European guideline (EuroGuiDerm) on atopic eczema: part I - systemic therapy.

The evidence- and consensus-based guideline on atopic eczema was developed in accordance with the EuroGuiDerm Guideline and Consensus Statement Development Manual. Four consensus conferences were held between December 2020 and July 2021. Twenty-nine experts (including clinicians and patient representatives) from 12 European countries participated. This first part of the guideline includes general information on its scope and purpose, the health questions covered, target users and a methods section. It also provides guidance on which patients should be treated with systemic therapies, as well as recommendations and detailed information on each systemic drug. The systemic treatment options discussed in the guideline comprise conventional immunosuppressive drugs (azathioprine, ciclosporin, glucocorticosteroids, methotrexate and mycophenolate mofetil), biologics (dupilumab, lebrikizumab, nemolizumab, omalizumab and tralokinumab) and janus kinase inhibitors (abrocitinib, baricitinib and upadacitinib). Part two of the guideline will address avoidance of provocation factors, dietary interventions, immunotherapy, complementary medicine, educational interventions, occupational and psychodermatological aspects, patient perspective and considerations for paediatric, adolescent, pregnant and breastfeeding patients.

European guideline (EuroGuiDerm) on atopic eczema - part II: non-systemic treatments and treatment recommendations for special AE patient populations.

The evidence- and consensus-based guideline on atopic eczema was developed in accordance with the EuroGuiDerm Guideline and Consensus Statement Development Manual. Four consensus conferences were held between December 2020 and July 2021. Twenty-nine experts (including clinicians and patient representatives) from 12 European countries participated. This second part of the guideline includes recommendations and detailed information on basic therapy with emollients and moisturizers, topical anti-inflammatory treatment, antimicrobial and antipruritic treatment and UV phototherapy. Furthermore, this part of the guideline covers techniques for avoiding provocation factors, as well as dietary interventions, immunotherapy, complementary medicine and educational interventions for patients with atopic eczema and deals with occupational and psychodermatological aspects of the disease. It also contains guidance on treatment for paediatric and adolescent patients and pregnant or breastfeeding women, as well as considerations for patients who want to have a child. A chapter on the patient perspective is also provided. The first part of the guideline, published separately, contains recommendations and guidance on systemic treatment with conventional immunosuppressive drugs, biologics and janus kinase (JAK) inhibitors, as well as information on the scope and purpose of the guideline, and a section on guideline methodology.

ETFAD/EADV Eczema task force 2020 position paper on diagnosis and treatment of atopic dermatitis in adults and children.

Atopic dermatitis (AD) is a highly pruritic, chronic inflammatory skin disease. The diagnosis is made using evaluated clinical criteria. Disease activity and burden are best measured with a composite score, assessing both objective and subjective symptoms, such as SCORing Atopic Dermatitis (SCORAD). AD management must take into account clinical and pathogenic variabilities, the patient's age and also target flare prevention. Basic therapy includes hydrating and barrier-stabilizing topical treatment universally applied, as well as avoiding specific and unspecific provocation factors. Visible skin lesions are treated with anti-inflammatory topical agents such as corticosteroids and calcineurin inhibitors (tacrolimus and pimecrolimus), which are preferred in sensitive locations. Topical tacrolimus and some mid-potency corticosteroids are proven agents for proactive therapy, which is defined as the long-term intermittent anti-inflammatory therapy of frequently relapsing skin areas. Systemic anti-inflammatory or immunosuppressive treatment is a rapidly changing field requiring monitoring. Oral corticosteroids have a largely unfavourable benefit-risk ratio. The IL-4R-blocker dupilumab is a safe, effective and licensed, but expensive, treatment option with potential ocular side-effects. Other biologicals targeting key pathways in the atopic immune response, as well as different Janus kinase inhibitors, are among emerging treatment options. Dysbalanced microbial colonization and infection may induce disease exacerbation and can justify additional antimicrobial treatment. Systemic antihistamines (H1R-blockers) only have limited effects on AD-related itch and eczema lesions. Adjuvant therapy includes UV irradiation, preferably narrowband UVB or UVA1. Coal tar may be useful for atopic hand and foot eczema. Dietary recommendations should be patient-specific, and elimination diets should only be advised in case of proven food allergy. Allergen-specific immunotherapy to aeroallergens may be useful in selected cases. Psychosomatic counselling is recommended to address stress-induced exacerbations. Efficacy-proven 'Eczema school' educational programmes and therapeutic patient education are recommended for both children and adults.

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.

Atopic eczema: burden of disease and individual suffering - results from a large EU study in adults.

BACKGROUND: Atopic eczema (AE, atopic dermatitis) is one of the most common non-communicable inflammatory skin diseases affecting 1-5% of the adult population in Europe with marked impairment in quality of life. In spite of great progress in understanding the pathophysiology of disturbed skin barrier and immune deviation, AE still represents a problem in daily clinical practice. Furthermore, the true impact of AE on individual suffering is often not recognized. OBJECTIVES: With a large European study, we wanted to provide insights into the actual suffering and individual burden of disease in adult patients with AE. METHODS: A total of 1189 adult patients (18-87 years, 56% female) with moderate to severe AE were recruited in nine European countries by dermatologists or allergists together with the help of patient organizations. A computer-assisted telephone interview was performed by experienced interviewers between October 2017 and March 2018. The following instruments were used to assess severity or measure quality of life: Patient-Oriented Eczema Measure (POEM), Dermatology Life Quality Index (DLQI), Hospital Anxiety and Depression Scale (HADS-D) and a newly developed Atopic Eczema Score of Emotional Consequences (AESEC). Patients were also asked to self-assess the severity of their disease. RESULTS: Despite current treatment, 45% of participants still had actual moderate to very severe AE in POEM. Due to their skin disease, 57% missed at least 1 day of work in the preceding year. DLQI showed moderate to extremely large impairment in 55%. According to HADS-D, 10% scored on or above the threshold of eight points with signs of depressive symptoms. Assessed with AESEC, 57% were emotionally burdened with feelings such as 'trying to hide the eczema', 'feeling guilty about eczema', having 'problems with intimacy' and more. Of persons actually suffering from severe AE, 88% stated that their AE at least partly compromised their ability to face life. CONCLUSIONS: This real-life study shows that adults with a moderate to severe form of AE are suffering more than what would be deemed acceptable. There is a need for increased awareness of this problem among healthcare professionals, policymakers and the general public to support research in the development of new and more effective treatments and provide access to better and affordable health care for affected patients.

European task force on atopic dermatitis position paper: treatment of parental atopic dermatitis during preconception, pregnancy and lactation period.

Atopic dermatitis (AD) is a common inflammatory skin disease that affects both children and adults, including a large number of adults of reproductive age. Several guidelines for the treatment of AD exist, yet specific recommendations for the treatment of pregnant or lactating women and for adults planning to have a child are often lacking. This position paper from the European Task force on Atopic Dermatitis (ETFAD) is based on up-to-date scientific literature on treating pregnant and lactating women as wells as adults with AD planning to have a child. It is based on the expert opinions of members of the ETFAD and on existing safety data on the proposed treatments, many of which are derived from patients with other inflammatory diseases or from transplantation medicine. For treating future parents, as well as pregnant and lactating women with AD, the use of topical treatments including moisturizers, topical corticosteroids, tacrolimus, antiseptics such as chlorhexidine, octenidine, potassium permanganate and sodium hypochlorite (bleach) is deemed to be safe. Ultraviolet (UV) therapy may also be used. Systemic treatment should be prescribed only after careful consideration. According to the opinion of the ETFAD, treatment should be restricted to systemic corticosteroids and cyclosporine A, and, in selected cases, azathioprine.

Measurement of healthcare quality in atopic dermatitis - development and application of a set of quality indicators.

BACKGROUND: Quality indicators are essential tools for the assessment of health care, in particular for guideline-based procedures. OBJECTIVE: Development of a set of indicators for the evaluation of process and outcomes quality in atopic dermatitis (AD) care. Application of the indicators to a cross-sectional study and creation of a global process quality index. METHODS: An expert committee consisting of 10 members of the German guideline group on AD condensed potential quality indicators to a final set of 5 outcomes quality and 12 process quality indicators using a Delphi panel. The outcomes quality and 7 resp. 8 process quality indicators were retrospectively applied to a nationwide study on 1678 patients with atopic dermatitis (AtopicHealth). Each individual process quality indicator score was then summed up to a global index (ranges from 0 [no quality achieved] to 100 [full quality achieved]) displaying the quality of health care. RESULTS: In total, the global process quality index revealed a median value of 62.5 and did not or only slightly correlate to outcomes quality indicators like the median SCORing Atopic Dermatitis (SCORAD; rp = 0.08), Dermatology Life Quality Index (DLQI; rp = 0.256) and Patient Benefit Index (PBI; rp = -0.151). CONCLUSION: Process quality of AD care is moderate to good. The healthcare process quality index does not substantially correlate to the health status of AD patients measured by 5 different outcomes quality indicators. Further research should include the investigation of reliability, responsiveness and feasibility of the proposed quality indicators for AD.

Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children: part II.

This guideline was developed as a joint interdisciplinary European project, including physicians from all relevant disciplines as well as patients. It is a consensus-based guideline, taking available evidence from other guidelines, systematic reviews and published studies into account. This second part of the guideline covers antimicrobial therapy, systemic treatment, allergen-specific immunotherapy, complementary medicine, psychosomatic counselling and educational interventions, whereas the first part covers methods, patient perspective, general measures and avoidance strategies, basic emollient treatment and bathing, dietary intervention, topical anti-inflammatory therapy, phototherapy and antipruritic therapy. Management of AE must consider the individual clinical variability of the disease. Systemic immunosuppressive treatment with cyclosporine, methotrexate, azathioprine and mycophenolic acid is established option for severe refractory cases, and widely available. Biologicals targeting the T helper 2 pathway such as dupilumab may be a safe and effective, disease-modifying alternative when available. Oral drugs such as JAK inhibitors and histamine 4 receptor antagonists are in development. Microbial colonization and superinfection may cause disease exacerbation and can require additional antimicrobial treatment. Allergen-specific immunotherapy with aeroallergens may be considered in selected cases. Psychosomatic counselling is recommended especially in stress-induced exacerbations. Therapeutic patient education ('Eczema school') is recommended for children and adult patients. General measures, basic emollient treatment, bathing, dietary intervention, topical anti-inflammatory therapy, phototherapy and antipruritic therapy have been addressed in the first part of the guideline.

Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children: part I.

This guideline was developed as a joint interdisciplinary European project, including physicians from all relevant disciplines as well as patients. It is a consensus-based guideline, taking available evidence from other guidelines, systematic reviews and published studies into account. This first part of the guideline covers methods, patient perspective, general measures and avoidance strategies, basic emollient treatment and bathing, dietary intervention, topical anti-inflammatory therapy, phototherapy and antipruritic therapy, whereas the second part covers antimicrobial therapy, systemic treatment, allergen-specific immunotherapy, complementary medicine, psychosomatic counselling and educational interventions. Management of AE must consider the individual clinical variability of the disease; highly standardized treatment rules are not recommended. Basic therapy is focused on treatment of disturbed barrier function by hydrating and lubricating topical treatment, besides further avoidance of specific and unspecific provocation factors. Topical anti-inflammatory treatment based on glucocorticosteroids and calcineurin inhibitors is used for flare management and for proactive therapy for long-term control. Topical corticosteroids remain the mainstay of therapy, whereas tacrolimus and pimecrolimus are preferred in sensitive skin areas and for long-term use. Topical phosphodiesterase inhibitors may be a treatment alternative when available. Adjuvant therapy includes UV irradiation, preferably with UVB 311 nm or UVA1. Pruritus is targeted with the majority of the recommended therapies, but some patients may need additional antipruritic therapy. Antimicrobial therapy, systemic anti-inflammatory treatment, immunotherapy, complementary medicine and educational intervention will be addressed in part II of the guideline.

BASALIT trial: double-blind placebo-controlled allergen immunotherapy with rBet v 1-FV in birch-related soya allergy.

BACKGROUND: Conflicting results exist on the effect of allergen immunotherapy (AIT) on pollen-related food allergy. We aimed to investigate the efficacy of one-year AIT with the folding variant (FV) of recombinant (r) Bet v 1 on birch-related soya allergy. METHODS: Of 138 subjects with Bet v 1 sensitization, 82 were positive at double-blind placebo-controlled food challenge (DBPCFC) with soya. A total of 56 of 82 were randomized in the ratio of 2:1 (active: placebo). Per-protocol population (PPP) had received ≥150 µg of allergen or placebo preparation. OUTCOME MEASURES: lowest observed adverse effect levels (LOAEL), postinterventional occurrence of objective signs (objS) at any dose level, sIgE/IgG4 against Bet v 1 and Gly m 4. Between-group changes were investigated (ancova, Mann-Whitney U-test, Fisher exact test). RESULTS: Baseline characteristics including LOAELs were comparable in both groups with objS and subjS occurring in 82% and 95% of active (n = 38) vs 78% and 83% of placebo group (n = 18). After AIT, objS occurred in 24% and 47%, respectively. LOAEL group differences showed a beneficial tendency (P = 0.081) for LOAELobjective in PPP (30 active, 15 placebo). sIgG4 raised only in active group (Bet v 1: P = 0.054, Gly m 4: P = 0.037), and no relevant changes occurred for sIgE. Only 56% of the intended sample size was recruited. CONCLUSION: For the first time, we present data on the effect of rBet v 1-FV on birch-related soya allergy. rBet v 1-FV AIT induced significant immunogenic effects. Clinical assessment showed a tendency in favour of the active group but did not reach statistical significance.

iDermatoPath - a novel software tool for mitosis detection in H&E-stained tissue sections of malignant melanoma.

BACKGROUND: Malignant Melanoma (MM) is characterized by a growing incidence and a high malignant potential. Besides well-defined prognostic factors such as tumour thickness and ulceration, the Mitotic Rate (MR) was included in the AJCC recommendations for diagnosis and treatment of MM. In daily routine, the identification of a single mitosis can be difficult on haematoxylin and eosin slides alone. Several studies showed a big inter- and intra-individual variability in detecting the MR in MM even by very experienced investigators, thus raising the question for a computer-assisted method. OBJECTIVE: The objective was to develop a software system for mitosis detection in MM on H&E slides based on machine learning for diagnostic support. METHODS: We developed a computer-aided staging support system based on image analysis and machine learning on the basis of 59 MM specimens. Our approach automatically detects tumour regions, identifies mitotic nuclei and classifies them with respect to their diagnostic relevance. A convenient user interface enables the investigator to browse through the proposed mitoses for fast and efficient diagnosing. RESULTS: A quantitative evaluation on manually labelled ground truth data revealed that the tumour region detection yields a medium spatial overlap index (dice coefficient) of 0.72. For the mitosis detection, we obtained high accuracies of above 83%. CONCLUSION: On the technical side, the developed iDermatoPath software tool provides a novel approach for mitosis detection in MM, which can be further improved using more training data such as dermatopathologist annotations. On the practical side, a first evaluation of the clinical utility was positive, albeit this approach provides most benefit for difficult cases in a research setting. Assuming all slides to be digitally processed and reported in the near future, this method could become a helpful additional tool for the pathologist.

[Teledermoscopy by mobile phones : Reliable help in the diagnosis of skin lesions?] / Teledermatoskopie mittels Smartphone : Zuverlässige Hilfe bei der Diagnostik von Hautläsionen?

BACKGROUND: Teledermoscopy is a promising modern technique to complement or to substitute dermatologic examination. OBJECTIVE: In this pilot study, we compared the outcomes of teledermoscopic consultations with clinical examinations and histologic results. METHODS: Conventional and dermatoscopic photos of single lesions were taken in 26 patients using a mobile phone and an attached handyscope optical system. Five resident physicians performed a clinical examination including dermoscopy while the teledermatologic and teledermoscopic photos were assessed by an experienced dermatologist. Examination results were compared regarding diagnosis, differential diagnoses, recommended further management, as well as subjective and objective accuracy of diagnosis. In addition, 23% of the lesions were excised and histologically examined. RESULTS: The most frequent diagnosis was "nevus cell nevus", followed by "subungual hematoma" and "basal cell carcinoma". The concordance of diagnoses was 92.3%; the concordance of recommended further management was 76.9%. Of the 6 histologically proven diagnoses, 66.7% were given the same diagnosis by teledermatoscopy and conventional clinical assessment. Concerning accuracy of diagnosis, teledermoscopy showed no disadvantage. CONCLUSIONS: Teledermatologic photos of single lesions combined with teledermatoscopic photos can be reliably and safely assessed. Especially when access to dermatologic examination is difficult, mobile teledermoscopy is a good and reliable alternative.

Added sensitivity of component-resolved diagnosis in hymenoptera venom-allergic patients with elevated serum tryptase and/or mastocytosis.

BACKGROUND: Anaphylaxis caused by hymenoptera venom allergy is associated with elevation of baseline serum tryptase (sBT) and/or mastocytosis in about 5% of patients. Up to now, no information has become available on single venom allergen sIgE reactivity and the usefulness of component-resolved approaches to diagnose this high-risk patient group. To address the component-resolved sIgE sensitization pattern and diagnostic sensitivity in hymenoptera venom-allergic patients with elevated sBT levels and/or mastocytosis, a panel of yellow jacket and honeybee venom allergens was applied on a widely used IgE immunoassay platform. METHODS: Fifty-three patients with mastocytosis and/or elevated sBT tryptase level and systemic reactions to hymenoptera venoms were analyzed for their IgE reactivity to recombinant yellow jacket and honeybee venom allergens by Immulite3 g. RESULTS: sIgE reactivity to Ves v 1, Ves v 5, Api m 1 to Api m 4 and Api m 10 was found at a similar frequency in hymenoptera venom-allergic patients with and without elevated sBT levels and/or mastocytosis. However, the use of the recombinant allergens and a diagnostic cutoff of 0.1 kUA /L allowed the diagnosis of patients with otherwise undetectable IgE to venom extract. The diagnostic sensitivity of yellow jacket venom allergy using the combination of Ves v 1 and Ves v 5 was 100%. CONCLUSIONS: In high-risk patients with elevated sBT levels and/or mastocytosis, the use of molecular components and decreasing the threshold sIgE level to 0.1 kUA /L may be needed to avoid otherwise undetectable IgE to hymenoptera venom extracts in about 8% of such patients.