Localization of apoptosis proteins and lymphocyte subsets in chronic rejection of human liver allograft

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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

Risk of severe allergic reactions to COVID-19 vaccines among patients with allergic skin diseases - practical recommendations. A position statement of ETFAD with external experts.

Since the introduction of active vaccination against SARS‐CoV‐2 infection, there has been a debate about the risk of developing severe allergic or anaphylactic reactions among individuals with a history of allergy. Indeed, rare cases of severe allergic reactions have been reported in the United Kingdom and North America. By February 2021 a rate of 4,5 severe allergic reactions occurred among 1 million patients vaccinated with the mRNA‐based COVID‐19 vaccines, which is higher than the generally expected rate of severe allergic reactions to vaccinations of around 1 in 1 million

European Task Force on Atopic Dermatitis (ETFAD): position on vaccination of adult patients with atopic dermatitis against COVID‐19 (SARS‐CoV‐2) being treated with systemic medication and biologics

The coronavirus disease 2019 (COVID‐19) pandemic is caused by rapid spread of different strains of the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). The severity of infection ranges from mild, or even asymptomatic, to very severe. Signs and symptoms include fatigue, fever, exanthemas, upper respiratory illness, loss of smell and taste, pneumonia, severe acute respiratory syndrome, and multi‐organ failure. Risk factors for a severe or lethal course include age, male gender, obesity, diabetes, cardiovascular disease, and immune suppression1

Malassezia sympodialis thioredoxin-specific T cells are highly cross-reactive to human thioredoxin in atopic dermatitis

BACKGROUND: IgE-mediated cross-reactivity between fungal antigens and human proteins has been described in patients with atopic dermatitis (AD), but it remains to be elucidated whether there is also cross-reactivity at the T-cell level. OBJECTIVE: We sought to explore cross-reactivity at the T-cell level between the fungal thioredoxin (Mala s 13) of the skin-colonizing yeast Malassezia sympodialis and its homologous human thioredoxin (hTrx). METHODS: T-cell lines (TCLs) were generated in the presence of rMala s 13 from the peripheral blood and from skin biopsy specimens of positive patch test reactions of patients with AD sensitized to Mala s 13 and hTrx. Patients with AD not sensitized to Malassezia species, healthy subjects, and patients with psoriasis served as control subjects. Mala s 13-specific T-cell clones (TCCs) were generated from TCLs. TCCs were characterized by antigen specificity, phenotype, and cytokine secretion pattern. Human keratinocytes were stimulated with IFN-γ, TNF-α, and IL-4, and the release of hTrx was determined by means of ELISA. RESULTS: Mala s 13-specific TCLs and TCCs from the blood and skin of patients with AD sensitized to Mala s 13 and hTrx were fully cross-reactive with hTrx. Mala s 13- and hTrx-specific TCCs could not be generated from control subjects. The majority of cross-reactive TCCs were CD4(+) and coexpressed cutaneous lymphocyte antigen. In addition to T(H)1 and T(H)2 TCCs, we could also identify TCCs secreting IL-17 and IL-22. After stimulation with IFN-γ and TNF-α, keratinocytes released substantial amounts of thioredoxin. CONCLUSION: In patients with AD sensitized to Malassezia species, cross-reactivity at the T-cell level to Mala s 13 and the homologous hTrx is detectable. hTrx autoreactive skin-homing T cells might be relevant for cutaneous inflammation in patients with AD

Current dermatology guidelines in Germany and Europe - A selection of clinically relevant recommendations

Clinical practice guidelines are systematically developed decision aids for specific medical conditions. In Germany, national dermatology guidelines are developed chiefly under the aegis of the German Dermatological Society in collaboration with the Professional Association of German Dermatologists. European and international dermatological guidelines also exist and are developed by a range of organisations, such as the European Centre for Guidelines Development, which was founded by the European Dermatology Forum in 2018. In the years 2019 and 2020, new or updated German national guidelines were published on topics such as pathological scars (hypertrophic scars and keloids), cutaneous lupus erythematosus, pyoderma grangrenosum, anal pruritus, anal eczema, anal canal and anal rim carcinomas, as well as the prevention of HPV-associated neoplasms through vaccination, syphilis and the systemic treatment of neurodermitis. A new European guideline on lichen planus closes a gap in the spectrum of guidelines available in Germany. Key recommendations and relevant changes in the guidelines are presented in this article.Medizinische Leitlinien sind systematisch entwickelte Entscheidungshilfen für die angemessene Vorgehensweise bei speziellen gesundheitlichen Problemen. Dermatologische Leitlinien in Deutschland werden führend von der Deutschen Dermatologischen Gesellschaft in Kooperation mit dem Berufsverband Deutscher Dermatologen herausgegeben. Darüber hinaus werden auch europäische und internationale dermatologische Leitlinien erstellt, u. a. durch das im Jahr 2018 vom European Dermatology Forum gegründete European Centre for Guidelines Development. In den Jahren 2019 und 2020 wurden unter anderem deutsche Leitlinien zu den Themen pathologische Narben (hypertrophe Narben und Keloide), kutaner Lupus erythematodes, Pyoderma gangraenosum, analer Pruritus, Analekzem, Analkanal- und Analrandkarzinome, Impfprävention HPV(humane Papillomviren)-assoziierter Neoplasien sowie Syphilis und Systemtherapie bei Neurodermitis überarbeitet oder neu erstellt. Auf der europäischen Ebene schließt die Leitlinie zum Lichen planus eine in Deutschland noch bestehende Lücke der vorhandenen Leitlinien. Schlüsselempfehlungen und wesentliche Neuerungen in den Leitlinien werden hier vorgestellt

Exacerbation of atopic dermatitis on grass pollen exposure in an environmental challenge chamber

Background: It has frequently been speculated that pruritus and skin lesions develop after topical exposure to aeroallergens in sensitized patients with atopic dermatitis (AD). Objective: We sought to study cutaneous reactions to grass pollen in adult patients with AD with accompanying clear IgE sensitization to grass allergen in an environmental challenge chamber using a monocenter, double-blind, placebo-controlled study design. Methods: Subjects were challenged on 2 consecutive days with either 4000 pollen grains/m3 of Dactylis glomerata pollen or clean air. The severity of AD was assessed at each study visit up to 5 days after challenge by (objective) scoring of AD (SCORAD). Additionally, air-exposed and non-air-exposed skin areas were each scored using local SCORAD scoring and investigator global assessments. Levels of a series of serum cytokines and chemokines were determined by using a Luminex-based immunoassay. The primary end point of the study was the change in objective SCORAD scores between prechallenge and postchallenge values. Results: Exposure to grass pollen induced a significant worsening of AD. Apronounced eczema flare-up of air-exposed rather than covered skin areas occurred. In grass pollen-exposed subjects a significantly higher increase in CCL17, CCL22, and IL-4 serum levels was observed. Conclusions: This study demonstrates that controlled exposure to airborne allergens of patients with a so-called extrinsic IgE-mediated form of AD induced a worsening of cutaneous symptoms

Supplementary Material for: Staphylococcal Exotoxins Induce Interleukin 22 in Human Th22 Cells

<b><i>Background:</i></b> We have shown previously that T cells from atopic dermatitis (AD) patients produce more IL-22 upon staphylococcal exotoxin stimulation compared to psoriasis patients and healthy controls. The role of staphylococcal exotoxins on polarized memory T helper (Th)22 cells which are enriched in inflamed AD skin remains elusive. Our aim was to investigate IL-22 production in response to staphylococcal enterotoxin B (SEB) and α-toxin stimulation in human memory T cells and polarized Th22 cells. <b><i>Methods:</i></b> IL-22 induction was investigated in human peripheral blood-derived CD4+CD45RO+CD45RA- T cells and polarized Th22 cells after SEB and sublytic α-toxin stimulation in a time-dependent manner at the mRNA and protein (ELISA) levels. <b><i>Results:</i></b> Th22 cells secreted more IL-22 compared to freshly isolated peripheral blood-derived memory T cells. SEB and α-toxin induced IL-22 in memory T cells as well as in Th22 cells. More IL-22 was induced by SEB and α-toxin in freshly isolated peripheral blood memory T cells compared to Th22 cells derived from memory T cells in long-term cell culture without polarization and Th22 cells under Th22-promoting conditions with IL-6 and TNF-α. No differences in IL-22 induction by staphylococcal exotoxins were observed between cells from AD compared to psoriasis patients and healthy controls. <b><i>Conclusions:</i></b> Increased IL-22 secretion can promptly be induced by staphylococcal exotoxins in skin infiltrating CD4+CD45RO+CD45RA- memory T cells and can potentially amplify chronic skin inflammation in AD in the context of bacterial colonization and infection. This should be investigated further in detail in lesional skin of AD and psoriasis patients

A position paper on the management of itch and pain in atopic dermatitis from the International Society of Atopic Dermatitis (ISAD)/Oriented Patient-Education Network in Dermatology (OPENED) task force

Atopic dermatitis (AD) is a disease that can have a high impact on quality of life, especially due to itch and skin pain. This paper utilizes expertise from members of the International Society of Atopic Dermatitis (ISAD)/Oriented Patient-Education Network in Dermatology (OPENED) task force to review the epidemiology, pathophysiology and exacerbating factors of itch and pain in atopic dermatitis. General principles of treatment are provided, as well as a more detailed evaluation of topical and systemic therapies. Educational and psychological approaches to itch and pain in atopic dermatitis are proposed, along with expert recommendations for the management of itch and pain in atopic dermatitis