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British Journal of Clinical Pharmacology Aug 2018To quantify the anti-inflammatory potency of topical corticosteroids and topical calcineurin inhibitors by measuring the contact allergic response to a... (Comparative Study)
Comparative Study Randomized Controlled Trial
AIMS
To quantify the anti-inflammatory potency of topical corticosteroids and topical calcineurin inhibitors by measuring the contact allergic response to a diphenylcyclopropenone (DPCP) challenge in de novo sensitized human volunteers.
METHODS
Two randomized, double-blind, vehicle-controlled studies were performed encompassing 76 volunteers: 29 in the first and 47 in the second study. Topical drugs were applied pre- and/or post-treatment in block designs. The compounds were tested simultaneously under occluded patch tests covering DPCP-induced dermatitis. Inhibitory responses were assessed by visual scoring and measurements of the oedema thickness with ultrasound.
RESULTS
When applied both before and after the DPCP challenge, significant anti-inflammatory effects were seen in descending order for tacrolimus 0.1% ointment, clobetasol propionate ointment, betamethasone valerate ointment and hydrocortisone butyrate ointment, while pimecrolimus cream, hydrocortisone ointment and vehicles had no significant effect. Only tacrolimus ointment (P < 0.01) demonstrated a consistent significant pre-treatment inhibitory effect compared with an untreated DPCP control.
CONCLUSIONS
This human testing method in which the inflammation of experimentally induced allergic patch test reactions is quantified by objective measurement allows an analysis of the anti-inflammatory potency of not only topical corticosteroids, but also of drugs that have no effect on vasoconstriction. The method allowed comparison of the potencies of four topical corticosteroids and two calcineurin inhibitors.
Topics: Administration, Cutaneous; Adult; Anti-Inflammatory Agents; Calcineurin Inhibitors; Cyclopropanes; Dermatitis, Allergic Contact; Dermatologic Agents; Double-Blind Method; Female; Glucocorticoids; Healthy Volunteers; Humans; Male; Ointments; Severity of Illness Index; Skin; Treatment Outcome; Ultrasonography; Vasoconstriction; Young Adult
PubMed: 29607554
DOI: 10.1111/bcp.13596 -
The Tohoku Journal of Experimental... Dec 2020Dysthyroid optic neuropathy is a severe manifestation of Graves' ophthalmopathy that can result in permanent vision loss. We report a 37-year-old pregnant woman with...
Dysthyroid optic neuropathy is a severe manifestation of Graves' ophthalmopathy that can result in permanent vision loss. We report a 37-year-old pregnant woman with Graves' ophthalmopathy which was deteriorated to dysthyroid optic neuropathy in the third trimester of pregnancy. Diplopia, bilateral eye lid retraction, lid edema and proptosis were observed in the 29th week of gestation. Thyroid-stimulating hormone (TSH) level was decreased with a normal level of free triiodothyronine (FT3) and an upper normal level of free thyroxine (FT4). Anti-TSH receptor antibodies (16.2 IU/L, reference range < 2.0 IU/L) and thyroid stimulating antibody (4,443%, reference range < 120%) were positive. Magnetic resonance imaging (MRI) demonstrated a significant enlargement of the extraocular muscles with a high signal intensity on T2-weighted image. She was diagnosed as Graves' ophthalmopathy and subclinical hyperthyroidism, and followed without treatment. In the 34th week of gestation, the symptom of color vision abnormality appeared, suggesting dysthyroid optic neuropathy. She delivered a female infant during the 36th week of gestation. Four days after delivery, she had a spontaneous orbital pain. MRI showed that the extraocular muscles were more enlarged than the findings in the 29th week of gestation. FT3 and FT4 levels were mildly elevated. Dysthyroid optic neuropathy was diagnosed. She was treated with methylprednisolone pulse therapy and retrobulbar injections of betamethasone valerate, and the ocular symptoms improved. The present case shows that the glucocorticoid therapy performed one week after delivery is effective against Graves' ophthalmopathy which was deteriorated to dysthyroid optic neuropathy during the third trimester of pregnancy.
Topics: Adult; Disease Progression; Female; Graves Ophthalmopathy; Humans; Magnetic Resonance Imaging; Postpartum Period; Pregnancy; Pregnancy Complications; Pregnancy Trimester, Third; Vision, Ocular
PubMed: 33268601
DOI: 10.1620/tjem.252.321 -
Acta Dermato-venereologica Jul 2015The proactive use of topical anti-inflammatory (TAI) therapy to address subclinical inflammation is an effective, contemporary clinical strategy for the management of... (Comparative Study)
Comparative Study Randomized Controlled Trial
The proactive use of topical anti-inflammatory (TAI) therapy to address subclinical inflammation is an effective, contemporary clinical strategy for the management of atopic dermatitis (AD). The interaction of a proactive TAI dose with the subclinical epidermal barrier defect in AD is yet to be determined. A randomised, observer-blind, functional mechanistic study in 17 subjects with quiescent AD was performed to compare the effect of a twice-weekly dose of betamethasone valerate (0.1%) cream (BMVc), against tacrolimus (0.1%) ointment (TACo) on the biophysical and biological properties of the epidermal barrier. Application of BMVc preserved epidermal barrier function and stratum corneum (SC) integrity, but significantly elevated skin-surface pH with concomitant loss of SC cohesion. By contrast, TACo improved SC integrity, exerted an overall hydrating action, and significantly reduced caseinolytic and trypsin-like protease activity. The differential effects reported support the proactive use of TACo to promote reparation of the subclinical barrier defect in AD.
Topics: Adult; Anti-Inflammatory Agents; Betamethasone Valerate; Calcineurin Inhibitors; Densitometry; Dermatitis, Atopic; Electric Capacitance; Epidermis; Humans; Hydrogen-Ion Concentration; Ointments; Peptide Hydrolases; Single-Blind Method; Skin Cream; Skin Physiological Phenomena; Tacrolimus; Water Loss, Insensible
PubMed: 25594610
DOI: 10.2340/00015555-2048 -
Journal of Dermatological Science Jun 2018Chronic eczema such as atopic dermatitis imposes significant socio-econo-psychologic burdens on the affected individuals. In addition to conventional topical treatments,...
BACKGROUND
Chronic eczema such as atopic dermatitis imposes significant socio-econo-psychologic burdens on the affected individuals. In addition to conventional topical treatments, phototherapy is recommended for patients with extensive lesions. Although immunosuppression is believed to explain its primary effectiveness, the underlying mechanisms of phototherapy remain unsolved. Ultraviolet irradiation generates various tryptophan photoproducts including 6-formylindolo[3,2-b]-carbazole (FICZ). FICZ is known to be a potent endogenous agonist for aryl hydrocarbon receptor (AHR); however, the biological role of FICZ in chronic eczema is unknown.
OBJECTIVE
To investigate the effect of FICZ on chronic eczema such as atopic dermatitis.
METHODS
We stimulated HaCaT cells and normal human epidermal keratinocytes (NHEKs) with or without FICZ and then performed quantitative reverse transcriptase polymerase chain reaction, immunofluorescence, and siRNA treatment. We used the atopic dermatitis-like NC/Nga murine model and treated the mice for 2 weeks with either Vaseline as a control, FICZ ointment, or betamethasone 17-valerate ointment. The dermatitis score, transepidermal water loss, histology, and expression of skin barrier genes and proteins were evaluated.
RESULTS
FICZ significantly upregulated the gene expression of filaggrin in both HaCaT cells and NHEKs in an AHR-dependent manner, but did not affect the gene expression of other barrier-related proteins. In addition, FICZ improved the atopic dermatitis-like skin inflammation, clinical scores, and transepidermal water loss in NC/Nga mice compared with those of control mice. On histology, FICZ significantly reduced the epidermal and dermal thickness as well as the number of mast cells. Topical FICZ also significantly reduced the gene expression of Il22.
CONCLUSION
These findings highlight the beneficial role of FICZ-AHR and provide a new strategic basis for developing new drugs for chronic eczema.
Topics: Animals; Basic Helix-Loop-Helix Transcription Factors; Betamethasone Valerate; Carbazoles; Cell Line; Cytochrome P-450 CYP1A1; Dermatitis, Atopic; Dermatophagoides farinae; Female; Filaggrin Proteins; Humans; Immunosuppressive Agents; Interleukins; Intermediate Filament Proteins; Keratinocytes; Mice; RNA, Messenger; RNA, Small Interfering; Receptors, Aryl Hydrocarbon; Skin; Up-Regulation; Water Loss, Insensible; Interleukin-22
PubMed: 29500077
DOI: 10.1016/j.jdermsci.2018.02.014 -
Indian Journal of Dermatology,... 2017Psoriasis is a T helper 1 cell-mediated chronic inflammation. Statins have been found to have anti-inflammatory and immunomodulatory effects targeting T helper 1 cells... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Psoriasis is a T helper 1 cell-mediated chronic inflammation. Statins have been found to have anti-inflammatory and immunomodulatory effects targeting T helper 1 cells and thus, are being investigated as treatments for psoriasis.
AIMS
To investigate the efficacy and safety of atorvastatin as adjunctive treatment for mild to moderate chronic plaque psoriasis; and the impact of atorvastatin on quality of life. The study also aimed to correlate the beneficial effects of atorvastatin with its lipid-lowering effects.
METHODS
Twenty-eight (19-65 year old) mild-moderate chronic plaque psoriasis patients were randomly assigned to two groups (treatment group: atorvastatin 40 mg OD; control group: placebo OD) and followed up for 6 months. All were allowed to use betamethasone valerate 0.1% ointment twice a day for a maximum of 3 weeks continuous application with 1-week rest periods in between. Primary outcome measures were the mean percentage reduction in Psoriasis Area and Severity Index (PASI) scores and percentage of patients achieving PASI-50.
RESULTS
Fourteen patients (treatment: 6, control: 8) completed the trial. Mean reductions in PASI scores between the treatment (2.15 ± 2.17) and control (1.69 ± 2.36) groups were not statistically significant (P = 0.636). Intention-to-treat analysis of PASI-50 showed increased risk of treatment failure with atorvastatin as adjunct but estimates were not significant. Changes in Dermatology Life Quality Index (DLQI) scores (P = 0.214) and high-sensitivity C-reactive protein (P = 0.884) were likewise not statistically significant. Reductions in PASI scores were not linearly correlated with reductions in total cholesterol (P = 0.924), triglycerides (P = 0.274), low-density lipoprotein-cholesterol (P = 0.636), high-density lipoprotein-cholesterol (P = 0.584), or high-sensitivity C-reactive protein levels (P = 0.906). Adverse effects in the treatment group were transient elevated transaminases (n = 1) and mild myalgia (n = 1).
LIMITATIONS
A 50% dropout rate was experienced. This remarkably high dropout rate decreases the robustness of the study results.
CONCLUSIONS
Although atorvastatin exhibited earlier percentage reduction in PASI scores, it was not able to produce an additional benefit compared to psoriatic patients applying steroid alone.
Topics: Adult; Aged; Anti-Inflammatory Agents; Atorvastatin; Betamethasone Valerate; Chronic Disease; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Middle Aged; Psoriasis
PubMed: 28540870
DOI: 10.4103/ijdvl.IJDVL_425_16 -
Clinical, Cosmetic and Investigational... 2018Scleroderma is traditionally managed with immunomodulatory agents such as methotrexate, mycophenolate mofetil and corticosteroids. There are anecdotal reports for, and...
Assessing the response of morphea and limited scleroderma to tranilast: a small prospective study comparing topical corticosteroids to a combination of topical corticosteroids and tranilast.
BACKGROUND
Scleroderma is traditionally managed with immunomodulatory agents such as methotrexate, mycophenolate mofetil and corticosteroids. There are anecdotal reports for, and theoretical reasons why, the anti-fibrotic agent tranilast may provide an additional treatment modality.
OBJECTIVE
The objective of the current study was to demonstrate if the addition of topical tranilast to an established regime resulted in an improvement in the Localized Scleroderma Assessment Tool (LoSCAT) and modified Rodnan score.
PATIENTS AND METHODS
A small double-blinded randomized prospective study of 11 pairs of treatment sites in four patients; three with morphea and one with limited scleroderma was performed. All patients continued with their prescribed treatment and applied 0.1% betamethasone valerate in PCCA PracaSil™ (B) to the control site with 0.1% betamethasone valerate and 1% tranilast (B/T) to the comparator site over a period of 3 months. Photographs and monthly LoSCAT scores were performed on the morphea patients and a modified Rodnan score on the limited scleroderma patient. Statistical analysis was via sign test.
RESULTS
The mean baseline LoScat score at the B treated sites was 6.6 which improved to 4.3 (= 0.16). The mean baseline LoScat score at the B/T treated sites was 5.75 which improved to 2.8 following treatment. (=0.04).
LIMITATIONS
This was a small single center study. The ideal concentration of tranilast is unknown. As all patients continued with standard management the expected response may be less than would have been anticipated in a single agent trial.
CONCLUSION
The role of tranilast in the management in scleroderma warrants further investigation in larger trials.
PubMed: 30013378
DOI: 10.2147/CCID.S160923 -
Pharmaceutical Research Apr 2017To examine whether in vitro and ex vivo measurements of topical drug product performance correlate with in vivo outcomes, such that more efficient experimental...
OBJECTIVE
To examine whether in vitro and ex vivo measurements of topical drug product performance correlate with in vivo outcomes, such that more efficient experimental approaches can be reliably and reproducibly used to establish (in)equivalence between formulations for skin application.
MATERIALS AND METHODS
In vitro drug release through artificial membranes, and drug penetration into porcine skin ex vivo, were compared with published human in vivo studies. Two betamethasone valerate (BMV) formulations, and three marketed econazole nitrate (EN) creams were assessed.
RESULTS
For BMV, the stratum corneum (SC) uptake of drug in 6 h closely matched data observed in vivo in humans, and distinguished between inequivalent formulations. SC uptake of EN from the 3 creams mirrored the in vivo equivalence in man (both clinically and via similar tape-stripping experiments). However, EN clearance from SC ex vivo did not parallel that in vivo, presumably due to the absence of a functioning microcirculation. In vitro release of BMV from the different formulations did not overlap with either ex vivo or in vivo tape-stripping data whereas, for EN, a good correlation was observed. No measurable permeation of either BMV or EN was detected in a 6-h in vitro skin penetration experiment.
CONCLUSIONS
In vitro and ex vivo methods for topical bioequivalence determination can show correlation with in vivo outcomes. However, these surrogates have understandable limitations. A "one-size-fits-all" approach for topical bioequivalence evaluation may not always be successful, therefore, and the judicious use of complementary methods may prove a more effective and reliable strategy.
Topics: Administration, Topical; Adrenal Cortex Hormones; Animals; Antifungal Agents; Betamethasone Valerate; Chemistry, Pharmaceutical; Drug Liberation; Econazole; Humans; Membranes, Artificial; Skin; Skin Absorption; Skin Cream; Swine; Therapeutic Equivalency
PubMed: 28097506
DOI: 10.1007/s11095-017-2099-1 -
Italian Journal of Pediatrics Jan 2023Corticosteroids are widely used in medicine. Few cases of central serous chorioretinopathy (CSC) have been reported following topical corticosteroid administration. We...
BACKGROUND
Corticosteroids are widely used in medicine. Few cases of central serous chorioretinopathy (CSC) have been reported following topical corticosteroid administration. We describe the first case of pediatric CSC related to topical corticosteroid administration.
CASE PRESENTATION
A 14-year-old boy presented with decreased vision, pigment epithelial detachments, and serous retinal detachments in the right eye after starting treatment for atopic dermatitis with Betamethasone Valerate 0.1% topical ointment. His condition resolved 2 weeks after discontinuing the steroid and administering Bromfenac 0.9 mg/ml eyedrops.
CONCLUSIONS
Although the pathogenesis of CSC is poorly understood, ophthalmologists should be informed about the potential link between CSC and topical corticosteroid treatment, and they should be aware that CSC might, albeit infrequently, affect children.
Topics: Male; Humans; Child; Adolescent; Central Serous Chorioretinopathy; Retinal Detachment; Glucocorticoids; Adrenal Cortex Hormones; Steroids
PubMed: 36597009
DOI: 10.1186/s13052-022-01386-4 -
European Journal of Pharmaceutics and... Apr 2015Polymeric film-forming systems (FFSs) are potential drug delivery systems for topical application to the skin. The FFSs form thin and transparent polymeric films in situ... (Comparative Study)
Comparative Study
Polymeric film-forming systems (FFSs) are potential drug delivery systems for topical application to the skin. The FFSs form thin and transparent polymeric films in situ upon solvent evaporation. Their application convenience and cosmetic attributes, superior to conventional semi-solids, may offer improved patient compliance. This study represents the first phase of an investigation into the use of FFSs for prolonged dermal drug delivery. FFS formulations were distinguished based on their ability to sustain the release of betamethasone 17-valerate (BMV) in vitro over 72 h. The effect of film-forming polymer (hydrophilic: hydroxypropyl cellulose (Klucel™ LF); hydrophobic: polymethacrylate copolymers (Eudragit® NE and Eudragit® RS), and polyacrylate copolymer (Dermacryl® 79) was first determined, and then the impact of incorporation of plasticisers (triethyl citrate, tributyl citrate, and dibutyl sebacate) was examined. The Klucel film released a significantly higher amount of BMV than the hydrophobic FFS, 42 versus 4 μg/cm(2), respectively. The release was increased when a plasticiser was incorporated, and with higher enhancement ratios achieved with the more lipophilic plasticisers. In conclusion, the results show that FFSs can sustain drug release (hence representing useful systems for prolonged dermal therapy) and emphasise the importance of the formulation on drug delivery, with the type of polymer being of greatest significance.
Topics: Acrylic Resins; Administration, Cutaneous; Animals; Betamethasone Valerate; Cellulose; Chemical Phenomena; Chemistry, Pharmaceutical; Delayed-Action Preparations; Dermatologic Agents; Diffusion; Drug Delivery Systems; Drug Liberation; Glucocorticoids; Hydrophobic and Hydrophilic Interactions; Mechanical Phenomena; Membranes, Artificial; Pharmaceutic Aids; Plasticizers; Polymerization; Polymethacrylic Acids; Skin; Sus scrofa
PubMed: 25595740
DOI: 10.1016/j.ejpb.2015.01.002 -
BMJ Case Reports Jun 2014A 54-year-old woman developed psoriasis on the plantar surface of her feet after 2 weeks of thalidomide 100 mg daily for the treatment of multiple IgG myeloma. She...
A 54-year-old woman developed psoriasis on the plantar surface of her feet after 2 weeks of thalidomide 100 mg daily for the treatment of multiple IgG myeloma. She did not have any previous history of psoriasis. Thalidomide was immediately stopped and topical treatment with calcipotriol ointment and β-methasone valerate was started. Psoriasis disappeared completely after 2 weeks of topical therapy. This is the first case of de novo psoriasis in a patient with multiple myeloma under treatment with thalidomide. Our observation provides further evidence of the potential paradoxical effect of thalidomide on tumour necrosis factor-α production.
Topics: Angiogenesis Inhibitors; Female; Humans; Middle Aged; Multiple Myeloma; Psoriasis; Thalidomide; Tumor Necrosis Factor-alpha
PubMed: 24973347
DOI: 10.1136/bcr-2014-204469