULTS: All patients were female and average age at biopsy was 34 years. Clinically, 83% (10 out of 12) were located on an extremity and all were ≤ 6 mm in diameter. Histologically, pagetoid Spitz nevi were characterized by individual intraepidermal epithelioid melanocytes mostly confined to the lower half of the epidermis. Most displayed epidermal hyperplasia, eosinophilic bodies and melanocytes with minimal pleomorphism. All displayed melanoderma and at least mild dermal inflammation. CONCLUSIONS: This represents the largest series of pagetoid Spitz nevi characterized to date. Although most clinicopathologic characteristics in our series correlated with those previously described, novel findings included occurrence in middle-aged adults, occurrence above the waist and demonstration of melanoderma in all lesions. Presence of dermal inflammation and melanoderma may contribute to atypical clinical appearance leading to biopsy despite their small clinical size. Recognition of these additional novel histologic features may aid dermatopathologists in distinguishing pagetoid Spitz nevi from melanoma.

Clinical Efficacy of Diphenylcyclopropenone in Alopecia Areata: Retrospective Data Analysis of 50 Patients.

Diphenylcyclopropenone (DPCP) is widely considered the most effective topical immunotherapy for refractory or extensive alopecia areata (AA), but questions regarding how long to try DPCP therapy before terminating and what factors are prognostic of therapeutic success still remain unanswered. In this retrospective study of 50 AA patients, we evaluated DPCP efficacy and identified patient factors predictive of therapeutic success/failure. The median duration of DPCP treatment was 3 years, with 47% patients experiencing their first regrowth in the first 6 months of DPCP therapy, 20% between 6 months-1 year, and 8% between 1-2 years. In our study, treatment success, defined as ⩾50% terminal hair regrowth, was reached in 71% of alopecia totalis patients and in 56% of alopecia universalis patients. Three factors were statistically significant predictors of poor treatment outcome-extent of hair loss before DPCP treatment, history of thyroid disease, and extent of body hair involvement. Relapse was observed in 44% of patients and significantly associated with history of thyroid disease. Common side effects were itching, rash, and local lymphadenopathy. The results of this study support our belief that DPCP therapy is a viable treatment option, can be successfully accomplished at home, and should not be terminated before 2 years.

ILK Index and Regrowth in Alopecia Areata.

There is insufficient data in the literature concerning optimal intralesional kenalog (ILK) dosing for the treatment of alopecia areata (AA). The purpose of this pilot study was to evaluate the utility of using the ratio of ILK received to initial Severity of Alopecia Tool (SALT) score to guide ILK dosing in patients with AA. Using photographic data from patients at baseline and 4-months follow-up, hair loss in 15 patients treated with AA was retrospectively graded using the SALT scores. The ILK received/initial SALT score (ILK index) was calculated for each patient, and the mean ILK index for patients who experienced significant (≥50%) and suboptimal (<50%) hair regrowth at 4 months follow-up were compared. Patients who experienced suboptimal hair regrowth had a lower ILK index on average than patients who experienced significant improvement. Although the difference did not meet significance (<0.1), the trend suggests that the ILK index, a novel calculation, may be a useful tool for guiding ILK dosing in the treatment of AA.

Eosinophil-rich syphilis: a report of four cases.

The differential diagnosis for eosinophil-rich skin lesions often includes a drug reaction, allergic contact dermatitis and rarely, response to a helminth infection. However, many unrelated entities, such as infections, neoplasms and inflammatory dermatoses, can have a prominent eosinophilic infiltrate. Syphilis is classically associated with plasma cells, but other patterns of inflammation have been reported, including ulcerative, granulomatous and eosinophil-rich. Classic teaching might indicate that the presence of eosinophils argues against a diagnosis of syphilis. We present four cases of secondary syphilis with increased eosinophils, ranging from 8 to >200 eosinophils per 10 high-power fields (×400 magnification). Patient 1 had lesions on the penis and scrotum, with greater than 200 eosinophils per 10 high-power fields. Patient 2 had lesions on the back, with 150 eosinophils per 10 high-power fields. Patient 3 had lesions on the bilateral arms, with 8 eosinophils per 10 high-power fields. Patient 4 had lesions involving the anus, with 17 eosinophils per 10 high-power fields. These cases highlight that the presence of an eosinophil-rich infiltrate on skin biopsy should not exclude syphilis from the differential diagnosis.

Periocular granuloma annulare: a case report and review of literature.

Granuloma annulare (GA) is a granulomatous dermatosis that rarely presents on the face and is extremely uncommon in the periocular region. We report our experience with the presentation and management of GA lesions on the eyelids of a 17-year-old girl. We performed a review of published literature and identified 13 cases of pediatric periocular GA. One additional case was identified upon review of all pediatric GA cases at the Cleveland Clinic Foundation. Review of these cases suggests that periocular GA is a benign condition that spontaneously regresses within a few months. GA nodules have a predilection for the upper eyelids. A greater incidence is noted in African American children. Awareness of the self-resolving nature of this condition can prevent unnecessary surgical excisions in affected children.

Association between alopecia areata, psoriasis vulgaris, thyroid disease, and metabolic syndrome.

Although the association between alopecia areata (AA), psoriasis, and other autoimmune diseases has been well reported in the literature, an association with metabolic syndrome has not been reported. We present two young women with the combination of severe psoriasis, androgen excess, metabolic syndrome, thyroiditis, and AA. Both women ultimately progressed to treatment-resistant alopecia universalis. This constellation of autoimmunity and metabolic syndrome presents a therapeutic challenge while highlighting the need for full laboratory assessment of AA patients. Careful selection of biological treatment regimens may offer therapeutic benefit for both their psoriasis and AA while giving us experience with the newer biologics in AA.

Morphologic mimickers of Cryptococcus occurring within inflammatory infiltrates in the setting of neutrophilic dermatitis: a series of three cases highlighting clinical dilemmas associated with a novel histopathologic pitfall.

A neutrophil-predominant inflammatory infiltrate in a cutaneous biopsy can be associated with a broad spectrum of diseases. Here we describe three cases showing a neutrophil-predominant dermal infiltrate admixed with abundant acellular bodies surrounded by capsule-like vacuolated spaces, which strikingly mimicked Cryptococcus. Two cases occurred within the settings of underlying hematologic malignancies; the third case was associated with immune dysregulation. Two patients were acutely ill in the medical intensive care unit. Fungal work-up, including cultures and multiple stains were negative. Because of clinical deterioration in these patients, transmission electron microscopy was pursued to definitively rule out fungal infection. In both cases, characteristics most compatible with autolysing human cells, not Cryptococcus, were identified. Chemotherapy and high-dose steroids were given, but both patients eventually succumbed to their diseases. To the best of our knowledge, these represent the first reported cases of autolysing human cells mimicking Cryptococcus organisms within neutrophilic infiltrates. They highlight the therapeutic dilemmas arising with histopathologic mimics, as well as the importance of thorough investigation to distinguish mimickers from true infectious organisms. We believe recognition of this microscopic pitfall will be useful to dermatopathologists faced with similar findings in the future, and may prevent unnecessary delay of appropriate therapy in acutely ill patients.