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The burden of atopic dermatitis (AD) appears to be increasing in adult and elderly patients. The aim of this study was to analyse the nationwide database of the Finnish Institute for Health and Welfare regarding the number of patients with AD and of general practitioner consultations in Finland during 2018. The database comprised the main diagnoses of all visits to public primary healthcare. There were 2,094,673 primary care patients (males/females 43.19/56.81%) and 20,905 patients with AD (1.00%) and 24,180 consultations due to AD (0.45%). The highest numbers of patients with AD were in the age groups 0–14 years (9,922 patients, 47.46%) and 15–65 years (9,144 patients, 43.74%). A substantial proportion of patients with AD were aged > 50 years (3,515 patients, 16.81%) or >65 years (1,947 patients, 9.31%). Regression analysis indicated a statistically significant association of age group with patient numbers (p = 0.032) and number of consultations (p = 0.030). There were no differences between direct age group comparisons (p = 0.303), sex (p = 0.389), or number of consultations/patient (p = 0.235). Patients with AD are prevalent in all age groups in Finnish primary care. Patient numbers were also relatively high in groups other than childhood, indicating that age-related distribution in primary care may be shifting to older ages.

Publisher Copyright: © 2021 GA²LEN. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd. This update and revision of the international guideline for urticaria was developed following the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. It is a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the Global Allergy and Asthma European Network (GA(2)LEN) and its Urticaria and Angioedema Centers of Reference and Excellence (UCAREs and ACAREs), the European Dermatology Forum (EDF; EuroGuiDerm), and the Asia Pacific Association of Allergy, Asthma and Clinical Immunology with the participation of 64 delegates of 50 national and international societies and from 31 countries. The consensus conference was held on 3 December 2020. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast cell-driven disease that presents with wheals, angioedema, or both. The lifetime prevalence for acute urticaria is approximately 20%. Chronic spontaneous or inducible urticaria is disabling, impairs quality of life, and affects performance at work and school. This updated version of the international guideline for urticaria covers the definition and classification of urticaria and outlines expert-guided and evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria.

Funding Information: BSreports personal fees from Allergopharma, during the conduct of the study; grants from National Health Programm, grant, personal fees from Polpharma, ASTRA, personal fees from Mylan, Adamed, patient ombudsman, national Centre for Research and Development, Polish Allergology Society. Funding Information: NGP reports personal fees from Novartis, Nutricia, HAL, MENARINI/FAES FARMA, SANOFI, MYLAN/MEDA, BIOMAY, AstraZeneca, GSK, MSD, ASIT BIOTECH, Boehringer Ingelheim, grants from Gerolymatos International SA, Capricare. Funding Information: CA reports grants from Allergopharma, grants from Idorsia, Swiss National Science Foundation, Christine Kühne‐Center for Allergy Research and Education, European Commission's Horison's 2020 Framework Programme, Cure, Novartis Research Institutes, Astra Zeneca, scibase, advisory role in Sanofi/Regeneron, grants from Glakso Smith‐Kline, advisory role in scibase. Funding Information: MJTreports grants from European Commission, SEAIC, ISCIII, personal fees from Diater laboratory, Leti laboratory, Aimmune Therapeutics. Funding Information: LK reports grants and personal fees from Allergopharma, MEDA/Mylan, LETI Pharma, Sanofi, grants from Stallergenes, Quintiles, ASIT biotech, grants from ALK Abelló, Lofarma, AstraZeneca, GSK, Inmunotk, personal fees from Allergy Therapeut., HAL Allergie, Cassella med; and Membership: AeDA, DGHNO, Deutsche Akademie für Allergologie und klinische Immunologie, HNO‐BV, GPA, EAACI. Funding Information: DPreports grants and personal fees from GlaxoSmithKline, personal fees from Menarini, Pliva, Belupo, AbbVie, Novartis, MSD, Chiesi, Revenio, personal fees and non‐financial support from Boehringer Ingelheim, non‐financial support from Philips. Funding Information: OP reports grants and personal fees from ALK‐Abelló, Allergopharma, Stallergenes Greer, HAL Allergy Holding B.V./HAL Allergie GmbH, Bencard Allergie GmbH/Allergy Therapeutics, Lofarma, ASIT Biotech Tools S.A., Laboratorios LETI/LETI Pharma, Anergis S.A., Glaxo Smith Kline, grants from Biomay, Circassia, Pohl‐Boskamp, Inmunotek S.L., personal fees from MEDA Pharma/MYLAN, Mobile Chamber Experts (a GA2LEN Partner), Indoor Biotechnologies, Astellas Pharma Global, EUFOREA, ROXALL Medizin, Novartis, Sanofi‐Aventis and Sanofi‐Genzyme, Med Update Europe GmbH, streamedup! GmbH, John Wiley and Sons, AS. Copyright: Copyright 2021 Elsevier B.V., All rights reserved. publishersversion published

Funding Information: This research was supported by Jane & Aatos Erkko Foundation. Non

Significance Contact dermatitis is an inflammatory skin disorder that arises from direct skin contact with irritants or allergens. Representing over 90% of occupational skin disorders, it has a considerable socioeconomic impact, and patients suffering from contact dermatitis can develop a notable physical handicap. Current diagnostic regimes rely on allergy testing, exposure specification, and follow-up visits. However, distinguishing the clinical phenotype of irritant and allergic contact dermatitis, which is important for appropriate therapeutic strategies, remains challenging. This study identifies and validates biomarkers to distinguish allergic and irritant contact dermatitis in human skin, to be used for the development of novel diagnostic methods and to guide clinical diagnosis., Contact dermatitis tremendously impacts the quality of life of suffering patients. Currently, diagnostic regimes rely on allergy testing, exposure specification, and follow-up visits; however, distinguishing the clinical phenotype of irritant and allergic contact dermatitis remains challenging. Employing integrative transcriptomic analysis and machine-learning approaches, we aimed to decipher disease-related signature genes to find suitable sets of biomarkers. A total of 89 positive patch-test reaction biopsies against four contact allergens and two irritants were analyzed via microarray. Coexpression network analysis and Random Forest classification were used to discover potential biomarkers and selected biomarker models were validated in an independent patient group. Differential gene-expression analysis identified major gene-expression changes depending on the stimulus. Random Forest classification identified CD47, BATF, FASLG, RGS16, SYNPO, SELE, PTPN7, WARS, PRC1, EXO1, RRM2, PBK, RAD54L, KIFC1, SPC25, PKMYT, HISTH1A, TPX2, DLGAP5, TPX2, CH25H, and IL37 as potential biomarkers to distinguish allergic and irritant contact dermatitis in human skin. Validation experiments and prediction performances on external testing datasets demonstrated potential applicability of the identified biomarker models in the clinic. Capitalizing on this knowledge, novel diagnostic tools can be developed to guide clinical diagnosis of contact allergies.

The European Academy of Allergy and Clinical Immunology (EAACI) organized the first European Strategic Forum on Allergic Diseases and Asthma. The main aim was to bring together all relevant stakeholders and decision-makers in the field of allergy, asthma and clinical Immunology around an open debate on contemporary challenges and potential solutions for the next decade. The Strategic Forum was an upscaling of the EAACI White Paper aiming to integrate the Academy's output with the perspective offered by EAACI's partners. This collaboration is fundamental for adapting and integrating allergy and asthma care into the context of real-world problems. The Strategic Forum on Allergic Diseases brought together all partners who have the drive and the influence to make positive change: national and international societies, patients' organizations, regulatory bodies and industry representatives. An open debate with a special focus on drug development and biomedical engineering, big data and information technology and allergic diseases and asthma in the context of environmental health concluded that connecting science with the transformation of care and a joint agreement between all partners on priorities and needs are essential to ensure a better management of allergic diseases and asthma in the advent of precision medicine together with global access to innovative and affordable diagnostics and therapeutics.

The cutaneous microbiome has been investigated broadly in recent years and some traditional perspectives are beginning to change. A diverse microbiome exists on human skin and has a potential to influence pathogenic microbes and modulate the course of skin disorders, e.g. atopic dermatitis. In addition to the known dysfunctions in barrier function of the skin and immunologic disturbances, evidence is rising that frequent skin disorders, e.g. atopic dermatitis, might be connected to a dysbiosis of the microbial community and changes in the skin microbiome. As a future perspective, examining the skin microbiome could be seen as a potential new diagnostic and therapeutic target in inflammatory skin disorders.

MicroRNAs (miRNAs) are short noncoding RNAs that suppress gene expression at the posttranscriptional level. Atopic dermatitis is a common chronic inflammatory skin disease characterized by the presence of activated T cells within the skin.

The mechanisms of inflammation in acne are currently subject of intense investigation. This study focused on the activation of adaptive and innate immunity in clinically early visible inflamed acne lesions and was performed in two independent patient populations. Biopsies were collected from lesional and non-lesional skin of acne patients. Using Affymetrix Genechips, we observed significant elevation of the signature cytokines of the Th17 lineage in acne lesions compared to non-lesional skin. The increased expression of IL-17 was confirmed at the RNA and also protein level with real-time PCR (RT- PCR) and Luminex technology. Cytokines involved in Th17 lineage differentiation (IL-1β, IL-6, TGF-β, IL23p19) were remarkably induced at the RNA level. In addition, proinflammatory cytokines and chemokines (TNF-α, IL-8, CSF2 and CCL20), Th1 markers (IL12p40, CXCR3, T-bet, IFN-γ), T regulatory cell markers (Foxp3, IL-10, TGF-β) and IL-17 related antimicrobial peptides (S100A7, S100A9, lipocalin, hBD2, hBD3, hCAP18) were induced. Importantly, immunohistochemistry revealed significantly increased numbers of IL-17A positive T cells and CD83 dendritic cells in the acne lesions. In summary our results demonstrate the presence of IL-17A positive T cells and the activation of Th17-related cytokines in acne lesions, indicating that the Th17 pathway is activated and may play a pivotal role in the disease process, possibly offering new targets of therapy.

This update and revision of the international guideline for urticaria was developed following the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. It is a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the Global Allergy and Asthma European Network (GA(2)LEN) and its Urticaria and Angioedema Centers of Reference and Excellence (UCAREs and ACAREs), the European Dermatology Forum (EDF; EuroGuiDerm), and the Asia Pacific Association of Allergy, Asthma and Clinical Immunology with the participation of 64 delegates of 50 national and international societies and from 31 countries. The consensus conference was held on 3 December 2020. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast cell-driven disease that presents with wheals, angioedema, or both. The lifetime prevalence for acute urticaria is approximately 20%. Chronic spontaneous or inducible urticaria is disabling, impairs quality of life, and affects performance at work and school. This updated version of the international guideline for urticaria covers the definition and classification of urticaria and outlines expert-guided and evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria., Urticaria and Angioedema Centers of Reference and Excellence (UCAREs and ACAREs); European Union (EU); 6th Framework Programme; Global Allergy and Asthma European Network (GA2LEN); European Academy of Allergology and Clinical Immunology (EAACI); Asia Pacific Association of Allergy, Asthma and Clinical Immunology (APAAACI); European Dermatology Forum (EDF)

Atopic dermatitis (AD) is a common pruritic skin disease with prevalence rates up to 20 % in children and 3 % in adults. Skin barrier defects combined with modified immune responses of the innate and adaptive immune system activate complex pathophysiological pathways that are involved in the development of this disease. AD is characterized by acute flare-ups as well as chronic eczematous pruritic skin lesions and dry skin. It is crucial to clarify the mechanisms underlying AD in order to devise mechanism-based therapeutic approaches. However, the immunological mechanisms participating in AD are far from being completely understood. This thesis investigates mechanisms believed to be involved in atopic skin inflammation by utilizing an AD-like experimental animal model as well as human patients. The AD-like mouse model was also used to examine the model's suitability for evaluating topical medications for treating AD. In addition, this thesis investigates some of the mechanisms in the so-called atopic march. Results highlight new molecular mechanisms involved in AD and the atopic march. Microbial superantigen, derived from Staphylococcus aureus exacerbates the allergen-induced skin inflammation mostly by a mixed Th1/Th2 type inflammation in the presence of both CD8+ and CD4+ T cells and elevated IgE concentrations. This kind of severe inflammation, induced by allergen and superantigen in the murine skin, was declined with topical corticosteroid and calcineurin inhibitor. According to these results, this AD model is both reproducible and suitable for testing novel treatment options in AD. Finally, a recently characterized Th2-promoting cytokine, IL-33, and its receptor, ST2, were investigated in murine models of AD and allergic asthma as well as in human AD and in different cell models. The results obtained from ST2-/- mice suggest that the IL-33/ST2 pathway can regulate innate immune responses and CD8+ T cell mediated responses in the skin and in lung tissue. However, ST2 appeared to be dispensable for the development of Th2 response in the sensitized skin, whereas it was the main inducer of Th2 cytokines in asthmatic airways. Together, these results obtained from the murine model of AD and from the skin of patients with AD reveal new molecular mechanisms involved in AD. Atooppinen ihottuma on yleinen ihosairaus erityisesti lapsilla, mutta se voi jatkua myös läpi elämän. Taudin kehittymiseen liittyy ihon pintakerroksen vaurio, joka muuttaa immuunijärjestelmän solujen aktivoitumista ja toimintaa. Atooppinen ihottuma ilmentyy akuuttina tai kroonisena kutisevana ja kuivana tulehdusalueena. Atooppisen ihottuman tautimekanismien selvittäminen on tärkeää, että voidaan kehittää tautimekanismeihin vaikuttavia hoitomuotoja. Tässä väitöskirjassa on tutkittu atooppisen ihottuman tautimekanismeja käyttäen kokeellista mallia ja potilasnäytteitä. Lisäksi tutkittiin soveltuuko kokeellinen malli ihmisillä käytettävien lääkeaineiden testaukseen. Lopuksi tutkittiin mekanismeja, jotka liittyvät ihon kautta tapahtuvaan herkistymiseen ja lopulta allergisen astman kehittymiseen kokeellisessa mallissa. Tulokset osoittavat, että stafylokokkibakteerin erittämä superantigeeni pahentaa ihotulehdusta kokeellisessa mallissa aiheuttaen Th1 ja Th2 tyypin tulehdusvälittäjäaineiden, sytokiinien lisääntyneen tuotannon. Superantigeenille herkistetyllä ihoalueella oli sekä CD4+ että CD8+ T soluja. Allergeenialtistetussa ihossa superantigeeni lisäsi CD8+ T solujen määrää. Lisäksi allergiaan liittyvien IgE luokan vasta-aineiden tuotanto lisääntyi superantigeenille altistetussa ihossa. Superantigeenin ja allergeenin aiheuttama tulehdusreaktio parantui huomattavasti topikaalisella kortikosteroidilla ja kalsineuriinisalpaajalla. Tulokset osoittavat, että mallia voidaan käyttää uusien atooppisen ihottuman hoitoon tarkoitettujen lääkeaineiden testaukseen. Väitöskirjassa tutkittiin myös hiljattain karakterisoidun tulehdusvälittäjäaineen, interleukiini-33:n ja sen reseptorin, ST2:n, ilmentymistä ja merkitystä atooppisessa ihottumassa, atooppisen ihottuman ja allergisen astman tautimalleissa ja solumalleissa. IL-33 tasot nousivat ihossa allergeeni- ja superantigeenialtistuksessa. Lisäksi filagriinin puutos, joka liittyy keskeisesti ihon pintakerroksen toimintaan, aiheutti spontaanisti IL-33 ja ST2 mRNA tuotannon lisääntymisen ihossa. ST2 on liitetty Th2 soluihin ja sen tuotanto lisääntyi antigeenin, superantigeenin ja ihovaurion yhteydessä. ST2 geenin puuttuminen hiirillä ei kuitenkaan vähentänyt Th2 tyypin sytokiinien tuotantoa atooppisen ihottuman mallissa. Lisäksi geenin puuttuminen lisäsi CD8+ T solujen, makrofaagien ja neutrofiilien määrää herkistetyllä iholla. Merkittävää oli Th2 tyypin sytokiinien väheneminen keuhkokudoksessa ihon kautta herkistetyillä hiirillä. Tuloksista saadaan uutta tietoa Th2 tyyppisestä reaktiosta ihossa ja keuhkoissa.

Atopic dermatitis (AD) is an allergic skin disease, characterized by relapsing eczema, dry skin and chronic skin inflammation. A large proportion of AD patients develop other allergies or asthma later in life. Allergic contact dermatitis (ACD) in turn, is one of the leading occupational diseases worldwide. Therefore, allergic skin diseases not only impair the quality of life of patients but also cause a great economical burden for the society. This thesis investigates some of the mechanisms behind allergic skin diseases. In an AD-model, an AD-like skin inflammation was induced by mechanical skin injury and epicutaneous sensitization. This induced a Th2 cytokine dominated inflammatory response at the site of allergen exposure, and elevation of allergy-related IgE antibody levels in the serum. The effects of skin colonizing bacteria Staphylococcus aureus derived enterotoxin B (SEB) were evaluated on the inflammatory response in AD-model. SEB application significantly exacerbated the allergen induced inflammatory response in the skin, increasing cellular infiltration, enhancing Th2 cytokine production and provoking Th1 cytokine production. Furthermore, SEB induced the production of SEB-specific IgE antibodies and enhanced the production of allergen-specific IgE antibodies. These results demonstrate that bacterial skin colonization may both augment the inflammatory response in AD patients and play a role in the chronification of the disease. Although regulatory T cells (Treg) are known to prevent allergic responses, their role in AD is still not clear. We utilized DEREG mice, in which the Foxp3+ Treg cells can be transiently depleted, to study the role of Foxp3+ Treg cells in the AD-like skin inflammation. The epidermal barrier in AD patients is often damaged by scratching or genetic defect. We observed that in the absence of Foxp3+ Treg cells, the skin injury alone induced a stronger inflammation compared with WT. The addition of allergen further enhanced the inflammatory response and especially increased the production of Th2 cytokines, suggesting that Foxp3+ cells are also essential in controlling the allergic responses in the skin. In addition, when allergen was administered into the lungs at a time point when the Treg compartment had been restored, augmented inflammatory response was observed in the lungs, indicating, that impaired Foxp3+ Treg function during skin sensitization may modulate the possible asthma responses developing later on. In the ACD-model, the skin inflammation was induced by epicutaneous application of oxazolone in two phases: sensitization, when memory cells against the hapten were generated and elicitation, when the same hapten was applied on the skin, resulting in a clinically observed inflammatory response. The role of Foxp3+ Treg cells was studied in these two phases and also in the clearance of the inflammation. The absence of Foxp3+ Treg cells in the sensitization phase dramatically exacerbated the skin inflammation, whereas the absence in the elicitation phase had no effect on the inflammatory response during the first 24 hours post challenge. Instead, both depletions severely impaired the resolution of the inflammation, most likely due to the impaired ability of restored Foxp3+ Treg cells to accumulate in the skin. These results reveal that Foxp3+ Treg cells are crucial during the sensitization phase in the LNs and during the resolution phase in the skin. CCR4 is a chemokine receptor which together with chemokine receptor CCR10 is involved in lymphocyte trafficking into the skin. Surprisingly, the ACD response in CCR4 knock-out mice was exacerbated as compared with WT. When the inflammatory response was followed at different time points after sensitization and challenge, increased proliferation of CD4+ cells was observed in CCR4-/- mice, indicating that CCR4 is somehow involved in the regulation of CD4+ cells during ACD responses. Atooppinen ihottuma on krooninen allerginen ihosairaus jota sairastaville saattaa kehittyä myöhemmin myös muita allergioita ja astmaa. Allerginen kosketusihottuma puolestaan on yksi merkittävimmistä ammattitaudeista. Tässä väitöskirjassa on tutkittu joitakin mekanismeja, jotka vaikuttavat näiden tautien syntyyn ja ylläpitoon. Atooppisen ihottuman tautimallissa tulehdusreaktio saadaan aikaan ihon kautta tapahtuvan allergeenialtistuksen avulla. Tämä aiheuttaa tulehdussolujen kulkeutumista ihoon sekä lisää allergiaan liittyvien Th2-tyypin tulehdusvälittäjäaineiden ja IgE-luokan vasta-aineiden määrää. Tässä väitöskirjassa selvitettiin, että erityisesti atooppista ihottumaa sairastavien iholla esiintyvän Staphylococcus aureus -bakteerin tuottama enterotoksiini B (SEB) merkittävästi pahentaa allergeenin aiheuttamaa ihotulehdusta ja lisäksi aikaansaa Th1 tyypin välittäjäaineiden tuottoa, joilla uskotaan olevan merkitystä taudin kroonistumisessa. Siksi bakteeri-infektioiden hallinta onkin tärkeää atooppista ihottumaa sairastavien hoidossa. Säätely T-solut säätelevät tulehdusreaktioiden voimakkuutta. Me selvitimme säätely-T-solujen roolia sekä atooppisessa ihottumassa että kosketusallergiassa hyödyntäen hiirikantaa, joilta säätely T-solut voidaan väliaikaisesti poistaa. Atooppista ihottumaa sairastavien ihon pintakerros on usein vaurioitunut kutinan aiheuttamasta raapimisesta tai geneettisestä mutaatiosta johtuen. Tutkimuksessamme havaitsimme, että säätely-T-solujen poissaollessa jo lievä ihovaurio aiheutti normaalihiirtä voimakkaamman ihotulehduksen. Allergeenialtistus pahensi tulehdusta entisestään, lisäten erityisesti Th2 tyypin välittäjäaineiden ja IgE luokan vasta-aineiden määrää. Lisäksi, kun allergeenia annosteltiin hiiren keuhkoihin aikapisteessä, jolloin säätely-T-solujen määrä oli jo palautunut normaaliksi, voitiin havaita pahentunut tulehdus keuhkoissa normaalihiiriin verrattuna mikä viittaa siihen, että heikentyneellä säätely-T-solujen toiminnalla saattaa olla pitkäaikaisia vaikutuksia. Allergisen kosketusihottuman mallissa ihotulehdus aiheutetaan kahdessa vaiheessa. Herkistysvaiheessa muodostuu allergeenia tunnistavia muistisoluja, mutta ei ihotulehdusta. Elisitaatiovaiheessa allergeenin annostelu iholle aiheuttaa tyypillisen kosketusallergiareaktion. Selvitimme säätely-T-solujen roolia näissä kahdessa eri vaiheessa. Säätely-T-solujen poistaminen herkistysvaiheessa johti merkittävästi pahentuneeseen ihotulehdukseen, kun taas poisto juuri ennen elisitaatiovaihetta ei vaikuttanut millään tavalla tulehdusvasteeseen ensimmäisten 24 tunnin aikana. Sen sijaan tulehdusreaktion lopettaminen viivästyi merkittävästi molemmissa ryhmissä, todennäköisesti siitä syystä, että säätely-T-solut eivät kulkeutuneet ihoon. Säätely-T-solujen toiminnalla on siis merkittävä rooli sekä atooppisen ihottuman että allergisen kosketusihottuman tulehdusreaktion synnyssä ja/tai tulehduksen voimakkuuden ja pituuden säätelyssä. CCR4 on kemokiinireseptori, jota yhdessä kemokiinireseptori CCR10:n kanssa tarvitaan T-solujen kulkeutumisessa ihoon. Hiirillä, joilta puuttuu kemokiinireseptori CCR4, kehittyy odotusten vastaisesti pahentunut allerginen kosketusihottuma normaalihiireen verrattuna. Havaitsimme, että ns. auttaja-T-solut jakaantuivat nopeammin CCR4-/- hiiressä, viitaten siihen, että CCR4 reseptorilla on jokin rooli näiden solujen jakautumisen säätelyssä.

Occupational rhinitis is mainly caused by work environment and not by stimuli encountered outside the workplace. It differs from rhinitis that is worsened by, but not mainly caused by, workplace exposures. Occupational rhinitis can develop in response to allergens, inhaled irritants, or corrosive gases. The thesis evaluated the use of challenge tests in occupational rhinitis diagnostics, studied the long-term health-related quality of life among allergic occupational rhinitis patients, and the allergens of wheat grain among occupational respiratory allergy patients. The diagnosed occupational rhinitis was mainly allergic rhinitis, which was caused by occupational agents, most commonly flours and animal allergens. The non-IgE-mediated rhinitis reactions were less frequent and caused more often asthma than rhinitis. Both nasal challenges and inhalation challenges were found to be safe tests. The inhalation challenge tests had considerably resource-intensive methodology. However, the evaluation of nasal symptoms and signs together with bronchial reactions saved time and expense compared with the organization of multiple individual challenges. The scoring criteria used matched well with the weighted amount of discharge ≥ 0.2 g and in most cases gave comparable results. The challenge tests are valuable tools when there is uncertainty whether the patient's exposure should be reduced or discontinued. It was found that continuing exposure decreases health-related quality of life among patients with allergic occupational rhinitis despite of rhinitis medications, still approximately ten years after the diagnosis. Health-related quality of life among occupational rhinitis patients without any longer occupational exposure was mainly similar than that of the healthy controls. This highlights the importance of the reduction and cessation of occupational exposure. To achieve this, 17% of occupational rhinitis patients had been re-educated. Alpha-amylase inhibitors, lipid transfer protein 2G, thaumatin -like protein, and peroxidase I were found to be relevant allergens in Finnish patients with occupational respiratory wheat allergy. Of these allergens, thaumatin-like protein and lipid transfer protein 2G were found as new allergens associated with baker's rhinitis and asthma. The knowledge of the new clinically relevant proteins can be used in the future in the development of better standardized diagnostic preparations. Ammattinuha: diagnoosi ja terveyteen liittyvä elämänlaatu Ammattinuhalla tarkoitetaan työssä esiintyvän tekijän pääasiallisesti aiheuttamaa nuhaa. Se eroaa työn pahentamasta, (tai samanaikaisesta muusta) nuhasta, jossa työympäristö ei ole pääasiallinen nuhan syy. Väitöskirjatyössä tutkittiin ammattinuhan diagnosoinnissa käytettäviä altistuskokeita, allergiseen ammattinuhaan sairastuneiden pitkäaikaista elämänlaatua sekä ammattinuhan yhden pääaiheuttajan, vehnän, allergeeneja ja niiden esiintymistä ammattinuhaa tai -astmaa sairastavilla vehnäallergikoilla. Ammattinuhat todettiin yleensä allergiseksi nuhaksi, ja tavallisimmin ammattinuhan aiheuttajia olivat jauhot ja eläimet. Ei-allergista nuhaa esiintyi selvästi harvemmin kuin allergiaa. Työperäisillä aineilla tehtävät nenä- ja kammioaltistuskokeet todettiin analyyseissä turvallisiksi testeiksi, koska vakavia, vaikeasti hoidettavia allergiareaktioita ei niissä ollut esiintynyt. Ammattinuha todettiin 47% nenäaltistustestein tutkituista potilaista. Kammioaltistustesteissä 13% potilaalle tuli positiivisen testin kriteerit täyttävä nuhaoireisto, niissä astmareaktiot olivat yleisempiä (25%). Altistustestit ovat arvokkaita, kun on epävarmaa voiko altistuminen jatkua tai tuleeko potilaan vaihtaa työtä. Työterveyslaitoksen käyttämä pisteytyskriteeri antoi pääasiassa yhteneväisen tuloksen eritemittauksen kanssa, joka tukee oletusta eri testimenetelmien pääosin samanlaisista tuloksista työperäisen allergian testauksissa. Vaikka kammioaltistuskoe vaatii paljon resursseja, voidaan kammioaltistuksessa yhdistää keuhkoputkialtistus ja nenäaltistus, mikä säästää aikaa ja kustannuksia verrattuna kahteen eri tutkimukseen. Jos työperäinen altistuminen allergeeneille oli jatkunut keskimäärin 10 vuotta ammattinuhan toteamisen jälkeen, terveyteen liittyvä elämänlaatu oli ammattinuhaan sairastuneilla alentunut, nuhalääkityksestä huolimatta. Altistumattomien potilaiden elämänlaatu oli pääosin samankaltainen kuin terveillä verrokkihenkilöillä. Väitöstutkimus korostaa ammattinuhapotilaiden altistumisen vähentämisen tai lopetuksen tarvetta. Ammattinuhapotilaat ja verrokkihenkilöt eivät eronneet toisistaan työssäkäynnin suhteen, mutta merkittävä osa (17 %) ammattinuhapotilaista oli uudelleenkoulutettuja. Useita vesiliukoisia vehnän allergeeneja puhdistettiin ja tunnistettiin. Niiden merkitystä hengitystieallergeeneina tutkittiin leipurin nuhaa ja / astmaa sairastavilla vehnäallergisilla potilailla ihopistotestein. Tutkimuksessa löydettiin kaksi uutta merkityksellistä vehnän allergeenia leipurin ammattinuhassa ja/ tai astmassa. Tietoa uusista vehnän työperäistä hengitystieallergiaa aiheuttavia merkittävistä valkuaisaineista voidaan jatkossa hyödyntää kehitettäessä leipurin nuhaa ja astmaa testaavia testejä.

The skin microbiome – Investigations on skin malignancies and preterm newborn skin Skin disorders have been associated with specific microbiome changes and raised an interest in developing new diagnostic methods and treatments. Our object was to investigate the microbiome in skin cancer (melanoma) and inflammatory skin disorders (parapsoriasis) and to explore the skin microbiome in very low birth weight infants in intensive care and possible association to neonatal sepsis. Microbiome samples were taken of 15 cutaneous melanomas and 17 benign melanocytic nevi, of 13 patients with parapsoriasis and 12 very low birth weight infants during treatment in intensive care. Sequencing was carried out on 454 GS-FLX Titanium and Illumina MiSeq platforms and the data was analyzed by bioinformatics. There were no significant differences in the microbiome of melanomas, melanocytic nevi and controls. Additionally, the microbiome showed no significant differences between parapsoriasis and the same patient’s healthy skin. We observed a high cutaneous microbial diversity in most of the infants at birth and there was a decrease in diversity during the first three weeks of life. There was no association between microbiome changes and neonatal sepsis. The results suggest that microbiome swab sampling may not be helpful in diagnostics of melanoma or parapsoriasis. Moreover, microbiome changes seem not to play a role in parapsoriasis. We could demonstrate that very low birth weight infants in intensive care have a high cutaneous microbial diversity during the first days of life regardless of the way of delivery, prematurity causes or perinatal infections. The diversity decreases during the first weeks of life possibly due to intensive care treatment and antibiotics. Neonatal sepsis is not linked to microbiome changes and it is likely that other factors play a role, e.g. skin injury by medical devices and concomitant infections. Ihon mikrobiomi - tutkimuksia ihosyövissä ja vastasyntyneiden keskosten ihossa Väitöskirjassa tutkittiin ihon mikrobiomia uusilla molekyyligenetiikkaan pohjautuvilla tutkimusmenetelmillä, jotka ovat herättäneet kiinnostusta diagnoosimenetelmien ja hoitomuotojen löytämiseksi. Tavoitteena oli selvittää mikrobiomi ihosyövässä (melanooma) ja tulehduksellisissa ihosairauksissa (parapsoriasis) sekä kartoittaa mikrobiomi erittäin alhaisen syntymäpainon keskosissa tehohoidossa ja sen mahdollista yhteyttä verenmyrkytykseen. Mikrobiominäytteitä otettiin 15 melanoomasta ja 17 hyvänlaatuisesta melanosyyttiluomesta, 13 parapsoriasis potilaasta ja 12 erittäin alhaisen syntymäpainon keskosesta tehohoidon aikana. Analysointi toteutettiin molekyyligenetiikkaan pohjautuvilla sekvensointimenetelmillä. Merkittäviä eroja mikrobiomissa tai bakteeriston diversiteetissä ei tullut esille melanoomien ja hyvänlaatuisten luomien välillä. Ihon mikrobiomissa ei myöskään todettu merkittäviä eroja parapsoriasis ihottuman ja terveen näköisen ihon välillä. Useimmilla keskosilla havaittiin syntyessä korkea ihon bakteeriston monimuotoisuus (diversiteetti). Kolmen ensimmäisen elinviikon aikana diversiteetti kaventui, mutta tämä ei ollut ajallisessa yhteydessä verenmyrkytykseen. Löydöksemme viittaavat siihen, että mikrobiomin tutkimisesta ei ole hyötyä melanooman diagnostiikassa. Emme myöskään havainneet viitteitä siitä, että mikrobiomin muutoksilla tai stafylokokkibakteereilla olisi merkitystä parapsoriasiksessa. Pystyimme osoittamaan mikrobiomin korkean diversiteetin keskosten ensimmäisinä elinpäivinä riippumatta syntymistavasta, keskosuuden syystä tai infektioista. Vastasyntyneiden verenmyrkytys ei ollut yhteydessä mikrobiomin muuttumiseen ja tämän taustalla on luultavasti muita tekijöitä kuten ihoa lävistävät lääkinnälliset laitteet tehohoidossa tai samanaikaiset infektiot.