5α-Tetrahydrocorticosterone: A topical anti-inflammatory glucocorticoid with an improved therapeutic index in a murine model of dermatitis.

BACKGROUND AND PURPOSE: Glucocorticoids are powerful anti-inflammatory drugs, but are associated with many side-effects. Topical application in atopic dermatitis leads to skin thinning, metabolic changes, and adrenal suppression. 5α-Tetrahydrocorticosterone (5αTHB) is a potential selective anti-inflammatory with reduced metabolic effects. Here, the efficacy and side-effect profile of 5αTHB were compared with hydrocortisone in preclinical models of irritant dermatitis. EXPERIMENTAL APPROACH: Acute irritant dermatitis was invoked in ear skin of male C57BL/6 mice with a single topical application of croton oil. Inflammation was assessed as oedema via ear weight following treatment with 5αTHB and hydrocortisone. Side-effects of 5αTHB and hydrocortisone were assessed following chronic topical steroid treatment (28 days) to non-irritated skin. Skin thinning was quantified longitudinally by caliper measurements and summarily by qPCR for transcripts for genes involved in extracellular matrix homeostasis; systemic effects of topical steroid administration also were assessed. Clearance of 5αTHB and hydrocortisone were measured following intravenous and oral administration. KEY RESULTS: 5αTHB suppressed ear swelling in mice, with ED50 similar to hydrocortisone (23 µg vs. 13 µg). Chronic application of 5αTHB did not cause skin thinning, adrenal atrophy, weight loss, thymic involution, or raised insulin levels, all of which were observed with topical hydrocortisone. Transcripts for genes involved in collagen synthesis and stability were adversely affected by all doses of hydrocortisone, but only by the highest dose of 5αTHB (8× ED50 ). 5αTHB was rapidly cleared from the systemic circulation. CONCLUSIONS AND IMPLICATIONS: Topical 5αTHB has potential to treat inflammatory skin conditions, particularly in areas of delicate skin.

Bullous impetigo-like irritant contact dermatitis caused by perfume.

Contact dermatitis usually presents as erythematous macules, papules, and vesicles. Sometimes, unusual clinical presentations of contact dermatitis are reported, including pustular, lymphomatoid, lichenoid, and pigmented variants. We describe the first patient with bullous irritant contact dermatitis caused by perfume, mimicking impetigo lesions. We report this case to raise awareness concerning the possibility of serious cutaneous reactions, such as bullous impetigo-like irritant contact dermatitis due to perfumes which are ubiquitous, especially after direct contact with the solution. Perfume ingredients, such as fragrance, solvents, and preservatives all may cause or contribute to irritant contact dermatitis.

The role of interleukin-1ß in the immune response to contact allergens.

Interleukin-1ß (IL-1ß) is an important pro-inflammatory cytokine that has an effect on almost every cell lineage in the body. By blocking IL-1ß and investigating the IL-1ß signaling pathway, several studies have demonstrated a central role of IL-1ß in the response to contact allergens. This review summarizes the current literature regarding the basic immunological mechanisms mediated by IL-1ß in the different phases of allergic contact dermatitis (ACD) and highlights potential IL-1ß-targeted treatment options, which in the future may be relevant in the treatment of patients with ACD. This review is based primarily on studies using various mouse models and human in vitro studies, since clinical studies on the effect of IL-1ß in ACD are lacking.

Are Topical Corticoids Efficacious in Acute Irritant Dermatitis: The Evidence.

Topical corticosteroid therapies are widely utilized, despite the controversial results of corticoid therapy in irritant contact dermatitis as a local inflammatory reaction after repeated or single skin exposure to a chemical substance. Although corticoids may reduce the inflammatory response to the irritant, their antiproliferative effects may reduce skin barrier recovery while allowing further penetration of irritants if exposure continues. This overview reexamines the efficacy of corticosteroids in irritant contact dermatitis therapy, and with the minimal controlled experimental data currently available, notes the need for same-in this common clinical entity.

Fiberglass dermatitis: clinical presentations, prevention, and treatment - a review of literatures.

Fiberglass dermatitis is a common form of occupational irritant contact dermatitis. Individuals experience a negative reaction to fiberglass fragments because of mechanical irritation. This review comprehensively analyzes the information in the existing literature on fiberglass dermatitis. Recognizing the different environmental risks factors for acquiring fiberglass dermatitis is necessary for better diagnosis and prevention. In addition to the identification of high-risk populations exposed to fiberglass particles, the common clinical presentation and preventive measures that can reduce the risk of acquiring fiberglass dermatitis are thoroughly discussed.

Anatomical site differences of sodium lauryl sulfate-induced irritation: randomized controlled trial.

BACKGROUND: Sodium lauryl sulfate (SLS)-induced contact dermatitis is a commonly used model for testing the effects of different topical formulations. According to the guidelines, the volar forearms are the preferred testing site; however, other anatomical locations have been used in previous research, particularly the upper back as the clinically used site for testing different antigens. OBJECTIVES: To investigate the existence of anatomical variations of the skin response to irritation and its effects on the response to treatment. METHODS: Irritation was induced with SLS on symmetrical sites on both forearms and sides of the upper back with additional sites exposed to water as controls. Half of the sites were treated with emollient cream while the other half were left untreated. Irritation was assessed using bioengineering methods and clinical scoring. The trial was registered at ClinicalTrials.gov as NCT03231813. RESULTS: Upper back skin showed higher reactivity to irritants with stronger barrier disruption (measured by Tewameter® , 80·2 ± 18·3 vs. 48·0 ± 24·2 g m-2  h-1 ), more pronounced erythema (measured by Mexameter® , 186·5 ± 88·4 vs. 92·1 ± 58·2 arbitrary units) and dryness (measured by Corneometer® , -28·6 ± 14·5 vs. 2·7 ± 16·9 arbitrary units). Skin recovery rates were also influenced by anatomical location with the upper back showing faster recovery (316·7 ± 223·1 vs. 156·2 ± 198·5). Treatment did not lead to improvement in measured parameters, regardless of anatomical location. CONCLUSIONS: The skin's reaction to irritant and recovery was dependent on anatomical location. The location where testing was conducted should always be reported, as treatments tested across different locations could not be directly compared with each other.

Cariniana domestica fruit peels present topical anti-inflammatory efficacy in a mouse model of skin inflammation.

To investigate the topical anti-inflammatory activity of the crude extract of Cariniana domestica fruit peels (CdE), its dichloromethane, n-butanol, and ethyl acetate (EtAc) fractions, and steroids (ß-sitosterol, lupeol, and stigmasterol) isolated from the EtAc fraction in models of irritant contact dermatitis (ICD) croton oil-induced in mice. We induced skin inflammation by single (acute; 1 mg/ear) and multiple (chronic; 0.4 mg/ear) croton oil application. We topically applied C. domestica (CdE, fractions, and gel formulations) and ß-sitosterol, lupeol, and stigmasterol immediately after applying croton oil. HPLC-DAD chromatography of the EtAc fraction and stability of the gel formulations were verified. HPLC-DAD of the EtAc fraction revealed the stigmasterol, lupeol, and ß-sitosterol presence. CdE and EtAc fraction gels showed no organoleptic or pH changes at room temperatures. CdE and dichloromethane, n-butanol, and EtAc (1 mg/ear) fractions decreased the acute ear edema with maximum inhibition (Imax) of 97 ± 2, 86 ± 1, 81 ± 4, and 95 ± 2%, respectively. CdE and EtAc fraction gel presented similar effects, with respective Imax of 85 ± 6% (3%;15 mg/ear) and 82 ± 2% (1%;15 mg/ear). ß-sitosterol (7.5 µg/ear), lupeol (10 µg/ear), and stigmasterol (5.7 µg/ear) also reduced this parameter by 46 ± 8, 51 ± 7, and 62 ± 7%, respectively. All topical treatments reduced the inflammatory cells' infiltration in the acute ICD model. CdE reduced the ear edema by 77 ± 4% (1 mg/ear) and the inflammatory cell infiltration in the chronic ICD model. CdE's anti-inflammatory effect was accompanied by a minimum development of adverse effects. C. domestica demonstrates a promising potential for the development of a topical anti-inflammatory agent. Graphical abstract Cariniana domestica, popularly known as jequitibá-roxo, presented topical anti-inflammatory activity in an acute and chronic irritant contact dermatitis croton oil-induced in mice. The crude extract (solutions and gel formulations) and different fractions obtained from fruit peels of C. domestica showed topical antiinflammatory activity on skin inflammation models with minimum adverse effects in preliminary toxicological studies (behavior and biochemical parameters). Moreover, the HPLC analysis revealed the presence of ß-sitosterol, stigmasterol and lupeol, which also presented topical anti-inflammatory effect in the acute irritant contact dermatitis croton oil-induced. Our findings support the use of this species as a promising topical antiinflammatory agent.

Non-glaucoma periocular allergic, atopic, and irritant dermatitis at an academic institution: A retrospective review.

PURPOSE: To better understand the nature of periocular dermatitis (PD) patient presentation, treatment, time-to-cure, and referral pattern for allergy testing in an ophthalmic academic center. METHODS: A retrospective chart review of 344 patients diagnosed with PD between January 1, 2000 and November 30, 2016 at the Edward S. Harkness Eye Institute was performed. Eighty patients were eligible for the study. The primary endpoint was the time-to-cure. Cox proportional hazards regression was performed to assess if there was a significant difference between time-to-cure in patients treated with: 1) combination topical steroid/antibiotic (n = 6) vs. topical steroid alone (n = 40) and 2) combination topical steroid and oral antihistamine (n = 5) vs. topical steroid alone (n = 40). RESULTS: The median age of eligible patients was 57.69 years old, 66.25% of patients were female, and 41.25% had a history of atopy. Seven patients in total were referred for allergy testing. A significant difference was found in likelihood of cure when comparing combination topical steroid and oral antihistamine versus topical steroid alone, adjusting for age and gender (aHR = 3.97, 95% CI: 1.40-11.25). No significance was found when comparing combination topical steroid/antibiotic versus topical steroid alone (aHR = 1.96, 95% CI: 0.72-5.27). CONCLUSION: Patients treated with topical steroid and oral antihistamine were approximately 4 times more likely to experience cure in comparison to patients treated with topical steroids alone. While the majority of patients were not referred for formal allergy testing, this would likely be of benefit.

Differential effects of functionally different histamine H4 receptor ligands on acute irritant dermatitis in mice.

The anti-inflammatory effects of histamine H4 receptor (H4R) antagonists opened new therapeutic options for the treatment of inflammatory/allergic diseases, but the role of H4R in inflammation is far from being solved. Aim of the present study was to investigate the role of structurally related H4R ligands of the aminopyrimidine class with different efficacies and functionalities (neutral antagonist ST-994, partial agonist ST-1006, inverse agonist ST-1012, and partial inverse agonist ST-1124) on croton oil-induced ear edema and pruritus in mice. The H4R ligands were administered subcutaneously before topical application of croton oil. While ST-1006 and ST-1124 were ineffective at any dose tested (10-100 mg/kg), both ST-994 and ST-1012 (30 and 100 mg/kg) significantly reduced croton oil-induced ear edema. Moreover, ST-994, ST-1006, and ST-1124, but not ST-1012, significantly inhibited croton oil-induced ear pruritus at 30 mg/kg. In accordance with results obtained with the reference H4R antagonist JNJ7777120 (100 mg/kg), histological examination of inflamed ear tissue indicated that treatment with ST-994 (30 mg/kg) led to a significant reduction in the inflammatory severity score and in the number of eosinophils infiltrating the tissue, while the number of degranulated mast cells in inflamed tissues was increased in comparison with the number of intact mast cells. These data indicate that croton oil-induced ear inflammation and pruritus seem to be clearly, but variably, affected by the H4R ligands tested. The potential advantage of dual effect of the H4R neutral antagonist ST-994 has to be carefully considered as a new therapeutic approach to the treatment of inflammatory diseases.

Topical ROR Inverse Agonists Suppress Inflammation in Mouse Models of Atopic Dermatitis and Acute Irritant Dermatitis.

The retinoic acid receptor-related orphan receptors RORα and RORγ are critical for the functions of specific subsets of T cells and innate lymphoid cells, which are key drivers of inflammatory disease in barrier tissues. Here, we investigate the anti-inflammatory potential of SR1001, a synthetic RORα/γ inverse agonist, in mouse models of atopic dermatitis and acute irritant dermatitis. Topical treatment with SR1001 reduces epidermal and dermal features of MC903-induced atopic dermatitis-like disease and suppresses the production of type 2 cytokines and other inflammatory mediators in lesional skin. In the epidermis, SR1001 treatment blocks MC903-induced expression of TSLP and reverses impaired keratinocyte differentiation. SR1001 is also effective in alleviating acute dermatitis triggered by 12-O-tetradecanoylphorbol-13-acetate. Overall, our results suggest that RORα/γ are important therapeutic targets for cutaneous inflammation and suggest topical usage of inhibitory ligands as an approach to treating skin diseases of inflammatory etiology.

The potential benefits of using aloe vera in stoma patient skin care.

Individuals living with an ostomy may suffer from a variety of peri-stomal skin complications related to the use of their stoma appliance or accessories. These conditions can be serious enough to significantly impact on a patient's quality of life and may result in severe clinical complications (such as infection). This article is a review of the literature with the objective of investigating and presenting evidence for the well-documented use of aloe vera in the prevention of skin conditions similar to those seen in peri-stomal skin complications. An exploration for the potential use of aloe vera directly or indirectly (as an adjunct to medical devices such as wafers) in stoma patients is presented with the view that this use may be beneficial in the prevention of such peri-stomal skin complications.