A phase 2a study investigating the effects of ritlecitinib on brainstem auditory evoked potentials and intraepidermal nerve fiber histology in adults with alopecia areata.

Reversible axonal swelling and brainstem auditory evoked potential (BAEP) changes were observed in standard chronic (9-month) toxicology studies in dogs treated with ritlecitinib, an oral Janus kinase 3/tyrosine kinase expressed in hepatocellular carcinoma family kinase inhibitor, at exposures higher than the approved 50-mg human dose. To evaluate the clinical relevance of the dog toxicity finding, this phase 2a, double-blind study assessed BAEP changes and intraepidermal nerve fiber (IENF) histology in adults with alopecia areata treated with ritlecitinib. Patients were randomized to receive oral ritlecitinib 50 mg once daily (QD) with a 4-week loading dose of 200 mg QD or placebo for 9 months (placebo-controlled phase); they then entered the active-therapy extension and received ritlecitinib 50 mg QD (with a 4-week loading dose of 200 mg in patients switching from placebo). Among the 71 patients, no notable mean differences in change from baseline (CFB) in Waves I-V interwave latency (primary outcome) or Wave V amplitude on BAEP at a stimulus intensity of 80 dB nHL were observed in the ritlecitinib or placebo group at Month 9, with no notable differences in interwave latency or Wave V amplitude between groups. The CFB in mean or median IENF density and in percentage of IENFs with axonal swellings was minimal and similar between groups at Month 9. Ritlecitinib treatment was also not associated with an imbalanced incidence of neurological and audiological adverse events. These results provide evidence that the BAEP and axonal swelling finding in dogs are not clinically relevant in humans.

Health Utility Measures Among Patients with Androgenetic Alopecia After Hair Transplant.

BACKGROUND: Hair loss causes significant psychosocial distress to patients. Health utility measurements offer an objective, quantitative assessment of health-related quality of life (QOL). METHODS: We performed a prospective cohort study on patients with hair loss between January 1, 2018 and December 31, 2020. Patient metrics were compared with layperson perception of alopecia, prospectively collected between August 1 and December 31, 2017. Health utility measures were quantified using the visual analog scale (VAS), standard gamble (SG), and time trade-off (TTO) in quality-adjusted life-years (QALYs) and relative to the minimal clinically important difference (MCID). Bonferroni correction to the significance threshold was performed. RESULTS: Thirty-one patients with alopecia were compared with 237 laypeople. Patient metrics for female hair loss were all significantly lower than laypeople measures (VAS QALYs 0.65 ± 0.21 vs. 0.83 ± 0.18, p = 0.0001). Mean SG QALYs were lower for patients in the male alopecia state (0.86 ± 0.23 vs. 0.96 ± 0.12, p = 0.0278). Post-hair transplant improvement in TTO was significantly greater for patients (+ 0.08 ± 0.12 vs. + 0.02 ± 0.09, p = 0.0070) and significantly more often exceeded the MCID (45.2% vs. 16.9%, p = 0.0006). CONCLUSIONS: Alopecia negatively impacts QOL, and the true patient experience is more taxing than what is perceived by laypeople. Hair transplantation improves QOL more for male patients than common perception. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Primary Alopecia Neoplastica: A Novel Case Report and Literature Review.

Alopecia neoplastica (AN) is caused by neoplastic cells damaging hair follicles, resulting in patchy hair loss like cicatricial alopecia and alopecia areata. AN has predominantly described cutaneous metastasis to the scalp from primary visceral malignant tumors. Less frequently, AN results from a primary scalp neoplasm. Compared to "secondary AN," there is a paucity of literature on "primary AN." Herein, we present a comprehensive literature review of primary AN and introduce a unique case of amelanotic melanoma causing primary AN. Including our presented case, 11 cases of primary AN have been reported with causative scalp neoplasms including angiosarcoma, hemangioendothelioma, syringomatous carcinoma, ectopic extramammary Paget's disease, and primary desmoplastic melanoma. 27.3% (3 of 11) of cases were misdiagnosed and treated for a primary alopecia, and 36.4% (4 of 11) of lesions were present for multiple years or an unknown amount of time, likely due to difficulty in recognizing scalp lesion or misdiagnosis. All patients required surgical excision with 36.4% (4 of 11) requiring chemotherapy, radiation, or photodynamic therapy. Two patients with scalp angiosarcoma died from their aggressive disease. Due to the risks of malignant primary AN if allowed to progress, primary AN should be considered in patients presenting with scarring alopecia.

Subcutaneous metastasis from an atypical pulmonary carcinoid tumor.

Pulmonary carcinoid tumors are uncommon neuroendocrine tumors that rarely metastasize to the skin. We report the case of a 71-year-old woman with a longstanding history of primary atypical pulmonary carcinoid tumor who presented with a new tender cutaneous nodule. Immunostaining of the nodule was consistent with metastatic atypical carcinoid tumor of the skin including positive staining for neuroendocrine markers chromogranin and synaptophysin. Dermatologists should consider cutaneous neuroendocrine metastasis when evaluating new nodules in patients with stable pulmonary carcinoid tumors or in those with concomitant concerning respiratory symptoms.

Using deep learning for dermatologist-level detection of suspicious pigmented skin lesions from wide-field images.

A reported 96,480 people were diagnosed with melanoma in the United States in 2019, leading to 7230 reported deaths. Early-stage identification of suspicious pigmented lesions (SPLs) in primary care settings can lead to improved melanoma prognosis and a possible 20-fold reduction in treatment cost. Despite this clinical and economic value, efficient tools for SPL detection are mostly absent. To bridge this gap, we developed an SPL analysis system for wide-field images using deep convolutional neural networks (DCNNs) and applied it to a 38,283 dermatological dataset collected from 133 patients and publicly available images. These images were obtained from a variety of consumer-grade cameras (15,244 nondermoscopy) and classified by three board-certified dermatologists. Our system achieved more than 90.3% sensitivity (95% confidence interval, 90 to 90.6) and 89.9% specificity (89.6 to 90.2%) in distinguishing SPLs from nonsuspicious lesions, skin, and complex backgrounds, avoiding the need for cumbersome individual lesion imaging. We also present a new method to extract intrapatient lesion saliency (ugly duckling criteria) on the basis of DCNN features from detected lesions. This saliency ranking was validated against three board-certified dermatologists using a set of 135 individual wide-field images from 68 dermatological patients not included in the DCNN training set, exhibiting 82.96% (67.88 to 88.26%) agreement with at least one of the top three lesions in the dermatological consensus ranking. This method could allow for rapid and accurate assessments of pigmented lesion suspiciousness within a primary care visit and could enable improved patient triaging, utilization of resources, and earlier treatment of melanoma.

Androgenetic Alopecia in Gender Minority Patients.

Androgenetic alopecia (AGA) is the most common type of hair loss in adults and may be particularly distressing for gender minority patients, given the close relation between hair and gender expression. Furthermore, use of gender affirming hormones such as testosterone in transmen and estrogen/antiandrogens in transwomen has a direct effect on hair growth distribution and density. Clinicians should thus be knowledgeable about the effects of sex hormones on the hair growth cycle to comfortably diagnose and treat AGA in gender minority patients.

Development of Lichen Planopilaris-Like Alopecia following Occupational Exposure to Trichloroethylene and Tetrachloroethylene.

BACKGROUND: We report a case of acute and severe lichen planopilaris (LPP)-like alopecia in a 35-year-old male construction worker following occupational exposure to trichloroethylene (TCE) and tetrachloroethylene (PCE). CASE REPORT: Two weeks after initiating ground-intrusive construction at a previous dry-cleaning facility site, the patient developed sudden scalp pruritus and associated patchy hair loss. As subsequent scalp biopsies revealed LPP, he was started on hydroxychloroquine at 200 mg twice daily and clobetasol solution once daily. Despite treatment, the patient's hair loss rapidly progressed to involve >95% of his scalp within 3 years. An official "work clean" policy report revealed high-concentration exposure to TCE and PCE. CONCLUSION: Although causation cannot be proven, the close temporal relationship and rapid progression of LPP-like alopecia in an atypical patient demographic support a strong correlation between chemical exposure to TCE/PCE and scarring hair loss.

Histologic and clinical cross-sectional study of chronic hair loss in patients with cutaneous chronic graft-versus-host disease.

BACKGROUND: While scalp alopecia represents a distinctive feature of chronic graft-versus-host disease (cGVHD), little is known about the clinical and histologic presentation of hair loss. OBJECTIVES: We sought to classify the clinical presentations and histologic findings of chronic hair loss in patients with cutaneous cGVHD. METHODS: A prospective cohort of 17 adult hematopoietic cell transplantation (HCT) recipients with cutaneous cGVHD was enrolled. Dermatologic examinations were performed, and punch biopsy specimens of the scalp were obtained. Biopsy specimens were analyzed with hematoxylin-eosin and immunohistochemical stains in all cases and fluorescence in situ hybridization analyses in specific cases. RESULTS: Clinically, 4 patterns of hair loss were described-patchy nonscarring (41.2%), diffuse nonscarring (11.8%), diffuse sclerotic (11.8%), and patchy sclerotic (5.9%). The location of the inflammatory infiltrate on hematoxylin-eosin-stained specimens correlated with the hair loss pattern patients had clinically, with cell populations around the bulb and bulge in nonscarring and sclerotic cases, respectively. Fluorescence in situ hybridization studies in female cGVHD patients with male donors demonstrated green Y chromosomes limited to the area of the hair follicle affected by inflammatory cells. CONCLUSION: This study describes the various clinical and histologic subtypes of long-standing alopecia in adult cGVHD patients and suggests that this alopecia may be a direct manifestation of cGVHD of the hair follicle.

The effect of scalp cooling on CIA-related quality of life in breast cancer patients: a systematic review.

PURPOSE: Chemotherapy-induced alopecia (CIA) remains a distressing adverse event of cancer treatment but may be prevented by scalp cooling. The effectiveness of scalp cooling, however, is dependent on the chemotherapy regimen with successful hair preservation (i.e., < 50% hair loss) in 41-59% of women on taxane-based therapies in comparison to 16-36% on anthracycline-based therapies. Despite the potential utility, use of scalp cooling has shown a more equivocal impact on quality of life (QoL). In this review, we aim to evaluate the use of scalp cooling for CIA and quantitative QoL measures. METHODS: A systematic review of PubMed, Embase, Web of Science, and Cochrane databases for clinical studies on scalp cooling to prevent CIA published before October 29, 2018 was performed. Clinical studies with 5 or more patients that reported on a quantitative QoL measure were included and graded according to a modified five-point scale from the Oxford Centre for Evidence-Based Medicine. RESULTS: Studies meeting inclusion criteria included 4 randomized clinical trials (RCT), 8 cohort studies, and 1 cross-sectional study with 1282 unique patients. The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (QLQ-C30: 46%) and Breast Cancer Module (QLQ-BR23: 46%) represented the most commonly used QoL assessments. Overall, 4 (31%) of the 13 studies concluded that scalp cooling was associated with significant improvements in QoL measures; 8 (62%) determined that there was either non-significant or no improvements; and 1 (7.7%) provided a mixed conclusion. Although 2 (50%) RCT demonstrated that scalp cooling can effectively prevent CIA depending on the chemotherapy regimen, these studies did not show that successful hair preservation was associated with improved QoL measures. CONCLUSIONS: This review demonstrates that scalp cooling is not consistently associated with significant QoL improvements as assessed by EORTC QLQ-C30 and -BR23. Representing a critical limitation, more than one-third of the studies did not subcategorize QoL outcomes for successfully or unsuccessfully scalp-cooled patients but rather reported on QoL measures for all scalp-cooled patients in general. Failure to prevent hair loss in patients undergoing an expensive and potentially uncomfortable treatment likely contributes to decreased well-being, impacting the overall distribution of QoL measures in scalp cooling patients compared to controls. Future studies should incorporate validated QoL instruments specific to hair disease and classify QoL outcomes for scalp-cooled patients based on the degree of hair preservation.

Lipofibromatosis-like neural tumor: Case report of a unique infantile presentation.

A 14-month-old boy presented with a slow-growing, asymptomatic back plaque, which was biopsied and found to have S100 positivity, sparse CD34 staining, and no significant mitotic activity, nuclear pleomorphism, or necrosis; genetic workup found LMNA-NTRK1 gene fusion, overall consistent with lipofibromatosis-like neural tumor (LPF-NT). LPF-NT is rare, with 14 cases previously reported, and our patient is the first report of this diagnosis in infancy. This case report and literature review includes comparison of similar diagnoses including lipofibromatosis, low-grade malignant peripheral nerve sheath tumor, infantile fibrosarcoma, and dermatofibrosarcoma protuberans and serves to aid detection of LPF-NT presenting in pediatric patients by highlighting similarities and differences that should prompt consideration. LPF-NT shows locally aggressive behavior only and should not be confused with conditions that have potential for distant spread. However, case reports of metastasizing LMNA-NTRK1 tumors draw into question whether growths with this gene fusion exist on a spectrum of disease severity. Our patient was treated with wide local excision and has developed no complications or evidence of recurrence with 6 months of follow-up time.