Search

Topical glucocorticoids, well-known anti-inflammatory drugs, induce multiple adverse effects, including skin atrophy. The sex-specific effects of systemic glucocorticoids are known, but sexual dimorphism of therapeutic and side effects of topical steroids has not been studied. We report here that female and male mice were equally sensitive to the anti-inflammatory effect of glucocorticoid fluocinolone acetonide (FA) in ear edema test. At the same time, females were more sensitive to FA-induced skin atrophy. We recently reported that REDD1 (regulated in development and DNA damage 1) plays central role in steroid atrophy. We found that REDD1 was more efficiently activated by FA in females, and that REDD1 knockout significantly protected female but not male mice from skin atrophy. Studies using human keratinocytes revealed that both estradiol and FA induced REDD1 mRNA/protein expression, and cooperated when they were combined at low doses. Chromatin immunoprecipitation analysis confirmed that REDD1 is an estrogen receptor (ER) target gene with multiple estrogen response elements in its promoter. Moreover, experiments with GR and ER inhibitors suggested that REDD1 induction by these hormones was interdependent on functional activity of both receptors. Overall, our results are important for the development of safer GR-targeted therapies suited for female and male dermatological patients.

Background Intramuscular corticosteroid injections are frequently used for a variety of conditions in dermatology practice. Unfortunately, many complications are associated with systemic and local administration of corticosteroids. Localized subcutaneous lipoatrophy is among the most common adverse effects that can lead to permanent disfigurement. Autologous blood is collected from peripheral veins and injected immediately to the affected tissue with the intention of stimulating the body's own tissue-healing mechanisms through cellular and humoral mediators. Aims Although platelet-rich plasma therapy, produced by centrifugation of autologous blood, is very popular in dermatology practice, autologous blood injection (ABI) is not routinely preferred. With this case, it was aimed to report that ABI can be a safe and effective option in the treatment of steroid atrophy. Patients/methods A case of steroid atrophy in a female patient treated successfully with ABI was presented. Results A 17-year-old female patient presented with epidermal/dermal atrophy, depigmentation, and subcutaneous fat atrophy after intramuscular corticosteroid injection. ABI treatment was initiated because there were no signs of spontaneous improvement after 6 months. 4 cc autologous blood was injected in small volumes into the superficial, middle, and deep parts of the atrophic tissue. After 2 sessions of ABI, the size and depth of the atrophy were markedly improved and depigmentation was resolved. Conclusion There are several treatment options for localized steroid atrophy with varying success rates. This is the first report that shows ABI is a simple, effective, and safe procedure for correction of corticosteroid-induced cutaneous and subcutaneous atrophy with satisfying results.

Necrobiosis lipoidica (NL) is a rare granulomatous disease of unknown etiology. Multiple therapies may be used with varying efficacy. We report a pediatric patient with a history of type I diabetes mellitus and NL with minimal response to an ultrapotent topical steroid, topical calcineurin inhibitor, and intralesional triamcinolone, complicated by steroid atrophy, who rapidly responded after addition of doxycycline.

Highlights • Development of late skin reactions are less common with steroid treatment during ERT. • Combination of a local corticosteroid and radiotherapy did not result in atrophy. • Adjuvant corticosteroid treatment did not increase in late skin toxicity. • Seven of the twenty-one patients who underwent mastectomy developed telangiectasia., Purpose The aim of this study was to evaluate whether treatment with a local potent corticosteroid during adjuvant external radiotherapy (ERT) of breast cancer is associated with late skin toxicity. Material and methods Sixty patients (32 treated with potent corticoid cream versus 28 controls treated with moisturizer) who had been included in a randomized study on prophylactic local corticosteroid treatment under adjuvant ERT in 2009 and 2010 were subjected to a follow-up study in 2016. Assessments of skin texture were registered according to the Late Radiation Morbidity Scoring Scheme (RTOG). Dryness, skin colour and skin thickness were objectively measured using non-invasive instruments. The patients were assessed for differences between their treated and untreated breasts. Results Skin atrophy was not noticed in any of the 60 patients. Objective instrumental measurements did not reveal any significant differences in skin dryness, colour, pigmentation or skin thickness over the average follow-up time of six years. Clinical assessment based on the RTOG scoring system revealed that the odds ratio of having late skin problems in patients treated with moisturizer compared to patients treated with corticosteroid was 3.2 (95% CI: 1.0–10.1). Patients reported minor cosmetic dermatological sequelae. Seven patients developed telangiectasia, which caused cosmetic inconvenience. Conclusion In this study, prophylactic corticosteroid treatment to ameliorate radiation dermatitis during adjuvant ERT of breast cancer was not associated with an increase in late skin toxicity nor did it result in skin atrophy. This study is limited by its small sample size, and the risk for false positive findings.

Summary The majority of people with psoriasis have localized disease, where topical therapy forms the cornerstone of treatment. We set out to summarize evidence on the relative efficacy, safety and tolerability of different topical treatments used in plaque psoriasis. We undertook a systematic review and meta-analyses of randomized trial data of U.K.-licensed topical therapies. The primary outcome was clear or nearly clear status stratified for (i) trunk and limbs; and (ii) scalp. Network meta-analyses allowed ranking of treatment efficacy. In total, 48 studies were available for trunk and limb psoriasis, and 17 for scalp psoriasis (22 028 patients in total); the majority included people with at least moderate severity psoriasis. Strategies containing potent corticosteroids (alone or in combination with a vitamin D analogue) or very potent corticosteroids dominated the treatment hierarchy at both sites (trunk and limbs, scalp); coal tar and retinoids were no better than placebo. No significant differences in achievement of clear or nearly clear status were observed between twice- and once-daily application of the same intervention or between any of the following: combined vitamin D analogue and potent corticosteroid (applied separately or in a single product), very potent corticosteroids, or potent corticosteroids (applied twice daily). Investigator and patient assessment of response differed significantly for some interventions (response rates to very potent corticosteroids: 78% and 39%, respectively). No significant differences were noted for tolerability or steroid atrophy, but data were limited. In conclusion, corticosteroids are highly effective in psoriasis when used continuously for up to 8 weeks and intermittently for up to 52 weeks. Coal tar and retinoids are of limited benefit. There is a lack of long-term efficacy and safety data available on topical interventions used for psoriasis.

Subcutaneous atrophy is a known complication of steroid injections. Excellent results with fat grafting for the treatment of steroid atrophy have been documented. However, the benefit of treating steroid-induced subcutaneous atrophy in an extremity diagnosed with complex regional pain syndrome (CRPS) has not been described. CRPS, known formerly as reflex sympathetic dystrophy or RSD, causalgia, or reflex neurovascular dystrophy, is a severe, progressive musculoskeletal pain syndrome characterized by pain which is disproportionate to the severity of the inciting event, edema, or skin changes. Common treatment modalities include pharmacotherapy, physical therapy, and nerve blocks-each therapy producing varying results. We present a literature review of CRPS and the case of a 15-year-old female who developed CRPS of the left lower leg after arthroscopic debridement with retrograde drilling of an osteochondral lesion. Steroid atrophy of the involved area following a saphenous nerve block complicated the patient's treatment course. The area of atrophy was treated with autologous fat grafting. Following the adipose injection procedure, the patient experienced almost complete resolution of her CPRS-associated pain symptoms, along with improved cosmetic appearance of the area.

There are multiple potential complications from treatment of peripheral nerve entrapments. Some of the complications are due to the proximity of other structures (lung, blood vessels). Infection and nerve injury can occur any time a needle or probe is introduced through the skin. Other complications come from the medications injected (local anesthetic systemic toxicity, steroid atrophy, phenol neuritis) or the energy used (RF burns). Knowledge of a potential complication may help decrease the risks.

Background Atopic dermatitis (AD) is a common skin condition among Asians. Recent studies have shown that Asian AD has a unique clinical and immunologic phenotype compared with European/American AD. Objective The Asian Academy of Dermatology and Venereology Expert Panel on Atopic Dermatitis developed this reference guide to provide a holistic and evidence-based approach in managing AD among Asians. Methods Electronic searches were performed to retrieve relevant systematic reviews and guidelines on AD. Recommendations were appraised for level of evidence and strength of recommendation based on the U.K. National Institute for Health and Care Excellence and Scottish Intercollegiate Guidelines Network guidelines. These practice points were based on the consensus recommendations discussed during the Asia Pacific Meeting of Experts in Dermatology held in Bali, Indonesia in October 2016 and April 2017. Results The Expert Panel recommends an approach to treatment based on disease severity. The use of moisturizers is recommended across all levels of AD severity, while topical steroids are recommended only for flares not controlled by conventional skin care and moisturizers. Causes of waning efficacy must be explored before using topical corticosteroids of higher potency. Topical calcineurin inhibitors are recommended for patients who have become recalcitrant to steroid, in chronic uninterrupted use, and when there is steroid atrophy, or when there is a need to treat sensitive areas and pediatric patients. Systemic steroids have a limited role in AD treatment and should be avoided if possible. Educational programs that allow a patient-centered approach in AD management are recommended as an adjunct to conventional therapies. Recommendations on the use of phototherapy, systemic drugs, and emerging treatments are also included. Conclusion The management of AD among Asians requires a holistic approach, integrating evidence-based treatments while considering accessibility and cultural acceptability.

Summary Background 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. Objectives 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. Patients/methods 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. Results 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. Conclusions 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.

Background/aims: Atrophy is a distressing side effect of potent corticosteroids. After open application of a high potency steroid, we monitored atrophogenicity by a variety of non-invasive methods. Methods: Volar forearms were treated twice daily for 3 or 4 weeks, with clobetasol propionate cream (Temovate®). The following methods were used: 1) confocal microscopy, 2) transepidermal water loss (TEWL), 3) dimethyl sulfoxide whealing, 4) sodium hydroxide erosions, 5) analysis of stratum corneum lipids, and 6) B-scan ultrasound. Results: Confocal microscopy revealed thinning of the epidermis, decreased microvasculature and decreased size of keratinocytes. Evaporimetry demonstrated transepidermal water loss. Whealing to dimethyl sulfoxide was enhanced. Sodium hydroxide erosions formed more quickly. The amount of ceramides, cholesterol, and free fatty acids was reduced. Ultrasound showed thinning of the dermis. Conclusion: Non-invasive methods are very useful for quantifying the atrophogenicity of topical corticosteroids.

The use of hyaluronic acid for atrophy has not been documented in the literature. In this manuscript we present a case of a patient treated with the aforementioned filler with enthusiastic results. This case shows yet another potential application for these novel products.

Background/alms: Optical coherence tomography is a new in vivo imaging tool originally developed to investigate the eye. We undertook a preliminary investigation of experimental and clinical dermatological applications. Methods: We obtained optical coherence tomography images of ethnic groups, of cutaneous changes induced by exposure to water and dimethyl sulfoxide, of corticosteroid atrophy and of acne vulgaris. Results: Optical coherence tomography was able to visualize specific structural changes in stratum corneum and viable epidermis in these diverse conditions. Conclusions: The high lateral and axial resolution of 4 urn and 7 μm, respectively, and the image quality of this prototype make optical coherence tomography a promising instrument for clinical and investigative dermatology.

Background/aims: Atrophy is the most common adverse effect of topical corticosteroids. The objective of this study was to determine whether atrophogenicity of a potent steroid could be demonstrated in a 3-week period of open application using non-invasive bioengineering methods. Methods: Volar forearms were treated twice daily for 3 weeks with clobetasol propionate cream. The following methods were used: 1) B-scan ultrasound; 2) Silflo-replicas for microtopogra-phy; 3) scanning electron microscopy; 4) Cutometer for bio-mechanical assessments; 5) colorimetry for measuring skin color; 6) evaporimetry for transepidermal water loss; 7) polarized light photos; 8) sticky slides for corneocyte sizing; 9) D'Squames for estimating scaling; and 10) biopsies for histologic evaluation of atrophy Results: After only 1 week, Silflo-replica showed that glyphic patterns had been partially obliterated. At the same time, ultrasound scans showed dermal thinning, which increased over the 3-week period. Extensibility by Cutometer decreased steadily during the treatment. Image analysis of ?Squames revealed an increase in scaliness. Evaporimetry showed an increase in trans-epidermal water loss. Atrophy was confirmed by histology. Conclusion: The use of non-invasive bioengineering techniques provides a powerful tool to monitor atrophogenicity in a short period of open applications.

Hairless mice, effective as a model for the prevention of steroid atrophy by tretinoin, were used to examine the effectiveness of tretinoin as a therapeutic agent for the reversal of steroid atrophy. Skh-1 mice were treated topicaUy with 0.05% clobetasol propionate for 3 weeks, followed by either 0.05% tretinoin or vehicle for 3 weeks. Appropriate controls were included. Striking tretinoin effects were a marked reversal of epidermal and subcutaneous muscle atrophy and an increase in the steroid-reduced glycosaminoglycan levels that significantly exceeded vehicle effects. Rapid recovery of fibronectin, collagen and non-collagenous protein levels with vehicle treatment confounded tretinoin results. Although the hairless mouse is not an ideal model for the treatment of steroid atrophy, the results suggest a possible therapeutic value for tretinoin.

Background We describe 12 patients with an atrophying dermatitis in whom the biopsy findings were compatible with tinea versicolor. Design We encountered 12 skin biopsies from 12 patients in whom a clinically atrophying dermatosis was associated with light microscopic (LM) evidence of atrophy and epidermal colonization by Pityrosporum sp. Formalin-fixed, paraffin-embedded tissue sections were cut at 5 microns and stained with H&E, alcian blue-PAS and PAS-diastase preparations. Results Five men and seven women aged 17–73 years in whom lesions characterized as atrophic plaques, patches or macules prompted clinical differential diagnoses including parapsoriasis or mycosis fungoides (MF), anetoderma, lupus erythematosus, and steroid atrophy. A LM examination showed epidermal colonization with pityrosporum hyphae and spores accompanied by variable epidermal and dermal atrophy characterized by rete-ridge effacement, subepidermal fibroplasia, pigment incontinence and elastolysis. Conclusions Atrophying cutaneous lesions comprise part of the clinical spectrum of tinea versicolor for which we propose the term ‘atrophying tinea versicolor’. The pathogenetic basis is unclear but could be the sequela of delayed type hypersensitivity and the release by T-helper lymphocytes of leukotrienes which perturb collagen metabolism and/or keratinocyte growth. Lesions may be mistaken clinically for MF or other atrophying dermatoses.

A 24-month follow up of a previously reported case of successful hyaluronic acid filler use in steroid atrophy is presented. The patient had persistence of the volume and appearance of her scar with sustained satisfaction 24 months after hyaluronic acid treatment, without the need for repeat injection. This case suggests expansion of the use of hyaluronic acid fillers to include scar atrophy, as persistence of a desired cosmetic appearance for 2 years is demonstrated.

The most common morphological finding in muscle biopsies in longstanding fibromyalgia is type II fiber atrophy. This can be found in many other conditions such as disuse atrophy, affections of the corticospinal tracts, steroid atrophy, and other different neuromuscular disorders. An increase in lipid droplets and a slight proliferation of mitochondria in type I muscle fibers are correlated with the duration of fibromyalgia. In some cases we could find some ragged red fibers (RRF) which histochemically show a pronounced accumulation of lipids and mitochondria and single fiber defects of cytochrome-c-oxidase. In some fibromyalgia patients with RRF, we could find deletions of the mitochondrial genoma.

We report an elderly patient with lymphangiectases arising within skin affected by photoaging, steroid atrophy, and inflammation. Bullous lesions appeared in several sites following a year of topical corticosteroid applications for neurodermatitis. Light and electron microscopy showed that the bullae consisted of dilated lymphatic vessels within the dermis. There was also marked nodular elastosis and attenuation of dermal collagen. We suggest that this patient's lymphangiectases resulted from abnormal structure and function of the dermis due to photoaging and steroid atrophy.

Two forms of highly purified bovine dermal collagen (Zyderm I and II Collagen Implant) are currently in widespread clinical use for the treatment of dermal soft tissue defects. These materials, which closely resemble human collagen, are administered via injection in a series of outpatient treatments. With successive injections, small amounts of collagen are deposited to fill areas deficient in soft tissue. A review of the literature indicates that these materials can be used safely and effectively to correct certain scars, age-related wrinkles, areas of steroid atrophy, and small surgical defects.

The histological changes induced by 1 month’s applications of various corticosteroids to normal forearm skin were studied. Marked epidermal atrophy was present at 1 month with the more potent steroids, but the dermal changes were minimal or absent. The methods outlined in this study could serve as a useful model for assessing the unwanted atrophogenic action of potent corticosteroid preparations.

Steroid atrophy was induced in 3 volunteers by the continuous, occlusive application of clobetasol propionate to the forearms for 6 weeks. The changes were followed sequentially by light, scanning, and transmission electron microscopy. A 59% decrease in viable epidermal thickness was noted after the sixth week of treatment, as well as a flattening of the dermal-epidermal junction. The 3-dimensional architecture of the dermis was strikingly reorganized. This was largely brought about by resorption of the ground substance as revealed by a progressive dimunition of Hale's stain for acid mucopolysaccharides. Loss of ground substance resulted in decreased spaces between collagen and elastic fibers as shown by scanning and transmission electron microscopy. The fibrous network consequently collapsed, yielding a more compact papillary and reticular dermis. This compression caused the reorientation of both collagen and elastic fibers. However, no differences in collagen and elastin fine structure were noted. Fibroblasts were shrunken but not reduced in density. A marked decrease in number of mast cells was noted in 3-week specimens and virtually no mast cells were observed after 6 weeks. We found that the primary effect of short-term steroid use was a rearrangement of the geometry of the denial fibrous network. This was not due to alterations in the fibers themselves but a secondary consequence of the loss of ground substance.

SUMMARY In a blind trial a non-fluorinated steroid, 0.1% hydrocortisone butyrate, was compared with 1% hydrocortisone alcohol on twenty-eight patients suffering from steroid induced atrophy superimposed on rosacea and perioral dermatitis. The hydrocortisone butyrate did not behave like a fluorinated steroid, in that it did not prevent the beneficial effect of tetracycline nor the disappearance of telangiectasis and atrophy. In twenty-eight patients, hydrocortisone butyrate was superior in fifteen, in six hydrocortisone alcohol, and in seven the results were equal. It is concluded that although hydrocortisone butyrate is as effective as triamcinolone acetonide or fluocinolone in the treatment of psoriasis and eczema, it does not prevent the recovery of steroid atrophy on the face, and thus may not even cause it.

A histological method of ranking topical steroid preparations according to the degree of epidermal thinning they cause in pig skin has been shown to be applicable to human skin. A 0-05% ointment of the new compound, clobetasone butyrate (Molivate), has been shown to cause less thinning than either fluocinolone acetonide 0-025% (Synalar) or flurandrenolone 0-0125% (Haelan) when applied without the use of occlusive dressings for 3 weeks to the human forearm.

Corticosteroids cause severe atrophy of skeletal muscle. We have assessed the oxidative capacity of rat skeletal muscles following prolonged steroid administration. Dexamethasone caused severe atrophy and loss of oxidative capacity. Hydrocortisone also caused severe atrophy and loss of oxidative capacity, but to a lesser extent. These effects were reversible. White muscles were more severely affected than red. Palmitate oxidation was less severely affected than that of other substrates. Diphenylhydantoin failed to reverse the effects of steroid treatment on muscle. Administration of dexamethasone to hypophysectomized rats caused them to lose weight and undergo muscular wasting, but did not result in oxidative deficits. Thus, mitochondrial defects do not represent the primary lesion in steroid atrophy. Additional hormonal actions are probably involved in the pathogenesis of steroid atrophy.

SummaryComparisons of ultrasonic, radiographic and micrometer methods in the measurement of skin thickness were made in 16 volunteers before and after 1-month' s treatment with four clobetasol propionate formulations. Correlations between the methods were highly significant (r=0.68 to 0.75). Correlations in the females were better than in the males suggesting that measurements in women are more easily made. Percentage reductions in skin thickness after steroid treatment were ranked in an identical order, whichever method was used. Each of the three methods, therefore, was shown to be effective. Ultrasound was the preferred technique but the micrometer screw gauge was shown to be a reasonable alternative.