A survey among dermatologists: diagnostics of superficial fungal infections - what is used and what is needed to initiate therapy and assess efficacy?

BACKGROUND: Superficial fungal infections are common. It is important to confirm the clinical diagnosis by mycological laboratory methods before initiating systemic antifungal treatment, especially as antifungal sensitivity and in vitro susceptibility may differ between different genera and species. For many years, the gold standard for diagnosis of superficial fungal infections has been direct fungal detection in the clinical specimen (microscopy) supplemented by culturing. Lately, newer molecular based methods for fungal identification have been developed. OBJECTIVE: This study was initiated to focus on the current usage of mycological diagnostics for superficial fungal infections by dermatologists. It was designed to investigate whether it was necessary to differentiate between initial diagnostic tests and those used at treatment follow-up in specific superficial fungal infections. METHODS: An online questionnaire was distributed among members of the EADV mycology Task Force and other dermatologists with a special interest in mycology and nail disease. RESULTS: The survey was distributed to 62 dermatologists of whom 38 (61%) completed the whole survey, 7 (11%) partially completed and 17 (27%) did not respond. Nearly, all respondents (82-100%) said that ideally they would use the result of direct microscopy (or histology) combined with a genus/species directed treatment of onychomycosis, dermatophytosis, Candida- and Malassezia-related infections. The majority of the dermatologists used a combination of clinical assessment and direct microscopy for treatment assessment and the viability of the fungus was considered more important at this visit than when initiating the treatment. Molecular based methods were not available for all responders. CONCLUSION: The available diagnostic methods are heterogeneous and their usage differs between different practices as well as between countries. The survey confirmed that dermatologists find it important to make a mycological diagnosis, particularly prior to starting oral antifungal treatment in order to confirm the diagnose and target the therapy according to genus and species.

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.

[Pollen allergy and immunotherapy]. / Pollenallergien und Immuntherapie.

Pollinosis affects up to 25 % of the Swiss-population and increased substantially during the last century. Main causative pollens are birch and related pollens, ash pollen and grass pollen and to a lesser extent also mugwort. Diagnosis of Pollinosis is based on anamnesis, skin tests and determination of specific IgE in the serum. Treatment includes allergen avoidance, pharmacotherapy and allergen-specific immunotherapy (SIT). A proper patient and allergen extract selection, an ideally adapted application regimen and good patient-guidance as well as good compliance and treatment adherence are decisive for the success of the SIT. SCIT is the regimen of choice with well demonstrated efficacy, safety and long term effect. Nowadays SLIT is an additional complementary approach that mainly for grass pollen also offers good efficacy with good safety. Under such conditions immunotherapy leads to a benefit in more than 80 % of pollinosis-patients. Component-resolved diagnosis is a very useful and important step in more specific diagnosis. Several approaches studying changed application regimens and using molecular technologies to improve the efficacy of SIT are undergoing and will possibly substantially improve the efficacy, safety and acceptance of SIT.

How to design and evaluate randomized controlled trials in immunotherapy for allergic rhinitis: an ARIA-GA(2) LEN statement.

Specific immunotherapy (SIT) is one of the treatments for allergic rhinitis. However, for allergists, nonspecialists, regulators, payers, and patients, there remain gaps in understanding the evaluation of randomized controlled trials (RCTs). Although treating the same diseases, RCTs in SIT and pharmacotherapy should be considered separately for several reasons, as developed in this study. These include the severity and persistence of allergic rhinitis in the patients enrolled in the study, the problem of the placebo, allergen exposure (in particular pollen and mite), the analysis and reporting of the study, the level of symptoms of placebo-treated patients, the clinical relevance of the efficacy of SIT, the need for a validated combined symptom-medication score, the differences between children and adults and pharmacoeconomic analyses. This statement reviews issues raised by the interpretation of RCTs in sublingual immunotherapy. It is not possible to directly extrapolate the rules or parameters used in medication RCTs to SIT. It also provides some suggestions for the research that will be needed. Interestingly, some of the research questions can be approached with the available data obtained from large RCTs.

Antimicrobial silk clothing in the treatment of atopic dermatitis proves comparable to topical corticosteroid treatment.

BACKGROUND: Atopic dermatitis (AD) is aggravated by mechanical irritation and bacterial colonization. OBJECTIVE: This study compared the efficacy of an antimicrobial silk fabric (DermaSilk) with that of a topical corticosteroid in the treatment of AD. METHODS: Fifteen children were enrolled and wore a dress, where the left side was made of DermaSilk and the right side was made of cotton. The right arm and leg were treated daily with the corticosteroid mometasone for 7 days. The treatment efficacy was measured with a modified EASI (Eczema Area and Severity Index) and with an assessment by the patients/parents and by a physician. All patients were evaluated at baseline, as well as 7 and 21 days after the initial examination. RESULTS: All parameters showed that, irrespective of the treatment, there was a significant decrease of eczema after 7 days. No significant difference between DermaSilk-treated and corticosteroid-treated skin could be observed. CONCLUSION: DermaSilk showed potential to become an effective treatment of AD.

In vitro and in vivo allergenicity of recombinant Bet v 1 compared to the reactivity of natural birch pollen extract.

BACKGROUND: Diagnostic procedures using natural extracts show only limited quantitative correlation between in vivo and in vitro results. Highly pure recombinant allergens might show more predictive findings. OBJECTIVE: The aim of this study was to compare natural birch pollen extract (BPE) and recombinant Betula verrucosa (rBet v 1) for their diagnostic value comparing skin prick tests (SPTS) and nasal provocation tests (NPTS) with specific IgE in the serum. METHODS: Thirty-four patients allergic to birch pollen and five healthy controls were investigated. SPT and NPT were performed with BPE and rBet v 1 at different concentrations. Specific serum IgE was measured by the Pharmacia CAP system. RESULTS: Commercial BPE and rBet v 1 (10 micro g/mL) were able to elicit similar allergenic reactions in vivo and IgE binding in vitro. SPT reflects immediate-type allergy as determined by NPT to a higher degree than specific IgE, for both reagents. To cause allergic reactions in NPT, higher amounts of rBet v 1 were needed than for skin tests and the sensitivity was lower than with BPE. CONCLUSION: rBet v 1 alone is sufficient for a reliable diagnosis of birch pollen allergy in most patients and induces comparable skin test reactivity as BPE, but less allergic reactions in nasal provocations.

Recombinant allergens for skin testing.

Skin testing is a basic diagnostic procedure widely used to explore immediate-type reactions to allergen preparations in vivo. Despite their reliability, if standardized extracts are used, skin tests suffer from limited reproducibility due to difficulties in preparing consistently standardized extracts from natural raw material. Starting from allergen-encoding cDNAs, large amounts of highly pure allergens with a high batch-to-batch consistency satisfying the quality requirements of medicinal products manufactured by recombinant DNA technology can be produced. These reagents are expected to be qualitatively superior to the commercially available allergen preparations used for the in vitro and in vivo diagnosis of allergic conditions. In this article the current literature available on skin testing with such recombinant allergens (rAllergens) is reviewed and critically analyzed. To date many different rAllergens of various pollens, moulds, mites, bee venom, latex and celery have been used in skin testing in more than 1,600 allergic and control individuals. Skin prick tests as well as intradermal skin tests with rAllergens prove to be highly specific and safe. The diagnostic sensitivity of single rAllergens is generally lower than those obtained with allergen extracts, but can be considerably increased by using rAllergen panels covering the most important allergenic structures present in a given complex allergenic extract. Moreover, quantitative skin testing with single rAllergens allows interesting insights into correlations between the in vivo and in vitro sensitization to a given allergen. In conclusion, skin testing with rAllergens offers a highly specific and safe additional diagnostic tool to elucidate patient- and disease-specific sensitization patterns which will be needed for the development of patient-tailored immunotherapeutic treatments.

[Pollen as the cause of allergies]. / Pollen als Auslöser von Allergien.

Pollinosis or hay fever is the most common allergic disease in Switzerland. For symptoms during spring pollens of birch and related trees (alder, hazel) and also ash tree are responsible, while hay fever during summer is mainly caused by pollens of grasses, rye and mugwort. These main plant pollen allergens, relevant cross-reactivities with other pollen and food allergens are reviewed in this article. The well-established methods of pollen-counting in Switzerland allow to define the varying amounts of measurable pollen depending on geographic and climatic conditions. Similarly clinical symptoms, the diagnostic work-up of pollen allergies and therapeutic aspects including preventive measures, symptomatic therapy and specific immunotherapy are presented. Finally, occupational and travelling aspects of pollinosis are briefly discussed.

In vitro investigation of cross-reactivity between birch and ash pollen allergen extracts.

Allergenic cross-reactivity between members of the Fagales family (birch, alder, hazel, and beech) and between members of the Oleaceae family (ash, olive, lilac, and privet) is well known, but little is known about possible cross-reactivity between these two groups of trees, in particular between birch and ash, both of which flower in the spring. Various immunochemical methods including RAST inhibition, Western blot, and Western blot inhibition have been used in this study to show that there is partial cross-reactivity between birch and ash pollens. Enzyme allergosorbent test measurements were performed on sera from 35 patients with hay fever in spring by using birch and ash pollen allergen disks. The major allergen of birch, Bet v 1, was readily detectable in the birch pollen extract, but a homologous allergen in the ash pollen extract was barely detectable. Common allergens could be determined in the high molecular weight region. Ash pollen should be included in diagnostic procedures for spring pollinosis and should be considered for use in specific immunotherapy.