Systemic anti-inflammatory treatment of atopic dermatitis during conception, pregnancy and breastfeeding: Interdisciplinary expert consensus in Northern Europe.

Treating atopic dermatitis (AD) in pregnant or breastfeeding women, and in women and men with AD aspiring to be parents is difficult and characterized by uncertainty, as evidence to inform decision-making on systemic anti-inflammatory treatment is limited. This project mapped consensus across dermatologists, obstetricians and patients in Northwestern Europe to build practical advice for managing AD with systemic anti-inflammatory treatment in men and women of reproductive age. Twenty-one individuals (sixteen dermatologists, two obstetricians and three patients) participated in a two-round Delphi process. Full consensus was reached on 32 statements, partial consensus on four statements and no consensus on four statements. Cyclosporine A was the first-choice long-term systemic AD treatment for women preconception, during pregnancy and when breastfeeding, with short-course prednisolone for flare management. No consensus was reached on second-choice systemics preconception or during pregnancy, although during breastfeeding dupilumab and azathioprine were deemed suitable. It may be appropriate to discuss continuing an existing systemic AD medication with a woman if it provides good disease control and its benefits in pregnancy outweigh its risks. Janus kinase (JAK) inhibitors, methotrexate and mycophenolate mofetil should be avoided by women during preconception, pregnancy and breastfeeding, with medication-specific washout periods advised. For men preconception: cyclosporine A, azathioprine, dupilumab and corticosteroids are appropriate; a 3-month washout prior to conception is desirable for methotrexate and mycophenolate mofetil; there was no consensus on JAK inhibitors. Patient and clinician education on appropriate (and inappropriate) AD treatments for use in pregnancy is vital. A shared-care framework for interdisciplinary management of AD patients is advocated and outlined. This consensus provides interdisciplinary clinical guidance to clinicians who care for patients with AD before, during and after pregnancy. While systemic AD medications are used uncommonly in this patient group, considerations in this article may help patients with severe refractory AD.

[Mucinous nevus]. / L'image du mois. Naevus mucineux.

Mucinous nevus is an exceptional entity and presents as flesh-colored to brownish papules or plaques, coalescing to form a pigmentary or verrucous lesion with either a blaschkoid, linear, grouped or zosteriform disposition. It usually appears at birth or during early childhood, but late onset has also been described. Mucinous nevus does not require additional work-up as no internal pathologies have been described. Abstention of any therapeutic intervention is usually preferred.

: Le naevus mucineux est une entité exceptionnelle, se présentant par des papules ou des plaques de couleur chair à brunâtre qui confluent sous la forme d'une lésion pigmentaire ou verruqueuse de distribution blaschkoïde, linéaire, groupée ou zostériforme. Il est le plus souvent congénital ou d'apparition précoce, mais des formes tardives ont également été rapportées. Le naevus mucineux n'est jamais associé à une pathologie interne et ne nécessite pas d'exploration complémentaire. Au vu du caractère bénin, l'abstention thérapeutique est généralement la règle.

[Atopic dermatitis : the therapeutic revolution is underway]. / Dermatite atopique : la révolution thérapeutique est en marche.

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 inhibitors¼ (upadacitinib, baricitinib, etc.). This article provides an inventory of the existing or imminent therapeutic options for atopic dermatitis.

: Les perspectives thérapeutiques pour les patients atteints de dermatite atopique modérée à sévère ont été complètement bouleversées en 2017 avec l'arrivée sur le marché de la première thérapie ciblée, le dupilumab. Cet anticorps monoclonal dirigé contre les interleukines 4 et 13 permet d'atteindre des scores d'amélioration clinique encore inespérés il y a quelques années. Depuis, d'autres biothérapies comme le tralokinumab sont arrivés sur le marché européen, mais également des petites molécules appelées «inhibiteurs JAK¼ (upadacitinib, baricitinib, etc.). Cet article présente un état des lieux des options thérapeutiques existantes ou imminentes pour la prise en charge de la dermatite atopique.

[Köbner's phenomenon in dermatology]. / Cas clinique. Le phénomène de Köbner en dermatologie.

Köbner's phenomenon and its related phenomena are dermatological curiosities that are still partially misunderstood. The Köbner phenomenon is by far the best known and the most studied. It is characterized as the appearance of an inflammatory or infectious dermatosis in an area of healthy skin after skin trauma. The dermatoses most frequently concerned are psoriasis, lichen planus and vitiligo. The inverse Köbner phenomenon and the Renbök phenomenon are two very similar phenomena. The first represents the disappearance of a skin lesion after skin trauma. The second is characterized by a skin trauma that is more specifically induced by another dermatosis. Finally, the Wolf's isotopic phenomenon corresponds to the appearance of a new dermatosis on an area of the skin that was previously the site of another healed dermatosis.

Le phénomène de Köbner et les phénomènes qui lui sont apparentés sont des curiosités dermatologiques, encore partiellement incomprises. Le phénomène de Köbner est de loin le plus connu et le plus étudié. Il correspond à l'apparition d'une lésion cutanée caractéristique d'une dermatose en zone de peau saine après traumatisme cutané. Parmi les dermatoses concernées, on peut citer le psoriasis, le lichen plan et le vitiligo. Le phénomène de Köbner inverse et le phénomène de Renbök sont deux phénomènes très similaires. Il s'agit de la disparition d'une lésion cutanée après traumatisme cutané pour le phénomène de Köbner inverse. Ce traumatisme cutané est induit plus spécifiquement par une autre dermatose dans le phénomène de Renbök. Enfin, le phénomène isotopique de Wolf correspond à l'apparition d'une nouvelle dermatose sur une zone cutanée qui a précédemment été le siège d'une autre dermatose guérie.

[Management of mycosis fungoide : focus on brentuximab vedotin]. / Comment je traite le mycosis fongoïde : à propos du brentuximab védotine, une nouvelle arme thérapeutique.

Recently, brentuximab vedotin (BV) (Adcetris®) obtained the reimbursement in Belgium for the treatment of the primary cutaneous NKT-cell lymphomas mycosis fungoides (MF), large cell anaplastic lymphoma and lymphomatoid papulosis type A. BV is a monoclonal antibody directed against the CD30 expressed on tumoral T cells. The inhibition of this pathway releases the process of apoptosis leading to the cell death of the tumoral cells. BV is reimbursed after the use of another systemic treatment without success and if the number of CD30 positive atypical T-cells is larger than 10 %. BV is administered intravenously every 3 weeks with a dosing of 1,8 mg/kg with a maximum of 16 courses. The response rates exceed 75 %. In some instances, interesting treatment responses have been observed with BV in CD30 negative patients. The principal adverse effects are neutropenia and peripheral neuropathy. Two patients are presented with longstanding multi-resistant MF that were successfully treated with BV.

Récemment, le brentuximab védotine (BV) (Adcetris®) a obtenu le remboursement en Belgique pour le traitement du lymphome cutané primitif de type mycosis fongoïde (MF), du lymphome anaplasique à larges cellules et de la papulose lymphomatoïde de type A. Le BV est un anticorps monoclonal dirigé contre le CD30 exprimé par les cellules T tumorales. L'inhibition de cette voie de signalisation induit un processus d'apoptose et conduit à la mort cellulaire. Le BV est remboursé après l'échec d'un autre traitement systémique et lorsque le nombre de cellules T atypiques exprimant le CD30 en immunohistochimie excède 10 % de la population totale sur une biopsie cutanée. Le BV est administré par voie intraveineuse toutes les 3 semaines à la posologie de 1,8 mg/kg, avec un maximum de 16 cures. Les taux de réponse globale excèdent 75 %. Certains patients négatifs pour le CD30 ont également montré une réponse thérapeutique intéressante. Les principaux effets indésirables du BV sont la neutropénie et la neuropathie périphérique. Les cas de deux patients avec un MF de longue date et multi-résistant, ayant répondu favorablement au BV, sont présentés dans cet article.

[Pediatric cutaneous mastocytosis]. / Cas clinique : La mastocytose cutanée pédiatrique.

Mastocytosis are orphan diseases characterized by the accumulation of mast cells in one or more organs. A distinction is made between systemic forms (10 %) and pure cutaneous forms (90 %), the latter being mainly pediatric and generally having a spontaneously favourable prognosis. In the absence of a systemic sign, the diagnostic criteria for cutaneous mastocytosis are Darier's sign, in principle, pathognomonic, as well as skin histology confirming mast cell infiltration. The treatment is essentially preventive (avoidance of factors triggering degranulation) and symptomatic (antihistamine agents).

Les mastocytoses sont des maladies orphelines caractérisées par l'accumulation de mastocytes dans un ou plusieurs organes. On distingue les formes systémiques (10 %) des formes cutanées pures (90 %). Ces dernières sont principalement pédiatriques et ont, généralement, un pronostic spontanément favorable. En cas d'absence de signe d'appel systémique, les critères de diagnostic de mastocytose cutanée sont le signe de Darier, en principe, pathognomonique ainsi que l'histologie cutanée affirmant l'infiltration mastocytaire. Le traitement est essentiellement préventif (éviction des facteurs déclenchant la dégranulation) et symptomatique (médicaments antihistaminiques).

[Actual treatments of psoriasis : from etanercept to anti-IL17 and anti-IL23 antagonists]. / Les traitements actuels du psoriasis : de l'étanercept aux antagonistes anti-IL17 et -IL23.

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.

Le psoriasis est une maladie chronique inflammatoire cutanée qui affecte environ 2 à 3 % de la population. Le spectre varie d'une atteinte limitée aux coudes et genoux jusqu'à l'érythrodermie psoriasique. L'impact sur la qualité de vie, le prurit, les douleurs des atteintes palmo-plantaires, l'atteinte articulaire et les comorbidités constituent les plaintes majeures des patients. La prise en charge repose sur des traitements locaux à base de dermocorticoïdes, avec ou sans dérivés de vitamine D, la photothérapie UVA ou UVB, les traitements conventionnels comme le méthotrexate, la ciclosporine et l'acitrétine, et, depuis une bonne dizaine d'années, les traitements biologiques. Les traitements biologiques pour les psoriasis modérés à sévères ont spectaculairement progressé avec, à chaque avancée, de meilleurs résultats thérapeutiques et des profils de sécurité de plus en plus sûrs. Cet article discute des avancées des traitements biologiques du psoriasis en démarrant avec les antagonistes du TNF? comme l'étanercept, l'adalimumab et l'infliximab, jusqu'aux derniers arrivés, les antagonistes anti-IL17 et anti-IL 23, les anti-PDE-4 et les inhibiteurs JAK.

[Locally advanced and metastatic cutaneous squamous cell carcinoma treated with cemiplimab]. / Carcinome spinocellulaire cutané localement avancé et métastatique traité par cémiplimab.

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.

Le traitement du carcinome spinocellulaire cutané (cSCC) localement avancé et/ou métastatique repose essentiellement sur la chirurgie et, éventuellement, sur une radiothérapie de la zone chirurgicale et de l'aire ganglionnaire afférente. Malheureusement, certains cas ne sont plus opérables ou accessibles à la radiothérapie et un traitement systémique est alors indiqué. Les chimiothérapies sont peu efficaces et potentiellement toxiques. Une étude récente évaluant l'efficacité et la tolérance du cémiplimab, un antagoniste PD1, dans les cSCC localement avancés et métastatiques, démontre une réponse objective confirmée de 49 % et de 47 %, respectivement, avec un maintien de la réponse d'au moins 6 mois de 63 % et de 60 %, respectivement. Nous présentons le cas d'un patient avec un cSCC localement avancé au niveau du front, avec effraction osseuse et adénopathies cervicales, ayant eu de multiples chirurgies et radiothérapies. Il a présenté une réponse partielle au cémiplimab avec un profil de tolérance satisfaisant.

[Treatment of mucocutaneous toxicity of target therapy in oncology]. / Comment je traite les toxicités mucocutanées des thérapies ciblées en oncologie.

The spectrum of the mucocutaneous adverse effects of directed oncologic therapies, such as anti-EGFR, anti-VEGF, anti-TK and anti-BRAF, presents similarities but also differences compared to that of the classic chemotherapeutics. This article reviews the dermatological toxicities of the targeted therapies, with 11 clinical cases, including mucositis and oral toxicities, the acne-like eruptions, nail changes and complications, the «hand/foot¼ syndrome, radiosensitization, alopecias, xerosis and skin fissures. After a brief clinical case presentation and theoretical issues, the clinical management is discussed in detail.

Le spectre des effets indésirables mucocutanés des thérapies ciblées (hors immunothérapies), comme les anti-EGFR, anti-VEGF, anti-TK et anti-BRAF, présente des similarités avec celui des traitements chimiothérapeutiques classiques, mais également des lésions plus spécifiques. Cet article abordera les toxicités dermatologiques des thérapies ciblées, à l'aide de 11 illustrations cliniques : les mucites et toxicités endobuccales, les éruptions acnéiformes, les modifications et complications unguéales, le syndrome main/pied, la radiosensibilisation, les alopécies, la xérose et les fissures cutanées. Après une brève description clinique et quelques notions théoriques, la prise en charge dermatologique est détaillée.

[What's new in the treatment of suppurative hidradenitis in 2018 ?] / Quoi de neuf dans le traitement de l'hidradénite suppurative en 2018 ?

Hidradenitis suppurativa (HS), also known as Verneuil's disease and acne inversa, is a chronic inflammatory skin disease characterized by a dysfunction of the pilosebaceous structures resulting in occlusion and inflammation. The disease usually starts after puberty, on average between twenty and thirty years, with subcutaneous painful inflammatory nodules, abscess collections, fistulization and scars mainly in the axillary, inguinal, sub-mammary, perineal and perianal regions. It is a multifactorial disease with the most commonly cited risk factors or aggravating factors being smoking, obesity, and HS family history. The first line of treatment relies on antibiotics, including tetracyclins, clindamycin and rifampycin. In case of non-response, TNF? antagonists, more specifically adalimumab, may be considered.

L'hidradénite suppurative (HS), aussi connue sous le nom de maladie de Verneuil et d'acne inversa, est une maladie inflammatoire chronique caractérisée par un dysfonctionnement des structures pilo-sébacées aboutissant à l'occlusion et à l'inflammation de celles-ci. Elle se manifeste souvent après la puberté, en moyenne entre vingt et trente ans, par des nodules sous-cutanés inflammatoires, des collections abcédées, des fistules et des cicatrices au niveau principalement des régions axillaires, inguinales, sous-mammaires, périnéale et périanale. Il s'agit d'une maladie multifactorielle dont les facteurs de risque ou facteurs aggravants les plus fréquemment cités sont le tabagisme, l'obésité et l'histoire familiale d'HS. La première ligne de traitement fera appel aux antibiotiques de type tétracycline, clindamycine et rifampicine. En seconde intention, on aura recours aux antagonistes TNF? et, plus précisément, à l'adalimumab.

Autoimmune progesterone dermatitis.

Autoimmune progesterone dermatitis (APD) is an exceptional condition affecting young women of childbearing age with a high prevalence during the third decade of life. The diagnosis should be confirmed using an intradermal skin test to progesterone, during the follicular phase of the menstrual cycle. APD represents an early manifestation of autoimmune disease. A case of APD is presented who after curative treatment did not develop other autoimmune diseases during a 6-year follow-up. Dermatologists, gynecologists and obstetricians should be aware of this rare but highly invalidating entity.

Non-dermatophyte Dermatoses Mimicking Dermatophytoses in Humans.

Human dermatophytic cutaneous infections usually present as single or multiple slowly progressing annular erythemato-squamous lesions with a tendency to central healing on the hairless skin. In the intertriginous regions (feet, inguinal, axillar, submammary), dermatophytic colonisations and infections manifest as whitish, slightly hyperkeratotic, pruritic and sometimes fissurated lesions. On the scalp, dermatophytic infections commonly lead to single or multiple more or less inflammatory and alopecic lesions. On the plantar and palmar aspects of the feet and hand, dermatophytosis presents as an eczema-like chronic dermatosis. Abscess-like lesions may occur due to zoophilic dermatomycosis. Dermatophytic infections of the nails reveal ill-defined whitish-yellowish colorations of the distal end or the lateral aspects of the nails, sometimes combined with partial nail embrittlement or even complete destruction. Despite the ubiquity of dermatophytic skin infections and their usually highly typical clinical features, a differential diagnosis has to be considered, in particular when treatment is not efficient or when treatment resistance occurs. This review presents the differential diagnosis in terms of frequency as well as the diagnostic methods permitting the distinction of annular, intertriginous, alopecic, palmoplantar, abscess-like and onychodystrophic lesions.

[Rosacea]. / La rosacea.

Rosacea is a common centro-facial dermatosis with a high socio-esthetic impact. Different subtypes are distinguished, classified into grades according to their severity. This classification is essential for therapeutic management. In general, rosacea remains difficult to treat as its pathophysiology is still not entirely understood. Future research is needed for a better understanding of this disease and the development of targeted treatments.

[Cutaneous adverse effects of TNFalpha antagonists]. / Les effets cutanés indésirables des antagonistes du TNFalpha.

The TNFalpha antagonists, including adalimumab, etanercept and infliximab, represent a class of anti-inflammatory and immunosuppressive drugs. Although cutaneous adverse effects are uncommon, they are varied. There is no particular risk profile to develop cutaneous adverse effects. The principal acute side effects are injection site reactions and pruritus. The major long term cutaneous side effects are infectious and inflammatory conditions. Neoplastic skin diseases are exceptional. The association with other immunosuppressive agents can increase the risk of developing cutaneous adverse effects. Some adverse effects, such as lupus erythematosus, require immediate withdrawal of the biological treatment, while in other cases temporary withdrawal is sufficient. The majority of the other cutaneous adverse effects can be dealt without interrupting biologic treatment. Preclinical and clinical investigations revealed that the new biologics, aiming IL12/23, IL23 and IL17, present a similar profile of cutaneous adverse effects, although inflammatory skin reactions may be less often encountered compared to TNFalpha antagonists.

Seasonal variations in vitamin D levels in melanoma patients: a single-centre prospective pilot comparative study.

BACKGROUND: More than 90% of vitamin D synthesis is dependent on UV exposure. Photosensitive disorders such as lupus erythematosus, protoporphyria and xeroderma require strict sun avoidance, and vitamin D deficiency has been demonstrated in these patients. Melanoma patients are also instructed to avoid sun exposure and may hence be expected to be vitamin D deficient. MATERIALS AND METHODS: Winter and summer vitamin D levels were compared in a group of melanoma patients (n =61) and age- and phototype-matched controls (n = 53) without photosensitive disorders. RESULTS: Oral supplementary vitamin D intake was reported in 32.7% of the melanoma patients and in 15.1% in the control group. Despite oral supplementation, only 25% of the melanoma patients and the controls presented with vitamin D levels of 30 ng/mL or higher. In non-supplemented subjects in the melanoma and control groups, respectively, mean winter vitamin D levels were below the recommended threshold at 12.6 ng/mL vs. 13.2 ng/mL, respectively, but not statistically different. These values increased significantly in both groups during the summer to 24.6 and 23.8 ng/mL respectively. CONCLUSION: Unexpected, significant increases in vitamin D levels were seen in melanoma patients during summer, suggesting non-adherence with photoprotective measures and reflecting a heliophilic behaviour. Vitamin D supplementation is recommended in melanoma patients during both winter and summer.

[Bilateral prophylactic mastectomy for women at very high risk for breast cancer: beyond the technique]. / Mastectomie bilatérale prophylactique chez les patientes à très haut risque de cancer mammaire: au-delà de la technique...

Bilateral prophylactic mastectomy is the most efficient risk management strategy for women at very high risk for breast cancer. Different methods can be used. The implementation of such a strategy must respond to the request of a well informed patient.

[Microsurgical breast reconstruction: for whom and how?]. / Reconstruction mammaire microchirurgicale: pour qui et comment?

Breast reconstruction is now an integral part of breast cancer treatment. There are several different procedures that make use of flaps or prostheses, or a combination of the two. Which of these procedures is indicated depends on the sequelae of the initial treatment and the patient's wishes and morphology. However, the constraints caused by the prosthetic material and the now regular use of microsurgical techniques have greatly favoured the purely autologous options. The different surgical techniques and their respective advantages and disadvantages will be described, before considering the timing of the various stages of the procedure. We will also give a summary of our experience with free flaps.

[About the reticence to specific immunotherapy in alergic subjects]. / A propos de la réticence a l'immunothérapie spécifique chez les personnes allergiques: les nouvelles données de la littérature.

The increasing number of allergic subjects and the alteration of their quality of life are major concerns of public health. Symptomatic treatments of allergic diseases are not always able to improve the patient's complaints. Allergic exploration aims to identify IgE-dependant mechanisms and subsequently to prove the responsibility of the detected allergen in the allergic disease. The efficacy of the specific immunotherapy (SIT) using allergens in either subcutaneous or sublingual forms has been proven in rhinitis, conjunctivitis, asthma and IgE-induced reactions to hymenoptera venom. The lack of training in allergology is an important reticence of general practitioners and specialists to prescribe SIT. Furthermore, the duration of the treatment and its important cost in Belgium (where, only venom SIT is reimbursed by the Social Security) interfere significantly with the compliance of the patients.