Perceptions, Utilization, and Cost Assessment of Sebaceous Hyperplasia Treatment Modalities: A Pilot Survey.

BACKGROUND: Sebaceous hyperplasia (SH) is a common, benign but cosmetically bothersome skin condition preferentially affecting older adults. Despite multiple treatment options, there is no universally accepted first-line treatment for SH nor standard pricing for said approaches.  Methods: A survey aimed at evaluating treatment approaches and their respective costs was disseminated on the Orlando Dermatology Aesthetic and Clinical Conference email listserv.  Results: Out of 224 dermatologists who participated in the survey (response rate 9.2%), most treated patients with SH (95.98%). In-office procedures were used more than pharmacologic treatments (P=<0.05). Treatments most used by respondents included electrodesiccation (ED; 83.9%), cryosurgery (35.3%), oral isotretinoin (32.6%), and carbon dioxide (CO2) laser (19.2%). Cryosurgery and ED priced between <$200 to $400. Most reported 1 to 2 sessions to achieve lesion clearance for ED, CO2 laser, and cryosurgery. Twenty-one percent reported 3-4 sessions with cryosurgery. Chemical peels, diode lasers, and photodynamic therapy required between 2-4 sessions. Respondents indicated lesions were most unlikely to recur with ED and CO2 laser. Most dermatologists (86.39%) agreed or strongly agreed that they were exposed to new treatments methods for SH through this survey and 86.49% of dermatologists were interested in learning about treatments employed by others. CONCLUSION: SH is a common issue that presents in the dermatologist's office. These data highlight the perception that ED is the most common approach employed, associated with lower costs, and requiring fewer sessions to achieve resolution. More data is needed and wanted to better determine best practices for the management of SH.J Drugs Dermatol. 2024;23(2):29-37.  doi:10.36849/JDD.7734.

Treating Cutaneous Immune-Related Adverse Events from Immune Checkpoint Blockade.

Immune checkpoint inhibitors (ICPis) have revolutionized outcomes in various advanced malignancies. Therapeutic restoration of a robust T-cell response against malignant cells is also at the root of distinct cutaneous immune-related adverse events (cirAEs). As approved indications for ICPis increase and interdisciplinary collaboration with oncology grows, identifying the most common skin toxicities from ICPis, particularly on melanin-rich skin,1 and understanding treatment strategies are increasingly crucial for dermatologists. This brief review highlights common cirAEs and summarizes the latest evidence for interventions.

Curcumin nanoparticles as a photoprotective adjuvant.

With rising skin cancer rates and interest in preventing photoaging, adjuvants for sunscreens are in high demand. The potential of curcumin has been posited due to its anti-inflammatory, antioxidant and wound healing properties. In prior studies, curcumin decreased UV-induced inflammation, apoptotic changes in human keratinocytes and dermal fibroblasts, and the expression of matrix metalloproteinases. However, curcumin's utility has been hindered by poor aqueous solubility and rapid degradation in vivo. To overcome these limitations, we synthesized curcumin nanoparticles (curc-np), which offer sustained topical delivery and enhanced bioavailability. Curc-np and controls were applied to the skin of BALB/c mice prior to UVB irradiation. Twenty-four hours later, mice pretreated with curc-np showed less erythema, induration and scale compared to controls. Histopathology showed fewer sunburn cells, and TUNEL assay indicated decreased apoptosis in curc-np treated mice. Immunohistochemistry illustrated less p53 expression in skin pretreated with curc-np. Furthermore, cytokine analysis revealed significantly less IL-6 and significantly greater anti-inflammatory IL-10 in skin of curc-np-treated mice as compared to controls. Taken together, our results reinforce curcumin's established anti-inflammatory effects in the skin and highlight its potential as a photoprotective adjuvant when delivered through nanoparticles. Further investigation alongside sunscreens against UV-induced damage is warranted.

Pyoderma Gangrenosum Occurring in the Setting of Hypercortisolism Associated With Adrenocortical Adenoma: A Pathophysiological Paradox.

Pyoderma gangrenosum (PG) is a challenging, rare, ulcerating skin disease characterized by neutrophilic abundance and absence of infection, often associated with systemic diseases. We present a 25-year old previously healthy female with a 1.5-year history of treatment refractory PG. Features of Cushing’s syndrome such as facial plethora, striae, and lipodystrophy were noted on exam, which prompted several studies that ultimately revealed an adrenal adenoma. Following surgical excision of the adenoma, symptoms rapidly resolved and systemic immunosuppressants were discontinued. This rare case highlights the importance that adrenal adenoma and resultant Cushing’s syndrome may be a driver of PG despite the pathophysiologic paradox. J Drugs Dermatol. 2021;20(1):95-97. doi:10.36849/JDD.5566.

Control of systemic inflammation through early nitric oxide supplementation with nitric oxide releasing nanoparticles.

Amelioration of immune overactivity during sepsis is key to restoring hemodynamics, microvascular blood flow, and tissue oxygenation, and in preventing multi-organ dysfunction syndrome. The systemic inflammatory response syndrome that results from sepsis ultimately leads to degradation of the endothelial glycocalyx and subsequently increased vascular leakage. Current fluid resuscitation techniques only transiently improve outcomes in sepsis, and can cause edema. Nitric oxide (NO) treatment for sepsis has shown promise in the past, but implementation is difficult due to the challenges associated with delivery and the transient nature of NO. To address this, we tested the anti-inflammatory efficacy of sustained delivery of exogenous NO using i.v. infused NO releasing nanoparticles (NO-np). The impact of NO-np on microhemodynamics and immune response in a lipopolysaccharide (LPS) induced endotoxemia mouse model was evaluated. NO-np treatment significantly attenuated the pro-inflammatory response by promoting M2 macrophage repolarization, which reduced the presence of pro-inflammatory cytokines in the serum and slowed vascular extravasation. Combined, this resulted in significantly improved microvascular blood flow and 72-h survival of animals treated with NO-np. The results from this study suggest that sustained supplementation of endogenous NO ameliorates and may prevent the morbidities of acute systemic inflammatory conditions. Given that endothelial dysfunction is a common denominator in many acute inflammatory conditions, it is likely that NO enhancement strategies may be useful for the treatment of sepsis and other acute inflammatory insults that trigger severe systemic pro-inflammatory responses and often result in a cytokine storm, as seen in COVID-19.

Is TNF-α Inhibitor-Induced Psoriasiform Dermatitis Always Psoriasiform?

Tumor necrosis factor-α inhibitors (TNFIs) have significantly improved the quality of life for patients with psoriasis and psoriatic arthritis. Despite their beneficial effects, TNFIs have been reported to cause paradoxical 'psoriasiform' eruptions.1 Although this nomenclature has become pervasive in the dermatology lexicon, there is a growing body of literature highlighting the protean clinical presentation of this eruption (Figure 1), which could ultimately lead to a delayed diagnosis.2-5 The diversity of the morphology highlights the importance of identifying key histopathologic characteristics, which to date have not been well-characterized.2

The Influence of Supportive Oncodermatology Interventions on Patient Quality of Life: A Cross-Sectional Survey.

BACKGROUND: Dermatologic adverse events (dAEs) secondary to anticancer treatments reduce patients’ quality of life (QOL) and result in interruptions in anticancer therapy. OBJECTIVE: Determine if a comprehensive supportive oncodermatology program improves patients’ QOL scoring. METHODS: This was a cross-sectional survey of adult cancer patients enrolled in the George Washington University Supportive Oncodermatology Clinic. All patients were above age 18 years and received dermatologic care between May 1, 2017 and November 1, 2019. Fifty-five patents meeting inclusion criteria were invited to complete an online survey with questions adapted from the Dermatology Life Quality Index (DLQI) and Patient Satisfaction Questionnaire (PSQ-18). RESULTS: Survey initiation rate was 61.8% (34/55) and completion rate 88.2% (30/34). Average QOL score prior to treatment was 6.5 (moderate effect on QOL) and 3.8 (small effect) afterwards (P=0.0005; 95% CI -3.9 to -1.). Average satisfaction score was 4.15 ± 0.7 (satisfied). Impact on treatment adherence earned the lowest score (3.67, neutral to satisfied). LIMITATIONS: Recall bias Conclusion: Enrollment was significantly associated with improved QOL. Dermatologic care also resulted in overall satisfied patient outcomes, although many patients were unsure if these dermatologic interventions aided in anticancer treatment adherence, highlighting the need for evidence-based management strategies for dAEs. J Drugs Dermatol. 2020;19(5):  doi:10.36849/JDD.2020.5040.

Spironolactone use does not increase the risk of female breast cancer recurrence: A retrospective analysis.

BACKGROUND: Spironolactone is used off-label for androgenic alopecia because of its ability to arrest hair loss progression and long-term safety profile. However, little is known about the safety of spironolactone in breast cancer (BC) survivors. Because spironolactone has estrogenic effects, there is a theoretical risk for BC recurrence. Given that spironolactone is an important tool in the treatment of alopecia, we investigated whether spironolactone increased risk for BC recurrence. OBJECTIVE: To determine whether spironolactone is associated with increased BC recurrence. METHODS: A retrospective analysis was conducted using the Humana Insurance database. Patients with a history of BC were identified using International Classification of Diseases codes, stratified by spironolactone prescription, and also matched 1:1 using propensity score analysis. Patient characteristics and cancer recurrence rates between both cohorts were compared and analyzed. RESULTS: BC recurrence developed in 123 patients (16.5%) who were prescribed spironolactone compared with 3649 patients (12.8%) who developed BC recurrence without spironolactone prescribed (P = .004). After propensity matching, adjusted Cox regression analysis showed no association between spironolactone and increased BC recurrence (adjusted hazard ratio, 0.966; 95% confidence interval, 0.807-1.156; P = .953). LIMITATIONS: Retrospective study. CONCLUSION: Spironolactone was not independently associated with increased BC recurrence and may be considered for the treatment of alopecia in BC survivors.

Hydrogen Peroxide Topical Solution, 40% (w/w) for the Treatment of Seborrheic Keratoses: A Review

HP40 (Eskata™) is a stabilized, topical solution of 40% hydrogen peroxide (H2O2) packaged in an applicator pen that is US FDA-approved to treat seborrheic keratoses (SKs). By harnessing the oxidative capabilities of H2O2 , 1-2 treatments with HP40 produced a higher rate of clearance of four SKs per patient compared to vehicle in two phase 3 trials. The clearance rate was higher for the face than the trunk and extremities. Similarly, the risks of pigmentary changes and scarring from HP40 were lower for the face than other locations. Further, based on an ex vivo study, HP40 may be less cytotoxic to melanocytes than cryotherapy, but clinical trials comparing these therapies are needed. Limitations of HP40 are its low efficacy and requirement of multiple treatments, which can result in elevated costs. The application can also be time-consuming, though extenders or even staff members can apply it. Therefore, HP40 may be better reserved for the treatment of facial SKs.

A Survey-Based Comparison of Sun Safety Practices in a Representative Cohort of the General Public Versus Attendees of a Skin Cancer Screening

A large proportion of data on photoprotective practices is yielded from free skin cancer screenings. However, the sun safety practices of populations who seek these skin cancer screenings may differ from the general public. To examine differences in skin cancer prevention practices and risk factors, we surveyed pedestrians at six locations in Washington, DC (public group, n=285) and attendees of a free skin cancer screening (screening group, n=144) using an IRB-approved survey. The screening group was older and included more individuals with fair skin than the public group. Respondents from the screening group were significantly more likely to always wear sunscreen, always seeks shade, and always or sometimes wear sun-protective clothing than the public group (P<0.05). To examine whether younger and non-white participants, who were less likely to attend our free screening, have different practices and risk factors than older and white participants, respectively, we compared survey answers for all participants by age and race. White participants were more likely to always or sometimes wear sunscreen and sun-protective clothing than non-white participants (P<0.05). Patients over 61 years were more likely to always seek shade and wear sun-protective clothing than those younger than 31 years (P<0.05). Therefore, free skin cancer screenings need to be better popularized among non-white and younger populations or more effective educational vehicles are needed. J Drugs Dermatol. 2019;18(7):649-653.

A Survey-Based Comparison of Sun Safety Practices in a Representative Cohort of the General Public Versus Attendees of a Skin Cancer Screening

A large proportion of data on photoprotective practices is yielded from free skin cancer screenings. However, the sun safety practices of populations who seek these skin cancer screenings may differ from the general public. To examine differences in skin cancer prevention practices and risk factors, we surveyed pedestrians at six locations in Washington, DC (public group, n=285) and attendees of a free skin cancer screening (screening group, n=144) using an IRB-approved survey. The screening group was older and included more individuals with fair skin than the public group. Respondents from the screening group were significantly more likely to always wear sunscreen, always seeks shade, and always or sometimes wear sun-protective clothing than the public group (P<0.05). To examine whether younger and non-white participants, who were less likely to attend our free screening, have different practices and risk factors than older and white participants, respectively, we compared survey answers for all participants by age and race. White participants were more likely to always or sometimes wear sunscreen and sun-protective clothing than non-white participants (P<0.05). Patients over 61 years were more likely to always seek shade and wear sun-protective clothing than those younger than 31 years (P<0.05). Therefore, free skin cancer screenings need to be better popularized among non-white and younger populations or more effective educational vehicles are needed. J Drugs Dermatol. 2019;18(7):649-653.

Hydrogen peroxide and cutaneous biology: Translational applications, benefits, and risks.

Hydrogen peroxide (H2O2) is an endogenous reactive oxygen species that contributes to oxidative stress directly as a molecular oxidant and indirectly through free radical generation. Topically applied 1% to 45% H2O2 can be used for a range of clinical purposes, which will be reviewed here in addition to its safety. In concentrations from 1% to 6%, H2O2 has antimicrobial properties and can act as a debriding agent through its effervescence, making low-concentration H2O2 useful for wound care. H2O2 has also been shown to promote venous insufficiency ulcer healing, but studies in other wound types are needed. In 1% formulations, H2O2 is used outside the United States to treat acne and has shown efficacy similar to or greater than benzoyl peroxide, with reduced side effects. In a concentration of 40%, H2O2 is US Food and Drug Administration-approved to treat seborrheic keratoses and may cause fewer pigmentary changes than cryotherapy, although elimination often requires 2 to 4 treatments. However, H2O2 should be used with caution, as exposure can cause adverse effects through its oxidant capabilities. Low H2O2 concentrations cause only transient symptoms (blanching and blistering), but exposure to 9% to 45% H2O2 can cause more severe skin damage, including epidermal necrosis leading to erythema and bullae. Overall, H2O2 has numerous therapeutic uses, and novel indications, such as treating actinic keratoses and skin cancers, continue to be explored.

A Review of the Dermatologic Symptoms of Idiopathic Mast Cell Activation Syndrome

Since the first reported cases in 2007, idiopathic mast cell activation syndrome has been increasingly recognized. Understanding of the cutaneous manifestations of this condition is imperative for dermatologists given the substantial clinical heterogeneity in its presentation and high estimated prevalence. A review of PubMed® and SCOPUS® databases was performed in order to investigate the most common dermatologic manifestations of idiopathic mast cell activation syndrome. Evidence to date suggests that flushing, pruritus, and clotting dysfunction or bleeding disorder are the most frequently observed dermatologic symptoms in idiopathic mast cell activation syndrome, while dermatographism has been identified as a common finding in patients as well. Mast cell activation syndromes have also been linked to connective tissue disorders, including an Ehlers-Danlos Syndrome-like phenotype possibly mediated by matrix metalloproteinases and tryptase released by mast cells. Current literature regarding dermatologic manifestations of idiopathic mast cell activation syndrome is limited by the heterogeneity of studies including clinical descriptions, inconsistency of diagnostic criteria implemented, and a paucity of literature available. This work provides a guide for dermatologists to strengthen diagnostic acuity for idiopathic mast cell activation syndrome, therefore contributing toward a goal of helping patients to receive timely, effective, and targeted therapy. J Drugs Dermatol. 2019;18(2):162-168.

Managing Seborrheic Keratosis: Evolving Strategies and Optimal Therapeutic Outcomes.

Seborrheic keratosis (SK) is the most common skin tumor seen by dermatologists in everyday practice. Although the lesions are mostly benign, many patients still elect to have asymptomatic SK removed. The historical standards of treatment are cryosurgery and electrocautery, two surgical options that are effective at lesion removal but have high rates of postoperative adverse events such as treatment-site scarring and pigmentary alterations. The cosmetic outcomes of SK treatment modalities are of keen interest to dermatologists, as the American population becomes increasingly more diverse. In this article, the inclusion of darker Fitzpatrick skin types into clinical studies investigating post-treatment side effects of SK therapy is reviewed. The recent approval of a 40% hydrogen peroxide topical formulation is discussed in light of these issues, and several non-invasive topical treatments that optimize cosmetic outcomes of SK lesion removal are highlighted. Finally, treatment strategies aimed at reducing cost and minimizing the burden of adverse sequelae are provided. J Drugs Dermatol. 2018;17(9):933-940.

Eruptive Sebaceous Hyperplasia: A Rare Consequence of Systemic Corticosteroids.

BACKGROUND: Eruptive sebaceous hyperplasia is a rare and poorly understood consequence of immunosuppression, most commonly with cyclosporine, following organ transplantation. To date, there have been no reports documenting eruptive sebaceous hyperplasia associated with the utilization of immunosuppression outside of this clinical scenario. OBSERVATION: A 43-year-old Caucasian male with a significant history for Crohn's disease presented with the sudden appearance of multiple asymptomatic growths now present for several weeks. They were first noted two weeks following the initiation of a slow prednisone taper prescribed for a recent exacerbation of Crohn's disease. Skin examination revealed multiple 1-3mm, soft, skin colored to yellowish, dome-shaped, umbilicated papules on the forehead and the bilateral lateral/malar cheeks, clinically suggestive and confirmed histologically as sebaceous hyperplasia. CONCLUSION: To our knowledge, this is the first reported case of eruptive sebaceous hyperplasia secondary to the use of prednisone in a patient with Crohn's disease. This case brings awareness to the unique side effect of prednisone induced sebaceous hyperplasia, and demonstrates the importance of educating patients with Crohn's disease of this potential side effect when prescribing this medication.

J Drugs Dermatol. 2018;17(1):118-120.

Nanoparticle-Encapsulated Doxorubicin Demonstrates Superior Tumor Cell Kill in Triple Negative Breast Cancer Subtypes Intrinsically Resistant to Doxorubicin.

The effect of size and release kinetics of doxorubicin-nanoparticles on anti-tumor efficacy was evaluated in a panel of human cancer cell lines, including triple-negative breast cancer (TNBC) cells that frequently demonstrate resistance to doxorubicin. Different nano-formulations of sol-gel-based Doxorubicin containing nanoparticles were synthesized. Increased cell kill in chemoreffactory triple-negative breast cancer cells was associated with the smallest size of nanoparticles and the slowest release of Dox. Modeling of dose-response parameters in Dox-sensitive versus Dox-resistant lines demonstrated increased EMax and area under the curve in Dox-resistant mesenchymal TNBC cells, implying potentially favorable activity in this molecular subtype of breast cancer. Mesenchymal TNBC cells demonstrated a high rate of fluorescent bead uptake suggestive of increased endocytosis, which may partially account for the enhanced efficacy of Dox-np in this subtype. Thus, manipulation of size and release kinetics of this nanoparticle platform is associated with enhanced dose-response metrics and tumor cell kill in therapeutically recalcitrant TNBC cell models. This platform is easily customizable and warrants further exploration.

Managing Seborrheic Keratoses: Evolving Strategies for Optimizing Patient Outcomes.

The seborrheic keratosis is the most common benign skin tumor of middle-aged and elderly adults, affecting nearly 83 million individuals in the US alone. Although these are benign lesions, many patients still undergo some form of treatment. Clinicians are frequently presented with a challenge when determining whether to remove a seborrheic keratosis, and which treatment modality to use when doing so. The most commonly used method of removal is cryotherapy, however there are numerous other options that can be employed with varying degrees of efficacy. In this article, we highlight the use of topical keratolytics, vitamin D analogues, and lasers, to name a few. We also address potential side effects associated with these treatment options, as well as discuss patients' preferences and concerns. We conclude with the most recent advances in topical treatments currently under clinical investigation, and offer treatment strategies aimed at maximizing patient satisfaction.

J Drugs Dermatol. 2017;16(11):1064-1068.