Use Of Topical Glucocorticoids Research Articles

Therapeutic Effect of Liquiritin Carbomer Gel on Topical Glucocorticoid-Induced Skin Inflammation in Mice.

Glucocorticoids are often used and highly effective anti-inflammatory medications, but prolonged topical application may alter the epidermis' normal structure and function, potentially resulting in a number of adverse effects. Topical glucocorticoid-induced skin inflammation is a dangerous condition that develops after topical glucocorticoid use. The patients become dependent on the medication and, even after the medication is stopped, the dermatitis symptoms recur, severely impairing their quality of life. Thus, the need to aggressively confront Topical glucocorticoid-induced skin inflammation is critical. Prior research has demonstrated that topical administration of licorice's flavonoid component liquiritin stimulates epidermal proliferation, which in turn enhances the creation of collagen and the healing of wounds. Therefore, the purpose of this work was to determine if topical use of liquiritin carbomer gel can treat glucocorticoid-induced changes in mice skin epidermal function, and the mechanisms involved. The findings demonstrated that, in the mice model of topical glucocorticoid-induced skin inflammation, liquiritin carbomer gel aided in the restoration of skin barrier function. These outcomes may have been caused by enhanced expression of the proteins Aquaporin 3, Keratin 10, and Claudin-1, as well as the restoration of epidermal hyaluronan content. In the meantime, liquiritin carbomer gel dramatically decreased the expression of TNF-α, IL-1β, IL-6, IFN-γ, and IgE in mice, according to ELISA tests. Furthermore, topical treatment of liquiritin carbomer gel boosted the expression of superoxide dismutase, catalase, and decreased malondialdehyde expression, potentially counteracting the detrimental effects of glucocorticoids on the epidermis. In summary, these findings imply that topical liquiritin carbomer gel can treat glucocorticoid-induced skin damage through various mechanisms of action.

Hair and nail cortisol levels are associated and affected by glucocorticoid use

Hair and nail cortisol is increasingly studied as a physiologic proxy for chronic stress response. Glucocorticoid use is an expected confounder for cortisol measurement, yet there remains little evidence of whether external cortisol use should be subject to exclusion in study subjects. In a group of 209 youth (15–22 year-olds), we analyzed hair and fingernail cortisol concentrations. We assessed topical, nasal, oral, and injectable glucocorticoid use via a questionnaire. Extensively validated methods were used for hair and nail cortisol extraction and measurements. The median value of hair cortisol was 10.2 pg/mg (n=200), and the median value of nail cortisol was 7.06 pg/mg (n=203). Topical glucocorticoid use significantly increased hair and nail cortisol concentrations (p<0.005). Hair and nail cortisol concentrations were positively associated (p<0.0001, n=194). Spearman correlation coefficients demonstrated that the positive correlation between hair and nail cortisol values was higher in participants who used external glucocorticoids. Topical glucocorticoids moderated the association between hair and nail cortisol values (p=0.006). Based on these findings, we recommend that the assessment of topical glucocorticoid use must be performed when collecting hair/nail samples and that subjects reporting glucocorticoid use should be excluded from all future hair and nail cortisol studies; also, all outliers must be excluded to account for glucocorticoid medication underreporting and yet-unknown confounders.

Adrenal Insufficiency after Long-term use of Topical Glucocorticoids in Patients with Advanced Cutaneous T-cell Lymphomas: A Case Series.

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Modern techniques and features of selective keratoplasty

Selective keratoplasty involves replacing the affected layers of the cornea with similar donor tissue. In case of pathological changes in the middle and posterior stroma, deep anterior lamellar keratoplasty (DALK) is performed. Chronic corneal edema caused by endothelial dysfunction is an indication for endothelial keratoplasty - Descemet membrane endothelial keratoplasty (DMEK) or Descemet Stripping Endothelial Keratoplasty (DSAEK). Compared to penetrating keratoplasty (PK), these operations are characterized by a low risk of damage to intraocular structures and a relatively short rehabilitation period. Complications of selective keratoplasty include the formation of a false chamber between the lamellar graft and the recipient's cornea, ocular hypertension during anterior chamber air tamponade. Persistent epithelial defect can be a sign of primary graft failure in DALK, DSAEK and DMEK. Selective keratoplasty is characterized by a lower incidence of immune rejection than PK. In some cases, DALK can be complicated by corneal changes related to suture fixation of the graft. Long-term postoperative use of topical glucocorticoids can cause ocular hypertension and cataracts.

DMARD treatment and skin cancer : Recognition, state of knowledge and prevention

Epithelial tumors differ in cellular origin, risk factors, incidence, and treatment. This article discusses the extent to which the use of disease-modifying antirheumatic drugs (DMARD) is associated with an increased risk for the development of skin tumors and for which substances the risk may be increased. In addition, some practical dermatological recommendations for rheumatologists are presented. The most frequent tumors of the skin are classified according to their cellular origin into malignant melanoma (MM) and so-called keratinocyte cancer (KC). The clinical presentation of these tumors differs and also the risk for the development of these epithelial skin tumors under DMARD treatment varies depending on the drug and tumor entity. As rheumatologists frequently see these patients for follow-up, it is essential to know the clinical findings as well as the corresponding risk factors of the specific tumor entities. Agenerally valid and reliable estimation of the risk for the development of epithelial skin tumors under DMARD treatment can only be formulated in the form of tendencies at the present time due to the lack of data. The relevant literature shows that regular intensive dermatological screening is recommended. Patients undergoing immunosuppressive or immune-modulating treatment should be instructed in self-inspection of the skin, receive regular dermatological check-ups and be instructed in strict UV protection methods. Lesions that do not heal or recurrently bleed should be referred for apunch biopsy to rule out or diagnose an epithelial skin tumor, as should atypical inflammatory lesions that do not heal with the use of topical glucocorticoids. An interdisciplinary approach in patient management is the key to success in ensuring the maximum quality of life with the lowest possible risk of developing epithelial skin tumors for these patients.

Skin atrophy caused by topical glucocorticoids is less common in patients with atopic dermatitis than in those with psoriasis.

Although the long-term use of topical glucocorticoids (TGC) may induce skin atrophy including striae distensae (SD), patients with atopic dermatitis (AD) appear to have lesser degree of skin atrophy than those with psoriasis (PSO). Periostin, encoded by POSTN, is involved in tissue remodelling processes of chronic AD lesions. This study was designed to investigate the difference in the occurrence of skin atrophy in patients with AD or PSO when treated with TGC and to elucidate the association between skin atrophy and periostin. Big data analysis using Korean Health Claims Database was performed to determine the prevalence of SD in AD and PSO patients. Blood and skin eosinophils count and dermal fibrosis between AD and PSO patients were compared, and immunohistochemistry for periostin and mRNA sequencing in the dermis were performed. Animal experiments using AD and PSO murine model were conducted. Big data analysis revealed that patients with AD have significantly lesser degree of SD than patients with PSO. The ratio of the dermal fibrous tissues and eosinophil counts were significantly higher in AD patients. In AD skin, periostin was more widely distributed in the entire dermis and POSTN mRNAs were significantly upregulated. Dermal thickness and fibrosis were significantly higher in AD mice even after TGC treatment. A significant positive correlation was observed between dermal fibrosis and tissue eosinophil counts. Lesser skin atrophy in AD patients even after long-term TGC application could be resulted from skin fibrosis caused by increased tissue eosinophils and periostin deposition.

099 Skin atrophy due to topical glucocorticoids is less common in patients with atopic dermatitis than psoriasis

Atopic dermatitis (AD) and psoriasis are the most common chronic inflammatory dermatitis treated with topical glucocorticoids (GC). Although long-term use of topical GC may induce skin atrophy including striae distensa (SD), AD patients appear to cause less skin atrophy compared to psoriasis. Chronic AD lesions are characterized by eosinophil infiltration and dermal fibrosis. Periostin, encoded by POSTN gene, augments TGF-β production in eosinophils and inversely activated eosinophils can induce periostin production in fibroblasts. Periostin involves in tissue remodeling such as fibrosis and lichenification of chronic AD lesion. This study was designed to reveal that AD patients have less skin atrophy due to skin fibrosis related with eosinophils and periostin compared to psoriasis. For the skin atrophy including SD, we enrolled AD and psoriasis patients with similar ages and treatment durations. For the skin fibrosis and eosinophils, we compared lesional and non-lesional skin from the patients with AD, psoriasis, and allergic contact dermatitis (ACD). Also, we compared mRNA expression in the dermis from the mouse model of AD or psoriasis. AD patients have less SD than psoriasis. In AD patients, the ratio of the dermal fibrous tissues was significantly higher than psoriasis. Tissue and blood eosinophils were significantly higher in AD patients than ACD as well as psoriasis. Dermal thickness and fibrosis were significantly higher in AD mice than psoriasis even after the treatment with topical GC. There was a significant positive correlation between dermal fibrosis and tissue eosinophils counts. The mRNAs of POSTN, TGFB1, COL11A1, MMP1, and IL1R2 were significantly up-regulated in AD mice than psoriasis. We found that AD patients had less skin atrophy than psoriasis after the long-term use of topical GC. It might be resulted from the skin fibrosis caused by upregulation of tissue eosinophils and periostin.

Perioperative/Postoperative Anti-Inflammatory Therapy During/After Corneal Surgery/Transplantation

Surgical trauma, and foreign material - such as sutures or implants or antigens during tissue transplantation - may cause inflammatory reactions. Inflammatory reactions after surgical interventions distant from the vascularised limbus and without opening of the anterior chamber of the eye are usually very muted, because of the corneal immune and angiogenic privilege. A milestone in the therapy and prophylaxis of inflammation after corneal surgery has been the use of topical glucocorticoids since the 1950s. When these are used, it is important to consider the cataractogenic effect of long-term use, the possibility of steroid-induced increase in intraocular pressure (so-called steroid response), the increased risk for microbial infection and the inhibition of epithelialisation. The available glucocorticoids differ in their ability to penetrate into the eye (prednisolone best), their immunosuppressive activity (dexamethasone best) and their ability to induce a steroid response (loteprednol etabonate and fluorometholone least). Preservative-free formulations are only available for dexamethasone. The different properties must be taken into account when choosing the "best" glucocorticoid: If there is a risk of delay in epithelialisation of the wound, topical steroids should be avoided or if necessary, phosphate- and preservative-free dexamethasone should be used with caution. If efficiency in the posterior cornea or in the anterior chamber is important, e.g. after penetrating keratoplasty, prednisolone acetate should be used. If a steroid response is known, loteprednol etabonate or fluorometholone should be used. When allogeneic tissue is transplanted, long-term topical glucocorticoid use over 24 months or longer is necessary. After high-risk keratoplasty with allogeneic donor tissue, supplemental systemic immunosuppressive therapy with calcineurin inhibitors or mycophenolate mofetil over 6 to 12 months is recommended.

Use of emollients and topical glucocorticoids among adolescents with eczema: data from the population-based birth cohort BAMSE.

Knowledge regarding how adolescents treat their eczema is sparse. To explore the use of emollients and topical glucocorticoids in adolescents with eczema in relation to sex and disease severity, and to study dispensing patterns of topical glucocorticoids. Questionnaire-based data on symptoms of eczema, eczema severity and treatment with emollients and topical glucocorticoids were obtained from 3108 adolescents in the Swedish population-based birth cohort BAMSE. Severity of reported eczema was evaluated with the BAMSE Eczema Severity Score (BESS) in a questionnaire and with the Patient-Oriented Eczema Measure in clinically examined patients with current eczema (n=247). Information on dispensed topical glucocorticoids was obtained from the Swedish Prescribed Drug Register. In all, 10% of the adolescents reported eczema in the preceding year: 73% mild, 17% moderate and 10% severe according to BESS. Almost all used emollients, whereas use of topical glucocorticoids was reported by 55%, with no significant difference between sexes. The likelihood of treatment with emollients and topical glucocorticoids increased when the adolescents had symptoms of current eczema [adjusted odds ratio (OR) 5·95, 95% confidence interval (CI) 1·90-18·8], but not if they had more severe eczema compared with mild eczema (adjusted OR 1·57, 95% CI 0·58-4·25). Among those with reported eczema, 24% had a topical glucocorticoid dispensed in the preceding year, and among those with moderate-to-severe current eczema 24% had a dispensed potent topical glucocorticoid. This population-based study indicates that adolescents with eczema are undertreated or completely untreated, even those with severe eczema.

Clinical analysis of fungal keratitis in patients with and without diabetes.

We compared the clinical characteristics, treatments, and prognoses of fungal keratitis in patients with and without diabetes. Patients diagnosed with fungal keratitis at Shandong Eye Institute between January 2010 and December 2016 were retrospectively reviewed and classified as diabetic and nondiabetic groups. One-hundred-and-eleven patients (111 eyes) with diabetes and 740 patients (740 eyes) without diabetes were included. The diabetic patients showed significantly older (p< 0.05) and lower male:female ratio (p<0.05). Plants trauma was the primary risk factor in both groups, and there was no significant difference of pathogen type (the most common was Fusarium genus, followed by Alternaria and Aspergillus genera). Multivariate logistic regression analyses revealed that diabetes and topical glucocorticoid use were the independent risk factors for the severity of fungal keratitis. The recurrent infection rate between the diabetic and nondiabetic patients during the follow-up (6 to 24 months) after penetrating keratoplasty (PKP) was not significantly different. Although the recurrent epithelial defect, rejection, and best-corrected visual acuity were similar between the patients with matched bed/graft size (7.75/8.0 mm) in the two groups 1 year after PKP, the incidence of delayed re-epithelialization (>7 days) was significantly higher in diabetic patients (3/10 versus 2/43 in nondiabetic patients, p<0.05). More specially, the diabetic patients with the duration ≥10 years showed more significantly delayed re-epithelialization than those with the diabetic duration less than 10 years (3/5 versus 1/26, p<0.05). In conclusion, the diabetes mellitus is an independent risk factor that affect the severity of fungal keratitis. Corneal re-epithelialization was significantly delayed after PKP in the diabetic patients, especially with the duration ≥10 years.

Use of topical glucocorticoids: a population-based cohort study.

Little is known about the prescriptions of topical glucocorticoids in the general population. To report an overall picture of topical glucocorticoid prescriptions in France. This study used the Echantillon Généraliste de Bénéficiaires (EGB) database, a 1/97th random sampling of the French population covered by the main national healthcare insurance system (approximately 90% of the whole population). All patients prescribed topical glucocorticoids over a 5-year period (1 January 2011 to 31 December 2015) were identified using a specific code list for topical glucocorticoids. Over the 5-year study period, 662 531 individuals were recorded for at least 1 day in the EGB. Among them, 220 345 (33.3%) were prescribed at least once topical glucocorticoid. The prevalence of topical glucocorticoid prescription increased regularly from 2011 (11.7%) to 2015 (12.5%). A total of 922 026 tubes of topical glucocorticoids were dispensed, mainly high-potency glucocorticoids, and were mainly prescribed by general practitioners (73.1%). A total of 1713 (0.8%) patients were prescribed at least 24 tubes over a calendar year. These patients were more frequently men (P < 0.001) and older (P < 0.001) than the overall population of patients prescribed topical glucocorticoids. The 124 844 tubes prescribed to these patients had stronger potency than those prescribed to the overall population (P < 0.001) and were mostly prescribed by general practitioners (68.1%). The reasons for prescription were available for only 371 patients (21.7%) and were mainly psoriasis, auto-immune bullous dermatoses and eczema. About 12% of the French general population is prescribed topical glucocorticoids at least once each year. Most prescriptions are issued by general practitioners, dermatologists being the prescribers in less than one-quarter of cases.

Atopic Dermatitis: Insights on Pathogenesis, Evaluation and Management

Background: Atopic Dermatitis (AD) is a highly pruritic chronic inflammatory skin disease that commonly presents during early childhood. Several studies indicate that the disease is very common in western world with lifetime prevalence in children of 10% to 20%. Data sources: We make recommendations regarding the evaluation and management of AD in children based on systematic literature searches using the best-available evidence from PubMed, Medline, Google Scholar, NICE, the American Academy of Dermatology and the World Allergy Organization. Results: AD has an immunologic basis. Both innate and adaptive immune responses are impaired in AD patients. Intense pruritus is a hallmark of the disease which leads to extensive scratching and further breakdown of the skin barrier. Treatment of AD may be topical or systemic. Topical corticosteroids and calcineurin inhibitors are used as topical anti-inflammatory agents. Patients should be carefully instructed in the use of topical glucocorticoids to avoid side effects. Conclusions: Treatment of atopic eczema should be based on a “stepped-care plan” where treatments are stepped up or down depending on the assessment of the state of the child’s skin by the physician. Physicians who treat children with mild to moderate AD should tell children and their caregivers that AD is a lifelong illness.

Tachyphylaxis to topical glucocorticoids; what is the evidence?

Common belief holds that as topical glucocorticoids are used over time the less effective they become, a phenomenon called tolerance or tachyphylaxis. To determine what evidence supports the concept of tachyphylaxis to glucocorticoids. We searched Medline and Google Scholar for articles on tachyphylaxis to glucocorticoids published through October 2012. Rapid tolerance, tachyphylaxis, to non-clinical effects of glucocorticoids has been reported in literature. However, clinically significant tolerance to topical glucocorticoids has not been identified in clinical trials. We did not identify any evidence that clinical efficacy of glucocorticoids in inflammatory skin diseases significantly diminishes during long term continuous use. Tachyphylaxis or tolerance to clinical effects of topical glucocorticoids in inflammatory skin diseases is not fully characterized or well studied. Based on available data in literature, there is no clinical trial supporting the concept that topical glucocorticoids lose effectiveness over time, nor that intermittent use of topical glucocorticoids is more effective than continuous use.

Update on topical glucocorticoid use in children

This monograph reviews recent studies, examining topical glucocorticoid use in children. Emphasis is placed on mechanism of action, relative potency, cutaneous absorption, adverse affects, steroid phobia, and treatment compliance. Recent literature has shown that over 80% of patients prescribed topical glucocorticoids are fearful of side effects and fail to use them appropriately. This lack of compliance leads to decreased therapeutic benefits. Despite this 'steroid phobia', multiple studies indicate that proper use of glucocorticoids in children is well tolerated and effective. Recent studies have failed to show clinically significant hypothalamic-pituitary-adrenal suppression and cutaneous atrophy in children. High-potency steroids have been shown to cause growth restriction when used during pregnancy. Steroid allergy occurs with a prevalence of 2.7% and should be considered in children who fail to respond as expected to topical glucocorticoids. Topical glucocorticoids continue to be well tolerated, effective and cost-effective in the treatment of inflammatory cutaneous conditions in children.

Hypothalamic–Pituitary–Adrenal Axis Suppression Related to Topical Glucocorticoid Therapy in a Child with Psoriatic Exfoliative Erythroderma

Exfoliative erythroderma is a rare presentation of psoriasis in children and adults. We report a 9-year-old girl with exfoliative erythroderma secondary to plaque-type psoriasis who developed hypothalamic-pituitary-adrenal axis suppression resulting from topical treatment with a medium-potency glucocorticoid. This case emphasizes the need for awareness of this potentially life-threatening complication of topical glucocorticoid use, particularly in patients who have significant compromise of barrier function secondary to widespread skin disease.

Treatment of juvenile idiopathic arthritis-associated uveitis

To update the current understanding of the risk factors for poor outcomes in juvenile idiopathic arthritis-related uveitis. In addition, current therapies, both traditional and biological, are reviewed. Male sex, independent of age or antinuclear antibody status, is associated with increased ocular morbidity. Having anterior chamber inflammation on first exam increases the risk of developing vision-threatening eye complications. Presence of one complication increases the risk of developing another. Risk of cataract development associated with topical glucocorticoid use is better defined. Longer duration of remission on therapy has been found to decrease the risk of disease flare after discontinuation of methotrexate. Recent studies of both nonbiological and biological therapies for arthritis-related uveitis are discussed. With a better understanding of risk factors associated with the ocular morbidity of uveitis associated with juvenile idiopathic arthritis, aggressive therapies can be targeted for improved visual outcomes. Alternative treatments to avoid long-term corticosteroid use include the use of antimetabolites and biological therapies. More prospective comparator studies and/or use of multicenter databases are needed to better understand best treatments.

Bonnes pratiques de l’utilisation des dermocorticoïdes en dermatologie canine

The authors make recommendations for the optimal use of topical glucocorticoids in routine practice based on their experience in canine dermatology and evidence from the literature. The rationale behind the use of topical glucocorticoids is reminded, as are the main factors to consider in the selection of the appropriate product from current therapeutic armamentarium, taking into account notably the anti-inflammatory power and side effects of glucocorticoid compounds, their percutenous penetration and absorption, as well as available veterinary presentations. The specific circumstances and instructions for use of topical glucocorticoids are developed in each of their main indications (atopic dermatitis, flea allergy dermatitis, pyotraumatic dermatitis, contact dermatitis, auto-immune dermatitis, perianal fistulas), as are reminded the limits to their use and potential side effects, underlining the need for proper education of the owner and good therapeutic monitoring of the patient. [Display omitted]

Repeated topical application of glucocorticoids augments irritant chemical-triggered scratching in mice

Topical glucocorticoids, widely used for the treatment of a variety of dermatitises, are known to exacerbate atopic dermatitis after long-term or inappropriate use. In some animal models, topical glucocorticoids augment the allergic cutaneous inflammation after repeated application, suggesting a relationship between these and clinical observations. We investigated whether topical glucocorticoids augment itching, rather than inflammation, resulting in the exacerbation of atopic dermatitis. Mice receiving repeated topical application of glucocorticoids, betamethasone valerate or dexamethasone, to the ear for 1 week showed significantly higher scratching frequency after application of an irritant chemical, 2,4-dinitrofluorobenzene (DNFB) or 12-O-tetradecanoilphorbol 13-acetate (TPA) than those receiving either a glucocorticoid or irritant chemical alone. In contrast, the increase in ear thickness induced by application of TPA was significantly suppressed by dexamethasone. Substance P (SP) and nerve growth factor (NGF) levels were higher in the ear receiving betamethasone valerate followed by DNFB application than in that receiving DNFB alone. In addition, histopathological studies revealed an increased density of nerve fibers in the ear receiving betamethasone valerate or dexamethasone followed by DNFB application. Oral administration of betamethasone valerate was not associated with an increase in either scratching frequency or SP or NGF level in the ear. These results suggest that repeated topical application of glucocorticoids may augment irritant chemical-triggered scratching through an increase in SP and NGF levels and nerve fiber density at the application site. These findings might explain the etiology of the exacerbation of atopic dermatitis and other dermatitises, occurring after long-term or inappropriate use of topical glucocorticoids.

Cushing Syndrome and Suppression of the Hypothalamic-Pituitary-Adrenal Axis After Chronic Use of Topical Glucocorticoids

Topical and inhaled corticoids are considered to be safe even though some reports point out the risks, especially in children. We describe 2 adults in whom the chronic use of topical steroids led to Cushing syndrome. Patients treated with potent topical corticoids should be informed about the possibility of developing Cushing syndrome. Adrenal reserve should be monitored in those patients treated with glucocorticoids for long periods, regardless of the administration route.

Insight into the molecular mechanisms of glucocorticoid receptor action promotes identification of novel ligands with an improved therapeutic index

Glucocorticoids are highly effective in the therapy of inflammatory and autoimmune disorders. Their beneficial action is restricted because of their adverse effects upon prolonged usage. Topical glucocorticoids that act locally have been developed to significantly reduce systemic side effects. Nonetheless, undesirable cutaneous effects such as skin atrophy persist from the use of topical glucocorticoids. There is therefore a high medical need for drugs as effective as glucocorticoids but with a reduced side-effect profile. Glucocorticoids function by binding to and activating the glucocorticoid receptor that positively or negatively regulates the expression of specific genes. Several experiments suggest that the negative regulation of gene expression by the glucocorticoid receptor accounts for its anti-inflammatory action. This occurs through direct or indirect binding of the receptor to transcription factors such as activator protein-1, nuclear factor-kappaB or interferon regulatory factor-3 that are already bound to their regulatory sites. The positive action of the receptor occurs through homodimer binding of the receptor to discrete nucleotide sequences and this possibly contributes to some of the adverse effects of the hormone. Glucocorticoid receptor ligands that promote the negative regulatory action of the receptor with reduced positive regulatory function should therefore show improved therapeutic potential. A complete separation of the positive from the negative regulatory activities of the receptor has so far not been possible because of the interdependent nature of the two regulatory processes. Nevertheless, considerable improvement in the therapeutic action of glucocorticoid receptor ligands is being achieved through the use of key molecular targets for screening novel glucocorticoid receptor ligands.