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.

Flemish network on rare connective tissue diseases (CTD): patient pathways in systemic sclerosis. First steps taken.

Despite the low prevalence of each rare disease, the total burden is high. Patients with rare diseases encounter numerous barriers, including delayed diagnosis and limited access to high-quality treatments. In order to tackle these challenges, the European Commission launched the European Reference Networks (ERNs), cross-border networks of healthcare providers and patients representatives. In parallel, the aims and structure of these ERNs were translated at the federal and regional levels, resulting in the creation of the Flemish Network of Rare Diseases. In line with the mission of the ERNs and to ensure equal access to care, we describe as first patient pathways for systemic sclerosis (SSc), as a pilot model for other rare connective and musculoskeletal diseases. Consensus was reached on following key messages: 1. Patients with SSc should have multidisciplinary clinical and investigational evaluations in a tertiary reference expert centre at baseline, and subsequently every three to 5 years. Intermediately, a yearly clinical evaluation should be provided in the reference centre, whilst SSc technical evaluations are permissionably executed in a centre that follows SSc-specific clinical practice guidelines. In between, monitoring can take place in secondary care units, under the condition that qualitative examinations and care including interactive multidisciplinary consultations can be provided. 2. Patients with early diffuse cutaneous SSc, (progressive) interstitial lung disease and/or pulmonary arterial hypertension should undergo regular evaluations in specialised tertiary care reference institutions. 3. Monitoring of patients with progressive interstitial lung disease and/or pulmonary (arterial) hypertension will be done in agreement with experts of ERN LUNG.

Nipple eczema: A systematic review and practical recommendations.

The nipple is the focal point of the human breast and serves important physiological, sexual, and aesthetic purposes. It can be affected by atopic, irritant, and allergic contact eczema, which often reduce the patient's quality of life. The objective of this article is to discuss the different types of nipple eczema and highlight relevant differential diagnoses and treatment options. A systematic search of PubMed was conducted to identify and critically appraise the existing literature on the topic. All articles on nipple eczema were considered eligible, regardless of publication date, language or study design. A final of 33 manuscripts on nipple eczema remained. The scarce literature and the limited number of high-quality manuscripts impedes provision of structured data on nipple eczema. To securely reach the educative value of this manuscript, the systematic review was combined with a manual databank search and selected manual search of textbooks. The differential diagnosis of nipple eczema encompasses among others nipple psoriasis, nipple candidiasis and Paget's disease. In case of diagnostic uncertainty, swabs or biopsies are indicated. Treatment of nipple eczema needs to rapidly control the signs and symptoms of the disease, since it can have a negative effect on quality of life and can lead to premature arrest of breastfeeding. The key treatment step is starting with topical corticosteroids or calcineurin inhibitors, both of which are considered safe during lactation. Avoidance of provoking factors, such as repetitive friction, chemical agents, or allergens, can help. The use of nipple protection devices can be proposed for nursing women and sometimes adjusting of latch/suck positioning during breastfeeding is needed. Furthermore, patients should be advised to moisturize the nipple intensively and to switch to emollient wash products. Warm water compresses, black tea compresses or commercially available tannin containing topicals can provide comfort.

Development of a patient-reported experience measure for chronic inflammatory skin diseases.

BACKGROUND: Patient involvement and high-quality patient-provider interactions are critical factors for quality of care in chronic inflammatory skin diseases. Also, assessing the patient's perspective contributes to optimizing care delivery and patient's experience. Until today, no user-friendly tools to measure patient experiences exist within immunodermatology. OBJECTIVES: The aim of this study was to identify the relevant items for patient's experience in immunodermatology and develop a concise questionnaire to assess patient's experience in routine clinical care. METHODS: Potential relevant items for measuring patient's perspective of immunodermatology care were identified by a literature search. From this longlist, a shortlist from patient's perspective was distilled by semi-structured interviews with a diverse patient group. This list was reduced to final items using a modified Delphi method in a multi-stakeholder focus group. For each item, one question was formulated to generate the Patient-Reported Experience Measure (PREM) questionnaire. A first internal validation was achieved by an email round. RESULTS: Forty longlist items were categorized into five domains (access to care, patient centeredness, access to information, care process and satisfaction). During interview rounds, 19 shortlist items were selected if mentioned by ≥40% of interviewees. Via the focus group, the most important items were chosen by participant consensus. For each item, a question was formulated. The final PREM covers 11 items (plus 2 in case of a first consult). The first internal validation showed that the tool is clear, understandable and has an ideal length. CONCLUSION: This short user-friendly PREM can be used in scientific and routine settings to improve care for patients who suffer from chronic inflammatory skin diseases.

Tralokinumab plus topical corticosteroids in adults with severe atopic dermatitis and inadequate response to or intolerance of ciclosporin A: a placebo-controlled, randomized, phase III clinical trial (ECZTRA 7).

BACKGROUND: Patients with severe atopic dermatitis (AD) not controlled with topical therapy have limited treatment options. Ciclosporin A (CSA) is a commonly used, broad immunosuppressant in AD, but treatment with CSA requires monitoring for potentially serious adverse effects. In a previous phase III trial, tralokinumab plus topical corticosteroids (TCS) as needed provided early and sustained improvements in AD signs and symptoms. OBJECTIVES: To evaluate the efficacy and safety of tralokinumab plus TCS in adult patients with severe AD whose disease was not adequately controlled with CSA or who had contraindications to oral CSA. METHODS: In this 26-week, multicentre, parallel, randomized, double-blind, placebo-controlled, phase III trial, European adults with severe AD were randomized 1 : 1 to subcutaneous tralokinumab 300 mg or placebo every 2 weeks plus TCS as needed. The primary endpoint was a 75% improvement in Eczema Area and Severity Index (EASI 75) at week 16. RESULTS: In total, 277 patients were randomized. At week 16, more patients treated with tralokinumab plus TCS vs. placebo plus TCS achieved EASI 75 [64·2% vs. 50·5%; difference 14·1% (95% confidence interval 2·5-25·7); P = 0·018], which increased further up to week 26. Improvements in AD severity were accompanied by early improvements in patient-reported outcomes, including Dermatology Life Quality Index, Patient-Oriented Eczema Measure, pruritus and sleep interference. Tralokinumab plus TCS also showed a higher EASI75 response at week 16 among patients who had previously failed CSA therapy vs. placebo plus TCS (57% vs. 41%). The overall incidence of adverse events was similar between treatment arms. CONCLUSIONS: Tralokinumab 300 mg plus TCS as needed was effective and well tolerated in patients with severe AD whose disease was not adequately controlled with CSA or who had contraindications to oral CSA.

Hidradenitis suppurativa is associated with childhood and lifetime traumatic events: a case-control study.

BACKGROUND: Negative life events in childhood can increase the susceptibility to autoimmune and inflammatory diseases. Hidradenitis suppurativa (HS) is a systemic inflammatory disease affecting the apocrine sweat glands, characterized by abscesses, fistulas and inflammatory nodules. It is unknown whether adult HS is associated with traumatic events. OBJECTIVE: To investigate the association between childhood and total lifetime traumatic events and the presence of HS. METHODS: We conducted a matched (1 : 3) case-control study with 71 HS patients and 213 controls. Patients were matched on age, gender and level of education. Questionnaires on general and demographic information, as well as the Traumatic Experience Checklist and the Hospital Anxiety and Depression Scale, were completed. RESULTS: The number of traumatic events (OR: 1.20 per trauma, P value < 0.05), and childhood traumatic events (yes vs. no, OR 3.59, P value < 0.05) and the number of childhood traumatic events (OR 1.35 per trauma, P value < 0.05) were correlated with an increased risk of developing HS. Detailed analysis showed that childhood emotional traumatic events (OR 5.03, P value < 0.05) were significantly associated with the development of HS. CONCLUSION: Number of lifetime traumatic events and childhood traumatic events are associated with HS. This association is strongest for emotional childhood traumas. The increased prevalence of childhood traumas in HS patients can be one of the underlying mechanisms leading to systemic inflammation in these patients.

Overview on vitamin D and sunbed use.

Vitamin D seems to be associated with a protective effect in a vast range of diseases, including cardiovascular, autoimmune and oncologic conditions. Since ultraviolet (UV) B light is the most important prerequisite for the cutaneous synthesis of vitamin D, sunbeds are able to increase serum vitamin D levels, although only transiently in most cases. In this scenario, the artificial tanning industry relentlessly tries to promote the use of sunbeds as a 'safe' therapeutic measure to achieve an adequate serum vitamin D status. The World Health Organization classified UV-emitting tanning devices, as well as the whole UV spectrum, as group-1 carcinogens, as they significantly increase the risk of melanoma and non-melanoma skin cancer. In case of vitamin D deficiency or insufficiency, the current risk-benefit ratio is therefore in favour of vitamin D supplementation instead of sunbed use. Artificial tanning devices should never be considered as an option to achieve an appropriate vitamin D status. Their supposedly beneficial effects, vastly publicised by the artificial tanning industry, are not worth the carcinogenic risk associated with sunbed use.

Skin lesions, differential diagnosis and practical approach to potential survivors of torture.

As the international refugee crisis has reached new proportions (BMJ, 355, 2016 and i5412), survivors of torture increasingly present in treating physicians with an array of acute or chronic skin lesions. Physicians should be aware of common presentations and likely differential diagnoses in order to avoid mislabelling or under-recognizing torture. Survivors of torture also frequently suffer from psychological sequelae, such as post-traumatic stress disorder, and appropriate referrals are essential in order to improve recovery trajectory. Skin sequelae are the most common physical findings of torture. Not all skin lesions seen in tortured survivors are due to perpetrator inflicted injuries, and many dermatological conditions can mimic lesions typical of torture, as can scars as a result of folk remedies or cultural practices specific to geographical regions. Medical documentation of torture includes injury and lesion description. While forensic dermatology and other forensic specialties use an injury description taxonomy, and the standard dermatologic taxonomy uses an anatomic description, they are complementary sciences for lesions inflicted by torture. This results in an opportunity for learning across disciplines in order to improve evidence documentation for survivors of torture. This article describes features of common skin lesions consistent with torture, including their clinical appearances, differential diagnoses, patterns of injury and appropriate clinical descriptions.

JAK1/3 inhibition preserves epidermal morphology in full-thickness 3D skin models of atopic dermatitis and psoriasis.

BACKGROUND: Janus kinase (JAK) inhibition may be a promising new treatment modality for inflammatory (skin) diseases. However, little is known about direct effects of kinase inhibitors on keratinocyte differentiation and function as well as skin barrier formation. OBJECTIVE: Our aim was to address the direct impact of kinase inhibition of the JAK1/3 pathways by tofacitinib on keratinocyte immune function and barrier formation in atopic dermatitis (AD) and psoriasis. METHODS: 3D skin equivalents of both diseases were developed and concurrently pretreated with tofacitinib. To induce AD, 3D skin equivalents were stimulated with recombinant human IL-4 and IL-13. Psoriasis-like conditions were induced by incubation with IL-17A, IL-22 and tumour necrosis factor α (TNFα). The activation of signal transducer and activator of transcription (STAT)1, STAT3 and STAT6 was assessed by Western blot analysis. Microarray analysis and quantitative real-time PCR were used for gene expression analysis. RESULTS: Tofacitinib pretreatment preserved epidermal morphology and reduced STAT3 and STAT6 phosphorylation of AD-like and STAT3 phosphorylation of psoriasis-like culture conditions in 3D skin models compared to sham-controls. Filaggrin expression was fully maintained in the AD-like models, but only partially in psoriasis-like conditions after pretreatment with tofacitinib. In addition, tofacitinib upregulated DSC1, FLG and KRT1. Using gene expression analysis, downregulation of POSTN and IL24 was observed in AD-like conditions, whereas downregulation of IL20 and IL1B was observed in psoriasis-like conditions. CONCLUSION: JAK1/3 inhibition counteracted cytokine-induced AD- and psoriasis-like epidermal morphology and enhanced keratinocyte differentiation in 3D skin models. This effect was more pronounced in the AD-like models compared to the psoriasis-like 3D skin models.