Circadian clocks guide dendritic cells into skin lymphatics.

Migration of leukocytes from the skin to lymph nodes (LNs) via afferent lymphatic vessels (LVs) is pivotal for adaptive immune responses1,2. Circadian rhythms have emerged as important regulators of leukocyte trafficking to LNs via the blood3,4. Here, we demonstrate that dendritic cells (DCs) have a circadian migration pattern into LVs, which peaks during the rest phase in mice. This migration pattern is determined by rhythmic gradients in the expression of the chemokine CCL21 and of adhesion molecules in both mice and humans. Chronopharmacological targeting of the involved factors abrogates circadian migration of DCs. We identify cell-intrinsic circadian oscillations in skin lymphatic endothelial cells (LECs) and DCs that cogovern these rhythms, as their genetic disruption in either cell type ablates circadian trafficking. These observations indicate that circadian clocks control the infiltration of DCs into skin lymphatics, a process that is essential for many adaptive immune responses and relevant for vaccination and immunotherapies.

European e-Delphi process to define expert consensus on electrochemotherapy treatment indications, procedural aspects, and quality indicators in melanoma.

BACKGROUND: Skin metastases are an important co-morbidity in melanoma. Despite broad adoption, electrochemotherapy implementation is hindered by a lack of treatment indications, uncertainty regarding procedural aspects, and the absence of quality indicators. An expert consensus may harmonize the approach among centres and facilitate comparison with other therapies. METHODS: An interdisciplinary panel was recruited for a three-round e-Delphi survey. A literature-based 113-item questionnaire was proposed to 160 professionals from 53 European centres. Participants rated each item for relevance and degree of agreement on a five-point Likert scale, and received anonymous controlled feedback to allow revision. The items that reached concordant agreement in two successive iterations were included in the final consensus list. In the third round, quality indicator benchmarks were defined using a real-time Delphi method. RESULTS: The initial working group included 122 respondents, of whom 100 (82 per cent) completed the first round, thus qualifying for inclusion in the expert panel (49 surgeons, 29 dermatologists, 15 medical oncologists, three radiotherapists, two nurse specialists, two clinician scientists). The completion rate was 97 per cent (97 of 100) and 93 per cent (90 of 97) in the second and third rounds respectively. The final consensus list included 54 statements with benchmarks (treatment indications, (37); procedural aspects, (1); quality indicators, (16)). CONCLUSION: An expert panel achieved consensus on the use of electrochemotherapy in melanoma, with a core set of statements providing general direction to electrochemotherapy users to refine indications, align clinical practices, and promote quality assurance programmes and local audits. The residual controversial topics set future research priorities to improve patient care.

Electrochemotherapy is an effective locoregional therapy for skin metastases from melanoma, a problem faced by almost half of patients with metastatic disease. The lack of comparative studies and the heterogeneity of its clinical application among centres make it challenging to support consistent, evidence-based recommendations. To address this unmet need, a three-round online survey was conducted to establish a consensus on treatment indications, standard operating procedures, and quality indicators. In the survey, a panel of 100 European melanoma experts agreed on 56 statements that can be used to improve patient selection, homogenize treatment application, and monitor outcomes.

[Surgical treatment of hidradenitis suppurativa]. / Prise en charge chirurgicale de l'hidradénite suppurée.

Hidradenitis suppurativa (HS) is a chronic relapsing inflammatory disease that primarily affects the apocrine skin glands. Management options include risk factor modification, pharmacologic agents, and surgery. Many surgical management techniques exist, including incision and drainage, laser hair removal, deroofing, limited or wide local excision. Deroofing is an interesting alternative for simple superficial fistulas and potentially even for more complex lesions. Surgical treatment can be combined with drug treatment. The indication depends on a comprehensive and multidisciplinary assessment considering the severity and number of target lesions.

L'hidradénite suppurée (HS) est une maladie inflammatoire chronique récurrente qui affecte principalement les glandes cutanées apocrines. Les options de prise en charge comprennent la modification des facteurs de risque, les agents pharmacologiques et la chirurgie. De nombreuses techniques de prise en charge chirurgicale existent, notamment l'incision et le drainage, la thérapie au laser épilatoire, le deroofing et l'excision limitée ou large. Le deroofing est une alternative intéressante pour les fistules simples superficielles et, potentiellement, pour les lésions plus complexes. Le traitement chirurgical peut être combiné au traitement médicamenteux. L'indication dépend d'une évaluation globale et pluridisciplinaire prenant en compte la sévérité et le nombre de lésions.

[Dermatology - Latest developments in targeted therapies for atopic dermatitis, alopecia areata and chronic spontaneous urticaria]. / Dermatologie - Dernières avancées des thérapies ciblées dans la dermatite atopique, la pelade et l'urticaire chronique spontanée.

In recent years, a lot of targeted therapies have appeared on the market. The huge choice and rapid development make it sometimes difficult to stay up to date. This article reviews the latest therapies in the field of atopic dermatitis, alopecia areata and chronic spontaneous urticaria. Anti-IL-4 and anti-IL-13 antibodies and, more recently, JAK inhibitors have been proven to be effective for moderate to severe atopic dermatitis. JAK inhibitors seem promising for the treatment of severe alopecia areata. Ligelizumab and nemoli zumab will provide therapeutical options for chronic spontaneous urticaria and prurigo respectively. These breakthroughs will improve the quality of life of people suffering from invalidating dermatitis, at a certain price.

Depuis quelques années apparaissent sur le marché de multiples thérapies ciblées. Il est parfois difficile de s'y retrouver tant le choix est grand et l'avancée rapide. Cet article résume les nouveautés dans le domaine de la dermatite atopique, de la pelade et de l'urticaire chronique spontanée. Il a été démontré récemment que les anticorps anti-IL (interleukines)-4 et anti-IL-13 ainsi que les inhibiteurs des Janus kinases (JAK) étaient efficaces dans la dermatite atopique modérée à sévère. Dans la pelade sévère, les inhibiteurs des JAK semblent prometteurs. Le ligélizumab et le némolizumab vont compléter les options thérapeutiques de l'urticaire chronique et du prurigo respectivement. Ces avancées permettent d'améliorer la qualité de vie de personnes présentant des pathologies dermatologiques invalidantes, à un certain coût.

Skin Cancer Development in Solid Organ Transplant Recipients in Switzerland (Swiss Transplant Cohort Study).

IMPORTANCE: Skin cancer, in particular squamous cell carcinoma, is the most frequent malignancy among solid organ transplant recipients with a higher incidence compared to the general population. OBJECTIVE: To determine the skin cancer incidence in organ transplant recipients in Switzerland and to assess the impact of immunosuppressants and other risk factors. DESIGN: Prospective cohort study of solid organ transplant recipients in Switzerland enrolled in the Swiss Transplant Cohort Study from 2008 to 2013. PARTICIPANTS: 2,192 solid organ transplant recipients. MATERIALS AND METHODS: Occurrence of first and subsequent squamous cell carcinoma, basal cell carcinoma, melanoma and other skin cancers after transplantation extracted from the Swiss Transplant Cohort Study database and validated by medical record review. Incidence rates were calculated for skin cancer overall and subgroups. The effect of risk factors on the occurrence of first skin cancer and recurrent skin cancer was calculated by the Cox proportional hazard model. RESULTS: In 2,192 organ transplant recipients, 136 (6.2%) developed 335 cases of skin cancer during a median follow-up of 32.4 months, with squamous cell carcinoma as the most frequent one. 79.4% of skin cancer patients were male. Risk factors for first and recurrent skin cancer were age at transplantation, male sex, skin cancer before transplantation and previous transplantation. For a first skin cancer, the number of immunosuppressive drugs was a risk factor as well. CONCLUSIONS AND RELEVANCE: Skin cancer following solid organ transplantation in Switzerland is greatly increased with risk factors: age at transplantation, male sex, skin cancer before transplantation, previous transplantation and number of immunosuppressive drugs.

[Micrographic surgery and its variants]. / La chirurgie micrographique et ses variantes.

Cutaneous tumours can be ill-delineated and subclinical tumour can be missed when using the usual methods of pathology processing because only less than 1 % of the margin is examined. Micrographic surgery was developed to allow for examination of 100 % of the margin. It reduces the recurrence rate and spares healthy tissue thus reducing lesion size and facilitating reconstruction. This method is particularly suitable for peri-orificial cutaneous tumours of the face with high rates of local recurrence. Mohs micrographic surgery is the main technique for frozen tissue and there are other often under-recognized variations using permanent paraffin sections known as the «â€…collerette ¼ ( spaghetti), «â€…muffin ¼ or the «â€…Tübinger Torte ¼ method.

Certaines tumeurs cutanées ont des ramifications infracliniques ponctuelles qui peuvent être non visualisées en histologie classique, puisque moins de 1 % des marges sont observées. La chirurgie micrographique s'est développée dans le but d'obtenir un contrôle histologique de 100 % des marges d'excision, aboutissant à un faible taux de récidive, tout en permettant une épargne des tissus sains. Les pertes de substance étant moins grandes, les reconstructions sont moins lourdes. Cette méthode s'applique tout particulièrement aux tumeurs péri-orificielles du visage à haut risque de récidive. Parmi les techniques sur tissu congelé, la plus connue est celle selon Mohs. Il existe d'autres variantes avec technique de fixation au formol, souvent méconnues et sous-utilisées, telles que la méthode de la collerette ( spaghetti), le muffin ou en gâteau.

[A plethora of choices: treating actinic keratoses]. / Traitement des kératoses actiniques†: l'embarras du choix.

Actinic keratoses are the most frequent precancerous lesions on Caucasian skin, often giving rise to squamous cell carcinomas. Appropriate prophylaxis, screening, and early intervention can substantially reduce the incidence of the latter. While isolated actinic keratoses can easily be treated by means of cryotherapy or curettage, multiple lesions often occurring on chronically sun-damaged skin demand more potent therapeutic strategies, such as topical cytostatic or immunomodulatory drugs, or photodynamic therapy. In this review, we give a practice-oriented overview on clinical manifestations, prevention, and treatment of actinic keratoses, and we emphasise the role of general practitioners in the management of this important pathology.

Les kératoses actiniques sont les lésions précancéreuses les plus fréquentes du phénotype caucasien, présentant un risque de transformation en carcinomes épidermoïdes cutanés. L'incidence de ces derniers peut être réduite par la prophylaxie, le dépistage et la prise en charge dermatologique précoce. Alors que les kératoses actiniques isolées peuvent être facilement traitées par la cryothérapie ou le curettage, les lésions multiples, survenant souvent sur la peau chroniquement endommagée par le soleil, exigent des stratégies thérapeutiques plus puissantes, telles que des médicaments topiques cytostatiques ou immunomodulateurs, ou la thérapie photodynamique (PDT). Cet article donne un aperçu pratique des manifestations cliniques, de la prévention et du traitement des kératoses actiniques, et souligne le rôle des médecins généralistes dans la gestion de cette pathologie importante.

[Phenolisation: treatment of choice for ingrown nails]. / Phénolisation†: traitement chirurgical de choix pour les ongles incarnés.

Ingrown nails are a common and painful pathology not always responding to local treatment. Destroying the matrix by application of phenol (phenolisation) has proven its superiority over the so called classic surgical methods. This is partially due to the exceptional properties of phenol: demyelinisation of the terminal nerve fibres provides long-term pain relief, the coagulation of proteins stops bleeding and the molecule has antiseptic properties. Phenolisation requires only few resources and can be widely used. Recurrence rates are particularly low at 2 %. We present this technique as the treatment of choice for ingrown nails.

L'ongle incarné est une pathologie fréquente et douloureuse ne répondant pas toujours à des soins locaux. La technique par destruction chimique par phénol (phénolisation) a montré sa supériorité par rapport aux méthodes chirurgicales dites classiques. Ceci s'explique par les propriétés particulièrement intéressantes du phénol : effet antalgique à long terme par démyélinisation des fibres nerveuses terminales, une cautérisation par coagulation des protéines ainsi que des propriétés antiseptiques. La phénolisation nécessite peu de matériel et peut s'appliquer à une large frange de la population. De plus, elle présente un taux de récidives particulièrement bas à 2 %. Pour toutes ces raisons, c'est un traitement de choix dans l'arsenal thérapeutique des ongles incarnés.

Swiss Practice Recommendations for the Management of Hidradenitis Suppurativa/Acne Inversa.

Hidradenitis suppurativa (HS) is a painful, inflammatory, debilitating skin disease with a chronic intermittent course. The central pathogenetic event seems to be the occlusion of the hair follicle. HS has a 1-year prevalence of about 1%. It typically presents after puberty with painful, deep-seated, inflamed lesions in the apocrine gland-bearing areas of the body: most commonly the axillae, inguinal, and anogenital regions. HS has a high negative impact on patients' quality of life even in patients with only limited disease burden, and the diagnosis of HS is often made with a long diagnostic delay. In this practical short version we present diagnostic and therapeutic recommendations which are based on a systematic literature search as well as an informal expert consensus of Swiss dermatologists and dermatosurgeons.

Ingenol Mebutate vs. Daylight Photodynamic Therapy in a Kidney Transplant Recipient.

We present the case of a 73-year-old male patient who had received a first renal transplant at 36 years and a second one at the age of 55 years. He is currently under immunosuppression with everolimus 2.5 mg/day and prednisone 5 mg/day. The patient presented with multiple actinic keratoses on both cheeks and the forehead and received treatment by ingenol mebutate 150 µg/g gel daily on 3 consecutive days on his right cheek and methyl aminolevulinate (MAL) photodynamic therapy activated by daylight (MAL-dPDT) on the forehead and the left cheek. MAL-dPDT treatment proved a feasible, repeatable, physician-directed method of treating field cancerization with limited morbidity for a period of 6 days. Treatment with ingenol mebutate gel was a feasible, possibly self-directed method of treating field cancerization with limited morbidity for 10 days in this immunosuppressed patient. Both treatments showed similar efficacy. At the time of treatment, the MAL daylight PDT ran at 3 times the cost of ingenol mebutate gel.

Ingenol Mebutate for Recalcitrant Chronic Actinic Cheilitis.

We present the case of a healthy 76-year-old man with a whitish, hyperkeratotic lesion of the lower lip diagnosed as actinic cheilitis (AC) previously treated with classic red light photodynamic therapy 5 years ago. Initial treatment with 5% imiquimod cream - also with intensified application - failed. After 2 cycles thrice daily, consecutive applications of 150 µg/g ingenol mebutate gel at 3 weeks' interval, the lesions cleared completely. Surprisingly, no pustular or crusting reaction or other side effect occurred contrary to expectation. Remission was stable for 10 months, when recurrence occurred. Ingenol mebutate proved to be a feasible and safe treatment in this otherwise refractory case of AC.

Cutaneous squamous cell carcinoma with perineural invasion: report on eight cases and review of the literature.

BACKGROUND: Perineural invasion (PNI) in cutaneous squamous cell carcinoma (SCC) is considered to be a negative prognostic factor. A lot of uncertainty remains regarding the classification, diagnosis, treatment and prognosis of SCC with PNI. OBJECTIVE: To describe typical courses of SCC with PNI and associated findings in order to suggest an optimized diagnostic and therapeutic approach. METHODS: We present eight cases of SCC with PNI, considering patient and tumor characteristics, histology, treatment and clinical course regarding local recurrence and metastasization. RESULTS: SCC patients with PNI have a higher rate of local recurrences and greater risk for metastasization than SCC patients without PNI. Age ranged from 68 to 77 years, 6 patients were male and 2 female, with all tumors localized on the head. Three patients had chronic lymphocytic leukemia. CONCLUSION: Based on the data of this series and the current literature, we make suggestions for better diagnostic and therapeutic management.

[Antisepsis of wounds: when and what?]. / Antisepsie des plaies: quand et quoi?

Bacterial colonisation of a wound is a normal process and usually not dangerous. The role of micro-organisms in the healing process is not fully elucidated, however it is well known that infection interrupts healing and even worse can severely threaten the organism. We present the different types of antiseptics that are used in treating wounds as well as their interactions. We would like to remind the reader that antiseptics are more effective than antibiotics with much fewer resistances. Finally, we provide a flow chart for a reasonable treatment of chronic wounds.

Unilateral favre-racouchot disease: evidence for the etiological role of chronic solar damage.

Favre-Racouchot disease commonly presents as comedones, cysts and elastosis in the periocular region of older men. Its etiology has been linked to several exogenous factors. Here we present 2 patients with strictly unilateral manifestation of the disease and a corresponding history of predominantly one-sided chronic occupational sun exposure and smoking, making the case for the causative role of these two factors.

Risk factors for early-onset basal cell carcinoma in a German institution.

BACKGROUND: Genetic predisposition and ultraviolet (UV) exposure are the most important risk factors for basal cell carcinoma (BCC). Recent reports have demonstrated an increasing incidence of BCC among younger patients. We investigated potential risk factors for sporadic BCC in a subset of young German patients. METHODS: Twenty-five patients with BCC at the age of 19 to 40 years (mean 34.4 years) were included in the study. They were selected from a total of 2,058 patients who received surgical treatment for BCC between December 2004 and November 2008. Patients were contacted by telephone interview and asked about sun habits, associated medical conditions, and lifestyle-related variables. Data were compared with interview results from sex-, age- and skin type-matched controls. RESULTS: We found 1.4% (29) of 2,058 BCC patients to be ≤40 years of age. Four patients had Gorlin-Goltz syndrome and were excluded from further analysis. Multivariate analysis showed tanning bed use (OR= 25.0; IC95%: 2.26-277.36) and smoking (OR=13.34; IC95%: 1.56-113.8) to be the most significant independent risk factors for BCC, while sunscreen use had a protective effect. CONCLUSION: BCCs in young patients were only rarely related to hereditary syndromes, but were associated with environmental carcinogens, i.e. UV radiation and smoking.

A new pathway in teaching dermatology.

New legislative requirements for medical licensure in 2003 made necessary restructuring of medical education at German universities. Since the hours of patient contact and the proportion of small group teaching were explicitly defined, many curricula had to be changed fundamentally. For the clinical years of its Medical Curriculum Munich (MeCuM(LMU)) the medical faculty of the Ludwig-Maximilian University in Munich (LMU) decided on a modular concept. For dermatology, this meant less lecture time, more student-patient interaction, the introduction of small group teaching, and the establishing of a catalogue of learning objectives. In cooperation with the Virtual University of Bavaria the internet was integrated into mandatory teaching for the first time. A faculty development program was instituted to increase teaching competence. All measures were designed to create an individual learning setting offering optimal support for every student. The large number of students remains the final nemesis.