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Lara el Hayderi, Fany Colson, Bita Dezfoulian, Arjen F Nikkels Department of Dermatology, CHU du Sart Tilman, University Hospital of Liège, Liège, Belgium Abstract: As TNF-α is a major factor in the immune defense against herpes zoster (HZ); an increased incidence and severity of HZ cases were suspected in patients undergoing treatment with TNF antagonists. Several studies and clinical experience provided evidence that the incidence of HZ increases by twofold to threefold in this patient category. The number of severe cases of HZ, with multisegmental, disseminated cutaneous, and/or systemic involvement, is also increased. Concerning psoriasis patients under biologicals, the clinician should be more alert for an eventual HZ event, in particular during the first year of biological treatment, and be aware of the possibility of more severe HZ cases. HZ may also undergo an age-shift toward younger patients. Rapid identification of risk factors for severe HZ, such as severe prodromal pains and/or the presence of satellite lesions, is recommended. The treatment recommendations of HZ in this patient group are identical to the recently published guidelines for the management of HZ. The live attenuated viral vaccine OKA/Merck strain anti-HZ vaccination is recommended before initiating biological treatment in psoriasis patients. The new adjuvanted anti-HZ vaccine will probably also benefit patients while on biological treatment. Keywords: herpes zoster, TNF antagonists, anti-IL17, anti-IL12/23, psoriasis, aciclovir

Targeted biologic drugs and small molecules have transformed the psoriasis treatment landscape in recent years. The Belgian healthcare system, in common with many others across Europe, must balance the burgeoning use of these transformative, yet expensive, drugs with the sustainable use of limited resources. Drawing on recent updates to the EuroGuiDerm and the German S2 psoriasis guidelines, eight Belgian dermatologists experienced in treating patients with psoriasis undertook a quasi-Delphi initiative to provide perspectives on the current opportunities and challenges in psoriasis. This update focuses on responsible ways to rationalize the use of innovative treatments (e.g. biologics and small molecules). Inherently, this required viewpoints on the International Psoriasis Council's new definition of severe psoriasis, defining psoriasis severity and the concept of treating to target. It discusses the appropriateness of using older biologics classes, biosimilars and personalized dosing and lastly, how teledermatology may play a role in providing sustainable, patient-centric psoriasis care. In addition, this manuscript includes the updated Belgian evidence-based treatment advice in psoriasis (BETA-PSO) to reflect recent data and drug approvals. The recommendations reflect the best practices for clinicians when using systemic and biologic therapies to treat patients with psoriasis and offer guidance on how they may prescribe these drugs sustainably and efficiently., (© 2024 European Academy of Dermatology and Venereology.)

Introduction: Lichen sclerosus (LS) is an inflammatory skin disease affecting all ages. LS typically involves the anogenital site where it causes itching and soreness. It may lead to sexual and urinary dysfunction in females and males; however, it may be asymptomatic. First signs of LS are redness and oedema, typically followed by whitening of the genital skin; sometimes fissuring, scarring, shrinkage and fusion of structures may follow in its course. LS is associated with an increased risk of genital cancer. LS has a huge impact on the quality of life of affected patients, and it is important to raise more awareness of this not uncommon disease in order to diagnose and treat it early., Objectives: The guideline intends to provide guidance on the diagnostic of LS, highlight important aspects in the care of LS patients (part 1), generate recommendations and treatment algorithms (part 2) on topical, interventional and surgical therapy, based on the latest evidence, provide guidance in the management of LS patients during pregnancy, provide guidance for the follow-up of patients with LS and inform about new developments and potential research aspects., Materials and Methods: The guideline was developed in accordance with the EuroGuiDerm Methods Manual v1.3 https://www.edf.one/de/home/Guidelines/EDF-EuroGuiDerm.html. The wording of the recommendations was standardized (as suggested by the GRADE Working Group). The guideline development group is comprised of 34 experts from 16 countries, including 5 patient representatives., Results: Ultrapotent or potent topical corticosteroids in females and males, adults and children remain gold standard of care for genital LS; co-treatment with emollients is recommended. If standard treatment fails in males, a surgical intervention is recommended, complete circumcision may cure LS in males. UV light treatment is recommended for extragenital LS; however, there is limited scientific evidence. Topical calcineurin inhibitors are second line treatment. Laser treatment, using various wave lengths, is under investigation, and it can currently not be recommended for the treatment of LS. Treatment with biologics is only reported in single cases., Conclusions: LS has to be diagnosed and treated as early as possible in order to minimize sequelae like scarring and cancer development. Topical potent and ultrapotent corticosteroids are the gold standard of care; genital LS is often a lifelong disease and needs to be treated long-term., (© 2024 European Academy of Dermatology and Venereology.)

Introduction: Lichen sclerosus (LS) is an inflammatory skin disease affecting all ages. LS typically involves the anogenital site where it causes itching and soreness; it may lead to sexual and urinary dysfunction in females and males; however, it may be asymptomatic. First signs of LS are usually a whitening of the genital skin, sometimes preceded by redness and oedema; fissuring, scarring, shrinkage and fusion of structures may follow in its course. LS is associated with an increased risk of genital cancer. LS has a huge impact on the quality of life of affected patients, and it is important to raise more awareness of this not uncommon disease in order to diagnose and treat it early., Objectives: The guideline intends to provide guidance on the diagnostic of LS (part 1), highlight important aspects in the care of LS patients, generate recommendations and treatment algorithms (part 2) on topical, interventional and surgical therapy, based on the latest evidence, provide guidance in the management of LS patients during pregnancy, provide guidance for the follow-up of patients with LS and inform about new developments and potential research aspects., Materials and Methods: The guideline was developed in accordance with the EuroGuiDerm Methods Manual v1.3 https://www.edf.one/de/home/Guidelines/EDF-EuroGuiDerm.html. The wording of the recommendations was standardized (as suggested by the GRADE Working Group). The guideline development group is comprised of 34 experts from 16 countries, including 5 patient representatives., Results: Ultrapotent or potent topical corticosteroids in females and males, adults and children remain gold standard of care for genital LS; co-treatment with emollients is recommended. If standard treatment fails in males, a surgical intervention is recommended, complete circumcision may cure LS in males. UV light treatment is recommended for extragenital LS; however, there is limited scientific evidence. Topical calcineurin inhibitors are second line treatment. Laser treatment, using various wave lengths, is under investigation, and it can currently not be recommended for the treatment of LS. Treatment with biologics is only reported in single cases., Conclusions: LS has to be diagnosed and treated as early as possible in order to minimize sequelae like scarring and cancer development. Topical potent and ultrapotent corticosteroids are the gold standard of care; genital LS is often a lifelong disease and needs to be treated long-term., (© 2024 European Academy of Dermatology and Venereology.)

Atopic dermatitis (AD) is a chronic inflammatory skin condition. The pathogenesis involves genetic, environmental, and immunological factors as well as a barrier dysfunction of the epidermis. Biomarkers may play a significant role in diagnosis, severity assessment, and treatment monitoring of AD. They are categorizable into diagnostic and prognostic as well as severity and stratification biomarkers, offering the potential for a more personalized treatment approach. Although there have been tremendous therapeutic advancements with interleukin (IL) antagonists and Janus kinase (JAK) inhibitors, the domain of biomarkers still requires further research to clarify their place in the diagnosis and prognosis of AD to unravel a better scientific basis for personalized medical care for patients with AD. This article reviews the various biomarkers in relation to the different AD phenotypes and endotypes., (© 2024. The Author(s).)

Herpes zoster (HZ) is caused by reactivation of the varicella-zoster virus. The life-time risk of developing HZ is ~ 30%. Management of HZ can be challenging due to limited efficacy of oral antivirals on pain control, and neuropathic pain that may require aggressive management. Post-herpetic neuralgia (PHN) can cause substantial pain and occurs in up to one-quarter of patients with HZ. Up to 48,000 HZ cases are estimated to occur annually in Belgium, estimated to cost almost 7 million euros in treatment. The recombinant zoster vaccine (RZV, Shingrix , GSK) was approved in Europe in 2017. In 2022, the Belgian Superior Health Council recommended vaccination with RZV for immunocompetent adults aged ≥ 60 years, and immunocompromised patients aged ≥ 16 years, including those receiving immunosuppressive therapy, in particular Janus kinase inhibitors. RZV showed high age-independent efficacy in preventing HZ infection and in clinical trials that has since been confirmed in real-world effectiveness studies. In clinical trials, protection was sustained for at least 10 years after vaccination. As of 1 November 2023, RZV is reimbursed for three immunocompromised patient groups aged ≥ 18 years: malignancy treated in the past 5 years, HIV infection, and organ or haematological stem cell transplantation or are a transplant candidate. HZ is vaccine-preventable and RZV provides a highly effective tool for HZ prevention. While reimbursement for some at-risk groups is welcomed, reimbursement currently falls well short of Superior Health Council recommendations. Adult immunisation strategies should be promoted to achieve high vaccination coverage against HZ, contributing to healthy aging in Belgium.

Background: Plaque psoriasis affects ~ 1% of the pediatric population, negatively impacting quality of life. The efficacy and safety of secukinumab in pediatric patients with moderate to severe or severe chronic plaque psoriasis have been established in two pivotal phase 3 trials (open-label, NCT03668613; double-blind, NCT02471144)., Objectives: The aims were to report the pooled safety of secukinumab up to 52 weeks from two studies in subgroups of pediatric patients stratified by age and bodyweight, and to present, alongside the pediatric data, the pooled safety data from four pivotal adult secukinumab trials., Methods: The safety of secukinumab was evaluated in subgroups of pediatric patients defined by age (6 to < 12 and 12 to < 18 years) and bodyweight (< 25 kg, 25 to < 50 kg, and ≥ 50 kg) in the pooled population. Patients received secukinumab low dose (LD; 75/75/150 mg), secukinumab high dose (HD; 75/150/300 mg), placebo, or etanercept (0.8 mg/kg). For safety analyses, data were pooled from the pediatric studies NCT03668613 and NCT02471144, and presented alongside the pooled data from four adult pivotal studies (NCT01365455, NCT01636687, NCT01358578, NCT01555125)., Results: A total of 198 pediatric patients (overall exposure: 184.6 patient-years [PY]) and 1989 adult patients (1749.5 PY) receiving secukinumab up to week 52 were included in this analysis. At week 52, the incidence of adverse events (AEs) was lower in the lower age and bodyweight subgroups. The AEs reported within these subgroups were consistent with the overall AEs reported in this analysis. Overall, exposure-adjusted incidence rates for treatment-emergent AEs were lower in the secukinumab-treated pediatric pool (198.8/100 PY) compared with the etanercept (266.3/100 PY) and adult pools (256.1/100 PY). Up to 52 weeks, the incidence rates of the AEs in the secukinumab-treated patients in the 6 to < 12 years subgroup and 12 to < 18 years subgroup were 167.7/100 PY and 214.7/100 PY, respectively. Similarly, incidence rates of the AEs in the secukinumab-treated patients in the < 25 kg, 25 kg to < 50 kg, and ≥ 50 kg subgroups were 177.3/100 PY, 192.5/100 PY, and 206.8/100 PY, respectively. Nasopharyngitis was the most frequently reported AE in secukinumab-treated pediatric patients across age (< 12 years: 11.8/100 PY; ≥ 12 years: 42.4/100 PY) and bodyweight (< 25 kg: 22.8/100 PY; 25 kg to < 50 kg: 19.0/100 PY; ≥ 50 kg: 43.0/100 PY). Of the 198 secukinumab-treated pediatric patients, one reported nail Candida, one reported skin Candida, and two reported vulvovaginal Candida. Transient and mostly mild events of neutropenia were observed with secukinumab, none leading to study treatment discontinuation. No incidence of treatment-emergent anti-drug antibodies was reported in pediatric patients treated with secukinumab., Conclusions: Secukinumab was well tolerated in pediatric patients with moderate to severe and severe plaque psoriasis across age and bodyweight subgroups. The overall safety profile of secukinumab in pediatric patients was consistent with that of adult patients., Gov Identifier: NCT03668613 (Novartis Study Code CAIN457A2311, referred to as A2311), actual study start date: August 29, 2018; actual primary completion date: September 19, 2019; estimated study completion date: September 14, 2023. NCT02471144 (Novartis Study Code CAIN457A2310, referred to as A2310), study start date: September 29, 2015; primary completion date: December 13, 2018; estimated study completion date: March 31, 2023., (© 2023. The Author(s).)

Atopic dermatitis (AD) is a Th2-type inflammatory disease characterized by an alteration of epidermal barrier following the release of IL-4 and IL-13. These cytokines activate type II IL-4Rα/IL-13Rα1 receptors in the keratinocyte. Whilst IL-2Rγ, that forms type I receptor for IL-4, is only expressed in haematopoietic cells, recent studies suggest its induction in keratinocytes, which questions about its role. We studied expression of IL-2Rγ in keratinocytes and its role in alteration of keratinocyte function and epidermal barrier. IL-2Rγ expression in keratinocytes was studied using both reconstructed human epidermis (RHE) exposed to IL-4/IL-13 and AD skin. IL-2Rγ induction by type II receptor has been analyzed using JAK inhibitors and RHE knockout (KO) for IL13RA1. IL-2Rγ function was investigated in RHE KO for IL2RG. In RHE, IL-4/IL-13 induce expression of IL-2Rγ at the mRNA and protein levels. Its mRNA expression is also visualized in keratinocytes of lesional AD skin. IL-2Rγ expression is low in RHE treated with JAK inhibitors and absent in RHE KO for IL13RA1. Exposure to IL-4/IL-13 alters epidermal barrier, but this alteration is absent in RHE KO for IL2RG. A more important induction of IL-13Rα2 is reported in RHE KO for IL2RG than in not edited RHE. These results demonstrate IL-2Rγ induction in keratinocytes through activation of type II receptor. IL-2Rγ is involved in the alteration of the epidermal barrier and in the regulation of IL-13Rα2 expression. Observation of IL-2Rγ expression by keratinocytes inside AD lesional skin suggests a role for this receptor subunit in the disease., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: It remains unclear whether multiple primary melanoma (MPM) patients have a worse survival prognosis compared with single primary melanoma (SPM) patients., Objectives: To investigate the demographics, histological features, and survival of MPM versus SPM patients., Methods: Cox regression analyses compared survival between SPM and MPM patients. Furthermore, demographics and histological features of the MPM cohort were compared with the SPM patients retrieved from dermatopathology files between 2000 and 2019., Results: Out of 3853 melanoma patients, 95 MPM patients were retrieved: 81 with two primary melanomas (85.2%) and 14.8% with three or more. Mean Breslow of the first melanoma was 0.84 mm [minimum (min): 0 mm, maximum (max): 16 mm, standard deviation (SD) 1.77] versus 0.37 mm (second MPM) (min: 0 mm, max: 2.5 mm, SD 0.50) and 0.33 mm (third MPM) (min: 0 mm, max: 0.6 mm, SD 0.22). The mean Breslow for the second MPM was significantly higher for men than women (0.59 mm versus 0.27 mm). First and second melanoma in MPM patients developed on preexisting melanocytic nevi in 13% and 12%, respectively. In contrast with the mean age of primary melanoma in Belgium for women (58.2 years) and men (63.3 years), MPM patients developed their first melanoma earlier, at 44.8 years and 54.6 years, respectively. The mean distribution of anatomical localization of primary and secondary melanoma was highly similar in women, whereas in men a shift towards lower extremities was observed (19% versus 28%). The thicker the primary melanoma was, the sooner the second appeared. Follow-up (2-4/year) versus (1/year) yielded a mean Breslow of 0.29 mm and 0.55 mm, respectively. Cox regression analysis with time-varying covariate revealed a tendency for a worse prognosis in 5-year survival rates, but this was not statistically significant (p = 0.09). Patient phenotypes were not available on the histological reports., Conclusion: A closer follow-up regimen of MPM versus SPM patients is probably justified., (© 2023. The Author(s).)

Background: The advancing evolution toward a Th2 immune environment confers a progressive immunosuppression in patients with longstanding cutaneous T-cell lymphoma (CTCL). The conjunction of the disease-related immunosuppression as well as the immunosuppressive character of some CTCL treatments increase the risk of infectious and neoplastic diseases, sometimes with fatal outcomes., Objectives: The aim of the study was to prospectively study the causes of death in a cohort of CTCL patients, in a tertiary university skin cancer center., Methods: All CTCL patients who died between 2008 and 2020 were included. The cause of the death was classified as directly or indirectly related or unrelated to CTCL., Results: Over the study period, 31 (13F/18m) patients with CTCL died (mean age: 75.2 years), mean delay between diagnosis and death: 3.2 years (min: 1, max: 12 years), 58.1% of death causes were classified as indirect (infection), 12.9% directly related (blastic transformation), 22.5% unrelated, and 6.5% of unknown cause. 51.6% of mycosis fungoides (MF) patients who died had early-stage disease (1A-2A) or were on remission. 45.2% of dead patients had advanced-stage MF (2B-4B). Mean CRP level is increased in patients who died from infection whereas LDH level increased in patients with blastosis. A tertiary center is expected to manage of a higher proportion of CTCL patients with advanced-stage disease., Conclusions: As infection represented more than 50% of the causes of death in CTCL patients, particular attention should be given to preventive measures such as anti-infective vaccination. Regular surveillance of CRP and LDH levels could be helpful for follow-up of MF patients, respectively, with regards to infection and blastosis., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Background: : Hereditary leiomyomatosis (HL) is an autosomal dominant condition due to a variety of fumarate hydratase (FH) mutations in which individuals tend to develop cutaneous leiomyomas, multiple uterine leiomyomas and are at risk for developing aggressive papillary renal cell carcinoma., Case Presentation: : A 26-year-old man with a past history of acute lymphoblastic leukemia (T-ALL) presented with numerous painful light brown papules and nodules spread all over his body except for the head, appearing since infancy. Similar lesions were present in his mother's family. A cutaneous biopsy revealed a cutaneous leiomyoma. His mother died from metastatic uterine neoplasia and his sister suffered from leiomyoma of the uterus. No renal cancer was reported in his family. A heterozygous pathogenic variant was detected in the FH gene., Conclusion: : To our knowledge, this is the first case possibly linking HL and T-ALL through FH deficiency.

The therapeutic prospects for patients with moderate to severe atopic dermatitis completely changed in 2017 with the arrival of the first targeted therapy, dupilumab. Achieving important clinical improvement scores are now possible with this monoclonal antibody directed against interleukins 4 and 13. Since that time, other agents such as tralokinumab arrived on the market, but also the small molecules called «JAK inhibitors» (upadacitinib, baricitinib, etc.). This article provides an inventory of the existing or imminent therapeutic options for atopic dermatitis.

Introduction: Non-dermatology medical specialties may refer patients for skin biopsies, searching for a particular diagnosis. However, the diagnostic impact of the skin biopsy is not clearly established. This article aims to assess the indications for, and evaluate the clinical relevance of, skin biopsies in non-dermatology medical specialties., Methods: A questionnaire was sent to 23 non-dermatology specialty departments in a university medical center, requesting a list of indications for skin biopsies, as well as to 10 staff dermatologists to collect the indications of skin biopsies requested by non-dermatology specialties. Once the indications were collected, a literature search was performed to evaluate their clinical value and relevance., Results: Eleven non-dermatology specialties provided a list of skin biopsy indications, to which staff dermatologists added seven more indications. A literature search revealed evidence-based medicine data for six diseases, that is, amyloidosis, peripheral autonomic neuropathy, Sneddon's syndrome, intravascular lymphoma, sarcoidosis, and chronic graft-versus-host disease. Results were questionable concerning infectious endocarditis, acute graft-versus-host-disease, and the lupus band test. Skin biopsy were not evidenced as useful for the diagnosis of calciphylaxis, systemic scleroderma, Behçet's disease, or hypermobile Ehlers-Danlos syndrome. For the diagnosis of Alport's syndrome, pseudoxanthoma elasticum, and vascular Ehlers-Danlos syndrome, skin biopsy is currently outperformed by genetic analyses. For diagnoses such as Henoch-Schönlein purpura and Sjögren's syndrome, skin biopsy represents an additional item among other diagnostic criteria., Conclusion: The usefulness of skin biopsy as requested by non-dermatology specialties is only evidenced for amyloidosis, peripheral autonomic neuropathy, Sneddon's syndrome, intravascular lymphoma, sarcoidosis, chronic graft-versus-host-disease, Henoch-Schönlein purpura, and Sjögren's syndrome., (© 2022. The Author(s).)

Introduction: Locally advanced basal cell carcinoma (laBCC) represents approximatively 1% of all BCCs. Metastatic BCC (mBCC) is even more rare. Most cases are observed in immunocompromised patients, particularly solid organ transplant recipients (OTRs). When surgery and/or radiation therapy for laBCC or mBCC is not reasonable, oral hedgehog inhibitor (HHI) therapy may be initiated. LaBCC or mBCC patients with primary or secondary resistance, progression or intolerance to HHIs could benefit from programmed cell death protein-1 (PD-1) inhibitors as this has recently been published for cemiplimab, a recombinant IgG4 human monoclonal antibody anti-PD-1 for the intravenous treatment of laBCC and mBCC., Areas Covered: Principal studies evaluating the efficacy and safety of cemiplimab for laBCC and mBCC are presented and discussed., Expert Opinion: Cemiplimab is the first FDA (2021) approved anti-PD-1 antagonist for the systemic treatment of laBCC and mBCC which had previously shown disease progression on or intolerance to HHIs. Experts currently recommend cemiplimab as a first-line systemic alternative. As cemiplimab therapy is associated with a risk of organ graft rejection, advantages and disadvantages should be evaluated for every individual OTR patient with laBCC or mBCC, eligible for cemiplimab therapy.

Introduction: Mycosis fungoides (MF) is the most frequent subtype of primary cutaneous T cell lymphomas (pCTCL). The diagnosis may be particularly difficult in the early stages as well as in atypical and rare clinical presentations. Furthermore, MF may simulate a large variety of common dermatologic disorders and patterns, both histopathologically and clinically., Methods: A literature search was performed to provide a comprehensive update on the rare and atypical MF manifestations as well as the dermatoses and dermatological patterns that could be imitated by MF., Results: A total of 114 publications were found describing a series of different dermatoses and dermatological patterns mimicked by MF, as well as some particular localizations of MF lesions and dermatoses that occur in preexisting MF lesions., Conclusions: The number of dermatoses that can be imitated by MF is ever-increasing. Patients with common dermatologic conditions that prove to be treatment refractory should be biopsied without delay, and sequentially as necessary, to prevent delay in diagnosis and progression of disease. Clinicopathologic correlation is the best way of diagnosis., (© 2021. The Author(s).)

Introduction: Psoriasis affects around 2% of children in Europe. The majority of cases is readily managed with topical treatments using corticosteroids without or with calcipotriol. More resistant and extensive moderate-to-severe cases require UVA or UVB phototherapies or conventional systemic treatment including ciclosporin, acitretin and methotrexate. However, these therapies are associated with a low tolerability and potential cumulative long-term adverse effects and toxicities., Areas Covered: About 15 years ago, the first biological appeared for the treatment of moderate-to-severe plaque type psoriasis in adult patients. Several years later, the first biologic treatment to be approved in children was etanercept, a soluble receptor that binds both tumor necrosis factor (TNF)-α and β followed by adalimumab, a monoclonal antibody against TNF-α, and currently by ustekinumab, a monoclonal IL12/23 p40 antagonist and, very recently, secukinumab and ixekizumab, both IL17 antagonists. All these biologic treatments brought significantly improved treatment results compared to light-based therapies and conventional treatments and present very good tolerance and safety profiles., Expert Opinion: Due to their excellent efficacy and safety profiles ustekinumab, secukinumab and ixekizumab could currently be considered as a first-line treatment options for moderate-to-severe childhood and adolescent psoriasis requiring a systemic treatment.

The management of melanoma is a typical example of a pluridisciplinary approach, in order to provide the patient with a rapid and adequate treatment plan after the initial diagnosis. Both in the domains of dermatology, pathology and oncology, enormous progress has been made. Recent advances permit a rapid access to diagnostic techniques using teledermoscopy, an improved diagnostic accuracy using dermoscopy, pre-interventional high-frequency ultrasound and optical coherence tomography, a determination of risk factors using immunohistochemistry and genetic analyses on the pathology samples. Furthermore, the development of immunotherapies, in particular the anti-PD1 antibodies, and the directed therapies, therapies permitting an increased number of patients to experience an increased survival with an acceptable tolerance profile in the event of metastatic lesions. This article describes the patient's care pathway, from the initial diagnosis, staging, to an eventual treatment and follow-up.

Introduction: Locally advanced cutaneous squamous cell carcinoma (lacSCC) is rare. Approximately one-fourth of the cases are observed among immunocompromised patients, in particular in solid organ transplant recipients (OTRs). LacSCC has a very poor prognosis. Surgery with or without radiotherapy remains the golden standard of treatment for cSCC. However, in advanced cases, there is a medical need for alternative treatment options. Classic systemic treatments include chemotherapy and/or EGFR inhibitors. Recently the effectiveness of programmed cell death protein-1 (PD-1) inhibitors has been demonstrated for lacSCC. Cemiplimab is a recombinant IgG4 human monoclonal antibody against the PD-1 protein for the intravenous treatment of lacSCC., Areas Covered: The principal studies evaluating the efficacy and safety of cemiplimab for lacSCC are presented., Expert Opinion: Cemiplimab is the first anti-PD-1 antibody that was FDA (2018) and EMA (2019) approved as a systemic treatment for lacSCC and/or metastatic cSCC when curative surgery or radiotherapy is no longer amenable. For this situation, experts currently recommend cemiplimab as a first-line systemic alternative. As cemiplimab therapy is potentially associated with a risk of organ graft rejection, pros and cons should be evaluated for every individual OTR patient with lacSCC.

Androgenic alopecia is a genetically determined and leads to a progressive hair loss of the vertex, affecting both men and women. It is related to an important psychological and social distress. Medical therapies include topical minoxidil, oral 5?-reductase inhibitors and oestroprogestative drugs with anti-androgen effects for women. The surgical option is autograft hair transplantation. Recently, phototherapy with low-level energy lasers became available. All these treatments may present adverse effects and their effectiveness is questionable. Subcutaneous injections of autologous platelet-rich plasma into the scalp represent an interesting alternative treatment for androgenetic alopecia, as monotherapy or as an adjuvant treatment. The methodology, the possible mechanisms of action and some initial clinical results of this treatment are presented.

Introduction: Teledermoscopy using smartphone-based applications is becoming more and more important in a setting of increasing frequency of skin cancer and difficult access to specialized care. The TELESPOT project aimed to provide rapid diagnosis and speed up patient flow between primary healthcare centers and a tertiary care center in Belgium. The aim of the present study is to describe the development of an in-house smartphone-based dermoscopy application, evaluate its real-life value in a series of primary healthcare centers, and present preliminary diagnostic data., Methods: Modified Likert scales were used to assess patient and general practitioner (GP) satisfaction rates for the system. Furthermore, a total of 105 photographic and dermoscopic images were acquired in a series of 80 patients at participating centers., Results: Overall, patient and GP satisfaction levels were 89% and 94%, respectively. High-priority management was recommended in 7.6% of cases (8/105: 3 basal cell carcinoma, 1 primary cutaneous B-cell lymphoma, 1 Spitz melanocytic nevus, 1 congenital nevus, 1 in situ melanoma, and 1 invasive melanoma, proven by histology)., Conclusions: The primary healthcare centers were highly satisfied with the TELESPOT project in terms of user-friendliness, efficacy, and reliability as well as in providing a reinforced image of first-line medicine efforts in combating skin cancer.

Background: Limited options are available for treatment of paediatric psoriasis., Objectives: To evaluate the efficacy and safety of ustekinumab in paediatric patients with psoriasis (≥ 6 to < 12 years of age)., Methods: CADMUS Jr, a phase III, open-label, single-arm, multicentre study, evaluated ustekinumab in paediatric patients with moderate-to-severe plaque psoriasis. Patients received weight-based dosing of ustekinumab (< 60 kg: 0·75 mg kg -1 ; ≥ 60 to ≤ 100 kg: 45 mg; > 100 kg: 90 mg) administered by subcutaneous injection at weeks 0 and 4, then every 12 weeks through week 40. Study endpoints (all at week 12) included the proportions of patients achieving a Physician's Global Assessment score of cleared/minimal (PGA 0/1) and ≥ 75%/90% improvement in Psoriasis Area and Severity Index (PASI 75/90), and change in Children's Dermatology Life Quality Index (CDLQI). Serum ustekinumab concentrations, antidrug antibodies and cytokine levels were measured through week 52. Safety was evaluated through week 56., Results: In total, 44 patients (median age 9·5 years) received at least one dose of ustekinumab. Three patients discontinued the study agent through week 40. At week 12, 77% of patients achieved PGA 0/1, 84% achieved PASI 75 and 64% achieved PASI 90 response. The mean change in CDLQI was -6·3. Trough serum ustekinumab concentrations reached steady state at weeks 28-52. The incidence of antidrug antibodies was 10% (n = 4). Mean serum concentrations of interleukin-17A/F and interleukin-22 were significantly reduced at weeks 12 and 52. Overall, 34 patients (77%) had at least one adverse event and three (7%) had a serious adverse event., Conclusions: Ustekinumab effectively treated moderate-to-severe psoriasis in paediatric patients, and no new safety concerns were identified. What is already known about this topic? Ustekinumab is approved for use in adolescents (≥ 12 to < 18 years of age) and adults (≥ 18 years) with moderate-to-severe psoriasis. What does this study add? Ustekinumab effectively treats moderate-to-severe psoriasis in paediatric patients (≥ 6 to < 12 years of age), with no new safety concerns. Linked Comment: Reich. Br J Dermatol 2020; 183:606-607., (© 2020 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Risankizumab, an interleukin (IL)-23 antagonist, is a highly effective treatment for moderate to severe psoriasis. Crusted scabies (CS) is a rare and severe form of scabies, occurring mainly in immunosuppressed patients and/or neurologically or mentally ill patients. A young girl with Down syndrome was diagnosed with a hyperkeratotic form of psoriasis. As treatment with topical dermocorticosteroids, UVB-phototherapy and acitretin for 6 weeks did not improve the lesions, two injections of risankizumab were administered. Following these injections, the lesions became rapidly even more severely crusted, and new lesions appeared on the extremities and the face of the patient. There was histological evidence of a high charge of scabies, leading to a diagnosis of CS. The patient was hospitalized and successfully treated by local permethrine and systemic ivermectine. This case suggests that even though anti-IL23 antagonists display an excellent overall safety profile, a particular caution for infections should still be respected in patients with underlying risk factors.

Introduction: Cutaneous metastases of breast cancer remain a therapeutic challenge. Oxygen flow-assisted topical administration of methotrexate 5% (OFAMTX, 5% methotrexate in a carrier solution) has recently been proven to be an efficacious alternative treatment for extramammary Paget's disease, which is considered to be an in situ mammary adenocarcinoma of the epidermis., Case Report: A 51-year-old patient with triple negative breast cancer presenting with biopsy-proven skin metastases on the chest agreed to a treatment with OFAMTX5%. The treatment duration was 2 weeks and consisted of twice-weekly sessions with OFAMTX5% applied to an area of skin of approximately 40 cm 2 . Skin biopsies were performed before and 2 months after procedure. The tolerance to the treatment was excellent, and no pain sensations were experienced. Two months post-procedure the treated area presented a post-inflammatory hyperpigmentation. No residual metastatic lesions were detectable on the control skin biopsy. Six months post-procedure the patient is still in clinical remission., Discussion: OFAMTX5% represents an alternative skin-directed, painless, patient-friendly and efficacious adjuvant treatment for superficial metastatic lesions of breast cancer. Larger series are required to evaluate the potential of OFAMTX5% for the treatment of superficial metastatic lesions of breast cancer.

Psoriasis is a chronic inflammatory skin disease affecting around 2-3 % of the population. The disease spectrum evolves from to the knees and elbows limited disease to erythrodermic psoriasis. The impact on the quality of life, the pruritus, the pain from palmo-plantar disease, arthropathic psoriasis and the comorbidities are the major complaints of the patients. The treatment relies on topical treatments with dermocorticosteroids with or without vitamin D derivatives, UVA or UVB phototherapy, conventional treatments including methotrexate, ciclosporin and acitretin, and, since around 15 years, biological treatments. The biological treatments for moderate to severe psoriasis progressed in a spectacular way with an improvement of clinical results and an amelioration of the safety profile at every step. This article discusses these developments from the TNF? antagonists, including etanercept, adalimumab and infliximab to the newly arrivals, the anti-IL17 and anti-IL23 antagonists, the anti-PDE-4 antagonists and the JAK inhibitors.

The molecular weight of methotrexate (MTX) makes cutaneous penetration difficult. Oxygen flow could enhance the skin permeation of MTX diluted in the proprietary LP3 carrier system. This pilot study aims to assess the efficacy, safety, and tolerance of oxygen flow-assisted LP3-MTX3% for treating superficial skin cancers. Patients with superficial basal cell carcinoma (n = 12), extramammary Paget disease (n = 5), classic mycosis fungoides (MF; n = 10), and folliculotropic MF (n = 6) were included in the study and were treated with four weekly applications of oxygen flow-assisted LP3-MTX3%. Photographs and biopsies were performed before and one month after treatment. At one month after treatment, the mean superficial basal cell carcinoma erythema-crusting-thickness clinical score, the extramammary Paget disease erythema-oozing-scaling/hyperkeratosis-pain/pruritus clinical score, and the modified composite assessment of index lesion severity classic MF and folliculotropic MF scores were improved by 77.5% ± 17.1% (P < 0.0001), 66.7% ± 22.9% (P = 0.011), 51.3% ± 32.2% (P = 0.0007), and 27.8% ± 32.0% (P = 0.086), respectively. At one month after treatment, histology revealed partial and total clearances for superficial basal cell carcinoma (1/12, 11/12), extramammary Paget disease (4/5, 1/5), classic MF (8/10, 2/10), and folliculotropic MF (6/6, 0/6). Tolerance was excellent and no pain was observed. MTX was never detectable in serum at baseline and 1, 2, 3, 8, 24, 48, and 72 hours post-treatment. In conclusion, the interesting therapeutic efficacy of oxygen flow-assisted LP3-MTX3% for treating superficial basal cell carcinoma, extramammary Paget disease, and MF lesions prompts further studies on a larger scale., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Besides the principal respiratory symptoms, the COVID-19 has been associated with an important array of dermatological manifestations. However, it is not always easy to distinguish whether these skin manifestations are the result of a direct action of the virus on epidermal and/or dermal cell populations, represent a paraviral phenomenon or are a rather fortuitous association. In this review the principal cutaneous manifestations associated with COVID-19 are described as well as their eventual value in terms of diagnostic aid or as prognostic factor. The palmoplantar ischemic pseudo-chilblains lesions are the most frequently observed and are useful for epidemiological purposes. The disseminated vesicular eruptions affect about 23 % of the patient and may witness an initial COVID-19 infection, whereas the vasculitic lesions are rather rare but are currently considered as a factor of bad prognosis.

Since decades the incidence of skin cancer is clearly rising. This alarming trend also applies to melanoma. It represents the 4th most common cancer in women and 6th in men in 2015. Early recognition and treatment reduce both morbidity and mortality. Screening is the cornerstone of secondary prevention. However, access to reliable and rapid diagnosis is hampered by several factors, including accessibility to specialized medicine. One of the solutions to this problem is to collaborate with the first-line medical care through a teledermatology system. The TeleSPOT project, Teledermoscopy Smartphone-based Pigmented lesion diagnosis Online Taskforce, aims to provide a remote diagnostic aid by dermatologists to distinguish suspect pigmented skin lesions and accelerate their management.

The treatment of locally advanced or metastatic cutaneous squamous cell carcinoma (cSCC) essentially relies on surgery and eventually radiotherapy of the treated site and afferent lymph nodes. Unfortunately, some cases are no candidates for surgery or radiotherapy and a systemic treatment may be indicated. Chemotherapies are only partially efficacious and associated with potential toxicities. A recent study evaluating the efficacy and tolerance of cemiplimab, a PD1 antagonist for locally advanced and metastatic cSCC demonstrated an objective response rate of 49 % and 47 % for locally advanced and metastatic cSCC, while maintaining a response of at least 6 months of 63 % and 60 %, respectively. We present a clinical case of a patient with a locally advanced cSCC of the forehead with bone resorption and cervical lymphadenopathies. After failure of multiple surgical interventions and radiotherapies, he responded partially to cemiplimab immunotherapy with a good safety profile.

Cutaneous manifestations related to alcohol intake and abuse are various. Most frequently, there are vascular lesions and cutaneous alterations secondary to hepatic dysfunction. Alcohol consumption represents also a risk factor for many cutaneous diseases, such as psoriasis, where its prevalence is high. Other cutaneous complications associated with alcohol are also discussed.