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Objectives and methods: Topical therapy is the first-line treatment in mild and moderate psoriasis. We performed a real-life study on topical therapies in psoriasis and observed a variation in the amounts of ointment patients applied during the study.Results: A statistically significant correlation was found between gender and the total amount of ointment used: women used more than men (p=.020). Also, heavier patients tended to use less ointment (p=.038).Conclusions: We look forward to seeing whether the current pressure to improve psoriasis treatment leads to more patients receiving systemic therapies or to better adherence to, and persistence with, topical therapies.

Bullous pemphigoid (BP) is the most common of pemphigoid diseases caused by autoantibodies against the structures of dermoepidermal junction followed by complement activation, innate immune cell infiltration, neutrophil proteinase secretion and subepidermal blister formation. The first-line treatment of BP is topical and systemic glucocorticoids (GC). Regulation of the immune system and inflammatory cells is the main target of GC actions. GCs act through genomic and non-genomic mechanisms. The human glucocorticoid receptor (GR) mediates most of the biologic effects of GC: cytosolic GR binds GCs and is capable to bind to glucocorticoid response elements in DNA and either transactivate or transrepress genes depending on the tissue and cell type. In addition, GR exerts rapid, non-genomic effects possibly mediated by membrane-localized receptors or by translocation to mitochondria. GCs can also interact directly with several enzymes and cytokines. As a target treatment for BP, the production of autoantibodies should be discontinued. GCs, in spite of their wide immunosuppressive actions, are weak to stop immunoglobulin G (IgG) autoantibody formation. However, both systemic and topical GCs are able to reduce the clinical symptoms of BP. GCs are used to inhibit the secondary inflammation and symptoms, such as blistering and pruritus, and it is shown that GC treatment will gradually decrease also the autoantibody formation. Our review article analyses the mode of action of GC treatment in BP, as far it is possible due to paucity of modern immunological studies.

Oral retinoids and tetracyclines have a major role in acne treatment. Here, we report for the first time the effect of isotretinoin and lymecycline therapy on the skin microbiota in cheek, back and armpit swab samples of acne vulgaris patients using 16S ribosomal RNA (16S rRNA) gene amplicon sequencing. Propionibacterium acnes was the most common in sebaceous areas of healthy and untreated acne skin and more abundant in back than cheek samples. Five taxa, including a Streptococcus taxon, differed significantly between the cheek samples of healthy controls and acne patients, and acne severity was positively correlated with the abundance of Propionibacterium . Both treatments reduced clinical acne grades and the abundance of Propionibacterium , while the abundance of several other taxa was significantly higher in treated cheek samples compared with untreated ones. Less variation was observed in back samples and none in armpit samples. There were no differences in alpha diversity between control and acne patients in any of the sampled skin areas, but the diversity of the microbiota on the cheek and the back was significantly increased after acne treatments. This study provides insight into the skin microbiota in acne and how it is modulated by systemic acne treatment.

The effects of topical calcipotriol/betamethasone combination therapy and betamethasone monotherapy on inflammatory T-cell numbers and molecular markers were compared in patients with psoriasis. Combination therapy down-regulated the expression of tumour necrosis factor (TNF)-α, interleukin (IL)-23A, IL-17A, S100A7, CCL-20 and interferon (IFN)-γ in skin and TNF-α, IL-6, IL-23A, T-bet and IFN-γ in peripheral blood mononuclear cells (PBMCs). Betamethasone monotherapy had less effect. Expression of FoxP3 in both skin and PBMCs was down-regulated by calcipotriol/betamethasone, but not by betamethasone. Immunohistochemical analysis revealed that calcipotriol/betamethasone reduced the numbers of CD4+ and CD8+ T cells and Tregs in psoriatic lesions more than betamethasone. Flow cytometric analyses demonstrated that calcipotriol/betamethasone decreased the numbers of circulating CD8+ T cells, Tregs, skin-homing Th17 memory cells and Th22 memory cells, while betamethasone had little or no effect. Glucocorticoid receptors GRα and GRß were expressed in psoriatic skin. In conclusion, calcipotriol increases the immunosuppressive power of betamethasone by suppressing the inflammatory TNF-α - IL-23 - IL-17 axis.

DRESS (drug reaction with eosinophilia and systemic symptoms) is a rare, severe multiorgan adverse drug reaction. Antiepileptic age's and antibiotics are the most frequently reported causative agents. Compared with other drug reactions, DRESS demonstrates a long latency period thus complicating recognition and diagnosis. DRESS is defined as presence of fever, skin eruption, hematologic abnormalities and systemic involvement, especially liver injury. Withdrawal of the culprit drug, commencement of systemic corticosteroid and supportive care are the mainstay of treatment. The majority of patients recover completely after drug withdrawal and appropriate therapy. Some patients suffer from chronic sequelae or even death.

Glucocorticoids are the most important and widely used treatment modality in dermatology. A large variety of topical as well as systemic preparations is available. Most patients treated with glucocorticoids respond quickly to the treatment, but some are considered insensitive or even resistant to glucocorticoid therapy. Currently, there is no known measurable variable, through which the response can be predicted. Glucocorticoids mediate their actions through glucocorticoid receptors (GR). Several isoforms of GR exist, but the α (GRα) and β (GRβ) isoforms are clinically the most important. Based on previous studies, it has been proposed that the abundance of GR isoforms or the GRβ: GRα –ratio could affect individual responsiveness to corticosteroid treatment. In particular, up-regulation of GRβ expression has been shown to be linked to resistance to corticosteroid treatment. This thesis comprises three sub-studies. Firstly, we wanted to determine whether GRα and GRβ are expressed in inflammatory skin diseases. Secondly, we examined if the expression is altered by corticosteroid treatment in eczema atopicum, bullous pemphigoid and psoriasis. Finally, we measured the effects of a topical vitamin D3 analogue (calcipotriol) combined with betamethasone compared with betamethasone monotherapy on inflammatory biomarkers of psoriasis. Our studies provide detailed novel data about the expression of GRα and GRβ. GRα and GRβ were shown to be expressed in the blood lymphocytes and lesional skin of patients with eczema atopicum, bullous pemphigoid and psoriasis, as well as in the skin of patients with eczema nummulare, lichen simplex chronicus and lichen ruber planus. Systemic corticosteroid treatment was shown to affect the expression of GRα and GRβ in eczema atopicum and bullous pemphigoid, but the inconsistent variation in their expression between patients prevented us from drawing firm conclusions. Neither GRα nor GRβ as a single marker were found to be a suitable predictor of corticosteroid responsiveness. Clinical and laboratory analyses showed that topical treatment of psoriasis with calcipotriol/betamethasone combination ointment is more beneficial measured by both than betamethasone monotherapy.

Acute generalized exanthematous pustulosis (AGEP) is a severe, almost exclusively drug-induced reaction pattern mediated by T cells. It presents with oedematous ery thema, followed by dozens of small non-follicular sterile pustules with widespread distribution. Skin symptoms typically appear after 1–5 days of treatment and are almost always accompanied by fever and leukocytosis. The clinical course is characterized by acute onset and spontaneous resolution over a period of 15 days. The use of antibacterial drugs, i.e. aminopenicillins, is mainly associated with AGEP (1–3).

Contact DermatitisVolume 75, Issue 1 p. 58-59 Contact Point Benzyl alcohol allergy mimicking corticosteroid allergy Minna E. Kubin, Corresponding Author Minna E. Kubin Department of Dermatology, University Hospital of Oulu and Oulu University, 90220 Oulu, FinlandCorrespondence: Minna Kubin, Department of Dermatology, Oulu University Hospital, PL 22, 90029 Oulu, Finland. Tel: +358 8 315 3508. E-mail: minna.kubin@ppshp.fiSearch for more papers by this authorRiitta Riekki, Riitta Riekki Department of Dermatology, University Hospital of Oulu and Oulu University, 90220 Oulu, FinlandSearch for more papers by this author Minna E. Kubin, Corresponding Author Minna E. Kubin Department of Dermatology, University Hospital of Oulu and Oulu University, 90220 Oulu, FinlandCorrespondence: Minna Kubin, Department of Dermatology, Oulu University Hospital, PL 22, 90029 Oulu, Finland. Tel: +358 8 315 3508. E-mail: minna.kubin@ppshp.fiSearch for more papers by this authorRiitta Riekki, Riitta Riekki Department of Dermatology, University Hospital of Oulu and Oulu University, 90220 Oulu, FinlandSearch for more papers by this author First published: 05 June 2016 https://doi.org/10.1111/cod.12562Citations: 6 Conflicts of interest: The authors declare no conflict of interests. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume75, Issue1July 2016Pages 58-59 RelatedInformation

BackgroundGlucocorticoids (GC) are the most commonly used antiinflammatory drugs in dermatology. The actions of GCs are mediated by the glucocorticoid receptor (GR). Alternative splicing of GR mRNA gives rise to different isoforms, GRα and GRβ being the most important. GRβ antagonizes the activity of GRα and its up-regulation has been associated with glucocorticoid insensitivity in several non-cutaneous inflammatory diseases.MethodsUsing immunohistochemical stainings, we analyzed the expression of GRα and GRβ in lesional skin samples of patients with atopic dermatitis, lichen ruber planus, eczema nummulare and lichen simplex chronicus.We also conducted a study of 13 severe atopic patients to investigate the effect of prednisolone treatment on the expression of GR isoforms using quantitative PCR, western blot and immunohistochemical analysis.ResultsGRα and GRβ were expressed in atopic dermatitis, lichen ruber planus, eczema nummulare and lichen simplex chronicus. Our novel finding was that GRα is abundant in keratinocytes and cutaneous neutrophils. Nuclear staining of both GRα and GRβ was strongest in keratinocytes of patients with lichen ruber planus, whereas the least nuclear positivity was detected in keratinocytes of patients with atopic dermatitis. In severe atopic dermatitis GRα and GRβ were expressed in both peripheral blood mononuclear cells and the skin. The expression of GRα and GRβ varied during prednisolone therapy but the changes were not related to treatment response or GC insensitivity.ConclusionGRα and GRβ are expressed in inflammatory dermatoses. In severe atopic dermatitis the increased expression of GRβ mRNA is not connected to insensitivity against prednisolone treatment.

Recent reports suggest that T-helper type 17 (Th17) and Th1 lymphocytes are involved in the pathogenesis of acne 1-3. Systemic isotretinoin remains the most efficient treatment for acne, but its complete mechanism of action is unknown. The current understanding is that isotretinoin reduces sebum production and the formation of comedones through influencing cell cycle progression, differentiation and apoptosis of sebocytes and keratinocytes 4. Isotretinoin may also indirectly lower the abundance of Propionibacterium acnes (P. acnes) as a result of sebum reduction. Retinoids have anti-inflammatory properties, downregulating Toll-like receptor 2 (TLR2) expression on monocytes 5 and neutrophil migration 6. In addition, retinoids inhibit inflammatory Th17 and promote regulatory T-cell (Treg) responses 7. Isotretinoin treatment also downregulates the expression of matrix metalloproteinases 9 and 13, which play a central role in inflammatory matrix remodelling 8. Furthermore, all retinoids stimulate the release of IL-10, granulocyte–macrophage-stimulating factor (GM-CSF) and monocyte chemotactic protein-1 (MCP-1) by monocytes and macrophages in vitro 9. How does isotretinoin treatment affect innate and adaptive immunity markers, and especially the Th17/Treg balance, in acne patients’ skin in vivo? We analysed the effect of oral isotretinoin 0.5 mg/kg/day in lesional and non-lesional skin areas in acne patients before and during treatment (approximately after 6 weeks of isotretinoin). Biopsied acne lesions were clinically early lesions. The infiltration of immune cells in the skin was examined by immunohistochemistry and the expression of inflammatory mediators in the skin by qRT-PCR and serum by Luminex assay. Detailed information on Materials and methods is given in Supporting Information. The clinical outcome of acne was significantly (P < 0.001) improved on the face and back during isotretinoin treatment based on acne severity grading (Fig. S1). To analyse the effect of isotretinoin in uninvolved skin of acne patients, the gene expression of immune markers was studied. The level of IL-1beta mRNA expression was slightly elevated in uninvolved skin in the acne patients compared with healthy volunteers, and its expression was markedly reduced by isotretinoin treatment with a long-lasting effect (Fig. 1a). Similarly, the expression of TLR2 was significantly reduced (P < 0.001) in uninvolved skin during treatment (Fig. 1b), but TLR4 was not modified by isotretinoin (Fig. 1c). In contrast, the level of psoriasin (S100A7) and lipocalin-2 (LCN2) mRNA, which were expressed at a significantly lower level in uninvolved skin in acne compared with healthy volunteers, was elevated by isotretinoin treatment (Fig. 1d,e). Transforming growth factor-beta (TGF-beta) was expressed at a significantly lower level in uninvolved skin in acne patients compared with healthy volunteers (Fig. 1f). Isotretinoin had no effect on the level of TGF-beta mRNA, which was also the case for Treg marker FOXP3 mRNA (Fig. 1g). To assess the effect of isotretinoin therapy on the extent of inflammation in acne lesions, we examined gene expression and cell infiltration in newly formed lesions. The expression of TLR2, TLR4, IL-8, IL-1beta, tumor necrosis factor (TNF)-alpha and IL-6 was elevated in the lesions in untreated acne, and newly formed lesions exhibited a similar extent of inflammation during isotretinoin treatment (Fig. S3a–f). Additionally, the expression of cytokines associated with adaptive immune responses including IL-12b, interferon (IFN)-gamma, IL-23A, IL-17A and IL-22 was equally amplified in early lesions in treated compared with non-treated acne lesions (Fig. 2a–e). Immunohistochemical analysis of the lesions showed similar counts of CD4+, CD8+, T-bet+ and IL-17A+ cells in the upper dermis and around the sebaceous follicles in treated and untreated acne (Table S2). The infiltration of FOXP3+ cells in the lesions as well as the expression of FOXP3 mRNA and anti-inflammatory cytokines TGF-beta and IL-10 mRNA in lesional tissue (Table S3, Fig. 2f–h) was also similar in treated and untreated acne. Furthermore, AMPs including human cathelicidin antimicrobial protein (HCAP18), S100A7, S100 calcium-binding protein A9 (S100A9), human beta-defensin-2 (HBD-2), HBD-3 and LCN2 were manifold elevated in the acne lesions, and to a similar extent in treated and untreated acne lesions (Fig. S4a–f). We also observed a trend towards higher mRNA expression of the apoptotic marker TRAIL (P = 0.058) in acne lesions during isotretinoin treatment (Fig. S4g). Interestingly, we found a significant increase in the number of CD68+ cells in dermal infiltrates of the lesions (P = 0.032) and uninvolved skin of acne patients (P = 0.037) during isotretinoin treatment compared with untreated skin (Table S2, Fig. S5a,b). Finally, we analysed serum levels of cytokines TNF-alpha, IL-10, IFN-gamma and IL-17A from ten acne patients and observed slightly (but not significantly) higher levels of these cytokines in untreated acne patients compared with healthy volunteers. Isotretinoin treatment showed a trend of lowering the level of TNF-alpha, IL-17A and IFN-gamma, but not IL-10, in the serum (Fig. S6). During the course of isotretinoin treatment, we observed significant downregulation of pro-inflammatory mediators IL-1beta and TLR2, as well as upregulation of antimicrobials S100A7 and LCN-2 mRNA in the uninvolved skin in the acne patients. Contrary to what we expected, isotretinoin treatment had no effect on the expression of inflammatory mediators including adaptive immune responses in the new lesions, which appeared during the treatment. In the serum, however, there was a slight (but non-significant) reduction of IL-17A and IFN-gamma due to reduced inflammation. In addition, the infiltration of macrophages in both uninvolved skin and lesions was significantly increased by isotretinoin treatment. The results concerning downregulation of TLR2, upregulation of S100A7 and LCN-2 and increased macrophage count in acne patients’ skin are in line with the previous in vitro and in vivo studies concerning the effects of retinoids (5, 9,S3–S5). Being expressed to a greater extent in unaffected skin in acne patients, IL-1beta, an important pro-inflammatory cytokine in immunopathogenesis of acne (S6), may thus serve as an initial reservoir for release under conditions of environmental challenge, which is attenuated by isotretinoin therapy. Taken together, our results suggest that isotretinoin may not reduce directly ongoing inflammation in the acne lesions themselves; instead, it modifies mechanisms that control immune homoeostasis, as seen in unaffected skin. We would like to thank Ms. Riitta Vuento and Mr. Petri Kelhälä for their expert assistance. Moreover, we are grateful to all patients for their contribution to this study. This study was supported by Helsinki-Uusimaa Hospital District Research Funds (to AL), the Finnish Dermatological Society and MRC Oulu Doctoral Program (to H-LK). H-LK, RP, NF, KT, HA and AL designed the study. HLK, NF, SL, JPV and MEK conducted the research. H-LK, RP, NF, JPV, MK, HA and AL analysed the data. KT, HA and AL contributed reagents/materials/analysis tools. H-LK, RP, NF, KT and AL wrote the article. The authors state no conflict of interest. Figure S1. Changes of clinical acne grades during isotretinoin treatment. Figure S2. The images illustrating a patients back before (a) and after 7.2 weeks of (b) isotretinoin treatment. Figure S3. Isotretinoin has no effect on the expression of inflammatory mediators in newly formed lesions. Figure S4. The effect of isotretinoin on the expression of AMPs and on apoptosis markers in acne skin. Figure S5. Isotretinoin treatment causes increased infiltration of macrophages in acne lesions. Figure S6. The effect of isotretinoin to serum levels of effector cytokines. Table S1. Study subjects characteristics. Table S2. Number of positively stained cells in lesional and nonlesional skin of acne patients before and in the course of isotretinoin treatment as assessed by immunohistochemistry. Data S1. Materials and methods. Data S2. Supplementary references. Data S3. Acknowledgements and authorship contributions. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

First-line treatments of bullous pemphigoid (BP) are topical and systemic glucocorticoids (GC). The actions of GC are mediated by glucocorticoid receptors (GR), which exist in several isoforms, of which GRα and GRβ are the most important. In many inflammatory diseases, up-regulation of GRβ is associated with GC insensitivity. The aims of this study were to determine the expression of GRα and GRβ in patients with BP and to investigate the effect of prednisolone treatment on the expression of GR isoforms in BP. Quantitative real-time PCR (qPCR) analysis demonstrated that GR isoform mRNAs are expressed in peripheral blood mononuclear cells (PBMC) from patients with BP. Expression of GRα and GRβ protein was confirmed by immunohistochemical staining of BP skin biopsies and by Western blot analysis and flow cytometric analysis of PBMCs. During prednisolone treatment, GRα and GRβ expression varied markedly, but changes were not suitable as a clinical marker of GC sensitivity in patients with BP.

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.

Contact DermatitisVolume 70, Issue 4 p. 255-256 Contact Points Allergic contact eczema caused by exotic wood material in sauna interior decoration Minna E. Kubin, Corresponding Author Minna E. Kubin Department of Dermatology, University Hospital of Oulu, Oulu, 90029 FinlandCorrespondence: Minna Kubin, Department of Dermatology, University Hospital of Oulu, PL 22, Oulu 90029, Finland. Tel: +358 8 315 3508; Fax: +358 8 315 3801. E-mail: [email protected]Search for more papers by this authorRiitta Riekki, Riitta Riekki Department of Dermatology, University Hospital of Oulu, Oulu, 90029 FinlandSearch for more papers by this author Minna E. Kubin, Corresponding Author Minna E. Kubin Department of Dermatology, University Hospital of Oulu, Oulu, 90029 FinlandCorrespondence: Minna Kubin, Department of Dermatology, University Hospital of Oulu, PL 22, Oulu 90029, Finland. Tel: +358 8 315 3508; Fax: +358 8 315 3801. E-mail: [email protected]Search for more papers by this authorRiitta Riekki, Riitta Riekki Department of Dermatology, University Hospital of Oulu, Oulu, 90029 FinlandSearch for more papers by this author First published: 14 March 2014 https://doi.org/10.1111/cod.12162Citations: 5 Conflicts of interest: The authors have declared no conflicts of interest. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article.Citing Literature Volume70, Issue4April 2014Pages 255-256 RelatedInformation

Contact DermatitisVolume 69, Issue 2 p. 121-122 Contact Point Contact allergy to western red cedar in sauna furnishing M. Kubin, Corresponding Author M. Kubin Department of Dermatology, University Hospital of Oulu, Oulu, 90029 FinlandCorrespondence: Minna Kubin, Department of Dermatology, PL 22, 90029 Oulu, Finland. E-mail: minna.kubin@ppshp.fiSearch for more papers by this authorR. Riekki, R. Riekki Department of Dermatology, University Hospital of Oulu, Oulu, 90029 FinlandSearch for more papers by this author M. Kubin, Corresponding Author M. Kubin Department of Dermatology, University Hospital of Oulu, Oulu, 90029 FinlandCorrespondence: Minna Kubin, Department of Dermatology, PL 22, 90029 Oulu, Finland. E-mail: minna.kubin@ppshp.fiSearch for more papers by this authorR. Riekki, R. Riekki Department of Dermatology, University Hospital of Oulu, Oulu, 90029 FinlandSearch for more papers by this author First published: 22 July 2013 https://doi.org/10.1111/cod.12070Citations: 3 Conflicts of interest: The authors have declared no conflicts. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume69, Issue2August 2013Pages 121-122 RelatedInformation