Long-term use of spironolactone for acne in women: A case series of 403 patients.

BACKGROUND: There are limited data regarding the long-term outcomes of spironolactone use for women with acne and its effect on truncal acne. OBJECTIVE: To comprehensively describe outcomes of patients treated with spironolactone in routine clinical practice, including long-term outcomes. METHODS: We performed a retrospective case series of 403 adult women treated for acne with spironolactone at an academic medical center between 2008 and 2019. Rates of objective, as assessed by Comprehensive Acne Severity Scale scores, and subjective acne clearance were evaluated, as well as rates of treatment discontinuation, dosage changes, and drug survival. Logistic regression was used to assess for association between incidence of menstrual adverse effects and combined oral contraceptive use. RESULTS: As evaluated by Comprehensive Acne Severity Scale scores, at the first follow-up, 75.5%, 84.0%, and 80.2% of patients with available data had reduction or complete clearance of acne on the face, chest, and back, respectively. The mean drug survival was 470.7 days. Menstrual adverse effects were less common among those using combined oral contraception (odds ratio, 0.23; 95% confidence interval, 0.11-0.50). LIMITATIONS: This study was conducted at a single academic medical center. CONCLUSIONS: Spironolactone improves clinical outcomes and is well tolerated for many adult women with acne using it for an extended duration.

Approaches to limit systemic antibiotic use in acne: Systemic alternatives, emerging topical therapies, dietary modification, and laser and light-based treatments.

Acne is one of the most common diseases worldwide and affects ∼50 million individuals in the United States. Oral antibiotics are the most common systemic agent prescribed for the treatment of acne. However, their use might be associated with a variety of adverse outcomes including bacterial resistance and disruption of the microbiome. As a result, multiple treatment guidelines call for limiting the use of oral antibiotics in the treatment of acne, although actual prescribing often does not follow these guidelines. In this review, the rationale for concerns regarding the use of oral antibiotics for the management of acne is reviewed. In addition, we will discuss our approach to complying with the intent of the guidelines, with a focus on novel topical agents, dietary modification, laser and light-based modalities, and systemic medications, such as spironolactone, combined oral contraceptives, and oral isotretinoin.

Neutrophilic dermatoses: Pathogenesis, Sweet syndrome, neutrophilic eccrine hidradenitis, and Behçet disease.

Neutrophilic dermatoses are a heterogeneous group of inflammatory skin disorders that present with unique clinical features but are unified by the presence of a sterile, predominantly neutrophilic infiltrate on histopathology. The morphology of cutaneous lesions associated with these disorders is heterogeneous, which renders diagnosis challenging. Moreover, a thorough evaluation is required to exclude diseases that mimic these disorders and to diagnose potential associated infectious, inflammatory, and neoplastic processes. While some neutrophilic dermatoses may resolve spontaneously, most require treatment to achieve remission. Delays in diagnosis and treatment can lead to significant patient morbidity and even mortality. Therapeutic modalities range from systemic corticosteroids to novel biologic agents, and the treatment literature is rapidly expanding. The first article in this continuing medical education series explores the pathogenesis of neutrophilic dermatoses and reviews the epidemiology, clinical and histopathologic features, diagnosis, and management of Sweet syndrome, neutrophilic eccrine hidradenitis, and Behçet disease.

Neutrophilic dermatoses: Pyoderma gangrenosum and other bowel- and arthritis-associated neutrophilic dermatoses.

Neutrophilic dermatoses are a heterogeneous group of inflammatory skin disorders that present with unique clinical features but are unified by the presence of a sterile, predominantly neutrophilic infiltrate on histopathology. The morphology of cutaneous lesions associated with these disorders is heterogeneous, which renders diagnosis challenging. Moreover, a thorough evaluation is required to exclude diseases that mimic these disorders and to diagnose potential associated infectious, inflammatory, and neoplastic processes. While some neutrophilic dermatoses may resolve spontaneously, most require treatment to achieve remission. Delays in diagnosis and treatment can lead to significant patient morbidity and even mortality. Therapeutic modalities range from systemic corticosteroids to novel biologic agents, and the treatment literature is rapidly expanding. The second article in this continuing medical education series reviews the epidemiology, clinical characteristics, histopathologic features, diagnosis, and management of pyoderma gangrenosum as well as bowel-associated dermatosis-arthritis syndrome and the arthritis-associated neutrophilic dermatoses rheumatoid neutrophilic dermatitis and adult Still disease.

Sweet syndrome in patients with and without malignancy: A retrospective analysis of 83 patients from a tertiary academic referral center.

BACKGROUND: Sweet syndrome is a neutrophilic dermatosis that may be categorized into classic, malignancy-associated, and drug-induced subtypes. Few studies have systematically analyzed this rare disorder. OBJECTIVE: To describe the clinicopathologic characteristics and treatment of Sweet syndrome and identify characteristics associated with concurrent malignancy. METHODS: We retrospectively reviewed patients with Sweet syndrome at the University of Pennsylvania from 2005 to 2015. RESULTS: We identified 83 patients (mean age, 57 years; 51% male) with Sweet syndrome: 30% with the classic form, 44% with the malignancy-associated form, 24% with the drug-induced form in the setting of malignancy, and 2% with the drug-induced form. Acute myeloid leukemia was the most common malignancy (in 24 of 83 patients [29%]). Filgrastim was the most common medication (used in 8 of 83 patients [10%]). Leukopenia (P < .001), anemia (P = .002), thrombocytopenia (P < .001), absence of arthralgia (P < .001), and histiocytoid or subcutaneous histopathology (P = .024) were associated with malignancy (χ2 test). LIMITATIONS: This was a retrospective study that represents patients from a single tertiary academic referral center, which may limit its generalizability to other settings. CONCLUSION: When caring for patients with Sweet syndrome, dermatologists should be aware of the potential association of leukopenia, anemia, thrombocytopenia, absence of arthralgia, and histiocytoid or subcutaneous histopathology with malignancy.

Trends in prescribing behavior of systemic agents used in the treatment of acne among dermatologists and nondermatologists: A retrospective analysis, 2004-2013.

BACKGROUND: Despite recommendations to limit the use of oral antibiotics and increasing support for hormonal agents in the treatment of acne, it is unclear whether there have been any significant changes in practice patterns. OBJECTIVE: To characterize changes in prescribing behavior for systemic agents in the treatment of acne in the United States between 2004 and 2013. METHODS: We conducted a retrospective analysis using the OptumInsight Clinformatics DataMart (Optum, Eden Prairie, MN). RESULTS: The number of courses of spironolactone prescribed per 100 female patients being managed for acne by dermatologists and nondermatologists increased from 2.08 to 8.13 and from 1.43 to 4.09, respectively. The median duration of therapy with oral antibiotics was 126 and 129 days among patients managed by dermatologists and nondermatologists, respectively, and did not change significantly over the study period. LIMITATIONS: The OptumInsight Clinformatics DataMart lacks information on acne severity and clinical outcomes. CONCLUSIONS: Additional work to identify patients who would benefit most from alternative therapies such as spironolactone, oral contraceptives, or isotretinoin represents a potential opportunity to improve the care of patients with acne.

BAP1: case report and insight into a novel tumor suppressor.

BACKGROUND: BRCA1-Associated-Protein 1 (BAP1) is a dynamic tumor suppressor which, when mutated, has been associated with an increased risk of uveal melanoma, cutaneous melanoma, mesothelioma, and several other cancers. Germline BAP1 mutations have been extensively studied, where they have been found to cause hereditary cancer susceptibility. However, their sporadic counterparts, tumors that display a loss of BAP1 expression due to somatically arising mutations in the BAP1 gene, remain a poorly described entity. CASE PRESENTATION: Here we present the case of a 49-year-old female who presented with an asymptomatic dome-shaped pink papule on the dorsal foot which was found on biopsy to be deficient in the BAP1 tumor suppressor. While the patient's family history did not suggest the presence of a familial cancer syndrome, germline genetic testing was performed and was negative. The patient underwent surgical excision of this sporadically appearing "BAPoma" by Mohs surgery. CONCLUSIONS: Given the relatively banal clinical appearance of these dome-shaped neoplasms, sporadic BAPomas may often be overlooked by clinicians and dermatologists. In addition to providing a representative case, here we also provide a synopsis of the current understanding of these neoplasms, both in terms of the histopathological features, as well as the molecular mechanisms underlying BAP1 function and its ability to prevent tumorigenesis.

Impact of store-and-forward (SAF) teledermatology on outpatient dermatologic care: A prospective study in an underserved urban primary care setting.

BACKGROUND: The clinical value of teledermatology in the primary care setting remains relatively unknown. OBJECTIVE: We sought to determine the impact of teledermatology on outpatient diagnosis, management, and access to dermatologic care in a resource-poor primary care setting. METHODS: We performed a prospective study of store-and-forward teledermatology consults submitted between January and November 2013 from 11 underserved clinics in Philadelphia to the University of Pennsylvania using mobile devices and the Internet. We assessed diagnostic and management concordance between primary care providers and dermatologists, time to consult completion, anticipated level of dermatology input in the absence of teledermatology, and number of consults managed with teledermatology alone. RESULTS: The study included 196 consults encompassing 206 dermatologic conditions. Diagnoses and management plans of primary care providers and dermatologists were fully concordant for 22% and 23% of conditions, respectively. The median time to consult completion was 14 (interquartile range 3-28) hours. At least 61% of consults would not otherwise have received dermatology input, and 77% of consults were managed with teledermatology alone. LIMITATIONS: Lack of a diagnostic gold standard, limited patient follow-up, and uncertain generalizability are limitations. CONCLUSION: Teledermatology is an innovative and impactful modality for delivering dermatologic care to outpatients in resource-poor primary care settings.

Cutaneous metastases from visceral malignancies mimicking interstitial granulomatous processes: a report of 3 cases.

There are multiple clinical and histopathologic presentations of cutaneous metastases. We report 3 cases of visceral malignancies metastasizing to the skin and histopathologically mimicking interstitial granulomatous processes, including granuloma annulare and interstitial granulomatous dermatitis. Histopathologic examination of skin biopsy specimens, from our patients with established histories of cancer, revealed malignant carcinoma-derived cells organized in an interstitial pattern. Of note, some of the lesional cells appeared relatively bland without significant cellular atypia. When examining a skin biopsy of a new lesion from a patient with a history of internal malignancy, it is important to perform immunohistochemical staining to evaluate for metastatic disease, even if the histological pattern is suggestive of a benign interstitial granulomatous process.

Acute and recurrent pustulosis: consolidating uncommon cases of follicular pustulosis induced by UV light and other triggers.

There are a growing number of patients with acute and recurrent pustular reactive dermatitis reported without clear parameters to define the entities. Consolidation of cases under the term acute and recurrent pustulosis (ARP) will aid dermatologists in diagnosing such patients in the future. Objective: Describe the parameters which define acute and recurrent pustulosis and communicate the high predominance for onset in young women based on reported cases. Methods: PubMed literature search for reports of recurrent follicularly centered neutrophilic eruptions. Results: According to the clinical characteristics of ARP, 23 patients were identified from prior reports. Interestingly, 20 out of 23 patients were women with a high predominance in early adulthood. Limitations: This is an understudied and underreported clinical entity. Therefore, limitations include availability of case reports and lack of prior research available on PubMed. Conclusion: ARP is defined as follicular pustules that occur and remit without treatment and within a week of an identifiable trigger, predominantly affecting women. Consolidating reports of ARP under clear criteria will aid clinical dermatologists in diagnosing this unreported dermatitis.

Identification of a neutrophil-specific PIK3R1 mutation facilitates targeted treatment in a patient with Sweet syndrome.

BackgroundAcute febrile neutrophilic dermatosis (Sweet syndrome) is a potentially fatal multiorgan inflammatory disease characterized by fever, leukocytosis, and a rash with a neutrophilic infiltrate. The disease pathophysiology remains elusive, and current dogma suggests that Sweet syndrome is a process of reactivity to an unknown antigen. Corticosteroids and steroid-sparing agents remain frontline therapies, but refractory cases pose a clinical challenge.MethodsA 51-year-old woman with multiorgan Sweet syndrome developed serious corticosteroid-related side effects and was refractory to steroid-sparing agents. Blood counts, liver enzymes, and skin histopathology supported the diagnosis. Whole-genome sequencing, transcriptomic profiling, and cellular assays of the patient's skin and neutrophils were performed.ResultsWe identified elevated IL-1 signaling in lesional Sweet syndrome skin caused by a PIK3R1 gain-of-function mutation specifically found in neutrophils. This mutation increased neutrophil migration toward IL-1ß and neutrophil respiratory burst. Targeted treatment of the patient with an IL-1 receptor 1 antagonist resulted in a dramatic therapeutic response and enabled a tapering off of corticosteroids.ConclusionDysregulated PI3K/AKT signaling is the first signaling pathway linked to Sweet syndrome and suggests that this syndrome may be caused by acquired mutations that modulate neutrophil function. Moreover, integration of molecular data across multiple levels identified a distinct subtype within a heterogeneous disease that resulted in a rational and successful clinical intervention. Future patients will benefit from efforts to identify potential mutations. The ability to directly interrogate the diseased skin allows this method to be generalizable to other inflammatory diseases and demonstrates a potential personalized medicine approach for patients with clinically challenging disease.Funding SourcesBerstein Foundation, NIH, Veterans Affairs (VA) Administration, Moseley Foundation, and H.T. Leung Foundation.

AAD/ACMS/ASDSA/ASMS 2012 appropriate use criteria for Mohs micrographic surgery: a report of the American Academy of Dermatology, American College of Mohs Surgery, American Society for Dermatologic Surgery Association, and the American Society for Mohs Surgery.

The appropriate use criteria process synthesizes evidence-based medicine, clinical practice experience, and expert judgment. The American Academy of Dermatology in collaboration with the American College of Mohs Surgery, the American Society for Dermatologic Surgery Association, and the American Society for Mohs Surgery has developed appropriate use criteria for 270 scenarios for which Mohs micrographic surgery (MMS) is frequently considered based on tumor and patient characteristics. This document reflects the rating of appropriateness of MMS for each of these clinical scenarios by a ratings panel in a process based on the appropriateness method developed by the RAND Corp (Santa Monica, CA)/University of California-Los Angeles (RAND/UCLA). At the conclusion of the rating process, consensus was reached for all 270 (100%) scenarios by the Ratings Panel, with 200 (74.07%) deemed as appropriate, 24 (8.89%) as uncertain, and 46 (17.04%) as inappropriate. For the 69 basal cell carcinoma scenarios, 53 were deemed appropriate, 6 uncertain, and 10 inappropriate. For the 143 squamous cell carcinoma scenarios, 102 were deemed appropriate, 7 uncertain, and 34 inappropriate. For the 12 lentigo maligna and melanoma in situ scenarios, 10 were deemed appropriate, 2 uncertain, and 0 inappropriate. For the 46 rare cutaneous malignancies scenarios, 35 were deemed appropriate, 9 uncertain, and 2 inappropriate. These appropriate use criteria have the potential to impact health care delivery, reimbursement policy, and physician decision making on patient selection for MMS, and aim to optimize the use of MMS for scenarios in which the expected clinical benefit is anticipated to be the greatest. In addition, recognition of those scenarios rated as uncertain facilitates an understanding of areas that would benefit from further research. Each clinical scenario identified in this document is crafted for the average patient and not the exception. Thus, the ultimate decision regarding the appropriateness of MMS should be determined by the expertise and clinical experience of the physician.