Corticosteroid-induced Skin Atrophy Research Articles

This is how I deal with corticosteroid-induced skin atrophy

This is how I deal with corticosteroid-induced skin atrophy

Biorevitalization of the skin with skin boosters: Concepts, variables, and limitations.

Aging leads to diminished capacity in the functionality of all the skin layers, which in turn leads to a structurally weak and esthetically unappealing skin which is dull, dehydrated, and inelastic. Skin boosters can be defined as biological materials or bio-actives that help or encourage the skin to increase or improve its function. Boosters have been used in treating skin structural changes associated with aging as well as other factors such as corticosteroid-induced skin atrophy. Restoring the loss in skin nourishment and vital components is the concept involved in biorevitalization of the skin. The authors aim to present an update and a short review of skin boosters in this commentary.

Multiple subcutaneous haematomas of the legs causing skin necrosis in an elderly patient affected by corticosteroid‐induced skin atrophy: Case report and review of literature

Corticosteroid-induced skin atrophy (CISA) consists of a thinning of the skin and subcutaneous tissues, representing the natural consequence of a prolonged glucocorticosteroids use, both systemic as well as topical. It is characterised by the loss of elasticity and skin thickness, associated with an increased skin fragility leading to ecchymoses, haematomas, and steroid purpura. The management of CISA is a challenge for physicians, as the pathology is reversible in a minimal percentage of cases and only after a short topical steroid or low-dose course therapy. Often wounds with large loss of substance represent the more common complication, after a surgical drainage which is often necessary. Skin necrosis with compartment syndrome of a leg is another potential risk for these patients. Here, we report a case of an elderly patient affected by multiple subcutaneous haematomas of the legs causing skin necrosis, arisen after the use of anticoagulants for a deep venous thrombosis. The patient was successfully treated with surgical drainage, negative pressure wound therapy (NPWT), and porcine xenograft with no complications. Finally, we discuss the evidence of the current literature on topic.

Topical corticosteroid-induced skin atrophy: a comprehensive review.

Skin atrophy is an adverse effect of topical corticosteroids (TCs) which, as an established non-life-threatening effect, has been poorly reported by trials involving these drugs. Atopic dermatitis and psoriasis are example of disorders that require repeated therapies with TCs; however, assessing the atrophogenic activity of TCs is still an issue. This study aims to review clinical data on skin atrophy induced by TCs. Searches of the PubMed, EMBASE, and Cochrane (Central) databases from 1965 to May 2013 were undertaken using the keywords 'corticosteroid', 'skin', and 'atrophy'. Skin and epidermal thickness values were retrieved from trials on healthy skin, and studies including skin atrophy as a safety endpoint in trials testing the efficacy of TCs were analyzed. Overall, 60 articles were retrieved. Whole skin and epidermal thickness were relevant parameters to measure early skin atrophy on healthy skin before it becomes clinically obvious. Epidermis thickness also seems to be more sensitive than whole skin thickness in detecting early atrophy; however, measuring skin atrophy still requires standardization. Further clinical trials on the atrophic effects of each TC are required to better evaluate their respective atrophic risks and their risk/benefit ratios. However, measuring epidermal or whole skin thickness will not be relevant in acute phases of inflammatory skin disorders treated with TCs because of the thickening induced by inflammation. In addition, skin atrophy seems to be induced by chronic TC use rather than by acute treatments. Long-term safety studies may be more relevant to evaluate atrophic activity.

Reversal of Murine Epidermal Atrophy by Topical Modulation of Calcium Signaling

Cytosolic Ca(2+) signals are performed by Ca(2+) releases from the endoplasmic reticulum and Ca(2+) influx from the extracellular medium. Releases rely on the refilling of the intracellular Ca(2+) stores by the Ca(2+) influx "Store-Operated Calcium Entry" (SOCE) via the channel Orai1. Here we show that Orai1 expression, SOCE amplitude, and epidermal proliferation are decreased in the epidermis of patients with skin fragility when compared with aged nonatrophic skin. Epidermal atrophy was induced in mice by the inhibition of Orai1 with small interfering RNA and the topical application of a SOCE blocker BTP2. The inhibition of Orai1 impaired the heparin-binding epidermal growth factor (HB-EGF)-induced Ca(2+) influxes and fully prevented the mitogen effect of HB-EGF in primary human keratinocytes. Importantly, epidermal proliferation correlated with Orai1 expression in mice. Conversely, the topical application of an Orai1 activator, the benzohydroquinone (BHQ), increased the epidermal thickness and proliferation, whereas the pro-proliferative effect of BHQ was prevented by the inhibition of Orai1. Finally, the topical application of BHQ reversed the epidermal atrophy induced by corticosteroids in mice. The topical modulation of Ca(2+) signals may thus be a promising therapeutic strategy in dermatology.

Inhibition of Putative Hyalurosome Platform in Keratinocytes as a Mechanism for Corticosteroid-Induced Epidermal Atrophy

The main limitation of using topical corticosteroids in dermatology is their atrophic effects on the skin. We have previously proposed a molecular platform composed of CD44, EGFR, and hyaluronate synthase (HAS) that is functionally defective in dermatoporosis, a chronic cutaneous insufficiency/fragility syndrome. In this study, we explored the molecular mechanisms of the skin atrophy induced by corticosteroids. We observed an important skin atrophy and a significant decrease of hyaluronic acid (HA), its main cell surface receptor CD44, and F-actin in mouse skin treated with topical clobetasol propionate (CP). Human keratinocytes exposed to CP showed an impaired HA secretion and diminished expression of CD44 and HAS3. CP also abolished filopodia of keratinocytes exposed to CP together with a redistribution of CD44 and F-actin depolymerization. We also show that HA fragments of intermediary size (HAFi) induced keratinocyte filopodia and protected them against CP. Topical HAFi induced hyperplasia in mouse epidermis and prevented CP-induced atrophy. Our results suggest that a CD44/EGFR/HAS platform associated with F-actin and filopodia of keratinocytes is the target of corticosteroids for their atrophogenic effects. These observations may lead to the development of new treatment and prevention strategies for corticosteroid-induced skin atrophy.

Fluorescence spectroscopy as a tool to detect and evaluate glucocorticoid-induced skin atrophy

Topical glucocorticoid (GC) therapy has been successfully used in the treatment of several common cutaneous diseases in clinical practice for a long time, and skin atrophy is one of the most typical cutaneous side effects of this therapy. The aim of this study was to evaluate the potential of noninvasive fluorescence spectroscopy (FS) technique in the detection and classification of GC-induced skin atrophy. A total of 20 male Wistar rats were used in the experimental protocol under controlled environmental conditions and with free access to food. One group received topical application of clobetasol propionate 0.05% for 14days to induce cutaneous atrophy (atrophic group) and the other (control) group received only vehicle application following the same protocol and schedule. Histological analyses and FS measurements with laser excitation at both 532nm and 408nm were obtained on days 1 and 15. The FS results were classified as "normal" or "atrophic" according by histological analysis. Fluorescence spectra obtained with excitation at 408nm allowed a clear distinction between the control and atrophic groups, and were more informative than the those obtained at 532nm. Our results reveal that, if correctly applied, FS allows noninvasive evaluation of corticosteroid-induced skin atrophy, and thus represents an important step towards better monitoring of undesirable side effects of cutaneous therapy.

Evaluation of the atrophogenic potential of different glucocorticoids using optical coherence tomography, 20-MHz ultrasound and profilometry; a double-blind, placebo-controlled trial

Skin atrophy is one of the main side-effects of topical corticosteroid therapy. Although the use of high-frequency ultrasound is an established method that has been studied previously, it allows measurements of the slow-reacting dermal thickness only. To investigate the decreasing epidermal thickness, which occurs earlier, we used optical coherence tomography (OCT), a high-resolution noninvasive imaging technique, and compared it with 20-MHz ultrasound and profilometry. In this double-blind placebo-controlled trial 20 healthy volunteers applied four different corticosteroids and the cream base formulation as placebo to the volar part of both arms once a day over a 4-week period. The epidermal thickness, the dermal thickness and the skin surface roughness were assessed using OCT, high-frequency ultrasound and profilometry. Each of the three methods allowed the detection and monitoring of significant corticosteroid-induced skin atrophy and its reversibility. The changes correlated with the potency of the steroids. The epidermal thickness decreased significantly in all test areas, even in the placebo and the untreated fields. As expected, the reduction in epidermal thickness was more pronounced and could be detected earlier by OCT than the reduction of dermal thickness using ultrasound. The epidermal surface roughness investigated using profilometry showed a slight smoothing. OCT allows a simple, fast and noninvasive in vivo measurement of the epidermal thickness. To evaluate the atrophogenic potential of corticosteroids it is more suitable than high-frequency ultrasound as epidermal thickness decreases earlier. In addition, epidermal thickness is a more sensitive indicator of steroid atrophy as the degree of thinning is much higher compared with the dermal atrophy. Profilometry might give further information; however, it would not be suitable for clinical use as the results were generally less pronounced. In the future, OCT might be useful to detect corticosteroid-induced side-effects at the beginning for monitoring the therapy.

Receptor-Selective Retinoids for Psoriasis

Topical and oral retinoids have been successfully used in antipsoriatic therapy over the last 50 years. Development of more selective agents has led to an improved efficacy and safety profile. The first topical receptor-selective retinoid to be approved for the treatment of plaque psoriasis is tazarotene. Topical tazarotene displays an onset of action and efficacy similar to those of other established antipsoriatic agents. Common adverse events of this agent such as pruritus, burning, local skin irritation, and erythema are limited to the skin and generally mild or moderate in severity. Although effective as monotherapy, evidence is accumulating that combining topical tazarotene with other established antipsoriatic therapies results in enhanced efficacy and reduced adverse events. In particular, concomitant use of topical tazarotene with a mid-potency or high-potency corticosteroid in the treatment of psoriatic plaques enhances efficacy and reduces the risk of corticosteroid-induced skin atrophy. Combination of phototherapy with tazarotene accelerates the clinical response and diminishes the cumulative UVB or psoralen plus UVA (PUVA) exposure load. Recently, an oral form of tazarotene has been developed. The results of completed phase III clinical trials of this agent indicate a beneficial effect in moderate to severe plaque psoriasis. Adverse events are generally of mild severity, and most of those observed, such as cheilitis and dry skin, are typical of hypervitaminosis A. Of note, oral tazarotene appears not to be associated with other adverse events that are typical of oral retinoids, including hypertriglyceridemia and hypercholesterolemia. However, since head-to-head trials with acitretin (the only retinoid currently approved for systemic therapy) have not been conducted, it is unclear whether tazarotene is any safer or more effective than acitretin. Moreover, the major drawback of oral tazarotene is teratogenicity, which may limit its use in female patients. Further studies evaluating long-term clinical outcomes with oral tazarotene and its use in combination therapies are awaited.

All Trans‐Retinoic Acid (ATRA) Elevated Eukaryotic Translation Initiation Factor 4A1 (eIF4A1) mRNA in ATRA‐Responsive Vitiliginous Epidermis

Chronic skin disorders that require long-term treatment with corticosteroids, such as vitiligo, may use a combination of topical corticosteroids and topical all-trans-retinoic acid (ATRA) to prevent corticosteroid-induced skin atrophy. Besides protecting against the side effects of corticosteroids, ATRA produces a better clinical outcome in some patients. This study examined whether ATRA influences the expression of mRNAs responsible for the clinical correlation. Differential display was performed using kits incorporating an annealing control primer. Epidermis from suction blisters taken from six patients diagnosed with a generalized type of vitiligo, who were included in a placebo-controlled paired-comparison left-right study using ATRA and vehicle for 3-6 months, were used. Ten differentially expressed mRNAs were identified in those six patients. Expression levels were restored to normal particularly in four types of mRNAs, which were matched with sequences encoding eukaryotic translation initiation factor 4A1 (eIF4A1), ribosomal protein L13, mediator of RNA polymerase to transcription (MRT) and ribosomal phosphoprotein PO. Of those mRNAs, the level of eIF4A1 mRNA showed a clinical correlation; The expression of eIF4A1 mRNA, examined by real-time PCR, was elevated in four patients who showed a favorable clinical response to ATRA, whereas no change or a decrease occurred in three patients whose clinical responses did not differ between ATRA and vehicle treatment. The eIF4A1 protein expression from the other two patients, one of them with a favorable response to ATRA, also showed a clinical correlation. Therefore, eIF4A1 mRNA may be an important gene related to ATRA effects, although further studies are required.

Effects of three topical retinoids on corticosteroid-induced skin atrophy in humans

Effects of three topical retinoids on corticosteroid-induced skin atrophy in humans

Corticosteroid induced skin atrophy and barrier impairment monitored with non-invasive methods

Corticosteroid induced skin atrophy and barrier impairment monitored with non-invasive methods

Effects of three topical retinoids on corticosteroid-induced skin atrophy in humans

Effects of three topical retinoids on corticosteroid-induced skin atrophy in humans

In Vivo Prevention of Corticosteroid-Induced Skin Atrophy by Tretinoin in the Hairless Mouse Is Accompanied by Modulation of Collagen, Glycosaminoglycans, and Fibronectin

In an earlier study we showed that tretinoin could prevent corticosteroid-induced skin atrophy in hairless mice. In this study, we examined the histochemical, biochemical, and immunochemical changes that accompanied the atrophy and its prevention. Mice were treated dorsally for 3 weeks in the morning and afternoon (AM:PM) as follows: 1) vehicle:vehicle, 2) steroid:vehicle, 3) steroid:tretinoin. Tretinoin concentration was 0.05% in an ethanol:propylene glycol vehicle. The steroid was clobetasol propionate (0.05%). The normally sparse dermal glycosaminoglycans were further reduced by steroid:vehicle treatment and increased to greater than vehicle:vehicle amounts by steroid:retinoid. Mast cells were similarly affected. Biochemical quantification of glycosaminoglycans confirmed the histochemical findings. Collagen, non-collagenous protein, and total protein content were reduced by the steroid. The latter two were returned to more normal levels by tretinoin whereas with collagen there was only a trend toward normal levels. Fibronectin, which was increased by the steroid:vehicle treatment, was reduced to more normal levels by steroid:tretinoin. We conclude that tretinoin has the ability to prevent the major steroid-induced biomechanical changes in hairless mouse dermal connective tissue that contribute to atrophy.

Topical all- trans-retinoic acid prevents corticosteroid-induced skin atrophy without abrogating the anti-inflammatory effect

We tested the ability of all- trans-retinoic acid to prevent corticosteroid-induced skin atrophy without lessening the anti-inflammatory effect of the steroids. Histologic study and skin-fold thickness in hairless mice treated topically with various steroids, followed by topical all- trans-retinoic acid, were used to measure prevention of atrophy. By both assessments, all- trans-retinoic acid prevented atrophy. Noninterference with the anti-inflammatory property of steroids was tested in a phorbol ester-induced mouse ear edema model and by histologic assessment of croton oil-induced inflammation of mouse dermis. We found that all- trans-retinoic acid did not interfere with steroid suppression of either edema or dermal inflammation. Thus all- trans-retinoic acid was effective in preventing steroid-induced atrophy without affecting the steroid's anti-inflammatory property.

Corticosteroid-Induced Cutaneous Atrophy and Telangiectasia

A bioassay for the evaluation of certain adverse effects of various corticosteroids was performed. Twenty-eight daily topical applications of corticosteroids to young rats produced reduction in body-weight gain, atrophy of the skin as determined by double skin-fold thickness micrometer measurement, and mild to severe telangiectasia. This animal model demonstrates corticosteroid-induced skin atrophy and telangiectasia and the correlation of the degree of atrophy and telangiectasia to body-weight change. Nine corticosteroids were evaluated by this method and are listed in terms of increasing severity of side-effects as follows: 1.0% hydrocortisone cream, 0.1% betamethasone valerate cream, 0.025% betamethasone benzoate cream, 0.05% flurandrenolide cream, 0.05% fluocinonide cream, 0.1% dexamethasone cream, and 0.03% flumethasone pivalate cream. Triamcinolone acetonide cream, 0.5%, and 0.2% fluocinolone acetonide cream resulted in death of the animals prior to completion of 28 days of topical application.