Isotretinoin and lymecycline treatments modify the skin microbiota in acne.

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.

Glucocorticoids: The mode of action in bullous pemphigoid.

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.

Clinical Efficiency of Topical Calcipotriol/Betamethasone Treatment in Psoriasis Relies on Suppression of the Inflammatory TNFα - IL-23 - IL-17 Axis.

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.

Antimicrobial peptides - a part of innate immunity.

Antimicrobial peptides (AMP) are evolutionary ancient molecules produced by nearly all living organisms, both prokaryotic and eukaryotic cells. More than 2000 AMPs have now been identified. These peptides are produced by most human cell types, such as those in the skin and mucous membranes and blood. Each tissue has a different spectrum of AMPs. Antimicrobial capacity depends on the structural characteristics such as charge and amphiphilicity that allow the insertion and/or penetration of AMP into the membranes of microorganisms or other cells. AMPs may have importance in the pathogenesis of neurodegenerative diseases and type 2 diabetes. The most investigated AMPs are defensins and cathelicidin LL-37.

[New insights in the pathogenesis and treatment of rosacea]. / Uusia näkemyksiä ruusufinnin patogeneesistä ja hoidosta.

The production of cathelicidin, an antimicrobial peptide is strongly increased in rosacea. Cathelicidin activates innate immunity, inflammation and angiogenesis. Cutaneous proteases produce inflammatory fragments of cathelicidin. UV-B irradiation and microbial components increase vitamin D3 and TLR2 expression in keratinocytes leading to an increase of cathelicidin production. Retinoids and doxycycline inhibit inflammation, proteases, angiogenesis and TLR2 expression. A multicenter study 2010 proved that isotretinoin with a dose of 0,3 mg/kg/d for 12 weeks and doxycycline with the dose of 100 mg/d for 14 days followed with 50 mg/d were equally effective. Doxycycline 40 mg/d is also effective in milder cases.

[The immune response against microbial infections in the skin--weak in atopic dermatitis and strong in psoriasis]. / Ihon mikrobipuolustus: heikko atopiassa ja vahva psoriaasissa.

The innate and adaptive immune responses have been better understood after the discovery of Toll-like receptors (TLRs), antimicrobial peptides and different populations of dendritic cells. In the skin there are 1 million T-cells per 1 cm2 and 20 billion in total. Naive T-cells activated by antigen-presenting cells can polarize in four directions and they express homing receptor CLA for operating in the skin when the antigen is first detected in the skin area. In psoriasis Th17 activation increases antimicrobial peptides. The IL-23/Th17 axis is largely absent in atopic dermatitis and may result in infections.

Patients with male gender or greater body weight use smaller amounts of topical therapy in psoriasis.

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.

IL-17/Th17 pathway is activated in acne lesions.

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-1ß, IL-6, TGF-ß, 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-ß) 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.

Long-term safety and efficacy of tacrolimus ointment for the treatment of atopic dermatitis in children.

Tacrolimus ointment is a topical calcineurin inhibitor for the treatment of atopic dermatitis. The primary objective of this open-label study was to assess the long-term safety of tacrolimus ointment. The primary end-point was the incidence of adverse events. Secondary end-points included the Eczema Area and Severity Index and a modified version of this index. A total of 466 children with atopic dermatitis, aged 2-15 years, applied 0.03% or 0.1% tacrolimus ointment twice daily for up to 29.5 months. Skin burning and pruritus were the most common application site events; their prevalence decreased over time. There was no increase in viral infections or other adverse events over time. Laboratory profiles were consistent with those reported in atopic populations. Substantial improvement in all efficacy end-points was observed by week 2 and maintained throughout the study. Long-term treatment with tacrolimus ointment is safe and effective in these patients with atopic dermatitis.

Solitary angiokeratoma of the tongue.

Angiokeratoma is a rare, cutaneous vascular disorder that can occur in several clinically distinct conditions. It usually presents as multiple, red to blue or black, asymptomatic papules on the skin. Oral mucosal involvement is common in the systemic form, but very rare in the localized forms of angiokeratomas. We report the second case of a solitary papular angiokeratoma of the oral cavity.