2020 IDEOM Annual Meeting: Actinic Keratosis Stakeholders Survey Identifies Gaps in Research and Care.

This is a report of the survey results from the International Dermatology Outcome Measures (IDEOM) actinic keratosis (AK) workgroup. The purpose of the survey was to compile a list of gaps within AK care and management that require refinement. The results were discussed at the IDEOM annual meeting held virtually on October 23–24, 2020. This built a framework with which the AK workgroup, which consisted of physicians, patients, and pharmaceutical scientists, discussed at length in their breakout session at the meeting. The electronic survey was distributed to patients, pharmaceutical scientists, and leading physician experts in the field via email on September 22, 2020, with a deadline of October 2, 2020. The survey consisted of three open-ended prompts concerning key gaps and/or unmet needs in (1) the care of AKs, (2) outcome measurement of AKs in clinical trials and, (3) the measurement of AKs in clinical practice. The results were qualitative, with a response rate of 47%. Responses included reform of outcome measures for clinical trials, a methodology for evaluating the efficacy of preventative measures, and a comparison of treatments to establish a treatment protocol, among other efforts. This paper will also provide a brief overview of the current state of the AK outcome measures, emphasizing the heterogeneity of the measures and detailing the AK workgroup's future efforts to create a reliable and applicable core outcome measure set. J Drugs Dermatol. 2022;21(2):128-134. doi:10.36849/JDD.6360.

Total Margin-Controlled Excision is Superior to Standard Excision for Keratinocyte Carcinoma on the Nose: A Veterans Affairs Nested Cohort Study.

BACKGROUND: Keratinocyte carcinoma (KC), including basal and squamous cell carcinoma, is the most common human malignancy. Limited real-world data have compared surgical outcome or cost between total margin-controlled excision (TMCE) and standard excision (SE), the two most common treatments for invasive KC. We compared reconstruction, margin status, and cost between TMCE and SE for KC on the nose at a Veterans Affairs (VA) healthcare system. METHODS: Randomly selected primary KCs on the nose ≤3 cm that were confined to soft tissue, without nerve or lymphovascular invasion, and treated with SE or TMCE between 2000 and 2010, were assessed. Utilization of flap or graft reconstruction and margin status following all surgical attempts were recorded. Costs were based on Current Procedural Terminology codes standardized to 2019 Medicare payments. RESULTS: Overall, 148 cases were included in each treatment group. Baseline characteristics were similar between groups, although SE tumor median diameter was 1 mm larger. SE was associated with increased utilization of flap or graft reconstruction (odds ratio 2.05, 95% confidence interval 1.16-3.59, p = 0.01). Positive margins were present in 24% of SEs initially and remained positive after the final recorded excision in 9% of cases. No positive final margins were noted in TMCE cases. SE cost per tumor was significantly higher than TMCE ($429.03 ± 143.55; p = 0.003). CONCLUSIONS: Surgical management of KC with SE is associated with increased reconstruction complexity, a significant risk of positive margins, and higher cost compared with TMCE. The 23% risk of positive margins supports National Comprehensive Cancer Network guidelines for the treatment of high-risk KC with TMCE, unless delayed reconstruction is employed.

Sulfasalazine-induced generalized vitiligo in a patient with dermatitis herpetiformis and celiac disease.

Vitiligo is an acquired idiopathic pigmentary skin disorder characterized by the development of white macules and patches due to the loss of functioning melanocytes. In this report, we describe a case of a patient with a longstanding history of dermatitis herpetiformis (DH) and celiac disease that developed rapidly progressing, biopsy-confirmed generalized vitiligo after 11 months of treatment with anti-inflammatory medication sulfasalazine, prescribed for the patient's DH. To the best of our knowledge, this is the first case report which has demonstrated the possible biochemical pathways, triggered by sulfasalazine, in the development of vitiligo.

Rapid, economical healing of two large Mohs surgery wounds with transforming powder dressing.

As dermatology has evolved into a medical/surgical specialty, care for the patient with difficult postsurgical wounds has emerged as an aspect of practice for an increasing number of dermatologists. Here, we present a transforming powder dressing which yielded fast, cost-effective healing of two such wounds, while also relieving the patient and his family of any wound care responsibility.

Necrotizing Granulomas in a Patient With Psoriasis and Sarcoidosis After Adalimumab-Medication-Induced Reaction or Reactivation of Latent Disease?

In this report, we describe a case of a patient with a clinical history of systemic sarcoidosis and psoriasis who developed biopsy-confirmed perforating and necrotizing cutaneous granulomas after 12 months of treatment with adalimumab, a tumor necrosis factor-alpha-inhibiting, anti-inflammatory, biologic medication, prescribed for the patient's psoriasis. Although rare reports of a "sarcoidosis-like" reaction associated with select tumor necrosis factor-alpha agents exist, to the best of our knowledge, perforating and necrotizing cutaneous granulomas after treatment with adalimumab has not been previously reported. Given the patient's history of systemic sarcoidosis, the differential diagnosis includes reactivation of latent sarcoidosis with adalimumab as a trigger.

Sterile pustulosis as a rare side effect of fractional bipolar radiofrequency device: a case report.

Fractional bipolar radiofrequency technology is associated with minimal downtime and rare side effects and become an increasingly popular tool in aesthetic dermatology practices. There is limited damage to the epidermis, and side effects such as post-inflammatory hypo/hyperpigmentation are rare. Transient erythema, edema, crusting, and persistent inflammatory papules have been previously reported. We report a rare case of sterile follicular pustulosis following treatment with bipolar fractional radiofrequency (eTwo technology). To the best of our knowledge, this unusual side effect has never been reported.

Detection of High-Risk Histologic Features and Tumor Upstaging of Nonmelanoma Skin Cancers on Debulk Analysis: A Quantitative Systematic Review.

BACKGROUND: Histologic analysis of tumor debulks from Mohs micrographic surgery (MMS) or wide local excision may lead to the detection of adverse features missed on initial biopsy. OBJECTIVE: Determine the incidence of (1) high-risk features on debulk analysis compared with initial biopsy and (2) upstaging of tumors on debulk analysis according to the American Joint Committee of Cancer-7th Edition (AJCC-7) and the Brigham and Women's Alternative (BWH) staging criteria. MATERIALS AND METHODS: A comprehensive search strategy using PubMed/MEDLINE, Web of Science, and EMBASE was conducted to identify articles published from 1960 to present that detail histology of initial biopsy and debulked tumor. RESULTS: Fourteen studies, encompassing 2,565 cases of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) were included in the data extraction process. BCCs (30.9%) were reclassified from a low-risk histologic subtype to a high-risk subtype on debulk analysis (p < .001). Cases with perineural invasion (89.4%) were detected on debulk analysis. SCC tumors (9.1% and 11.1%) were upstaged according to the AJCC-7 and BWH Alternative criteria, respectively. Ninety percent of high-risk BWH T2b SCCs were inaccurately staged lower on initial biopsy. CONCLUSION: Tumor debulk analysis in MMS may aid in the identification of additional high-risk features, thereby improving staging accuracy, treatment decisions and patient outcomes.

Ablative Fractional Laser-Assisted Topical Fluorouracil for the Treatment of Superficial Basal Cell Carcinoma and Squamous Cell Carcinoma In Situ: A Follow-Up Study.

BACKGROUND: The authors previously reported the safety and short-term efficacy of ablative fractional laser (AFXL)-assisted delivery of topical fluorouracil in the treatment of superficial basal cell carcinoma (sBCC) and squamous cell carcinoma in situ (SCCis). OBJECTIVE: This follow-up study was conducted to assess whether tumor clearance was sustained in this cohort of patients at >9 months post-treatment. METHODS: Thirty primary sBCC or SCCis <2 cm on the trunk or extremities were treated with AFXL and a single application of topical 5-fluorouracil 5% under occlusion for 7 days. Among the 26 patients who achieved tumor clearance at 4 to 8 weeks post-treatment, 20 patients presented for this follow-up study and underwent shave biopsy to confirm histologic clearance. Mean follow-up time was 15 months. RESULTS: Considering those who had persistent tumor at 4 to 8 weeks post-treatment and those who presented for follow-up at >9 months post-treatment, overall treatment success was 79% (95% confidence interval: 67%-96%), with 92% (11/12) for SCCis and 67% (8/12) for sBCC. Neither the tumor location nor size significantly impacted treatment outcome (p = .96 and 0.87, respectively). CONCLUSION: Ablative fractional laser-assisted topical fluorouracil is a reasonable noninvasive treatment option for primary SCCis and sBCC, especially for lesions located in areas where self-application is not possible, or when clinician-administered therapy is preferred.

Medical therapies for melasma.

Melasma is a common malady affecting all races with a higher incidence in Hispanics, Middle Eastern, Asians, and African origin females (Fitzpatrick skin phototypes III-V). Women are affected much more often than men. Melasma remains a significant cause of cosmetic morbidity and psychosocial embarrassment affecting quality of life necessitating effective and reliable treatment. Unfortunately, treatment remains unsatisfactory due to limited efficacy, adverse effects, and relapses after stopping treatment. Although chemical peels, laser and light therapies and dermabrasion may have utility, the evidence available for their efficacy is limited and they often cause post-inflammatory hyperpigmentation, particularly in individuals with darker skin types. Medical therapies remain mainstay in the management of melasma. The triple combination, hydroquinone 4%, tretinoin 0.05%, and fluocinolone acetonide 0.01% (Triluma, Galderma, Ft. Worth Texas, often modified incorporating different corticosteroids) remains the only US FDA-approved treatment for melasma and is the gold standard due its demonstrated efficacy across ethnicities. Oral tranexamic acid alone or in combination with other modalities has also shown significant efficacy. Several cosmeceuticals and botanical extracts used as skin lightening agents have been demonstrated to be useful. Physical sunscreens containing zinc oxide, iron oxide, titanium dioxide, and silicones provide photoprotective and camouflage effect. We propose that a multimodality approach to the treatment of melasma is the most effective treatment approach. This review is focused on the medical therapies for melasma.

Pulsed dye laser as a novel non-surgical treatment for basal cell carcinomas: response and follow up 12-21 months after treatment.

BACKGROUND AND OBJECTIVE: We showed previously that pulsed dye laser (PDL) is a potentially effective therapy for BCCs <15 mm on trunk and extremities. To follow-up, we conducted a study based on optimized parameters and expanded the duration of the study to at least 1 year after treatment. MATERIALS AND METHODS: Fourteen patients with 20 biopsy-proven BCCs on trunk and extremities, 8-35 mm in diameter, were treated. Each BCC received four consecutive PDL treatments at 3-4 week intervals. A 4 mm margin of clinically normal skin was also treated. Standardized photography was performed prior to each treatment and follow up visit. Patients were asked to consent for standard excision or at least scouting biopsies after treatment completion. RESULTS: Complete clinical response was seen with 19 of 20 treated BCCs, regardless of size and histologic subtype. One did not respond completely to therapy. All remaining 19 BCCs were followed between 12 and 21 months (median = 18 months) after the last PDL treatment. Of these 19 BCCs, only one recurred at 17 months follow up. The remaining 18 BCCs did not show any clinical signs of residual or recurrent tumor at 12-21 months follow-up. Overall, 90% (18/20 tumors) of treated BCCs in this study showed no clinical or histologic evidence of BCC more than 12 months after PDL treatment. Additionally, 18/19 (95%) BCCs less than or equal to 17 mm showed no evidence of residual or recurrent tumor clinically or on histology 12-21 months post-laser treatment. CONCLUSIONS: PDL treatment of BCC represents a novel, quick, and relatively non-painful treatment that does not usually produce scar and may represent an alternative treatment for certain types of BCC in the appropriate clinical setting. This study confirms prior findings regarding the efficacy of PDL in the treatment of BCC, with longer follow-up period.

The effect of 595 nm pulsed dye laser on superficial and nodular basal cell carcinomas.

BACKGROUND AND OBJECTIVE: Basal cell carcinomas (BCCs) have supporting vasculature that could serve as a target for 595 nm pulsed dye laser (PDL). The objective of this study was to determine the effect of repeated PDL treatments on BCCs of superficial and nodular subtypes and of varying diameters. STUDY DESIGN/MATERIALS AND METHODS: Twenty biopsy-proven BCCs received four 595 nm PDL treatments at 2-week intervals. The tumor and 4 mm of peripheral skin were treated using a set of previously optimized laser parameters: one pass, 15 J/cm2 energy, 3 ms pulse length, no cooling, and 7 mm spot size with 10% overlap. The treated area was excised and evaluated histologically for residual tumor. Histologic response rates of the PDL treated BCCs were compared with that of non-PDL treated, matched control tumors. RESULTS: Nearly all BCCs <1.5 cm in diameter (n = 12) showed complete response to four PDL treatments (91.7%; n = 11/12) versus 16.7% of controls (n = 2/12, P-value = 0.0003). BCCs > or =1.5 cm in diameter (n = 8) showed a complete response rate of 25% (n = 2/8) versus 0% of controls (n = 0/8, P-value = 0.2). Mean clinical tumor diameter of the complete responders was 1.1 cm (n = 13) versus 2.2 cm (n = 7) for incomplete responders (P-value = 0.005). Tumor histologic types among the complete responders included superficial, nodular, micronodular, and keratinizing. Incompletely responding BCCs showed a significant reduction in tumor burden after PDL treatment, with residual histologic tumor burden ranging from <1% to 29% of the original clinical tumor diameter, compared to 13-68% residual tumor burden for the corresponding controls (P-value = 0.05). CONCLUSIONS: PDL is an effective means of reducing tumor burden in patients with large BCCs and may be an alternative therapy in BCCs <1.5 cm in diameter.

Demographics, Risk Factors, and Incidence of Melanoma in Patients in the New England VA Healthcare system.

INTRODUCTION: A recent study found that the incidence of melanoma and melanoma-related mortality was decreasing in residents of the New England region. However, it is unknown whether this trend is conserved in Veterans of New England who constitute more than 14% of the national Veteran population. Given this, our goal was to analyze the incidence of melanoma in patients of Veteran Integrated Service Network-1 (VISN-1) (geographically consisting of VA health care facilities in Connecticut, Maine, Massachusetts, New Hampshire, Rhode Island, and Vermont) and to calculate an incidence rate ratio (IRR) of melanoma in VISN-1 compared to the general population. Additional goals were to ascertain the risk/susceptibility of this patient population with a view to improve quality of care and outcomes. MATERIALS AND METHODS: Data for 523 cases of melanoma [2000-2011] were obtained from the regional branch of the Veterans Affairs Central Cancer Registry (VACCR) within the geographic area comprising VISN-1. A detailed retrospective chart review was conducted on these cases to gather demographic, risk factor, and clinical practice data. Demographic and incidence data from VISN-1 were compared to the general population via data from Surveillance, Epidemiology and End Results Program (SEER) from the same time period. Person-years (PY) were calculated for both populations to measure IRRs which was further standardized for age and gender. RESULTS: VISN-1 patients were predominantly older (94.26% >50 years), Caucasian (99.43%) males (96.75%). Compared to the general population, VISN-1 patients experienced more invasive lesions defined as stage T1 or greater (4.33% vs. 57.12%, p < 0.001), but reduced melanoma-associated mortality (40.96% vs. 19.05%, p < 0.001) although all-cause mortality was approximately doubled (52.20% vs. 26.14%, p < 0.001). Metastatic disease-rates were similar in both [approximately 4% in both]. IRR of melanoma in VISN-1 patients was 0.36 (95% CI: 0.20-0.67; p = 0.0063) which persisted in all age groups/genders. 60.92% of VISN-1 patients had recreational sun-exposure history and 72.41% of tobacco use. 95.02% of melanomas were located in continuously/intermittently sun-exposed areas, 93.28% were surgically-treated with a median treatment delay of 31 days [range 18-48]. Median lost to follow-up was 0 day [range 0-681 days]. CONCLUSIONS: Compared to the general population, melanoma incidence was lower in the VISN-1 cohort, possibly due to decreased UV index in the New England region, protective effects of past tobacco use, improved access to care through the VA and regional public health educational efforts. Yet melanomas were more often invasive in the VISN-1 cohort due to advanced age and male sex both of which are associated with more advanced disease at diagnosis. A strength of this study is the calculation of IRR using PY as this method enhances accuracy of incidence calculations. The data were limited by the fact that the population was from one geographic region and consisted mainly of elderly Caucasian males. Descriptive variable data such as sun-protective habits and risk factors from military service are limited by potential recall bias given the retrospective study design. Further study is necessary to replicate these results and to compare our data to Veteran populations from different geographic regions within the USA.

Amyopathic dermatomyositis resembling stasis dermatitis.

This case describes an unusual presentation of dermatomyositis in a patient with ovarian carcinoma. The eruption appeared as a venous stasislike dermatitis. The temporal sequence of onset after chemotherapy administration suggested a possible drug-induced process. However, in the context of underlying ovarian carcinoma, a paraneoplastic process offered an alternative explanation for the dermatomyositis.

Chemoprevention of Basal and Squamous Cell Carcinoma With a Single Course of Fluorouracil, 5%, Cream: A Randomized Clinical Trial.

Importance: Keratinocyte carcinoma (ie, cutaneous basal and squamous cell carcinoma) is the most common cancer in the United States. Objective: To determine whether topical fluorouracil could prevent surgically treated keratinocyte carcinoma. Design, Setting, and Participants: The Veterans Affairs Keratinocyte Carcinoma Chemoprevention Trial was a randomized, double-blind, placebo-controlled trial of topical fluorouracil for chemoprevention of keratinocyte carcinoma. Participants were recruited from May 2009 to September 2011 from 12 Veterans Affairs medical centers and followed until June 30, 2013. Participants were veterans (n = 932) with a history of at least 2 keratinocyte carcinomas in the past 5 years; almost all were white males and the median age was 70 years. Interventions: Application of fluorouracil, 5%, (n = 468) or vehicle control cream (n = 464) to the face and ears twice daily for 2 to 4 weeks upon randomization. Main Outcomes and Measures: Surgically treated keratinocyte, basal cell, and squamous cell carcinoma risk on the face and ears in the first year after enrollment; and time to first surgically treated keratinocyte, basal cell, and squamous cell carcinoma. The a priori hypothesis was that fluorouracil would be effective in preventing these cancers. Results: Of 932 participants (916 men [98%]; 926 white [99%]; median age, 70 years), 299 developed a basal cell carcinoma end point (95 in year 1) and 108 developed a squamous cell carcinoma end point (25 in year 1) over 4 years (median follow-up, 2.8 years). Over the entire study, there was no difference between treatment groups in time to first keratinocyte, basal cell, or squamous cell carcinoma. During the first year, however, 5 participants (1%) in the fluorouracil group developed a squamous cell carcinoma vs 20 (4%) in the control group, a 75% (95% CI, 35%-91%) risk reduction (P = .002). The 11% reduction in basal cell carcinoma risk during year 1 (45 [10%] in the fluorouracil group vs 50 [11%] in the control group) was not statistically significant (95% CI, 39% reduction to 31% increase), nor was there a significant effect on keratinocyte carcinoma risk. However, a reduction in keratinocyte carcinomas treated with Mohs surgery was observed. Conclusions and Relevance: A conventional course of fluorouracil to the face and ears substantially reduces surgery for squamous cell carcinoma for 1 year without significantly affecting the corresponding risk for basal cell carcinoma. Trial Registration: clinicaltrials.gov Identifier: NCT00847912.

T-oligos augment UV-induced protective responses in human skin.

We have shown that DNA oligonucleotides substantially homologous to the telomere 3-prime overhang sequence (T-oligos) increase DNA repair capacity (DRC) in cultured human cells and decrease UV-induced mutation rate and photocarcinogenesis in mouse skin. To investigate the protective effects of T-oligos in intact human skin, paired skin explants obtained from adult donors were treated with T-oligos or diluent alone for 24 h, then UVB- or sham-irradiated, and processed after 6, 24, 48, 72, and 96 h for histological analysis. After UV irradiation apoptotic epidermal cells were comparable in diluent- and T-oligo-treated skin. Proliferating (Ki67+) cells were sparse in sham-irradiated skin and for 24 h after UV in both diluent- and T-oligo-treated specimens. However, compared to diluent controls, at 48 and 72 h T-oligos significantly inhibited UV-induced rebound hyperproliferation. Maximum and comparable cyclobutane pyrimidine dimers (CPDs) were detected immediately after UV irradiation in diluent- and T-oligo-treated skin, but CPDs were strikingly reduced in T-oligo- vs. diluent-treated skin at 24, 48, and 72 h. Total and activated p53 protein was increased in T-oligo- vs. diluent-pretreated skin at the time of irradiation, and up to 3-fold increases persisted for 24 h post-UV. Over 5 days, UV irradiation and T-oligo comparably increased expression of melanogenic proteins and each increased epidermal melanin content 3- to 5-fold, with distinct nuclear capping in many keratinocytes. In combination, these findings predict that T-oligo treatment will increase melanogenesis, prolong epidermal arrest, and increase DNA repair rate after UV irradiation, thus decreasing the severity of acute and chronic photodamage in human skin. Moreover, the data document an inducible SOS-like response consisting of increased melanogenesis and increased DNA repair capacity in human skin following UV-induced damage that is also produced by T-oligos in the absence of initial damage.