Sensory Neurons Co-opt Classical Immune Signaling Pathways to Mediate Chronic Itch.

Mammals have evolved neurophysiologic reflexes, such as coughing and scratching, to expel invading pathogens and noxious environmental stimuli. It is well established that these responses are also associated with chronic inflammatory diseases, including asthma and atopic dermatitis. However, the mechanisms by which inflammatory pathways promote sensations such as itch remain poorly understood. Here, we show that type 2 cytokines directly activate sensory neurons in both mice and humans. Further, we demonstrate that chronic itch is dependent on neuronal IL-4Rα and JAK1 signaling. We also observe that patients with recalcitrant chronic itch that failed other immunosuppressive therapies markedly improve when treated with JAK inhibitors. Thus, signaling mechanisms previously ascribed to the immune system may represent novel therapeutic targets within the nervous system. Collectively, this study reveals an evolutionarily conserved paradigm in which the sensory nervous system employs classical immune signaling pathways to influence mammalian behavior.

Identifying critical quality metrics in Mohs Surgery: A national expert consensus process.

BACKGROUND: Amid a movement toward value-based healthcare, increasing emphasis has been placed on outcomes and cost of medical services. To define and demonstrate the quality of services provided by Mohs surgeons, it is important to identify and understand the key aspects of Mohs micrographic surgery (MMS) that contribute to excellence in patient care. OBJECTIVE: The purpose of this study is to develop and identify a comprehensive list of metrics in an initial effort to define excellence in MMS. METHODS: Mohs surgeons participated in a modified Delphi process to reach a consensus on a list of metrics. Patients were administered surveys to gather patient perspectives. RESULTS: Twenty-four of the original 66 metrics met final inclusion criteria. Broad support for the initiative was obtained through physician feedback. LIMITATIONS: Limitations of this study include attrition bias across survey rounds and participation at the consensus meeting. Furthermore, the list of metrics is based on expert consensus instead of quality evidence-based outcomes. CONCLUSION: With the goal of identifying metrics that demonstrate excellence in performance of MMS, this initial effort has shown that Mohs surgeons and patients have unique perspectives and can be engaged in a data-driven approach to help define excellence in the field of MMS.

Pure and Mixed Variants of Desmoplastic Melanoma: A Single-Center, Retrospective, Clinicopathologic Review.

BACKGROUND: Desmoplastic melanoma (DM) is a rare melanoma variant. Prognostic indicators and survival vary widely and are further confounded by the histopathologic distinction between pure DM (pDM) and mixed DM (mDM) subtypes. The utility of current treatment guidelines is limited by the lack of evidence-based recommendations. OBJECTIVE: To compare the clinicopathologic characteristics of pure and mixed subtypes of DMs. METHODS: All cases of DM were identified from the Washington University in St Louis institutional pathology database between January 2000 and September 2022. Fifty-two cases were identified and subsequently categorized as pure ( n = 26) or mixed ( n = 26). Clinical and histopathologic data were collected and compared. RESULTS: There were no differences in demographics or tumor location between pure and mixed subtypes. Patients with mDM were more likely to have mitoses present ( p = .03). There were no differences in Breslow depth, tumor diameter, level of invasion, ulceration, and lymphovascular or perineural invasion. The utilization of sentinel lymph node biopsy ( p = .17) and sentinel lymph node positivity ( p = .67) were also similar. CONCLUSION: Despite histopathologic distinction between pDM and mDM, these subtypes were found to have similar clinicopathologic characteristics, including similar rates of sentinel lymph node metastasis.

Clinical features and management of eyelid margin nevi.

PURPOSE: Acquired melanocytic nevi are common eyelid lesions; however, their clinical presentation is not well documented. METHODS: In this retrospective study, clinical records were reviewed in patients evaluated between 2005 and 2022. RESULTS: Eyelid margin nevi (n = 150) were more commonly excised in female (78%) and Caucasian (86%) patients. Change in appearance/size were frequent presenting complaints, and 17% experienced ocular symptoms. Referring diagnosis included other benign lesions (11.3%), and concern for malignancy (16.7%). Many individuals (38.7%) noted their lesion for ≤5 years. Nevi were distributed across the 4 margins (9% peripunctal), and 88% had a regular base. Visible pigmentation was more common in non-Caucasians (95.2%) than Caucasians (41.1%). Lashes grew through 60.7% of nevi and were often misdirected.Nevi were treated with superficial excision and cauterization. Histologic subtypes included: dermal (86.6%), compound (9.4%), blue (2.7%), junctional (0.7%), lentiginous dysplastic (0.7%). An irregular base (p=0.042) and pigmentation (p=0.056) were more common in compound than dermal nevi. Lash line quality and appearance were improved in the majority of patients returning for follow-up, although postoperative trichiasis, marginal erythema, and residual pigmentation were observed. CONCLUSIONS: Melanocytic nevi commonly involve the eyelid margins and have a variety of presentations and appearances. Existing nevi can change, and new lesions appear throughout adulthood. Stable, benign appearing nevi can be observed. Shave excision provides a diagnosis and improved appearance for symptomatic or suspicious lesions, with few serious complications. Malignant transformation is rare, although evidence for recurrence warrants further evaluation.

Primary Cutaneous Mucinous Carcinoma: A Review of the Literature.

BACKGROUND: Primary cutaneous mucinous carcinoma (PCMC) is an exceedingly rare, low-grade tumor that histologically resembles mucinous carcinoma from other primary sites, such as the breast, gastrointestinal tract, and lungs. OBJECTIVE: The purpose of this article was to review the current literature on PCMC as it relates to epidemiology, clinical presentation, histopathology, immunohistochemistry, treatment, and prognosis. MATERIALS AND METHODS: An extensive literature review was conducted using PubMed and Ovid MEDLINE to identify articles related to PCMC. RESULTS: Several hundred cases have been reported in the medical literature, and surgical resection, whenever feasible, is the standard of care. CONCLUSION: The diagnosis of primary cutaneous mucinous carcinoma is one of exclusion, requiring a metastatic work-up to rule out distant primary. Mohs micrographic surgery is a tissue sparing technique that allows complete margin control of these rare neoplasia.

Clinical Characteristics of Basal Cell Carcinomas of the Vulva: An Institutional Retrospective Review.

BACKGROUND: There are limited data on the etiology, clinical characteristics, and optimal treatment of vulvar basal cell carcinoma (BCC). OBJECTIVE: This retrospective review may aid in treatment decisions for vulvar BCC. MATERIALS AND METHODS: A retrospective review of our institutional CoPath database was performed, using search terms to identify cases of vulvar BCCs from 2000 to 2018. RESULTS: A total of 35 cases of vulvar BCC were included. Patient age ranged from 33 to 97 years with a mean age of 70 years. Of the 35 cases, 28 (80%) involved the cutaneous vulva, 6 (17%) involved the suprapubic area, and 1 (3%) involved the clitoris. Most vulvar BCCs were treated by wide local excision (46%) and vulvectomies (37%), with 3 cases treated with Mohs (11%) and 2 with electrodesiccation and curettage (6%). Preoperative tumor sizes were 0.86 cm2 for Mohs, 0.94 cm2 for excision, and 1.54 cm2 for vulvectomy. The mean margins were 3 mm for Mohs, 4.4 mm for wide local excision, and 6 mm for vulvectomy. Most cases (77%) were identified and treated by gynecology. CONCLUSION: Mohs micrographic surgery should be considered for the advantages of being tissue sparing, evaluating the complete peripheral and deep margin, and avoiding the costs and risks of general anesthesia.

Gender Differences in Clinical Practice and Medicare Reimbursement Among Mohs Surgeons.

OBJECTIVE: To evaluate Medicare reimbursement and clinical activity between male and female dermatologic surgeons. MATERIALS AND METHODS: A retrospective review of the Medicare Provider Utilization and Payment data from 2018 was performed for all dermatologists performing MMS. Provider gender, place of service, number of services, and average payment per service was recorded for all relevant procedure codes. RESULTS: Women represented 31.5% of the 2,581 surgeons who performed MMS in 2018. Women were paid significantly less than men (mean difference, -$73,033). On average, women performed 123 fewer cases than their male counterparts. When surgeons were stratified by productivity, remuneration was the same. CONCLUSION: Remuneration from CMS was disparate between male and female dermatologic surgeons, which may be attributed to submission of fewer charges by women. Further efforts are necessary to better evaluate and address causes for this discrepancy, because greater parity of opportunity and pay would greatly benefit this subspecialty of dermatology.

Cancer of the Vulva: A Review.

BACKGROUND: Vulvar cancers, although rare, are becoming an increasingly serious threat to women's health. Cancer of the vulva accounted for 0.3% of all new cancers in the United States in 2019, with 6,070 newly diagnosed cases. This review details the epidemiology, pathogenesis, diagnosis, staging, and treatment of vulvar malignancies. OBJECTIVE: To review cancer entities of the vulva, including vulvar intraepithelial neoplasms, squamous cell carcinoma (SCC), malignant melanoma, basal cell carcinoma, neuroendocrine tumors, and adenocarcinomas. MATERIALS AND METHODS: Literature review using PubMed search for articles related to cancer of the vulva. RESULTS: Vulvar intraepithelial neoplasms represent premalignant precursors to SCC of the vulva. There are several different histopathologic subtypes of SCC, and treatment is dependent on characteristics of primary tumor and lymph node involvement. Melanoma is the second most common cancer to affect the vulva, and staging is based on tumor, node, and metastatic spread. CONCLUSION: Vulvar malignancies are rare, and diagnosis is dependent on biopsy and pathologic evaluation. Treatment for vulvar malignancies depends on histopathologic diagnosis but ranges from wide local excision with or without lymph node biopsy or dissection to radiation therapy with chemo- or immunotherapy. Overall survival varies by diagnosis.

Sun Protection Outreach Teaching by Students (SPOTS)-Evaluating the Efficacy of Skin Cancer Prevention Education for Adolescents.

BACKGROUND: The Sun Protection Outreach Teaching by Students (SPOTS) program addresses an unmet need by training medical students to teach adolescents about skin cancer prevention and early detection. OBJECTIVE: To measure (1) changes in adolescents' knowledge, attitudes, and behaviors regarding sun protection and (2) the impact on medical students' confidence in skin cancer preventive counseling. METHODS: Pre-SPOTS and 1-month post-SPOTS program surveys were completed by adolescent participants and medical student instructors. RESULTS: Amongst adolescent students, analysis of 1,142 pre-program surveys and 618 post-program surveys revealed statistically significant improvements in knowledge, attitudes, and behaviors. Among the favorable results, 26%, 41%, and 20% improvements over baseline were observed in SPF knowledge, preference for natural untanned skin, and intent to wear sunscreen, respectively (p < .001). One-third of adolescents reported having tried to increase sunscreen use. Amongst medical students, analysis of 78 pre-teaching and 74 post-teaching surveys revealed an increase in feeling "very confident" in counseling patients, from 23% pre-teaching to 82% post-teaching (p < .001). CONCLUSION: SPOTS demonstrated a dual benefit to adolescents and medical students. The program is available for dermatologists to implement in their communities.

Update in Soft-Tissue Filler-Associated Blindness.

BACKGROUND: Soft-tissue filler administration is an increasingly popular minimally invasive cosmetic procedure. Simultaneously, there have been a greater number of adverse events reported, including the devastating complication of blindness. OBJECTIVE: To report cases of filler-related blindness published since 2015. MATERIALS AND METHODS: The Ovid MEDLINE database was searched from January 1, 2015, to August 1, 2018, using a previously described Boolean string. RESULTS: Sixty new cases of filler blindness were identified. The most common type of filler reported was hyaluronic acid (HA) (N = 42, 70.0%), followed by autologous fat (N = 7, 11.7%), and calcium hydroxyapatite (CaHA) (N = 7, 11.7%). The most common injection locations were the nose (N = 33, 55.0%), glabella (N = 21, 35.0%), and forehead (N = 11, 18.3%). Ten cases reported vision restoration (16.7%). Four of the successful cases involved hyaluronidase administration, including 1 retrobulbar hyaluronidase injection. CONCLUSION: Since 2015, there have been 60 newly reported cases of soft-tissue filler blindness. Most recent cases have occurred with HA, which is a shift from previous reports. In HA cases, hyaluronidase injection may be successful in restoring vision if administered promptly. It is imperative for providers to be familiar with strategies for managing soft-tissue filler blindness.

Squamous Cell Carcinoma of the Hand: A Retrospective Study in Immunosuppressed and Immunocompetent Individuals.

BACKGROUND: Cutaneous squamous cell carcinoma (SCC) of the hand presents a treatment challenge because of the anatomical complexity of this location. Immunosuppressed patients are disproportionately affected by cutaneous SCC. Existing data on SCC of the hand are primarily presented in the orthopedic literature, and may thus be affected by referral bias. OBJECTIVE: Characterization of epidemiology and treatment outcomes for hand versus nonhand cutaneous SCC in immunosuppressed versus immunocompetent patients, across all clinical departments. MATERIALS AND METHODS: Single-institution retrospective cohort study of cutaneous SCC evaluated over 3 years and hand SCC over an additional 5 years. RESULTS: A cohort of 522 hand SCC cases (1,746 total SCC) was ascertained among 1,064 patients, of whom 175 were immunosuppressed. Occurrence on the hand was more common for SCC arising in immunosuppressed versus immunocompetent patients (38% vs 24% of cases respectively). Hand SCC cases demonstrated balanced laterality and comparable spectra of differentiation regardless of immunosuppression. No cases of hand SCC metastasis were observed over greater than 2 years' mean follow-up, and digital amputation was only required in approximately 1% of hand SCCs. CONCLUSION: In our cohort, assessment of hand SCC across all clinical departments suggests more favorable prognosis than reflected in the previous literature.

Postoperative Infections in Dermatologic Surgery: The Role of Wound Cultures.

BACKGROUND: Dermatologic surgery is associated with low postoperative infection rates, averaging from approximately 1% to 4.25%. Often, postoperative infections are treated empirically based on clinical diagnosis of infection, given it can take 48 to 72 hours for a wound culture to identify a pathogen. OBJECTIVE: We aimed to evaluate the efficacy of empiric antibiotics in dermatologic surgery postoperative infections and if wound cultures change postoperative antibiotic therapy. METHODS: A 7-center, retrospective analysis of postoperative infections, with culture data, in dermatologic surgery patients was performed. RESULTS: Of 91 cases of clinically diagnosed postoperative infection, 82.4% (n = 75) were successfully treated with empiric oral antibiotics (95% confidence interval [0.73-0.89], p < .0001). In 16 (17.6%) cases, initial empiric antibiotics were unsuccessful, and wound culture results altered antibiotic therapy in 9 cases (9.9%) with 6 (6.6%) of these cases requiring additional coverage for methicillin-resistant Staphylococcus aureus (MRSA). CONCLUSION: Empiric antibiotic treatment is usually appropriate for patients with postoperative surgical-site infections with wound cultures altering antibiotic management in a minority of cases. When empiric antibiotics fail, lack of MRSA coverage is usually the cause; therefore, providers should be aware of local MRSA prevalence and susceptibilities.

Sebaceous carcinoma: evidence-based clinical practice guidelines.

Sebaceous carcinoma usually occurs in adults older than 60 years, on the eyelid, head and neck, and trunk. In this Review, we present clinical care recommendations for sebaceous carcinoma, which were developed as a result of an expert panel evaluation of the findings of a systematic review. Key conclusions were drawn and recommendations made for diagnosis, first-line treatment, radiotherapy, and post-treatment care. For diagnosis, we concluded that deep biopsy is often required; furthermore, differential diagnoses that mimic the condition can be excluded with special histological stains. For treatment, the recommended first-line therapy is surgical removal, followed by margin assessment of the peripheral and deep tissue edges; conjunctival mapping biopsies can facilitate surgical planning. Radiotherapy can be considered for cases with nerve or lymph node involvement, and as the primary treatment in patients who are ineligible for surgery. Post-treatment clinical examination should occur every 6 months for at least 3 years. No specific systemic therapies for advanced disease can be recommended, but targeted therapies and immunotherapies are being developed.

Histopathologic upgrading of nonmelanoma skin cancer at the time of Mohs micrographic surgery: A prospective review.

BACKGROUND: Anecdotal experience and data from multiple retrospective studies have suggested that a significant percentage of nonmelanoma skin cancers (NMSCs) display an aggressive histologic subtype that is not diagnosed on initial biopsy. OBJECTIVE: To prospectively determine the proportion of NMSCs upgraded at the time of Mohs micrographic surgery (MMS) and examine the surgical parameters of upgraded lesions. METHODS: In this prospective, cross-sectional study, all patients undergoing MMS for NMSC at our institution over the course of 1 year were screened for inclusion. Frozen sections were reviewed independently by 2 fellowship-trained Mohs surgeons. RESULTS: In total, 265 of 2578 (10.3%) tumors displayed a more aggressive skin cancer histologic subtype on frozen-section analysis at the time of surgery than at the initial biopsy. Upgraded tumors required significantly more stages to reach tumor clearance, had a larger postoperative defect size, and more often required complicated repairs than nonupgraded tumors. LIMITATIONS: Single center study, limited time period, and cross-sectional design. CONCLUSION: A significant portion of MMS cases were upgraded at the time of surgery to a more aggressive subtype than that seen at the initial biopsy. Upgraded cases were larger and more surgically challenging than nonupgraded ones. This finding has important implications for primary dermatologists' referral practices and Mohs appropriate use criteria guidelines.

Emerging imaging technologies in dermatology: Part II: Applications and limitations.

Clinical examination is critical for the diagnosis and identification of response to treatment. It is fortunate that technologies are continuing to evolve, enabling augmentation of classical clinical examination with noninvasive imaging modalities. This article discusses emerging technologies with a focus on digital photographic imaging, confocal microscopy, optical coherence tomography, and high-frequency ultrasound, as well as several additional developing modalities. The most readily adopted technologies to date include total-body digital photography and dermoscopy, with some practitioners beginning to use confocal microscopy. In this article, applications and limitations are addressed. For a detailed discussion of the principles involved in these technologies, please refer to the first part of this review article.

Emerging imaging technologies in dermatology: Part I: Basic principles.

Dermatologists rely primarily on clinical examination in combination with histopathology to diagnose conditions; however, clinical examination alone might not be sufficient for accurate diagnosis and skin biopsies have associated morbidity. With continued technological advancement, there are emerging ancillary imaging technologies available to dermatologists to aid in diagnosis and management. This 2-part review article will discuss these emerging technologies including: digital photographic imaging, confocal microscopy, optical coherence tomography, and high-frequency ultrasound, as well as several additional modalities in development. In this first installment, the authors describe the breadth of technologies available and the science behind them. Then, in the second article, the authors discuss the applications and limitations of these technologies and future directions.

Atypical Fibroxanthoma: The Washington University Experience.

BACKGROUND: Atypical fibroxanthoma (AFX) is a rare dermal neoplasm typically occurring on sun-exposed skin in the elderly. As AFX remains a diagnosis of exclusion, updated characterization and treatment assessments are necessary to support informed diagnosis and management. OBJECTIVE: Characterization of contemporary AFX and surgical outcomes by Mohs micrographic surgery (MMS) and conventional local excision (LE). METHODS: Retrospective cohort analysis of all cases of AFX at our institution from January 2000 through July 2016. RESULTS: Among 75 cases with median age at diagnosis 73 years, most occurred on the head and neck (68) independent of age. Most treated cases (42) underwent MMS alone, with median tissue removal greater for LE (2.6 cm, 4.5 cm) than MMS (0.6 cm, 1.2 cm). Over a median 26 months of follow-up, 6 recurrences were observed among 50 cases, with metastases in 2 cases. Intent-to-treat recurrence rates were 3.4% for MMS and 25% for LE. One nonrecurrent and 2 recurrent cases received revised diagnoses after initial treatment, yielding a true recurrence rate of 8.5%. CONCLUSION: Despite diagnostic confounding by similar pathologies, surgical treatment of AFX remains effective. Tissue-sparing resection by MMS affords the potential for cosmetic and reconstructive advantage, without compromising recurrence compared with conventional excision.

Clinical Characteristics of Basal Cell Carcinoma in African Americans: A 10-Year Retrospective Review at a Single Academic Institution.

BACKGROUND: Basal cell carcinoma (BCC) is an uncommon diagnosis in African Americans, and as a result, there is a limited amount of data available. OBJECTIVE: We sought to describe the clinical characteristics of BCC in African Americans treated with Mohs micrographic surgery (MMS). METHODS: We performed a retrospective case series in an ambulatory referral center at a single academic institution from 2007 to 2017 to characterize BCCs in African Americans treated with MMS. RESULTS: A total of 17 patients, who identified as black or African American, with 18 BCCs were included for analysis. Patients were predominantly female (82%) with a mean age at diagnosis of 61 years. Seventy-eight percent of tumors were located in the head and neck region with 50% of BCCs located in high-risk areas. The average preoperative and postoperative defect size was 1.78 and 5.90 cm, respectively, with a mean number of 2.2 Mohs stages required for tumor clearance. One patient had Gorlin syndrome. CONCLUSION: The presented retrospective review adds to limited available reported studies regarding BCC in African Americans to potentially aid in early recognition of these tumors.