Dysplastic nevi with severe atypia: Long-term outcomes in patients with and without re-excision.

BACKGROUND: Dysplastic nevi with severe atypia (severely dysplastic nevi [SDN]) are frequently re-excised because of the concern that these lesions may in fact represent early melanoma. Data on long-term follow-up of these patients are limited. OBJECTIVE: We sought to determine the rate of subsequent melanoma development in patients with SDN who underwent re-excision versus those who did not and to determine factors associated with decision to re-excise. METHODS: A retrospective single institutional study was conducted with 451 adult patients (mean age 41.3 years) with SDN biopsied between November 1994 and November 2004, with clinical follow-up of at least 5 years. RESULTS: In 451 patients with SDN, re-excision was performed on 36.6%. Two melanomas were diagnosed in the re-excision specimens. Subsequent metastatic melanoma developed in 7 patients, all of whom had a history of melanoma. Margin comments influenced decision to re-excise. LIMITATIONS: This was a retrospective study at a single institution. CONCLUSION: Re-excision of all SDN may not be necessary.

Screening for melanoma in aging patients.

Despite recent advances, there is still no highly effective treatment of metastatic melanoma. By contrast, melanoma in situ essentially is a surgically curable disease. Therefore, the most promising approach to reducing melanoma mortality rates is the prompt detection and treatment of early-stage melanoma. The incidence of melanoma in the United States is increasing over time and the incidence increases with age. Thus early detection of melanoma via patient and physician screening in the aging population has the potential to substantially reduce melanoma mortality.

Clinical Utility of an AI-powered, Handheld Elastic Scattering Spectroscopy Device on the Diagnosis and Management of Skin Cancer by Primary Care Physicians.

BACKGROUND: Patients with lesions suspicious for skin cancer often present to primary care physicians (PCPs), who may have limited training in skin cancer diagnosis. OBJECTIVE: To measure the impact of an adjunctive handheld device for PCPs that employs elastic scattering spectroscopy (ESS) on the diagnosis and management of skin cancer. METHODS: Fifty-seven PCPs evaluated 50 clinical images of skin lesions (25 malignant and 25 benign), first without and then with knowledge of the handheld ESS device output, and in each case indicated if a lesion was likely to be benign or malignant. RESULTS: The diagnostic sensitivity of the PCPs with and without the use of the ESS device was 88% (95% CI, 84%-92%) and 67% (95% CI, 62%-72%), respectively (P < .0001). In contrast, no significant difference was observed in the diagnostic specificity. The management sensitivity of the physicians with and without the use of the ESS device was 94% (95% CI, 91%-96%) and 81% (95% CI, 77%-85%), respectively (P = .0009). Similarly, no significant difference was observed in the management specificity. CONCLUSION: The use of the ESS device may have the potential to help improve skin cancer diagnosis and confidence in management decision-making in a primary care setting.

Psoriasis in the transplant population.

Solid organ and stem cell transplants are increasingly common, and dermatologists will more frequently encounter and need to manage common skin diseases, such as psoriasis, in transplant patients. This review explores psoriasis remission and occurrence in recipients of solid organ and stem cell transplants. Hematopoietic and mesenchymal stem cell transplants may show potential for treating psoriasis in patients with leukemia or who have other medical conditions requiring stem cell transplant. The effects of solid organ transplant are less clear, partly due to limitations in the breadth of the literature. De novo psoriasis has been reported in recipients of solid organ transplants, but the reasons for this development have yet to be fully understood. Overall, the literature on this subject is limited to primarily case reports. Feasibility of studies on the subject may be a considerable barrier to further research assessing the use of transplant for treating psoriasis, but there is potential benefit from transplant for psoriasis patients. This subject should receive further exploration to fully understand these benefits.

BAP1 cancer syndrome: malignant mesothelioma, uveal and cutaneous melanoma, and MBAITs.

BACKGROUND: BRCA1-associated protein 1 (BAP1) is a tumor suppressor gene located on chromosome 3p21. Germline BAP1 mutations have been recently associated with an increased risk of malignant mesothelioma, atypical melanocytic tumors and other neoplasms. To answer the question if different germline BAP1 mutations may predispose to a single syndrome with a wide phenotypic range or to distinct syndromes, we investigated the presence of melanocytic tumors in two unrelated families (L and W) with germline BAP1 mutations and increased risk of malignant mesothelioma. METHODS: Suspicious cutaneous lesions were clinically and pathologically characterized and compared to those present in other families carrying BAP1 mutations. We then conducted a meta-analysis of all the studies reporting BAP1-mutated families to survey cancer risk related to the germline BAP1 mutation (means were compared using t-test and proportions were compared with Pearson χ2 test or two-tailed Fisher's exact test). RESULTS: Melanocytic tumors: of the five members of the L family studied, four (80%) carried a germline BAP1 mutation (p.Gln684*) and also presented one or more atypical melanocytic tumors; of the seven members of W family studied, all carried a germline BAP1 mutation (p.Pro147fs*48) and four of them (57%) presented one or more atypical melanocytic tumors, that we propose to call "melanocytic BAP1-mutated atypical intradermal tumors" (MBAITs). Meta-analysis: 118 individuals from seven unrelated families were selected and divided into a BAP1-mutated cohort and a BAP1-non-mutated cohort. Malignant mesothelioma, uveal melanoma, cutaneous melanoma, and MBAITs prevalence was significantly higher in the BAP1-mutated cohort (p ≤ 0.001). CONCLUSIONS: Germline BAP1 mutations are associated with a novel cancer syndrome characterized by malignant mesothelioma, uveal melanoma, cutaneous melanoma and MBAITs, and possibly by other cancers. MBAITs provide physicians with a marker to identify individuals who may carry germline BAP1 mutations and thus are at high risk of developing associated cancers.

The efficacy and safety of infliximab in patients with plaque psoriasis who had an inadequate response to etanercept: results of a prospective, multicenter, open-label study.

BACKGROUND: In patients with psoriasis and inadequate response (IR) to tumor necrosis factor-α antagonist treatment, the incremental benefit of switching to another tumor necrosis factor-α antagonist is unknown. OBJECTIVE: We sought to evaluate the clinical response to an etanercept-to-infliximab switch in patients with psoriasis and IR to etanercept. METHODS: Adults with moderate-to-severe plaque psoriasis and IR to etanercept (≥ 4 months) were eligible for this open-label study (called PSUNRISE). Patients had a Physician Global Assessment (PGA) score of at least 2 (mild) on a 5-point scale with etanercept, with or without concomitant oral systemic methotrexate or cyclosporine at baseline and during the study. Patients received intravenous infusions of infliximab 5 mg/kg at weeks 0, 2, 6, 14, and 22. PGA was used to evaluate efficacy at week 10 (primary end point) and week 26 (durability). Safety was evaluated through the end of the study. RESULTS: Of 215 patients, only 10 received concomitant immunomodulators. At week 10, 65.4% of patients (138 of 211; 95% confidence interval 58.6%-71.8%) achieved a PGA score of clear (0) or minimal (1) (primary end point). This response was durable through week 26, at which time 61.3% (122 of 199; 95% confidence interval 54.2%-68.1%) achieved a PGA score of clear (0) or minimal (1). There were no unexpected side effects or safety concerns. LIMITATIONS: This was an open-label, 26-week study; an incremental change of 1 PGA point, even mild to minimal, was considered clinically significant, as most psoriasis practitioners seek to achieve minimal psoriasis or clear skin. CONCLUSION: After switching to infliximab, a substantial proportion of patients with psoriasis and IR to etanercept experienced rapid and durable improvement.

Treatment of severe psoriasis with ustekinumab during pregnancy.

We present the case of a female, aged 22 years, with a long history of recalcitrant pustular psoriasis and psoriatic arthritis, treated with ustekinumab during pregnancy. The result of treatment was an uncomplicated pregnancy with delivery, at term, of a healthy boy. To our knowledge, this is the first reported use of ustekinumab in a human during pregnancy. Following a description of the case, we discuss the characteristics of ustekinumab and review the known information from human case reports, case series, and animal studies regarding the use of TNF-a inhibitors and ustekinumab during pregnancy. We also provide a short discussion of administration of ustekinumab during the time period when a mother is nursing and the potential for complications to infants in this setting.

Development of subacute cutaneous lupus erythematosus associated with the use of imiquimod to treat actinic keratoses.

The immunomodulating drug imiquimod is approved by the U.S. Food and Drug Administration (FDA) to treat actinic keratoses, non-facial superficial basal cell carcinomas and genital warts. This drug elicits its immunological response by binding to toll-like receptor 7 (TLR-7) on dendritic cells inducing the production of interferon alpha (IFN-alpha) and other inflammatory cytokines. The authors report the case of a 56-year-old female who developed subacute cutaneous lupus erythematosus (SCLE), as well as severe autoimmune retinitis following a vigorous response to imiquimod 5% cream that was prescribed to treat actinic keratoses. Given the important role of IFN-alpha in the pathogenesis of cutaneous lupus, it is likely that imiquimod either induced or unmasked an autoimmune tendency in this patient.

A Preliminary, Open Label, Single-arm Study of Calcipotriene/Betamethasone Topical Suspension as a Supplement to Non-biologic Systemic Therapy for Psoriasis.

BACKGROUND: Calcipotriene/betamethasone topical suspension is a topical therapy that is often used as monotherapy as a first-line treatment for plaque psoriasis. The objective of this preliminary, open label, single arm study was to determine the efficacy of adding a topical suspension to a traditional systemic therapy for psoriasis, either methotrexate or acitretin. METHODS: In this exploratory study, eight patients with chronic plaque psoriasis who were on stable methotrexate or acitretin treatment without clearance were treated with once-daily calcipotriene/betamethasone topical suspension. Subjects completed five study visits over 12 weeks. Primary outcome measure was improvement of two or more points in Investigator Global Assessment. Secondary endpoints included change in Body Surface Area, Dermatology Life Quality Index, and Patient's Global Assessment from baseline to Week 12. RESULTS: Overall, the median decrease in Investigator Global Assessment over 12 weeks was 1.5 points, with 50 percent of subjects experiencing a drop of two or more points in Investigator Global Assessment. All eight subjects had a reduction in Body Surface Area and Patient's Global Assessment. There was a mean decrease in Dermatology Life Quality Index score of 78.9 percent, showing improved patient quality of life. In addition, all patients tolerated the treatment well and 6 of 8 patients had improved satisfaction level with their treatment by the end of the study. CONCLUSION: The topical suspension was effective and well-tolerated in conjunction with stable methotrexate or acitretin treatment in all eight patients in this study. These results support the feasibility of a larger scale study to further investigate the efficacy of these treatment combinations. The trial is registered at ClinicalTrials.gov, number NCT01761019.

Anti-IL-36R antibodies, potentially useful for the treatment of psoriasis: a patent evaluation of WO2013074569.

The IL-36 family of cytokines and receptors seems to play a role in the pathogenesis of both pustular psoriasis, and the much more common variant, plaque-type psoriasis. Human skin biopsies from patients with psoriasis show overexpression of IL-36 and mice that lack the inhibitory IL-36 receptor (IL-36Ra) antagonist develop psoriasis, suggesting that signaling through the IL-36R may drive the skin lesions of psoriasis. Currently, no drugs targeting IL-36 are used in the treatment of psoriasis. The patent WO2013074569 describes an antibody to the IL-36R that is proposed as a potential therapy for psoriasis.

New diagnostic aids for melanoma.

Detection of melanoma at an early stage is crucial to improving survival rates in melanoma. Accurate diagnosis by current techniques including dermatoscopy remains difficult, and new tools are needed to improve our diagnostic abilities. This article discusses recent advances in diagnostic techniques including confocal scanning laser microscopy, MelaFind, SIAscopy, and noninvasive genomic detection, as well as other future possibilities to aid in diagnosing melanoma. Advantages and barriers to implementation of the various technologies are also discussed.

Advances and short comings in the early diagnosis of melanoma.

Malignant melanoma kills more people each year than any other skin cancer, with approximately 8000 lives lost and a cost of over 3 billion dollars annually in the US alone. Tumor depth is the most important prognostic factor in melanoma. Thus, early detection has the potential to diagnose melanoma when lesions are thinner, and to improve survival in primary melanomas. In this review, we discuss the implications, barriers, and advantages of melanoma screening, and describe the currently employed methods of detection, newly available modalities, and current areas of research. We also discuss the efficacy, advantages and disadvantages, and clinical practicality of each, and suggest various means of combining different methodologies as well as tailoring various strategies to individual patient needs.

The influence of age and sex on reasons for seeking and expected benefits of skin cancer screening.

OBJECTIVE: To determine the influence of age and sex on why individuals seek skin cancer screening and their understanding of its benefits. DESIGN: Voluntary survey. SETTING: Academic dermatology department. PARTICIPANTS: Individuals 18 years or older being seen for skin cancer screening from May to October 2009. MAIN OUTCOME MEASURES: Patients' reasons for seeking and perceived benefits of skin cancer screening and understanding of screening recommendations. RESULTS: Of 546 patients, 487 eligible individuals (89.2%) participated in the survey. Most (80.6%) sought screening without a particular lesion of concern. Women were more likely than men to present with a lesion they believed could be skin cancer (24.6% vs 11.9%; P < .001) or because they were concerned about previous sun exposure (34.3% vs 23.8%; P < .05). Individuals younger than 50 years were more likely than older patients to seek screening because of a family history of melanoma (30% vs 18.9%; P < .01). Men 50 years or older were more likely than other patients to seek skin cancer screening because of a previous skin cancer diagnosis (64.6% vs 40.8%; P < .001). Most patients believed that screening reduces the risk of death from skin cancer and prevents skin cancer. There was no consensus among patients regarding the frequency with which healthy adults should be screened for skin cancer. CONCLUSIONS: There is a need for better educational campaigns with specific recommendation for who should be screened for skin cancer. Men 50 years or older, the group at highest risk for death from melanoma, are most likely to seek screening only after being diagnosed as having a skin cancer.

Treatment of postsurgical pyoderma gangrenosum with a high-potency topical steroid.

Pyoderma gangrenosum is a rare disease characterized by chronic, nonhealing, noninfectious ulcers that can become exacerbated by trauma or manipulation, including surgical treatment. We describe the case of a 30-year-old woman who presented with a large ulcer at the site of an excisional cervical lymph node biopsy; she also had a smaller ulcer at the site of an earlier biopsy that had been previously well healed. The ulcers persisted despite local care, and the larger ulcer was exacerbated by surgical debridement. Histopathology revealed the presence of intense neutrophilic infiltrates with sterile microabscesses-a finding consistent with pyoderma gangrenosum. With 9 weeks of treatment with a high-potency topical steroid, both ulcers gradually healed.