Journal Article Corrected proof The limitations of persistence as a measure of efficacy of biologic therapies Get access Robert S Stern Robert S Stern Conceptualization, Writing - original draft Department of Dermatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA Email: rstern@bidmc.harvard.edu https://orcid.org/0000-0001-5491-149X Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, ljad322, https://doi.org/10.1093/bjd/ljad322 Published: 06 September 2023 Article history Received: 24 August 2023 Accepted: 25 August 2023 Published: 06 September 2023 Corrected and typeset: 14 October 2023

Until the early 2000s, treatment options for moderate-to-severe psoriasis were limited to a few systemic therapies, PUVA, and Narrowband-UVB. Since then, insights about the pathogenesis of psoriasis have led to the development of cytokine-based therapies which have revolutionized psoriasis management. However, with more than a dozen targeted therapies approved for psoriasis, keeping pace with the fast-growing repertoire of therapies and synthesizing the literature has become a more complex task.

British Journal of DermatologyVolume 185, Issue 1 p. 219-221 Research letter Longitudinal multicentre retrospective cohort study of treatment outcomes in extramammary Paget disease K.X. Liu, orcid.org/0000-0003-2071-5137 Department of Radiation Oncology, Brigham and Women's Hospital, Dana-Farber Cancer Institute, Boston, MA, USA Contribution: Data curation (equal), Formal analysis (equal), ​Investigation (equal), Writing - original draft (lead), Writing - review & editing (equal)Search for more papers by this authorV. Huang, Department of Dermatology, University of California Davis, Sacramento, CA, USA Contribution: Conceptualization (equal), Supervision (equal), Visualization (equal), Writing - review & editing (equal)Search for more papers by this authorC.A. Chen, Department of Dermatology, University of California San Francisco, San Francisco, CA, USA Contribution: Data curation (lead), Funding acquisition (equal), ​Investigation (equal), Writing - original draft (equal)Search for more papers by this authorC.P. Elco, Department of Pathology and Laboratory Medicine, Brown University, Providence, RI, USA Contribution: Data curation (equal), Formal analysis (equal)Search for more papers by this authorS.T. Chen, Department of Dermatology, Massachusetts General Hospital, Boston, MA, USA Contribution: Writing - review & editing (equal)Search for more papers by this authorR.S. Stern, orcid.org/0000-0001-5491-149X Department of Dermatology, Beth Israel Deaconess Medical Center, Boston, MA, USA Contribution: Conceptualization (equal), Formal analysis (equal), Methodology (equal), Supervision (equal), Validation (equal), Writing - review & editing (lead)Search for more papers by this authorP.A. Wu, Corresponding Author pawu@ucdavis.edu orcid.org/0000-0002-8042-5257 Department of Dermatology, University of California Davis, Sacramento, CA, USA Department of Dermatology, Beth Israel Deaconess Medical Center, Boston, MA, USA Correspondence: Peggy A. Wu. Email: pawu@ucdavis.edu Contribution: Conceptualization (lead), Formal analysis (equal), ​Investigation (equal), Methodology (equal), Software (equal), Supervision (lead), Writing - review & editing (lead)Search for more papers by this author K.X. Liu, orcid.org/0000-0003-2071-5137 Department of Radiation Oncology, Brigham and Women's Hospital, Dana-Farber Cancer Institute, Boston, MA, USA Contribution: Data curation (equal), Formal analysis (equal), ​Investigation (equal), Writing - original draft (lead), Writing - review & editing (equal)Search for more papers by this authorV. Huang, Department of Dermatology, University of California Davis, Sacramento, CA, USA Contribution: Conceptualization (equal), Supervision (equal), Visualization (equal), Writing - review & editing (equal)Search for more papers by this authorC.A. Chen, Department of Dermatology, University of California San Francisco, San Francisco, CA, USA Contribution: Data curation (lead), Funding acquisition (equal), ​Investigation (equal), Writing - original draft (equal)Search for more papers by this authorC.P. Elco, Department of Pathology and Laboratory Medicine, Brown University, Providence, RI, USA Contribution: Data curation (equal), Formal analysis (equal)Search for more papers by this authorS.T. Chen, Department of Dermatology, Massachusetts General Hospital, Boston, MA, USA Contribution: Writing - review & editing (equal)Search for more papers by this authorR.S. Stern, orcid.org/0000-0001-5491-149X Department of Dermatology, Beth Israel Deaconess Medical Center, Boston, MA, USA Contribution: Conceptualization (equal), Formal analysis (equal), Methodology (equal), Supervision (equal), Validation (equal), Writing - review & editing (lead)Search for more papers by this authorP.A. Wu, Corresponding Author pawu@ucdavis.edu orcid.org/0000-0002-8042-5257 Department of Dermatology, University of California Davis, Sacramento, CA, USA Department of Dermatology, Beth Israel Deaconess Medical Center, Boston, MA, USA Correspondence: Peggy A. Wu. Email: pawu@ucdavis.edu Contribution: Conceptualization (lead), Formal analysis (equal), ​Investigation (equal), Methodology (equal), Software (equal), Supervision (lead), Writing - review & editing (lead)Search for more papers by this author First published: 06 February 2021 https://doi.org/10.1111/bjd.19871 Funding sources: C.A.C. received a medical student award from the American Skin Association. Conflicts of interest: The authors declare no conflicts of interest. R.S.S. and P.A.W. contributed equally to this work. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume185, Issue1July 2021Pages 219-221 RelatedInformation

Citation for published version (APA): Brueggen, M. -C., Le, S. T., Walsh, S., Toussi, A., de Prost, N., Ranki, A., Didona, B., Colin, A., Horvath, B., Brezinova, E., Milpied, B., Moss, C., Bodemer, C., Meyersburg, D., Salavastru, C., Tiplica, G. -S., Howard, E., Bequignon, E., Bouwes Bavinck, J. N., ... Worswick, S. (2021). Supportive care in the acute phase of Stevens-Johnson syndrome and toxic epidermal necrolysis: an international, multidisciplinary Delphi-based consensus. BRITISH JOURNAL OF DERMATOLOGY. https://doi.org/10.1111/bjd.19893

British Journal of DermatologyVolume 185, Issue 2 p. 470-471 Obituary Professor Jean-Claude Roujeau (1944–2021) R.S. Stern, Corresponding Author rstern@bidmc.harvard.edu orcid.org/0000-0001-5491-149X Harvard Medical School, Beth Israel Deaconess Medical Center – Dermatology, Boston, MA, USASearch for more papers by this author R.S. Stern, Corresponding Author rstern@bidmc.harvard.edu orcid.org/0000-0001-5491-149X Harvard Medical School, Beth Israel Deaconess Medical Center – Dermatology, Boston, MA, USASearch for more papers by this author First published: 05 May 2021 https://doi.org/10.1111/bjd.20076Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume185, Issue2August 2021Pages 470-471 RelatedInformation

Actinic keratoses (AK) are rough skin lesions (patches) caused by long-term sun exposure in people with light skin. The prevalence of AK is high, affecting 24-60% of people above the age of 50. Having many AKs is a sign that a person may be more likely to develop skin cancer. This study, from the Netherlands, aimed to provide insight in the management (treatment) of AKs, by describing how healthcare services are used by people with AK, and its management by GPs and dermatologists. The authors found that a large proportion of people with AK are not aware of having AK, and thus not aware of an increased skin cancer risk. Its treatment at the GP largely seems inconsistent with guidelines, and 31% are directly referred to the dermatologist at the first GP appointment. These referrals are usually not related to the extensiveness of the AK, meaning how many AKs the person has. This causes a high burden in secondary care (e.g. hospitals, where people are referred to dermatologists) with patients who could be easily treated by the GP. At the dermatologists there is a high rate of follow-up of patients with AK, meaning they come back for further appointments. The authors conclude that their findings indicate inefficient use of healthcare resources. They suggest that to overcome this, motives of GPs and dermatologists for diverging from current guidelines in the management of AK need to be explored.

日光性角化病 (AK) 是浅色皮肤的人因为长期暴露在阳光下而引起的粗糙的皮肤损伤(斑片)。AK 的患病率高,在大于 50 岁人群中影响24‐60% 人口。存在很多 AK 表示此人更容易发生皮肤癌。这项来自荷兰的研究旨在通过描述 AK 人群如何使用医疗保健服务,以及 GP 和皮肤科医生对于此病的管理,来提供 AK 管理(治疗)见解。作者们发现,相当比例的 AK 人群不知道自己患有 AK,因此也不知道皮肤癌风险增高。GP 水平的治疗似乎普遍与指南不符,31% 的患者在第一次 GP 预约时被直接转诊给皮肤科医生。这些转诊通常与 AK 的广泛程度(即患者有多少 AK)无关。由于这些可以被 GP 轻松治疗的患者,导致二级医疗(例如医院,人们在这里被转诊给皮肤科医生)的负担增高。在皮肤科医生那里,AK 患者的随访率高,意味着他们会返回进行后续预约。作者们总结说,这些发现表明医疗保健资源的利用效率不足。他们指出,为了克服这种现象,应探明 GP 和皮肤科医生在管理 AK 方面偏离当前指南的动机。

The incidence of melanoma has increased dramatically in recent years. Over-the-counter sunscreen use in childhood has been shown to lower the lifetime risk of melanoma in Australia, but previous studies in the U.S. have failed to demonstrate benefit. We hypothesize that short follow-up and a failure to take into account inappropriate sunscreen application practices may contribute to the lack of positive findings. Here, we created a predictive model for the impact of different regimens of sunscreen use on melanoma incidence in the pediatric New York State Medicaid population. A Markov model was developed to analyze ideal use conditions (almost daily), some use (50% of ideal), and none. Total sunscreen use for children was estimated at about 15-20 ml per application, with the number of applications depending on time of year. The model population was based on SEER data and published literature. The model incorporated various salient population characteristics including gender, ethnicity (white, non-white), and sunbed use. The model time frame was 79 years, the average life expectancy in the U.S. Our model found that compared to no sunscreen use, ideal sunscreen application is associated with a significant 43% risk reduction of lifetime melanoma development, while some sunscreen application is associated with a 17.5% risk reduction. These findings suggest that in order to demonstrate reduction in melanoma incidence, it is important to ensure appropriate sunscreen application conditions and also to look at long-term follow-up.

Linked Articles:Gerbens et al. Br J Dermatol 2018; doi: . Garcia-Doval et al. Br J Dermatol 2018; 179:863-871. Grinich et al. Br J Dermatol 2018; 179:540-541.

Although rare, Stevens-Johnson syndrome and toxic epidermal necrolysis remain among the most devastating of acute conditions involving the skin. In the past 30 years, tremendous progress has been made in understanding the causes and pathobiology of this often life-threatening condition. Su et al demonstrate associations between IL 15 serum levels and the outcome of patients with Stevens-Johnson syndrome and toxic epidermal necrolysis. Their findings provide ideas for further investigations that may help us better understand the role of cytokines in this T-cell mediate disease and provides clues to possible new therapies.

Linked Article: Gómez‐García et al. Br J Dermatol 2017; 176:1633–1644. Tauber and Paul. Br J Dermatol 2017; 176:1669–1671.

Today, "big data" often generated by administrative activities or survey are used to inform many commercial, administrative and clinical decisions. Although they provide a broader perspective about disease and care than that available from clinical experience and research studies, inferences from these data need to be made cautiously.

Among white non-Hispanics older than 50 years, nonmelanoma skin cancer (NMSC) incidence is likely to exceed 3.5 million annually in the United States.1 From a clinical and public health perspective, identifying the characteristics of those at the highest risk would allow allocating limited resources to screen those most at need. Those with a prior NMSC are known to be at high risk, but data on the magnitude of and patient characteristics related to this risk are particularly important in deciding how these patients should be monitored. The United States Preventive Services Task Force (USPTF) and the National Cancer Institute (NCI) do not recommend skin cancer screening for all at-risk persons. The number of persons at risk for NMSC greatly exceeds the total number of visits each year to dermatologists. With a prevalence exceeding 13 million persons with a history of at least 1 NMSC,2 current annual screening of patients with a history of NMSC would alone account for more than one-third of visits to dermatologists.3,4 In this issue of JAMA Dermatology, Wehner et al5 provide data that help to identify patients at highest risk for subsequent NMSCs and highlight additional information needed to rationally direct resources for monitoring patients with this history. This study of 1284 immunocompetent patients with NMSC treated at a university academic practice and the San Francisco Veterans Administration assessed timing of subsequent basal cell cancer (BCC) or squamous cell cancer (SCC). Patients were followed up for an average of 5.7 years (0-12.3 years). Basal cell cancers (1234 [75.6%]) were more common than SCCs (399 [24.4%]). The authors found that the risk of a subsequent SCC or BCC occurring within 2 years of the first tumor was 41%, half as great as the risk after a non-first BCC or SCC (81%). For those who had a BCC at study entry and remained tumor free for 2 years, the incidence of BCC in subsequent years was relatively low, less than 5% per year. For comparable patients with SCC, the development of another SCC after year 2 was almost twice as high (data supporting this finding are reported by Wehner et al5 in their online supplemental materials). Subsequent tumors were usually of the same types: only 5.1% of the study cohort subsequently developed both BCCs and SCCs. These findings support those of prior studies indicating that patients tend to develop a single type of NMSC.6,7 Although the incidence of SCC is lower than that of BCC, the risk of developing a second tumor of the same type was higher in SCC: 69% of those with 1 SCC developed at least 1 additional tumor. Over half of the patients who had multiple SCCs were likely to develop another SCC within 2 years (Wehner et al,5 online supplemental materials). Given the higher morbidity and the risk of mortality with SCCs, closely monitoring patients with SCCs is clearly indicated. According to the findings of this study, about 12 patients with SCC would have to be screened each year to detect another SCC. For persons with a single BCC, a second BCC will be detected for about every 20 patients screened annually.5 In a similar study of the Dutch population, slightly higher numbers of persons with a BCC would need to be screened to detect another BCC.8 These risk and incidence estimates are in line with results from previous publications on subsequent NMSCs in patients with a history of NMSC.7 Both Australian and Dutch data suggest fairly long median intervals between new tumors (1.5 to ≥2 years).8,9 Reflecting this observation, Dutch guidelines suggest yearly follow-up only for patients with an SCC, 2 or more BCCs, or a BCC in a high-risk zone.8 The National Comprehensive Cancer Network (NCCN) recommends that every patient with a history of low-risk BCC or SCC be screened with skin examinations every 6 to 12 months for life.10 The data from this and prior studies combined with the high incidence of BCC suggest that the wisdom and feasibility of such a recommendation is in doubt. With an increased number of screenings, a higher proportion of BCCs is likely to be detected in sites other than the head and neck, forearms, and hands—areas such as the trunk, where superficial BCCs are the most common histologic subtype.11 The magnitude of benefit of earlier detection of slowgrowing asymptomatic tumors in less cosmetically sensitive areas is not clear.12 The frequency with which screenings will allow clinicians to detect a subsequent BCC of the head and neck or hands sooner (or later, due to waiting for the annual appointment) than it would otherwise be detected by an educated patient with a prior BCC is also uncertain. Nor is it known the extent to which regular dermatologic examinations for patients who have gone 2 years without a subsequent BCC result in earlier detection and better outcomes. For patients who remain tumor free for 2 years after the first BCC and who are likely to recognize a subsequent tumor, further follow-up may not provide much value. About two-thirds of BCCs occur on the head and neck.5,8,13 The authors did not analyze the association of anatomic site or histologic subtype on the first and subsequent NMSCs. This information could be useful to practitioners and patients in targeting areas for surveillance and identifying suspect lesions that could be NMSC. Related article page 382 Opinion

Despite widespread use of antioxidants, reactive oxygen species have important functions in normal tissues. Herein, we present an example of a physiological role for free radicals, and in particular, reactive oxygen species, that are suppressed by anti-oxidants. Free radicals catalyze the degradation of hyaluronan in synovial fluid, a tissue in which hyaluronidase activity is barely detectable. Articular cartilage requires a low oxygen environment. The process of hyaluronan peroxidation consumes significant amounts of molecular oxygen, thus keeping the tension of oxygen in the joint at a low but physiologically critical level. One concern is the change in physical activity between day and night, with periods of joint hyperemia and ischemia, respectively. Increased oxygen and the resulting oxidative stress would lead to chondrocyte dysfunction and cartilage damage. A mechanism for keeping oxygen levels low is required. We postulate that a mechanism indeed exists for the removal of excess oxygen. High-molar-mass hyaluronan turnover in synovial fluid utilizes peroxidative degradation, during which oxygen is massively consumed. The peroxidation itself may be initiated by hydrogen peroxide, which is produced by chondrocyte mitochondria, that can diffuse into the synovial fluid. The resulting decrease in available oxygen down-regulates hyaluronan peroxidation. This in turn prevents excessive oxygen consumption. It appears that free radicals and reactive oxygen species may be components of normal physiology, particularly in the synovial fluid of joints and articular cartilage. It is suggested therefore that indiscriminate use of anti-oxidants, vigorously promoted currently by health professionals and the health industry, be approached with caution.