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1.
New Topical Therapies for Psoriasis.
Lé, AM, Torres, T
American journal of clinical dermatology. 2022;(1):13-24
Abstract
Psoriasis is a chronic immune-mediated skin disease with a significant impact on patients' quality of life. Mild-to-moderate forms of the disease usually require long-term topical treatment, but prolonged use of corticosteroids and vitamin D analogues is limited by adverse effects. With further understanding of psoriasis pathogenesis, new molecules are emerging aiming to fulfil these clinical needs. Tapinarof, an aryl hydrocarbon receptor modulator, has completed a phase III study and demonstrated good efficacy results, even in long treatment courses, with a favourable safety profile. It additionally appears to have a promising remitting effect as patients presented with an average relapsing time of over 3 months. Roflumilast, a phosphodiesterase type 4 inhibitor, also underwent a phase III study with significant lesion improvement and notable pruritus management, and with no reported side effects. Roflumilast was evaluated as an option for intertriginous areas with good outcomes in a small sample, but larger trials are required. The Janus kinase-signal transducer and activator of transcription pathway has been targeted in recent clinical investigations with promising options, currently with brepocitinib pending phase IIb results. Ongoing preclinical studies involving interleukin-2 inhibition, RNA modulators and amygdalin analogues may lead to forthcoming clinical trials. New topical drugs are successfully emerging and future research comparing them to classical options will dictate their clinical role in the treatment of psoriasis.
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2.
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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3.
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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4.
Multi-Center, Double-Blind, Vehicle-Controlled Clinical Trial of an Alpha and Beta Defensin-Containing Anti-Aging Skin Care Regimen With Clinical, Histopathologic, Immunohistochemical, Photographic, and Ultrasound Evaluation.
Taub, A, Bucay, V, Keller, G, Williams, J, Mehregan, D
Journal of drugs in dermatology : JDD. 2018;(4):426-441
Abstract
BACKGROUND/
OBJECTIVES Anti-aging strategies utilizing stem cells are in the forefront. Alpha and beta defensins are natural immune peptides that have been shown to activate an LGR6-positive stem cell locus in the hair follicle, identified as the source of most new epidermal cells during acute wound healing. We investigated the ability of biomimetic alpha and beta defensin molecules, supplemented with supportive cosmetic ingredients, formulated into three skin care products, at improving the structure and function of aging skin.
METHODS A participant- and investigator -blinded, placebo-controlled, multi-center trial was performed in outpatient settings. Forty-four healthy female subjects, aged 41-71 years, skin types I-V, completed the study with 2/3 receiving full formula and 1/3 receiving the placebo formula. A skin care regimen of 3 products (serum, cream, and mask) containing alpha-defensin 5 and beta-defensin 3, and other cosmetic ingredients, was applied to the face, post-auricular, and neck skin two times per day for 12 weeks in those receiving full formula, whereas the placebo group received the identically packaged regimen without the active ingredients. Methods of evaluation included histopathology and immunohistochemistry (7 subjects), clinical evaluation of pores, superficial and deep wrinkles based on Griffiths scale, and high-resolution photography (all subjects). In addition, a subset of 15 patients were evaluated with the QuantifiCare system (3-dimensional imaging and skin care scores for evenness, pores, oiliness) and Cortex measurements (high-resolution skin ultrasound, TEWL, elasticity, color, and hydration). Data points for evaluation included baseline, 6 weeks, and 12 weeks. All patients used the same sunscreen and cleanser, which was provided to them.
RESULTS The full formula regimen caused a significantly (P equals 0.027) increased thickness of the epidermis as seen in histology, not seen in the placebo group, with no signs of inflammation. No excessive cell proliferation was detected in either group as measured by Ki67-immunohistochemistry. Reduction in visible pores, superficial wrinkles, oiliness, pigmentation, and improvement of skin evenness, were statistically significant. A trend for improvement was also observed in skin elasticity, TEWL, and hydration; these did not achieve statistical significance. Ultrasound and histopathology demonstrated increases in dermal thickness in individual patients, without statistical significance. Comprehensive improvement in all 5 parameters, including visible pores, hyperpigmentation, superficial and deep wrinkles, and epidermal thickness, was statistically significant when the subset of participants assigned for histology in full formula group was compared with the placebo group participants.
CONCLUSIONS A 3-product skin care regimen containing alpha and beta defensins globally improves the visual appearance and structure of aging skin without irritation, dryness, or inflammation. Specifically, this regimen increases epidermal thickness, reduces appearance of pores, reduces wrinkles, and reduces melanin. This skin care regimen stimulates rejuvenation without evidence of increase of a marker of carcinogenic stimulation. This data is consistent with the hypothesis that a defensin-containing skin care regimen activates the body's own dormant stem cells to generate healthy new epidermal cells.
J Drugs Dermatol. 2018;17(4):426-441.
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5.
Bleach for Atopic Dermatitis.
Maarouf, M, Shi, VY
Dermatitis : contact, atopic, occupational, drug. 2018;(3):120-126
Abstract
Individuals with atopic dermatitis (AD) have used bleach baths to treat superinfections, although their mechanism of action is not well understood. The ClinicalTrials.gov, National Eczema Association, and PubMed databases were searched for studies that investigate the role bleach plays in modulating AD. Fifteen studies were included in this review. Bleach bath improves clinical symptoms of AD and restores surface microbiome by eradicating bacteria, most notably Staphylococcus aureus. Many studies have noted that this antimicrobial effect has reduced the need for topical corticosteroids or topical antibiotics. In addition, bleach seems to have strong anti-inflammatory and antipruritogenic effects. Lastly, bleach baths seem to be safe on human skin, without disrupting epidermal barrier function. Although the effects of bleach are promising, studies that investigate the long-term use of bleach alone, without concomitant AD treatment modalities, are needed. The emergence of new bleach-containing products warrants future investigations to examine their effects on cutaneous microbiome, epidermal barrier function, and immunity.
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6.
Fixed combination calcipotriol plus betamethasone dipropionate aerosol foam in the treatment of psoriasis vulgaris: rationale for development and clinical profile.
Paul, C, Bang, B, Lebwohl, M
Expert opinion on pharmacotherapy. 2017;(1):115-121
Abstract
Psoriasis is a chronic, immune-mediated inflammatory disorder with a significant negative impact on quality of life. Most patients with mild-to-moderate psoriasis manage their disease with topical therapies; the most commonly used formulations contain corticosteroids and/or vitamin D3 analogues. However, adherence to topical treatment remains a significant issue as the daily treatment regimen can be cumbersome and time consuming and many patients do not obtain complete/almost complete clearance. Areas covered: Published pre-clinical and clinical data evaluating calcipotriol 50 µg/g (Cal) and betamethasone 0.5 mg/g as dipropionate (BD) aerosol foam in patients with psoriasis. Expert opinion: Cal/BD aerosol foam, a once-daily, alcohol-free, paraffin-based vehicle with emollient properties, was developed to increase the therapeutic options available to patients. Cal/BD aerosol foam is rapidly effective for treating psoriasis and the greater efficacy compared with the ointment and gel formulations is consistent and clinically relevant. This enhanced efficacy is due to improved skin penetration of the active ingredients following the formation of a stable supersaturated solution on the skin. Studies have shown increasing patient satisfaction with Cal/BD aerosol foam. It is hoped that this optimized formulation of Cal/BD will improve adherence and help to address the unmet medical needs of patients with mild-to-moderate psoriasis.
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7.
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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8.
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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9.
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.
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10.
Rosacea and rhinophyma.
Tüzün, Y, Wolf, R, Kutlubay, Z, Karakuş, O, Engin, B
Clinics in dermatology. 2014;(1):35-46
Abstract
Rosacea is a common and chronic inflammatory cutaneous disease with unknown etiology. The pathophysiology of rosacea is still poorly understood. Epidemiological studies indicate a genetic component, but a rosacea gene has not been detected yet. Recent molecular studies propose that an altered innate immune response is involved in the pathogenesis of the rosacea disease. Signs of rosacea are indicated by the presence of characteristic facial or ocular inflammation involving both the vascular and tissue stroma. A wide range of drug options is available for the treatment of rosacea, including several topical ones (metronidazole, antibiotics, azelaic acid, benzoyl peroxide, sulfacetamide/sulfur, retinoids) and oral ones (mainly tetracyclines, metronidazole, macrolides, isotretinoin). This review highlights the recent clinical and pathophysiological developments concerning rosacea.