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1.
Psoriasis and Treatment: Past, Present and Future Aspects.
Reid, C, Griffiths, CEM
Acta dermato-venereologica. 2020;(3):adv00032
Abstract
The management of psoriasis has evolved considerably over the past 100 years. This has occurred in parallel with our understanding of the pathogenesis of this common, complex and enigmatic disease. It should be celebrated as an outstanding example of successful translational research. With precise targeting of immune pathways for the treatment of psoriasis with new biologics and small molecules has come the realisation that the most effective approach to patient management is a holistic one which encompasses the biopsychosocial nature of the disease. This involves a stratified medicine approach to identifying the best drug for an individual allied to patient education, screening for comorbidity, and regular review as both the clinical presentation and the patient's needs will change over time. Al-though there is not yet a cure for psoriasis - the whole person, systems approach to patient management, that is in part dependent on early intervention, should help to ensure an optimal outcome.
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Low-dose calcipotriol can elicit wound closure, anti-microbial, and anti-neoplastic effects in epidermolysis bullosa keratinocytes.
Guttmann-Gruber, C, Tockner, B, Scharler, C, Hüttner, C, Common, JE, Tay, ASL, Denil, SLIJ, Klausegger, A, Trost, A, Breitenbach, J, et al
Scientific reports. 2018;(1):13430
Abstract
Recessive dystrophic epidermolysis bullosa (RDEB) patients suffer from chronic and repeatedly infected wounds predisposing them to the development of aggressive and life-threatening skin cancer in these areas. Vitamin D3 is an often neglected but critical factor for wound healing. Intact skin possesses the entire enzymatic machinery required to produce active 1-alpha,25-dihydroxyvitamin D3 (calcitriol), underscoring its significance to proper skin function. Injury enhances calcitriol production, inducing the expression of calcitriol target genes including the antimicrobial peptide cathelicidin (hCAP18), an essential component of the innate immune system and an important wound healing factor. We found significantly reduced hCAP18 expression in a subset of RDEB keratinocytes which could be restored by calcipotriol treatment. Reduced scratch closure in RDEB cell monolayers was enhanced up to 2-fold by calcipotriol treatment, and the secretome of calcipotriol-treated cells additionally showed increased antimicrobial activity. Calcipotriol exhibited anti-neoplastic effects, suppressing the clonogenicity and proliferation of RDEB tumor cells. The combined wound healing, anti-microbial, and anti-neoplastic effects indicate that calcipotriol may represent a vital therapeutic option for RDEB patients which we could demonstrate in a single-patient observation study.
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3.
Update on etiopathogenesis and treatment of Acne.
Bhat, YJ, Latief, I, Hassan, I
Indian journal of dermatology, venereology and leprology. 2017;(3):298-306
Abstract
Acne, the most common skin disease, is a disorder of pilosebaceous units that affects adolescents mainly and adults occasionally. The pathogenesis is multifactorial. Besides genetic predisposition, other major factors include the action of androgens, pro-inflammatory lipids acting as ligands of peroxisome proliferator-activated receptors in the sebocytes, toll-like receptor-2 acting on keratinocytes, recognition of pathogen-associated molecular patterns, cytokines, chemokines, inflammasomes, neuroendocrine regulatory mechanisms, diet and other pro-inflammatory targets implicated in the activation of immune detection and response. Most of these factors converge on mammalian target of rapamycin complex1 (mTORC1) activation which is further enhanced by the nutrient signaling of Western diet. This multitude of pathogenic factors has led to a new armamentarium of drugs for the treatment of acne. Topical anti-androgens, insulin-like growth factor-1 inhibitors, peroxisome proliferator-activated receptor-modulators, acetylcholine inhibitors, topical retinoic acid metabolism-blocking agents, vitamin D analogues, antimicrobial peptides, interleukin-1α and interleukin-1β blockers and immunotherapy are some of the novel treatment options.
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The Diagnosis and Treatment of Hair and Scalp Diseases.
Wolff, H, Fischer, TW, Blume-Peytavi, U
Deutsches Arzteblatt international. 2016;(21):377-86
Abstract
BACKGROUND Hair loss is caused by a variety of hair growth disorders, each with its own pathogenetic mechanism. METHODS This review is based on pertinent articles retrieved by a selective search in PubMed, on the current German and European guidelines, and on the authors' clinical and scientific experience. RESULTS Excessive daily hair loss (effluvium) may be physiological, as in the postpartum state, or pathological, due for example to thyroid disturbances, drug effects, iron deficiency, or syphilis. Androgenetic alopecia generally manifests itself in women as diffuse thinning of the hair over the top of the scalp, and in men as receding temporal hairlines and loss of hair in the region of the whorl on the back of the head. Alopecia areata is patchy hair loss arising over a short time and involving the scalp, eyebrows, beard, or entire body. The hair loss of alopecia areata is reversible in principle but hard to treat. Folliculitis decalvans is a form of alopecia with scarring, characterized by inflamed papules, pustules, and crusts at the edges of the lesions. Lichen planopilaris generally presents with small patches of baldness, peripilar erythema, and round areas of skin scaling. Kossard's frontal fibrosing alopecia is characterized by a receding hairline and loss of eyebrows. CONCLUSION Hair loss is a symptom, not a diagnosis. The pathogenesis of the alopecias involves a range of genetic, endocrine, immune, and inflammatory processes, each of which calls for its own form of treatment.
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The Vitamin D Analogue Calcipotriol Reduces the Frequency of CD8+ IL-17+ T Cells in Psoriasis Lesions.
Dyring-Andersen, B, Bonefeld, CM, Bzorek, M, Løvendorf, MB, Lauritsen, JP, Skov, L, Geisler, C
Scandinavian journal of immunology. 2015;(1):84-91
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Abstract
The vitamin D analogue calcipotriol is an immunomodulatory drug widely used to treat psoriasis; however, how calcipotriol affects the immune cells in psoriasis lesions is not fully understood. The aim of this study was to investigate the effect of calcipotriol on the frequency of CD4(+) and CD8(+) T cells and innate lymphoid cells (ILC) and their production of IL-17A, IFN-γ and IL-22 in psoriasis lesions in patients with chronic plaque psoriasis. Eighteen patients with psoriasis were included, and two similar psoriasis lesions were chosen for each patient. One lesion was treated with calcipotriol (50 μg/g) and the other with vehicle twice a day for 14 days. The clinical effect was measured by degree of erythema, scaling and induration in each lesion (SUM score). Skin biopsies were collected for histological and immunohistochemical analyses. Skin-derived cells were isolated and analysed by flow cytometry. After 14 days of treatment with calcipotriol, a significant clinical and histological effect was seen; however, we found no differences in the frequency of CD4(+) and CD8(+) T cells or ILC between calcipotriol- and vehicle-treated skin. The main finding was a significant decrease in CD8(+) IL-17(+) T cells in skin-derived cells from calcipotriol-treated skin, which was further supported by the absence of CD8(+) IL-17(+) T cells in immunohistochemical staining of calcipotriol-treated skin. No changes in the frequency of IL-22(+) or IFN-γ(+) cells were observed. Our findings show that the vitamin D analogue calcipotriol reduces the frequency of CD8(+) IL-17(+) T cells in psoriasis lesions concomitant with clinical improvement.