Vehicle-treated Side Research Articles

Interim Results of a Pilot, Prospective, Randomized, Double-Blinded, Vehicle- and Comparator-Controlled Trial on Safety and Efficacy of a Topical Inhibitor of Janus Kinase 1/2 (Ruxolitinib INCB018424 Phosphate 1.5% Cream) for Non-Sclerotic and Superficially Sclerotic Chronic Cutaneous Graft-Versus-Host Disease

Interim Results of a Pilot, Prospective, Randomized, Double-Blinded, Vehicle- and Comparator-Controlled Trial on Safety and Efficacy of a Topical Inhibitor of Janus Kinase 1/2 (Ruxolitinib INCB018424 Phosphate 1.5% Cream) for Non-Sclerotic and Superficially Sclerotic Chronic Cutaneous Graft-Versus-Host Disease

Blue Lagoon Algae Improve Uneven Skin Pigmentation: Results from in vitro Studies and from a Monocentric, Randomized, Double-Blind, Vehicle-Controlled, Split-Face Study

Introduction: Bathing in the Blue Lagoon (BL) in Iceland benefits patients with psoriasis. Accordingly, the BL water contains algae with biological activities that improve skin barrier function and affect T-cell responses relevant for psoriasis. Bathing in the BL is also becoming increasingly popular among healthy individuals and anecdotal evidence suggests positive effects on uneven skin pigmentation. Objective: The aim of the study was to address the impact of BL algae on skin pigmentation. Methods: In this work, in vitro gene expression studies in melanocytes and a noninvasive in vivo study were conducted. Results: We here report that normal human epidermal melanocytes, which had been treated with nontoxic concentrations of BL algae, show a significantly reduced expression of α melanocyte-stimulating hormone-induced expression of genes important for melanin synthesis, such as tyrosinase, tyrosinase-related protein 1, dopachrome tautomerase, melan A protein, and pre-melanosome protein. This in vitro observation prompted us to conduct a randomized, double-blind, intra-individual, comparative split-face in vivo study, in which 60 volunteers with pre-existing facial pigment spots were treated twice daily with a BL algae containing serum or a vehicle control. We found that constitutive skin pigmentation as determined by colorimetry (individual typology angle and luminescence) did not differ significantly between vehicle- and serum-treated skin sites. In marked contrast, digital photography under cross-polarized lighting and RBX technology (VISIA CR) revealed that the number of pigment spots in the serum-treated face decreased significantly compared to the vehicle-treated side. Conclusion: Thus, BL algae can affect human melanocyte function in vitro and reduce uneven facial skin pigmentation in vivo.

Assessment of the Efficacy and Safety of a Combination of 2 Topical Retinoids (RetinSphere) in Maintaining Post-Treatment Response of Acne to Oral Isotretinoin

IntroductionThe high rate of relapse of acne lesions following oral isotretinoin treatment is a common problem which remains unsolved. To avoid or minimize relapses, topical retinoids have been used for many years as maintenance treatment. However, adverse effects frequently occur. AimsTo determine the efficacy and safety of a new retinoid combination (Retinsphere technology) in maintaining post-treatment response to oral isotretinoin. Patients and methodsProspective, randomized, double-blind and vehicle-controlled study of 30 patients with acne previously treated with isotretinoin. Treatment with the retinoid combination was applied to one side of the face and vehicle was applied to the other, once daily, for 3 months. Standardized photographs were taken using RBX technology at baseline, 1.5 months and 3 months. The primary efficacy endpoint was the appearance of relapse on the treated side compared to the vehicle-treated side. Other endpoints included lesion count, investigator-reported improvement, patient-reported improvement, impact on quality-of-life, and side effects. ResultsAlthough the majority of patients did not reach the total target dose of oral isotretinoin, the relapse rate was significantly lower on the retinoid-treated side compared to the vehicle-treated side. Likewise, improved lesion count and excellent tolerance were observed. ConclusionsThis new retinoid combination (Retinsphere technology) were effective and safe as maintenance therapy after post-treatment response to oral isotretinoin in patients with acne.

Assessment of the Efficacy and Safety of a Combination of 2 Topical Retinoids (RetinSphere) in Maintaining Post-Treatment Response of Acne to Oral Isotretinoin

IntroductionThe high rate of relapse of acne lesions following oral isotretinoin treatment is a common problem which remains unsolved. To avoid or minimize relapses, topical retinoids have been used for many years as maintenance treatment. However, adverse effects frequently occur. AimsTo determine the efficacy and safety of a new retinoid combination (Retinsphere technology) in maintaining post-treatment response to oral isotretinoin. Patients and methodsProspective, randomized, double-blind and vehicle-controlled study of 30 patients with acne previously treated with isotretinoin. Treatment with the retinoid combination was applied to one side of the face and vehicle was applied to the other, once daily, for 3 months. Standardized photographs were taken using RBX technology at baseline, 1.5 months and 3 months. The primary efficacy endpoint was the appearance of relapse on the treated side compared to the vehicle-treated side. Other endpoints included lesion count, investigator-reported improvement, patient-reported improvement, impact on quality-of-life, and side effects. ResultsAlthough the majority of patients did not reach the total target dose of oral isotretinoin, the relapse rate was significantly lower on the retinoid-treated side compared to the vehicle-treated side. Likewise, improved lesion count and excellent tolerance were observed. ConclusionsThis new retinoid combination (Retinsphere technology) were effective and safe as maintenance therapy after post-treatment response to oral isotretinoin in patients with acne.

Inhibitory effect of topical adelmidrol on antigen-induced skin wheal and mast cell behavior in a canine model of allergic dermatitis.

BackgroundAdelmidrol is a semisynthetic derivative of azelaic acid and analogue of the anti-inflammatory compound palmitoylethanolamide (PEA). Based upon its physicochemical properties, adelmidrol is suitable for topical application. The main objective of the present study was to evaluate the efficacy of a topical adelmidrol emulsion on early and late inflammatory responses in hypersensitive dogs. Repeated intradermal injections of Ascaris suum extract were performed in both lateral thoracic areas of six conscious hypersensitive Beagle dogs, topically treated during 8 consecutive days. Adelmidrol (2%) was applied to one side and vehicle to the other. 24 hours after the last antigen challenge, two biopsies (adelmidrol- and vehicle-treated side) were obtained for each dog at the antigen injection site.ResultsA significant reduction in the antigen-induced wheal areas was observed on the 4th and 7th day of adelmidrol treatment. Moreover, cutaneous mast cell numbers were significantly decreased in biopsies obtained after 8 consecutive days of topical adelmidrol treatment.ConclusionsThe results obtained in the present study show that topical treatment with adelmidrol might represent a new therapeutic tool in controlling the early and late allergic inflammatory skin responses in companion animals.

Lesioning noradrenergic neurons of the locus coeruleus in C57Bl/6 mice with unilateral 6-hydroxydopamine injection, to assess molecular, electrophysiological and biochemical changes in noradrenergic signaling

The locus coeruleus (LC) is the major loci of noradrenergic innervation to the forebrain. Due to the extensive central nervous system innervation of the LC noradrenergic system, a reduction in the number of LC neurons could result in significant changes in noradrenergic function in many forebrain regions. LC noradrenergic neurons were lesioned in adult male C57Bl/6 mice with the unilateral administration of 6-hydroxydopamine (6OHDA) (vehicle on the alternate side). Noradrenergic markers were measured 3weeks later to determine the consequence of LC loss in the forebrain. Direct administration of 6OHDA into the LC results in the specific reduction of noradrenergic neurons in the LC (as measured by electrophysiology, immunoreactivity and in situ hybridization), the lateral tegmental neurons and dopaminergic neurons in the substantia nigra (SN) and ventral tegmental region were unaffected. The loss of LC noradrenergic neurons did not result in compensatory changes in the expression of mRNA for norepinephrine (NE)-synthesizing enzymes. The loss of LC noradrenergic neurons is associated with reduced NE tissue concentration and NE transporter (NET) binding sites in the frontal cortex and hippocampus, as well as other forebrain regions such as the amygdala and SN. Adrenoreceptor (AR) binding sites (α1- and α2-AR) were not significantly affected on the 6OHDA-treated side compared to the vehicle-treated side, although there is a reduction of AR binding sites on both the vehicle- and 6OHDA-treated side in specific forebrain regions. These studies indicate that unilateral stereotaxic injection of 6OHDA into mice reduces noradrenergic LC neurons and reduces noradrenergic innervation to many forebrain regions, including the contralateral side.

Resveratrol-Containing Gel for the Treatment of Acne Vulgaris

Acne vulgaris is a complex, chronic, and common skin disorder of pilosebaceous units. The major pathogenic factors involved are ductal hyperkeratinization, obstruction of sebaceous follicles resulting from abnormal keratinization of the infundibular epithelium, stimulation of sebaceous gland secretion by androgens, and microbial colonization of pilosebaceous units by Propionibacterium acnes, which promotes perifollicular inflammation. The aim of the study was to investigate the therapeutic effects of resveratrol, a natural phytoalexin produced by some spermatophytes, such as grapes and other plants, on acneic skin. Resveratrol was incorporated in a carboxymethylcellulose-based gel. The chemical stability of resveratrol after storage at 4°C for 30 days was investigated by high-performance liquid chromatography (HPLC). The resveratrol-containing hydrogel was administered to 20 patients affected by acne vulgaris enrolled in this single-blind study. The resveratrol-containing formulation was applied daily as a solo treatment on the right side of the face for 60 days, while the hydrogel vehicle was applied to the left side of the face as a control. To objectively evaluate the results, a digital photographic database was used to collect images. The number and type of lesions were recorded for each patient, to compare the Global Acne Grading System (GAGS) score before treatment with that obtained at the end of the study. Moreover, with the innovative technique of follicular biopsy, areas of acneic skin were prepared for histopathology. The average area occupied by microcomedones at baseline was compared with that at the end of treatment. HPLC analysis demonstrated that resveratrol, upon incorporation into the gel, did not convert to its cis-isomer when stored at 4°C for 30 days. All patients were satisfied with the active treatment and none experienced adverse effects. Clinical evaluation showed a 53.75% mean reduction in the GAGS score on the resveratrol-treated sides of the face compared with 6.10% on the vehicle-treated sides of the face. These data were supported by histologic analysis, which showed a 66.7% mean reduction in the average area of microcomedones on the resveratrol-treated sides of the face. The comparison with the vehicle-treated side of the face (9.7% reduction) showed a clinically relevant and statistically significant decrease of lesions in areas treated with resveratrol-containing hydrogel. This pilot study showed positive results for resveratrol gel in acne, and should be considered a valid starting point for further testing of the effectiveness of this molecule in different concentrations and formulations and in a larger group of patients.

Efficacy and safety of liposome‐encapsulated 4‐n‐butylresorcinol 0.1% cream for the treatment of melasma: A randomized controlled split‐face trial

Melasma is an acquired pigmentary disorder that most commonly occurs in women of child-bearing age. Melasma is therapeutically challenging, and most commercially available hypopigmenting agents include tyrosinase inhibitors, which regulate the rate-limiting step of melanogenesis. 4-n-Butylresorcinol has received considerable attention as a novel hypopigmenting agent in the last 15 years because it has an inhibitory effect against tyrosinase and tyrosinase-related protein-1. However, the hypopigmenting effect of 4-n-butylresorcinol in human subjects has only been shown in a few studies. Liposome encapsulation is known to improve stabilization and enhance penetration of the product. Therefore, this study was conducted to evaluate the hypopigmenting efficacy and safety of liposome-encapsulated 4-n-butylresorcinol 0.1% cream in patients with melasma. This was a randomized, double-blind, vehicle-controlled and split-face comparison study. Twenty-three patients with a clinical diagnosis of melasma were included. 4-n-Butylresorcinol 0.1% cream or vehicle was applied to each side of the face twice daily for 8 weeks. Clinical and photographic evaluations, Mexameter measurements and assessment of patient satisfaction and side-effects were performed at baseline, 4 and 8 weeks. All subjects completed the study. Mexameter measurements demonstrated that the melanin index of the 4-n-butylresorcinol-treated side showed a significant decrease when compared with the vehicle-treated side after 8 weeks (P = 0.043). No adverse reactions were observed throughout the study. Subjectively, 4-n-butylresorcinol was considered to be efficacious in more than 60% of the patients after 8 weeks of treatment. In conclusion, liposome-encapsulated 4-n-butylresorcinol 0.1% cream was well tolerated and showed significant higher efficacy than vehicle alone for the treatment of melasma.

The Efficacy and Safety of 4-n-butylresorcinol 0.1% Cream for the Treatment of Melasma: A Randomized Controlled Split-face Trial

Melasma is a common acquired symmetrical hypermelanosis that occurs on sun-exposed areas, and it is frequently observed among women. Various treatment modalities have been tried, but none are completely satisfactory. 4-n-butylresorcinol, which is a resorcinol derivative that has an inhibitory effect on both tyrosinase and tyrosinase-related protein-1, was introduced in 1995 and it has received increasing attention as a new hypopigmenting agent. However, the hypopigmenting effect of 4-n-butylresorcinol in human subjects has only been shown in a few studies. The aim of this study was to investigate the hypopigmenting efficacy and safety of 4-n-butylresorcinol 0.1% cream for the treatment of melasma. Twenty patients with melasma were enrolled to this randomized, double-blind, vehicle-controlled, split-face comparative study. The patients were instructed to apply 4-n-butylresorcinol 0.1% cream or vehicle to each side of the face twice daily for 8 weeks. Mexameter measurements were performed along with photography at baseline, 4 weeks and 8 weeks. Adverse events were observed and recorded throughout the study. All the patients completed the study. Mexameter measurements demonstrated that the melanin index of the treated side showed a significant decrease when compared with that of the vehicle-treated side after 4 weeks (p=0.006) and after 8 weeks (p<0.0005). All the adverse reactions were mild and transient. 4-n-butylresorcinol 0.1% cream showed rapid efficacy and it was well tolerated when used for the treatment of melasma.

Effects of vitamin C on dark circles of the lower eyelids: quantitative evaluation using image analysis and echogram

The pathogenesis of dark circles of the lower eyelid (DCLE) has been considered to involve stasis and hyperpigmentation of the eyelids. We have already reported that dermal thickness of lower eyelid skin may represent another factor that affects the appearance of DCLE. The aim of this study was to evaluate the efficacy of vitamin C, which is known to increase collagen, on DCLE through a clinical trial. Fourteen subjects with DCLE applied either 10% sodium ascorbate (ANa) or ascorbic acid glucoside (AG) lotion in split-face fashion (opposite side: vehicle only) for 6 months. Melanin index (MI), erythema index (EI), thickness and echogenicity of the dermis at bilateral lower eyelids was measured during this trial. Change in EI was significantly smaller on the ANa-treated side than on the vehicle-treated side. Dermal thickness tended to be thicker for the ANa-treated side than for the vehicle-treated side, although no significant difference was seen. Both EI and dermal thickness tended to change in parallel manner. On the other hand, no significant differences in changes of EI, MI, and dermal thickness were found between AG- and vehicle-treated sides. ANa may improve DCLE by thickening the eyelid dermis and concealing dark coloration due to congested blood.

A novel treatment option for photoaged skin

DNA damage as a result of ultraviolet (UV) exposure plays an important role in the progression of cutaneous aging. Both folic acid and creatine have been linked to the process of DNA protection and repair. This study aims to investigate the effects of a commercially available folic acid- and creatine-containing formulation to fight the clinical signs of premature skin aging. Both in vitro and in vivo home-in-use studies using a folic acid- and creatine-containing formulation were performed aiming to elucidate the efficacy in terms of improvement of skin regeneration, protection from UV-induced DNA damage (Comet assay), reduction of wrinkle volume, and skin visco-elasticity. Furthermore, clinical evaluation and photography were carried out to determine the improvement of clinically graded parameters after treatment. Cultured full-thickness epidermal skin models supplemented with folic acid and creatine after epithelial perturbation showed an accelerated skin regeneration compared to untreated control models. Similarly, application of a folic acid- and creatine-containing formulation significantly improved epidermal turnover in vivo as evidenced by smaller corneocytes derived from the treated sites relative to the vehicle-treated sides. In addition, topical in vivo application of this formulation significantly protected from UV-induced DNA lesions, increased skin firmness, and reduced wrinkle volume compared to untreated control areas. Expert grading confirmed a significant decrease of fine and coarse wrinkles in the periocular region as well as overall wrinkles, tactile roughness, and laxity. Taken together, these results show that the combination of folic acid and creatine significantly accelerates epidermal skin regeneration in vitro and in vivo. Together with the finding of improved biomechanical skin properties, we conclude that the described topical formulation provides an effective treatment option for (photo)-aged skin.

Time Course of Self-Desensitization of Oral Irritation by Nicotine and Capsaicin

Nicotine contacting mucous membranes elicits irritation that decreases with repeated exposures (self-desensitization). We investigated the time course of nicotine self-desensitization and compared it with that of capsaicin. Nicotine (300 mM, 10 microl) was applied to one-half of the dorsal tongue and vehicle to the other. Following a rest period ranging from 0.5 to 48 h, nicotine (5 microl) was reapplied to each side of the tongue and subjects indicated on which side they experienced stronger irritation and separately rated the intensity of the sensation on each side. After intervals of 0.5, 1, and 24 h, a significant majority of subjects chose the vehicle-treated side as having stronger irritation and assigned significantly higher intensity ratings to that side, indicating self-desensitization. The effect was not present after 48 h. By comparison, 10 parts per million (ppm) (33 microM) capsaicin induced significant self-desensitization at 1 but not 24 h, whereas a higher concentration of capsaicin (100 ppm, 330 microM) induced significant self-desensitization at intervals of 1, 24, and 48 h. These results indicate that initial exposure to nicotine or capsaicin can markedly attenuate irritant sensations elicited by subsequent exposure to these irritants hours to days later.

Protective Effect of Superoxide Dismutase Against Hair Graying in a Mouse Model¶

Oxygen free radicals play a role in the aging process, and the protective effect of various antioxidants has been intensively studied, in particular for cutaneous aging. Besides hereditary factors, free radical-mediated damage to melanocytes of the hair follicle has been considered as a mechanism for aging of the hair. It was the aim of this study to evaluate the role of photosensitization reactions for hair graying and to demonstrate potential protective effects of superoxide dismutase (SOD). Mice with black hair were depilated with the fingertips on a surface of 6 x 2.5 cm on both sides of the dorsum. The right side received five applications of a SOD-containing gel before exposure to psoralen (concentration 0.5 mg/mL) plus UV-A (365 nm, 4 J/cm2). The left side was pretreated in the same way with a gel free of SOD. When the hair started growing again, the SOD-protected side was covered with black hair, whereas the hair on the vehicle-treated side was gray or white in 27 of the 30 animals studied. The 0.01% SOD concentration was as protective as the 0.1% concentration. Heat-inactivated SOD, applied in another five animals, was not protective. Using fluorescent labeling of the SOD with fluorescein isothiocyanate, epifluorescence microscopy and digital imaging processing, we show that SOD applied to the skin surface penetrates through the follicular appendages, as well as through the unbroken stratum corneum. Our findings suggest that superoxide radicals, generated by interaction of UV-A light with the sensitizer, initiated the formation of secondary products with well-known DNA-damaging effects, such as lipid peroxidation products and tumor necrosis factor alpha. SOD prevented the damage to melanocyte DNA by dismutating superoxide. Photosensitization may be another mechanism for hair graying, which can be influenced by antioxidants. Given the large number of exogenous and endogenous sensitizers, this mechanism deserves further study for human hair graying.

Restoration of hair growth in mice with an alopecia areata-like disease using topical anthralin.

Anthralin is a widely used topical anti-psoriatic drug that may have an immunomodulating effect on alopecia areata (AA) as it does in psoriasis. The aims of the present study were to investigate the effects of anthralin on hair growth in balding C3H/HeJ mice affected by an AA-like disease and to study the underlying mechanisms. Affected C3H/HeJ mice were treated daily for 10 weeks on half of the dorsal skin with 0.2% anthralin and the contra-lateral side was treated with the vehicle ointment. The percentage of surface hair coverage and hair density was graded weekly for both sides and hair growth indices were calculated using these two variables. Hair regrowth was observed in 9/14 mice on the treated sides. Four mice displayed near complete replacement of normal density and length hairs. All the vehicle-treated sides showed either no change or continued hair loss. An RNase protection assay (RPA) showed that expression of tumor necrosis factor-alpha (TNF-alpha) and -beta were inhibited by anthralin upon successful treatment. It appears that anthralin may be an effective therapy for C3H/HeJ mice with AA and certain cytokines may be involved in the therapeutic effects of anthralin on restoring hair regrowth in AA-affected C3H/HeJ mice.

Topical Mechlorethamine Restores Autoimmune-Arrested Follicular Activity in Mice with an Alopecia Areata-Like Disease by Targeting Infiltrated Lymphocytes

Alopecia areata is an autoimmune disease targeted at hair follicles with infiltrated T lymphocytes probably playing an important role in the pathogenesis. It was reported in 1985 that mechlorethamine was effective on alopecia areata patients. This has never been confirmed since. The aims of the study were to investigate the effects of mechlorethamine on balding C3H/HeJ mice affected with an alopecia-areata-like disease and to study the underlying mechanisms. Mice were treated on half of the dorsal skin with mechlorethamine and the contralateral side was treated with the vehicle ointment. After 10 wk of mechlorethamine therapy, a full pelage of hair covered the treated side in all the mice and was maintained during the study, whereas the vehicle-treated sides showed either no change or continued hair loss. Immunohistochemistry revealed that infiltrated CD4+ and CD8+ lymphocytes were eliminated from the treated side. In vitro cell viability assay showed that lymphocytes were much more sensitive to the cytotoxic effects of mechlorethamine than skin and hair follicular cells. RNase protection assay and real-time reverse transcription polymerase chain reaction showed that tumor necrosis factor alpha/beta, interleukin-12, and interferon-gamma were inhibited by mechlorethamine upon successful treatment. Our findings support that mechlorethamine restores follicular activity by selectively targeting infiltrated lymphocytes in vivo in alopecia-areata-affected mice.

In Vivo Measurement of Ocular Circulation with the Laser Speckle Method—Development of Apparatus and Application in Ophthalmological Research

central retinal vein was 35.5 +/- 3.2 mm/sec with a correlation coefficient between them of 0.91. In a total of 4 eyes with impending central retinal vein or artery occlusion, measurements by the laser speckle method, and CDI method were carried out. The blood velocities measured by the both methods increased along with the treatment. A good correlation between the CDI results and the laser speckle results indicates validity and clinical potential of the present laser speckle method.

Use of induced cutaneous immediate-type hypersensitivity reactions to evaluate anti-inflammatory effects of triamcinolone topical solution in three dogs.

The anti-inflammatory effect of a triamcinolone topical solution (TTS) was evaluated by use of induced cutaneous immediate-type hypersensitivity reactions in dogs. Healthy dogs (n = 3) were treated on one side of the lateral thorax with TTS, and on the contralateral side with vehicle solution. After 7 days of treatment, serial dilutions of inflammatory stimuli (histamine, compound 48/80, anticanine IgE, substance P, and morphine sulphate) were injected intradermally on both sides. Resulting immediate reactions were subjectively scored, their diameters were measured in millimetres, and microcirculatory blood flow at each site was measured using laser Doppler velocimetry. The magnitude of the differences between TTS and vehicle-treated sides varied with the type of measurement and the stimulus used. With compound 48/80, anti-IgE, substance P, and morphine sulphate-injected sites, for at least one concentration, the reaction scores and sizes were notably less on the TTS-treated sides. Punch skin biopsy specimens were obtained from selected sites 24 h after injection. A pathologist examined stained tissue sections and scored each section as to degree of late-phase dermal cellular infiltrate. Dermal infiltrate scores were generally lower at the TTS-treated sites; the composite score from all TTS-treated sites was 30% lower than that from the vehicle-treated sites. Observations suggest that TTS may be effective in decreasing some aspects of the inflammatory response in canine skin.

Carbon monoxide, a novel neural messenger, does not modulate extracellular glutamate concentration in forebrain ischemia.

We investigated the role of carbon monoxide as a neural modulator of extracellular glutamate concentration in rat hippocampus CA1 in transient forebrain ischemia by using metalloporphyrins, which block the production of carbon monoxide through the inhibition of heme oxygenase (HO) activity. Infusion of 10 and 100 microM zinc protoporphyrin IX, which inhibits nitric oxide synthase activity as well as HO activity, significantly increased glutamate concentration compared with that on the vehicle-treated side. However, infusion of 100 microM tin mesoporphyrin IX, which inhibits only HO activity, did not affect glutamate concentration in ischemia. Our results therefore do not support the hypothesis that carbon monoxide acts as a neural messenger through the modulation of extracellular glutamate concentration in ischemia.

1α, 25-Dihydroxyvitamin D3 (calcitriol) ointment in psoriasis

The therapeutic efficacy and local and systemic safety of 3μg/g calcitriol ointment twice daily was assessed in a randomized, double-blind, vehicle-controlled, left-right study for 6 weeks treating 29 patients with severe chronic psoriatic plaques. The calcitriol treatment appeared to be very effective in improving erythema, induration, scaling and global severity of psoriatic plaques. The difference in clinical efficacy between calcitriol and vehicle ointment was highly significant as early as 1 week after the start of treatment. After 6 weeks, clearance of psoriatic lesions was found in 48% of calcitriol-treated sides and in 7% of vehicle-treated sides. Skin biopsies of calcitriol-treated sides revealed a reduction in epidermal hyperplasia, normalization of the keratinization process and decreased inflammation of the psoriatic skin. Calcitriol ointment did not cause cutaneous or systemic adverse reactions and did not induce disturbances of calcium and phosphorus horneo-stasis. Twice daily 3 μg/g calcitr...

Topical application of nonsteroidal anti-inflammatory drugs prevents vehicle-induced improvement of psoriasis

In a double-blind fashion, we compared the effect of topical application of 1% indomethacin cream or 1% meclofenamate cream with the effect of vehicle therapy alone in thirty patients with psoriasis. After 4 weeks' treatment of bilaterally symmetric psoriatic plaques, the indomethacin-treated sides were worse than the vehicle-treated sides in fourteen of twenty patients (p less than 0.01); the meclofenamate-treated sides were worse than the vehicle-treated sides in seven of ten patients (p less than 0.05). We suspect that the nonsteroidal anti-inflammatory drugs contributed to the maintenance of our patients' psoriasis by altering the arachidonic acid transformation cascade.