Skin Thinning Research Articles

Effects of Eggshell Membrane on Keratinocyte Differentiation and Skin Aging In Vitro and In Vivo.

Skin aging is one of the hallmarks of the aging process that causes physiological and morphological changes. Recently, several nutritional studies were conducted to delay or suppress the aging process. This study investigated whether nutritional supplementation of the eggshell membrane (ESM) has a beneficial effect on maintaining skin health and improving the skin aging process in vitro using neonatal normal human epidermal keratinocytes (NHEK-Neo) and in vivo using interleukin-10 knockout (IL-10 KO) mice. In NHEK-Neo cells, 1 mg/mL of enzymatically hydrolyzed ESM (eESM) upregulated the expression of keratinocyte differentiation markers, including keratin 1, filaggrin and involucrin, and changed the keratinocyte morphology. In IL-10 KO mice, oral supplementation of 8% powdered-ESM (pESM) upregulated the expression of growth factors, including transforming growth factor β1, platelet-derived growth factor-β and connective tissue growth factor, and suppressed skin thinning. Furthermore, voltage-gated calcium channel, transient receptor potential cation channel subfamily V members were upregulated by eESM treatment in NHEK-Neo cells and pESM supplementation in IL-10 KO mice. Collectively, these data suggest that ESM has an important role in improving skin health and aging, possibly via upregulating calcium signaling.

Orbital manifestations of hypercorticism

Nowadays, Cushing's syndrome (hypercortisolism) and its manifestations are well studied. The main symptoms of hyper-cortisolism are obesity, osteoporosis, cardiomyopathy, muscle atrophy, skin thinning and purple stretch marks (striae) on the body. In practice, obesity and osteoporosis are the most frequent symptoms that are found in 90% of cases. However, there are some patients with an implicit clinical picture of hypercorticism. Some cases might concomitant with exophthalmos. This review describes a rare symptom of hypercortisolism — exophthalmos. Exophthalmos is a pathological protruding of eyeballs. This symptom is known in the context of TED that occurs most commonly in patients with Graves' disease. The article compares the mechanisms of development of eye symptoms in Cushing's syndrome and thyroid diseases, especially the Graves' disease. It discusses possible molecular mechanisms leading to exophthalmia in patients with Cushing's syndrome. Factors affecting adipogenesis in vitro and in vivo are studied, in particular factors leading to an increase of orbital fatty tissue against of elevated cortisol levels. Hormonal signaling and transcription cascades responsible for adipocyte differentiation into mature fat cells are presented. Other orbital manifestations of hypercortisolism, which occur relatively rare in practice, are also discussed in the article. These include glaucoma as well as cataract, Lisha nodules and central serous chorioretinopathy. Clinical cases of Cushing's syndrome with different ocular manifestations are considered and appropriate conclusions have been drawn.

Орбитальные проявления гиперкортицизма

Nowadays, Cushing's syndrome (hypercortisolism) and its manifestations are well studied. The main symptoms of hyper-cortisolism are obesity, osteoporosis, cardiomyopathy, muscle atrophy, skin thinning and purple stretch marks (striae) on the body. In practice, obesity and osteoporosis are the most frequent symptoms that are found in 90% of cases. However, there are some patients with an implicit clinical picture of hypercorticism. Some cases might concomitant with exophthalmos. This review describes a rare symptom of hypercortisolism — exophthalmos. Exophthalmos is a pathological protruding of eyeballs. This symptom is known in the context of TED that occurs most commonly in patients with Graves' disease. The article compares the mechanisms of development of eye symptoms in Cushing's syndrome and thyroid diseases, especially the Graves' disease. It discusses possible molecular mechanisms leading to exophthalmia in patients with Cushing's syndrome. Factors affecting adipogenesis in vitro and in vivo are studied, in particular factors leading to an increase of orbital fatty tissue against of elevated cortisol levels. Hormonal signaling and transcription cascades responsible for adipocyte differentiation into mature fat cells are presented. Other orbital manifestations of hypercortisolism, which occur relatively rare in practice, are also discussed in the article. These include glaucoma as well as cataract, Lisha nodules and central serous chorioretinopathy. Clinical cases of Cushing's syndrome with different ocular manifestations are considered and appropriate conclusions have been drawn.

3D cell culture using a clinostat reproduces microgravity-induced skin changes

Exposure to microgravity affects human physiology in various ways, and astronauts frequently report skin-related problems. Skin rash and irritation are frequent complaints during space missions, and skin thinning has also been reported after returning to Earth. However, spaceflight missions for studying the physiological changes in microgravity are impractical. Thus, we used a previously developed 3D clinostat to simulate a microgravity environment and investigate whether physiological changes of the skin can be reproduced in a 3D in vitro setting. Our results showed that under time-averaged simulated microgravity (taSMG), the thickness of the endothelial cell arrangement increased by up to 59.75%, indicating skin irritation due to vasodilation, and that the diameter of keratinocytes and fibroblast co-cultured spheroids decreased by 6.66%, representing skin thinning. The α1 chain of type I collagen was upregulated, while the connective tissue growth factor was downregulated under taSMG. Cytokeratin-10 expression was significantly increased in the taSMG environment. The clinostat-based 3D culture system can reproduce physiological changes in the skin similar to those under microgravity, providing insight for understanding the effects of microgravity on human health before space exploration.

Facial Rejuvenation With Fat Grafting and Fillers.

Facial rejuvenation requires a multi-modality approach to address the sun damage, volume loss, and thinning of skin that occurs with aging. With age, the collagen fibrils that provide strength become fragmented and fibroblasts connections become weak, leading to skin laxity and loss of youthful skin. Fillers can lead to a more youthful appearance by providing volumetric support. Synthetic fillers such as hyaluronic acid products, calcium hydroxyapatite, polylactic acid, and polymethylmethacralate have bio-stimulatory affects, ranging from small effects on fibroblast production to prolonged stimulatory effects on dermal thickness and blood supply. Fat grafting is also an ideal technique for facial rejuvenation because it is readily available, natural, and has regenerative effects. This review describes a new technique of fat grafting for the face called Injectable Tissue Replacement and Regeneration that specifically addresses the different anatomic compartments of the face with volume loss. With this brief review, we aim to evaluate the currents trends of fat grafting and fillers in the management of facial rejuvenation, including the cellular changes that occur with facial aging, the bio-stimulatory effects of fillers, and the anatomic replacement of tissue with fat grafting. >Level of Evidence: 4.

Do treatments for vitiligo offer value for money?

British Journal of DermatologyVolume 184, Issue 5 p. e174-e174 Plain Language Summary Do treatments for vitiligo offer value for money? First published: 04 May 2021 https://doi.org/10.1111/bjd.19909AboutPDF 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 onEmailFacebookTwitterLinked InRedditWechat Abstract Vitiligo is a relatively common skin condition that causes white patches on the skin. Very little is known about the value for money of vitiligo treatments for the National Health Service (NHS) and patients. The HI-Light Vitiligo Trial was conducted in the UK and included 398 adults and 119 children with vitiligo. These volunteers were randomly allocated to one of three treatment groups: (i) corticosteroid ointment used every other week – normal care; (ii) handheld narrowband ultraviolet B (NB-UVB) light device used on alternate days; or (iii) both treatments used together. After 9 months of treatment, the success of the treatment and costs were compared with normal care. The treatments were generally safe and well-tolerated but took a considerable amount of time over the 9-month treatment period. Some participants (12%) reported minor burns (like sunburn) around the treated patches and 2·5% of participants reported skin thinning. For people receiving normal care (corticosteroid ointment alone) 17% achieved treatment success, at a cost of £600 per participant, for those receiving NB-UVB light, 22% achieved treatment success, at a cost of £774, and for both treatments together, 27% achieved success at a cost of £813. Overall, combination treatment was more expensive but also more effective than corticosteroid ointment alone. Combination treatment could be considered cost-effective if the NHS were willing to pay £1,932 per successful treatment. Linked Article: Sach et al. Br J Dermatol 2021; 184:840–848. Volume184, Issue5May 2021Pages e174-e174 RelatedInformation

271 “Moisturize and get off any steroid cream”: An analysis of social media posts regarding TCS use in AD

Analyses of online interactions among atopic dermatitis (AD) patients are limited. This study aims to analyze the content and engagement of online posts on topical corticosteroid (TCS) use in AD. Of 2047 posts extracted from 5 social media groups, 949 referenced TCS safety, defined as a higher-order theme (HOT). Within the HOT of TCS safety, 11 lower-order themes (LOTs) were identified: TCS use and Addiction/Withdrawal (36.7% of posts), Patterns of TCS use (15.0%), TCS use is harmful (9.8%), Avoidance of TCS use (9.0%), TCS use and Skin Thinning (7.9%), Other side effects of TCS use (7.4%), Fear of using TCS (4.0%), Overuse of TCS (3.6%), Questions about TCS use (2.8%), TCS use on the face (2.6%), and Benefits and Risks of TCS use (1.2%). Posts were assigned positive, negative, or neutral sentiment and an engagement score. Negative sentiment was more prevalent (n=655; 69.0%) compared to positive (n=60; 6.3%) or neutral sentiment (n=234; 24.7%). Sentiments were given a value of -1 (negative), 0 (neutral), and 1 (positive). All subgroups had negative mean sentiment scores (FB_EczemaSupportGroup -0.93, 95% CI [-1.01--.84]; r/eczema -.60 [-.64--.56]; r/SkincareAddiction -.50 [-1.01--.006]; r/TS_Withdrawal -.92 [-1.00--.84]; r/EczemaCures -.39 [-.74--.04]). Mean engagement was significantly higher (p<0.001) in subreddits compared to the Facebook group (FB_EczemaSupportGroup 0.9, 95% CI [0.37-1.42]; r/eczema 4.75 [3.97-5.54]; r/SkincareAddiction 7.3 [2.16-12.4]; r/TS_Withdrawal 9.16 [7.05-11.27]; r/EczemaCures 7.39 [3.66-11.1]). The information online regarding TCS use in AD is overwhelmingly negative; education efforts should incorporate concerns determined by sentiment and theme analysis.

Invasive giant pituitary macroadenoma causing Cushing disease; a case report

Introduction: Cushing disease is a rare entity, and among them, giant pituitary adenomas causing Cushing disease is rarer. Here we present a case of Cushing disease secondary to a giant pituitary macroadenoma. Case report: A 41-year-old female with poorly controlled diabetes mellitus and hypertension diagnosed for six months presented with a history of unintentional weight loss, polyuria and polydipsia for the same duration. There was change in her facial appearance with increased pigmentation, frontal balding and she also noted increase in the size of her abdomen. There were features of proximal muscle weakness. Symptoms of hypothyroidism, hypoadrenalism or hyperprolactinemia were absent, and she was amenorrhoeic following hysterectomy done a year back. Visual impairment, headache, abdominal pain, features suggestive of internal malignancy, especially lung and renal, including features of pheochromocytoma were absent. She denied a family history of similar illness. Her BMI was 20.44 kg/m–2. She had a prominent abdomen, round facies, hirsutism, male pattern hair loss, facial plethora and generalized pigmentation and thinning of skin. She also had hypertension and proximal muscle weakness. Rest of the examination was normal. Investigations revealed hypokalaemia, poorly controlled hyperglycaemia and, non-suppressed overnight dexamethasone suppression test. She had a elevated ACTH level, and a high dose dexamethasone suppression test showed suppression. Pituitary imaging with MRI revealed a 51x 62x 41 mm size sellar and a para sellar mass with heterogeneous echogenicity extending to the right temporal lobe. Further imaging for ectopic ACTH secretion was negative.She underwent transcranial surgery which was unsuccessful due to intraoperative bleeding, and radiotherapy was given postoperatively. Conclusion: Cushing disease due to giant pituitary macroadenomas are rare and may require secondary therapeutic measures in controlling the disease in case of failed surgery.

Management of skin thinning and aging: review of therapies for neocollagenesis; hormones and energy devices.

Hormone replacement therapy and various devices exist to treat signs of aging, such as skin thinning, yet there are no reviews summarizing or evaluating their role in neocollagenesis and the associated increase in skin thickness. To review the literature regarding stimulation and generation of new collagen in the dermis in two parts. Part 2 reviews oral and topical hormone replacement therapy as well as energy-based devices. The PubMed database was searched for related literature. Studies involving the use of hormone supplements and energy devices with a resultant change in collagen production or skin thickness were obtained and reviewed for evidence. Hormones, including estrogen, testosterone, and dehydroepiandrosterone, and human growth hormone have been reported with substantiating evidence for neocollagenesis and dermal thickening. Energy devices, including radiofrequency, ultrasound, and laser therapy, have also been reported to stimulate neocollagenesis. The results presented in certain literature are not based on randomized controlled trials. Hormone deficient individuals can regain skin thickness with hormone replacement therapy. Dermal heating can provide a substantial amount of neocollagenesis; however, laser technology, specifically CO2 , appears to be the most effective at increasing skin collagen and tightening.

Acrodermatitis chronica atrophicans: clinical and microbiological characteristics of a cohort of 693 Slovenian patients.

BackgroundInformation on large groups of patients with acrodermatitis chronica atrophicans (ACA) is limited.MethodsWe assessed clinical and microbiological characteristics of patients with ACA diagnosed at a single medical centre and compared findings in periods 1991–2004 vs. 2005–2018. The cohort is representative of Slovenian ACA patients.ResultsWe assessed 693 patients: 461 females and 232 males, with median age of 64 years. Median duration of ACA before diagnosis was 12 months. In all but 2 patients, the skin lesions were located on extremities, more often on the lower (70.0%) than the upper (45.2%), bilaterally in 42.4%. Reddish‐blue discoloration, swelling, thinning and wrinkling of skin were present in 95.2%, 28.1%, 46.4% and 20.5% of patients, respectively. Overall, 64.4% of patients reported constitutional symptoms, 23.1% had local symptoms, and 20.8% had symptoms/signs of peripheral neuropathy. Nodules, arthritis, joint deformity, muscle atrophy and paresis were rare (<3%). Borreliae were isolated from 200/664 (30.1%) skin samples; 92.8% were Borrelia afzelii. B. garinii and B. burgdorferi s.s. were more often isolated from the skin of male patients (OR = 4.17) and from those with arthropathy (OR = 11.74). Patients included in the more recent period were older, complained less often of constitutional symptoms but more often of local symptoms, and more often had local swelling but less often skin atrophy and bilateral involvement, probably as a consequence of earlier diagnosis.ConclusionsACA, typically caused by B. afzelii, usually affects older women. Clinical presentation depends on the duration of illness and probably on the Borrelia species causing the disease.

Experience With Autologous Nasal Septum Cartilage Combined With Conchal Cartilage in Nasal Tip Reconstruction.

There has been an increase in use of autologous costal cartilage for nasal tip shaping material. However, there are deficiencies in using this plastic material, such as a hard nasal tip, poor nasal tip elasticity and mobility postoperatively, and some nasal tip skin thinning that allows the shape of the cartilage grafts to be felt on the surface of the nasal tip skin. To address these problems, we have combined autologous nasal septum cartilage and conchal cartilage as nasal tip graft materials, which achieve a natural shape and realistic touch postoperatively. From January 2017 to September 2019, a total of 47 patients with nasal septal cartilage combined with conchal cartilage transplantation for nasal tip plasty were screened for a retrospective study. They were followed up and evaluated for 6 to 25 months postoperatively. The operation was performed through an incision in the nose. During the operation, a piece of septal cartilage was cut to make a columella strut. Using one side of the cavitas conchae and cymba conchae cartilage as the graft material, 2 long strips of cartilage were excised for the septum extension graft, and a piece of cap cartilage was transplanted to the top of the nasal tip cartilage scaffold. The time between the operation and follow-up was greater than 6 months, with the range of follow-up and evaluation being from 6 to 25 months. Forty-six patients were satisfied with the shape of the nose. One patient complained that the nasal tip was round and large after 1 month postoperatively, but after 6 months, he was satisfied with the shape of the nasal tip after daily use of a nasal clip. In one male case, the implant was removed more than 7 months postoperatively because of hematoma and infection secondary to nasal trauma. There were 2 cases of nasal tip numbness, both of which recovered spontaneously after 12 months. After the operation, the shape of the nasal tip was round, no cartilage contour was seen on the surface, no collapse of upper nasal tip, no obvious deviation of the nasal dorsum and columella, and no deformation and displacement of the nasal tip cartilage scaffold. At the 6-month follow-up visit, each patient palpated the nasal tip for evaluation. Most patients felt their nose felt realistic and that they had good nasal tip motion. Only 1 patient felt that the nasal tip and the nasal dorsum were moving together when the tip of the nose was being pushed. Nasal septum cartilage and conchal cartilage can be combined as a graft material for reconstruction of the nasal tip. This technique uses different characteristics of each of the 2 cartilages to achieve a more realistic and esthetic outcome.

Clinical and Biochemical Parameters at Presentation of Patients with Adrenal Insufficiency Attending a Tertiary Care Hospital

Background: Adrenal insufficiency is the clinical manifestation of deficient production or action of glucocorticoids, with or without deficiency of mineralocorticoids and adrenal androgens. It results from primary adrenal failure or secondary adrenal disease due to impairment of the hypothalamic–pituitary axis. Patients often have nonspecific symptoms such as weakness, fatigue, lethargy, anorexia, nausea, vomiting, fever, confusion or coma. Without appropriate therapy, shock progresses to coma and death. The aim of the study was to evaluate the clinical and biochemical parameters at presentation in patients admitted with adrenal insufficiency. Methods: Patients diagnosed with adrenal insufficiency fulfilling the diagnostic criteria were considered as study population. Purposive consecutive type of sampling method was applied. Data was collected in a structured questionnaire. All the data were analysed by SPSS V 22.0. Results: A total of 100 patients of adrenal insufficiency were included in the study. The most were in the age group of 51-60 years (33%), mean age ± SD was 50.82±13.51 years & 38% were male. In our study, 100% patients had generalized weakness, 88% had GI symptoms, 41% had vertigo and 18% had weight loss. Most of them (83%) had vomiting, 70% had nausea and only 17% had anorexia. 38% patients were anaemic and 23% had shock and 33% patients presented with adrenal crisis. In this study, 82% patient were hypotensive, 46% had postural hypotension. In our study, 56% had puffy face, 49% had history of weight gain, 26% had skin thinning. Mean Hb was 10.96 gm/dl, 25% had a serum creatinine of>1.2 mg/dl. Hypoglycaemia was present in 7%, 12% had high blood urea nitrogen, 71% had hyponatraemia, 39% had hyperkalaemia, 12% had hypercalcaemia and 20% had acidosis. Conclusion: Adrenal insufficiency presented with non-specific features like fatigue, weakness, vertigo, GI symptoms, unexplained fever or weight loss and specific pattern of biochemical findings like hyponatraemia, hyperkalaemia, mild acidosis, hypercalcaemia & hypoglycaemia. So, these features should raise the suspicion of adrenal insufficiency.

A labelling system improves parental comfort and willingness to use topical corticosteroids for paediatric atopic dermatitis.

ObjectivesIn the United Kingdom, atopic dermatitis (AD) affects 20% of children and topical corticosteroids (TCS) are a mainstay of AD treatment regimes. Many TCS have similar packaging despite significant differences in potency frequently leading to confusion, and along with misinformation and steroid phobia, potentially reducing treatment adherence. We aimed to evaluate parents' knowledge/concerns regarding TCS and explore benefits of/preference for a TCS‐labelling system.MethodHundred parents of children with AD attending paediatric dermatology and/or allergy appointments completed mixed‐methodology Survey 1 (knowledge‐quiz, TCS‐labelling options, feedback on what supports AD‐care). Thirty parents, adolescents, and healthcare professionals completed Survey 2. Qualitative/quantitative data was thematically/statistically analysed (SPSS v25) respectively.ResultsParents preferred the traffic light system (green = mild, yellow = moderate, red = potent; n = 71/100) and reported significantly increased willingness and comfort in using TCS if a labelling system was used p ≤ 0.001). Knowledge regarding TCS potency was lacking: 62% (n = 46/74) of mild TCS‐users overestimated potency; 51% (n = 67/131) of potent TCS‐users underestimated potency. Common concerns were TCS‐related skin thinning, long‐term side effects and themes for improved AD‐care/support included: better information, written plans, access to advice, involvement of certain staff. Parents wanted accessible information in various formats: verbally, electronic resources, leaflets, and education sessions.ConclusionsParents of children with AD confirmed significant concerns and demonstrated poor knowledge regarding TCS use. Our findings suggest that a simple labelling system may improve TCS adherence. Future work to test refined label prototypes and evaluating their impact on adherence and correct use is needed.

Randomized controlled trial of topical corticosteroid and home-based narrowband ultraviolet B for active and limited vitiligo: results of the HI-Light Vitiligo Trial.

Evidence for the effectiveness of vitiligo treatments is limited. To determine the effectiveness of (i) handheld narrowband UVB (NB-UVB) and (ii) a combination of potent topical corticosteroid (TCS) and NB-UVB, compared with TCS alone, for localized vitiligo. A pragmatic, three-arm, placebo-controlled randomized controlled trial (9-month treatment, 12-month follow-up). Adults and children, recruited from secondary care and the community, aged≥5years and with active vitiligo affecting<10% of skin, were randomized 1 :1 :1 to receive TCS (mometasone furoate 0·1% ointment+dummy NB-UVB), NB-UVB (NB-UVB+placebo TCS) or a combination (TCS+NB-UVB). TCS was applied once daily on alternating weeks; NB-UVB was administered on alternate days in escalating doses, adjusted for erythema. The primary outcome was treatment success at 9months at a target patch assessed using the participant-reported Vitiligo Noticeability Scale, with multiple imputation for missing data. The trial was registered with number ISRCTN17160087 on 8 January 2015. In total 517 participants were randomized to TCS (n=173), NB-UVB (n=169) and combination (n=175). Primary outcome data were available for 370 (72%) participants. The proportions with target patch treatment success were 17% (TCS), 22% (NB-UVB) and 27% (combination). Combination treatment was superior to TCS: adjusted between-group difference 10·9% (95% confidence interval 1·0%-20·9%; P=0·032; number needed to treat=10). NB-UVB alone was not superior to TCS: adjusted between-group difference 5·2% (95% CI-4·4% to 14·9%; P=0·29; number needed to treat=19). Participants using interventions with≥75% expected adherence were more likely to achieve treatment success, but the effects were lost once treatment stopped. Localized grade 3 or 4 erythema was reported in 62 (12%) participants (including three with dummy light). Skin thinning was reported in 13 (2·5%) participants (including one with placebo ointment). Combination treatment with home-based handheld NB-UVB plus TCS is likely to be superior to TCS alone for treatment of localized vitiligo. Combination treatment was relatively safe and well tolerated but was successful in only around one-quarter of participants.

Advancing skin delivery of α-tocopherol and γ-tocotrienol for dermatitis treatment via nanotechnology and microwave technology.

This study investigated combination nanocarrier and microwave system for α-tocopherol and γ-tocotrienol delivery against dermatitis, without skin thinning effect of steroids. The vitamin E was formulated into water-rich/water-poor nanoemulsions, and had their droplet size, zeta potential, morphology, therapeutic content, encapsulation efficiency and release, in vitro skin therapeutics/nanoemulsion penetration, retention and permeation profiles, and in vivo pharmacodynamics characteristics examined, with skin pre-treated by precision microwave when applicable. The nanoemulsions had droplet sizes <150nm and negative zeta potential values. The skin pre-treatment by microwave (1 mW/3985MHz) promoted therapeutics accumulation in epidermis through enhancing nanoemulsion penetration into skin. The combination nano- and microwave technologies fluidized skin lipid and protein domains with epidermal microstructures being fluidized to a greater extent than dermis, allowing a relatively high epidermal-to-dermal nanoemulsion distribution. Microwave of lower or higher than 3985MHz brought about lower skin therapeutics/nanoemulsion accumulation due to insufficient lipid/protein domain fluidization or microwave-skin interaction limiting at skin surfaces only. Using water-rich nanoemulsion with higher therapeutic release and skin pre-treatment with 3985MHz microwave, dermatitis was alleviated in vivo without skin thinning of standard steroid. The use of combination microwave and nanotechnology promotes vitamin delivery and translates to positive dermatitis treatment outcome that warrants future investigation.

Management guideline for Werner syndrome 2020. 7. Skin ulcer associated with Werner syndrome: Dermatological treatment.

Skin ulcers in Werner's syndrome often arise from hyperkeratotic lesions and trauma to pressure points such as the plantar region, and are more difficult to treat than wound healing in healthy individuals. Multiple factors contribute to the intractable skin ulcers in Werner's syndrome, including skin thinning, sclerosis, fatty tissue loss, impaired blood flow, calcification, and excessive pressure due to osteoarticular deformity. Treatment includes topical application of a keratolytic agent for keratosis around the ulcer. Treatment of ulcers is the same as for normal ulcers, and if the ulcer is associated with infection and necrotic tissue, surgical debridement with a scalpel or scissors should be performed as much as possible after washing with saline or mildly warm water or with an antibacterial agent. Topical medications that promote softening and debridement of the necrotic tissue are used with careful control of moisture in the wound. Topical agents that promote granulation should be used in wounds where necrotic tissue has been removed without infection. Dressings to maintain a moist environment in the wound may also be useful. If the wound does not improve with conservative treatment, surgical treatment should be considered. Geriatr Gerontol Int 2021; 21: 160-162.

Home-based narrowband UVB, topical corticosteroid or combination for children and adults with vitiligo: HI-Light Vitiligo three-arm RCT.

Systematic reviews suggest that narrowband ultraviolet B light combined with treatments such as topical corticosteroids may be more effective than monotherapy for vitiligo. To explore the clinical effectiveness and cost-effectiveness of topical corticosteroid monotherapy compared with (1) hand-held narrowband ultraviolet B light monotherapy and (2) hand-held narrowband ultraviolet B light/topical corticosteroid combination treatment for localised vitiligo. Pragmatic, three-arm, randomised controlled trial with 9 months of treatment and a 12-month follow-up. Sixteen UK hospitals - participants were recruited from primary and secondary care and the community. Adults and children (aged ≥ 5 years) with active non-segmental vitiligo affecting ≤ 10% of their body area. Topical corticosteroids [mometasone furoate 0.1% (Elocon®, Merck Sharp & Dohme Corp., Merck & Co., Inc., Whitehouse Station, NJ, USA) plus dummy narrowband ultraviolet B light]; narrowband ultraviolet B light (narrowband ultraviolet B light plus placebo topical corticosteroids); or combination (topical corticosteroids plus narrowband ultraviolet B light). Topical corticosteroids were applied once daily on alternate weeks and narrowband ultraviolet B light was administered every other day in escalating doses, with a dose adjustment for erythema. All treatments were home based. The primary outcome was self-assessed treatment success for a chosen target patch after 9 months of treatment ('a lot less noticeable' or 'no longer noticeable' on the Vitiligo Noticeability Scale). Secondary outcomes included blinded assessment of primary outcome and percentage repigmentation, onset and maintenance of treatment response, quality of life, side effects, treatment burden and cost-effectiveness (cost per additional successful treatment). In total, 517 participants were randomised (adults, n = 398; and children, n = 119; 52% male; 57% paler skin types I-III, 43% darker skin types IV-VI). At the end of 9 months of treatment, 370 (72%) participants provided primary outcome data. The median percentage of narrowband ultraviolet B light treatment-days (actual/allocated) was 81% for topical corticosteroids, 77% for narrowband ultraviolet B light and 74% for combination groups; and for ointment was 79% for topical corticosteroids, 83% for narrowband ultraviolet B light and 77% for combination. Target patch location was head and neck (31%), hands and feet (32%), and rest of the body (37%). Target patch treatment 'success' was 20 out of 119 (17%) for topical corticosteroids, 27 out of 123 (22%) for narrowband ultraviolet B light and 34 out of 128 (27%) for combination. Combination treatment was superior to topical corticosteroids (adjusted risk difference 10.9%, 95% confidence interval 1.0% to 20.9%; p = 0.032; number needed to treat = 10). Narrowband ultraviolet B light was not superior to topical corticosteroids (adjusted risk difference 5.2%, 95% confidence interval -4.4% to 14.9%; p = 0.290; number needed to treat = 19). The secondary outcomes supported the primary analysis. Quality of life did not differ between the groups. Participants who adhered to the interventions for > 75% of the expected treatment protocol were more likely to achieve treatment success. Over 40% of participants had lost treatment response after 1 year with no treatment. Grade 3 or 4 erythema was experienced by 62 participants (12%) (three of whom were using the dummy) and transient skin thinning by 13 participants (2.5%) (two of whom were using the placebo). We observed no serious adverse treatment effects. For combination treatment compared with topical corticosteroids, the unadjusted incremental cost-effectiveness ratio was £2328.56 (adjusted £1932) per additional successful treatment (from an NHS perspective). Relatively high loss to follow-up limits the interpretation of the trial findings, especially during the post-intervention follow-up phase. Hand-held narrowband ultraviolet B light plus topical corticosteroid combination treatment is superior to topical corticosteroids alone for treatment of localised vitiligo. Combination treatment was relatively safe and well tolerated, but was effective in around one-quarter of participants only. Whether or not combination treatment is cost-effective depends on how much decision-makers are willing to pay for the benefits observed. Development and testing of new vitiligo treatments with a greater treatment response and longer-lasting effects are needed. Current Controlled Trials ISRCTN17160087. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 64. See the NIHR Journals Library website for further project information.

Anti-Inflammatory and General Glucocorticoid Physiology in Skeletal Muscles Affected by Duchenne Muscular Dystrophy: Exploration of Steroid-Sparing Agents.

In Duchenne muscular dystrophy (DMD), the activation of proinflammatory and metabolic cellular pathways in skeletal muscle cells is an inherent characteristic. Synthetic glucocorticoid intake counteracts the majority of these mechanisms. However, glucocorticoids induce burdensome secondary effects, including hypertension, arrhythmias, hyperglycemia, osteoporosis, weight gain, growth delay, skin thinning, cushingoid appearance, and tissue-specific glucocorticoid resistance. Hence, lowering the glucocorticoid dosage could be beneficial for DMD patients. A more profound insight into the major cellular pathways that are stabilized after synthetic glucocorticoid administration in DMD is needed when searching for the molecules able to achieve similar pathway stabilization. This review provides a concise overview of the major anti-inflammatory pathways, as well as the metabolic effects of glucocorticoids in the skeletal muscle affected in DMD. The known drugs able to stabilize these pathways, and which could potentially be combined with glucocorticoid therapy as steroid-sparing agents, are described. This could create new opportunities for testing in DMD animal models and/or clinical trials, possibly leading to smaller glucocorticoids dosage regimens for DMD patients.

A prospective study on patterns of topical steroids self-use in dermatophytoses and determinants predictive of cutaneous side effects.

Nonprescription use of topical corticosteroids (TCS) is a significant concern. This can lead to cutaneous adverse effects, altered morphology of skin disorders and chronicity of cutaneous infections. To record and analyze the patterns of TCS use in patients with tinea corporis/cruris and analyze factors determining the development of cutaneous side effects. Hundred patients with a clinical diagnosis of tinea corporis/cruris who could recall the TCS preparation/s used were included. The TCS usage patterns were recorded and analyzed. Most patients had used very potent TCS (n = 66). Most reported using TCS intermittently for duration ranging from 1 to 4 weeks (n = 78). Relapse of symptoms occurred within 1 to 2 weeks of stopping TCS, triggering reuse. Cutaneous adverse effects were present in 44 patients (striae [n = 29], hypo/depigmentation [n = 11], skin thinning [n = 8], hypertrichosis [n = 1], tinea pseudoimbricata [n = 1]). There was a significant correlation between presence of cutaneous adverse effects and the total duration of TCS use (P = .0016), duration of disease (P = .016), and total amount of TCS used (P = .012). Use for >60 days and of >32 g were associated with 89% and 96.3% (respectively) probability of developing cutaneous adverse effects. Self-use of TCS is a worrisome trend. Intermittent use is a plausible reason for development of cutaneous side effects in only 44% patients.

Discovery of a Janus Kinase Inhibitor Bearing a Highly Three-Dimensional Spiro Scaffold: JTE-052 (Delgocitinib) as a New Dermatological Agent to Treat Inflammatory Skin Disorders.

Dermatologic disorders such as atopic dermatitis arise from genetic and environmental causes and are complex and multifactorial in nature. Among possible risk factors, aberrant immunological reactions are one of the leading etiologies. Immunosuppressive agents including topical steroids are common treatments for these disorders. Despite their reliability in clinical settings, topical steroids display side effects, typified by skin thinning. Accordingly, there is a need for alternate effective and well-tolerated therapies. As part of our efforts to investigate new immunomodulators, we have developed a series of JAK inhibitors, which incorporate novel three-dimensional spiro motifs and unexpectedly possess both excellent physicochemical properties and antidermatitis efficacy in the animal models. One of these compounds, JTE-052 (ent-60), also known as delgocitinib, has been shown to be effective and well-tolerated in human clinical trials and has recently been approved in Japan for the treatment of atopic dermatitis as the first drug among Janus kinase inhibitors.