calcipotriene and Dermatitis--Irritant

Side effects of topical corticosteroids limit their long-term use. Calcipotriene/calcipotriol (Dovonex/Daivonex) ointment is not associated with any of the side effects of corticosteroids and has been shown to thicken the skin in contrast to the cutaneous atrophy caused by topical steroids.. We attempted to determine whether the addition of calcipotriene to a regimen of topical steroids results in an improved benefit/risk ratio.. Published and unpublished data on combination regimens were reviewed.. In long-term regimens for psoriasis, substituting calcipotriene for topical corticosteroids may result in a steroid-sparing effect. Conversely, topical corticosteroids may suppress the development of local cutaneous irritation that occurs in patients treated with calcipotriene ointment.. Psoriasis regimens combining calcipotriene ointment with superpotent steroids such as halobetasol ointment can result in greater improvement and fewer side effects.

Topics: Administration, Cutaneous; Anti-Inflammatory Agents; Atrophy; Calcitriol; Clobetasol; Dermatitis, Irritant; Dermatologic Agents; Drug Combinations; Drug Interactions; Glucocorticoids; Humans; Irritants; Longitudinal Studies; Ointments; Psoriasis; Risk; Skin

Calcitriol and calcipotriol, two vitamin D derivatives, are available for topical treatment of psoriasis and have been shown to be effective.. To compare the efficacy and safety of calcitriol 3 microg/g and calcipotriol 50 microg/g.. This was a multicentre, randomized, investigator-masked, and parallel comparison in subjects with mild to moderate chronic plaque-type psoriasis receiving either calcitriol or calcipotriol ointment twice daily for 12 weeks. Efficacy evaluations comprised global improvement (on a 4-point scale from 0: no change or worse, to 3: clear or almost clear) assessed by the investigator and by the subject. Efficacy further included the 'dermatological sum score' at each study visit. Safety evaluations included adverse event reporting, cutaneous safety assessed by the investigator and cutaneous discomfort assessment by the subject (both on a 5-point scale from 0: none, to 4: very severe).. A total of 250 subjects of both gender were recruited. At week 12, the LSmean score of global improvement rated by the investigator was 2.27 for calcitriol and 2.22 for calcipotriol. This difference was not statistically significant, with calcitriol demonstrating to be non-inferior to calcipotriol for global improvement. This same parameter was scored by the subject, with a mean of 2.12 for calcitriol and 2.09 for calcipotriol. The percentage of patients with at least marked improvement tended to be in favour of calcitriol (95.7% vs. 85% for calcipotriol). However, differences were not statistically significant. The mean worst score for the cutaneous safety assessment was higher in the calcipotriol group (0.3 vs. 0.1 and 0.4 vs. 0.2, by the investigator and the patient, respectively). These differences were statistically significant in favour of a better safety profile for calcitriol (P=0.0035). Fourteen dermatological and treatment-related adverse events were reported with calcipotriol vs. only five with calcitriol for a total of 22 adverse events reported throughout the study.. Calcitriol administered twice daily over a 12-week treatment period demonstrated similar efficacy to calcipotriol, while showing a significantly better safety profile.

Topics: Administration, Cutaneous; Adolescent; Adult; Body Surface Area; Calcitriol; Calcium Channel Agonists; Chronic Disease; Dermatitis, Irritant; Dermatologic Agents; Drug Eruptions; Female; Follow-Up Studies; Humans; Male; Middle Aged; Ointments; Psoriasis; Safety; Single-Blind Method; Treatment Outcome

Hydrocolloid (HCD) dressings enhance the efficacy of topical corticosteroids.. We wanted to evaluate the effect of calcipotriol ointment under an HCD dressing in the treatment of psoriatic plaques.. In 9 psoriatic patients, we cleared one plaque using this approach and took biopsies at start, clearance and relapse. Clinical and immunohistochemical validation was assessed.. After an average treatment of 3.6 weeks, each lesion had cleared (apart from some residual erythema). The average remission period was 8 weeks. During this treatment, the number of cycling epidermal cells (Ki-67-positive nuclei) and the expression of keratin 14 and keratin 16 had decreased substantially. In biopsies taken from the skin immediately adjacent to the relapsing lesion, these markers remained reduced which indicated the prolonged effect of calcipotriol on epidermal differentiation.. It is speculated that combination therapy of calcipotriol with treatments with a different mode of action such as photo(chemo)therapy, corticosteroids and cyclosporine might be worthwhile.

Topics: Adult; Aged; Antigens, Nuclear; Apoptosis; Calcitriol; Colloids; Dermatitis, Irritant; Dermatologic Agents; ErbB Receptors; Female; Humans; Immunohistochemistry; In Situ Nick-End Labeling; Keratin-14; Keratins; Ki-67 Antigen; Male; Middle Aged; Nuclear Proteins; Occlusive Dressings; Ointments; Patient Dropouts; Psoriasis; Skin; Treatment Outcome

Eighteen patients with symmetric plaque-type psoriasis were recruited for an open, controlled, bilateral half-body comparison study to evaluate the efficacy of calcipotriol/tar/UVB vs. anthralin/tar/UVB in a day care treatment setting. No patient had been on systemic antipsoriatic agents for at least 3 months prior to enrolment. One half-body was arbitrarily assigned to treatment with gradually increasing concentrations of anthralin as tolerated. The other half-body received calcipotriol ointment twice daily. Both sides received UVB and additional coal tar distillate in accordance with our standard day care regimen. Patients who were admitted to the day care program attended the clinic for UVB, anthralin, and calcipotriol on weekdays for two consecutive weeks. Anthralin was applied to psoriatic plaques on one side in the following fashion: anthralin 0.1% with salicylic acid 3% in zinc oxide paste on days 1 and 2; anthralin 0.2% with salicylic acid 3% in zinc oxide paste on days 3-5; anthralin 1% with salicylic acid 3% in hydrophilic petrolatum for 60 min on days 8-10 to thicker lesions; and anthralin 2% with salicylic acid 3% in hydrophilic petrolatum for 60 min on day 11 to thicker lesions. On the contralateral side, calcipotriol ointment 0.05 microgram/mL (Leo Pharmaceuticals, Ajax, Ontario) was applied to lesions twice daily. No anthralin or calcipotriol was applied on weekends. All patients applied coal tar oil 50% (Doak Oil Forte, Trans CanaDerm, St-Laurent, Québec, equivalent to 5% coal tar distillate) with salicylic acid 5% in hydrophilic petrolatum to their lesions at home in the evenings and on weekends. UVB (FSX72T12 lamps, National Biologic Corporation, Twinsburg, Ohio) was administered twice daily on weekdays in increasing doses as tolerated (to erythema) prior to the application of the topical medications. No trial medications were applied to the face, scalp, or genital regions. For clinical evaluation, the standard Psoriasis Activity and Severity Index (PASI) score was modified by splitting the score for area under 10%; the modified score (mPASI) for an area of coverage of 1%-4% was 0.5 and for an area of 5%-9% was 1. The head and neck area was excluded from the analysis since neither anthralin nor calcipotriol was used at these sites. Each half-body was considered to represent 100% in the area score determination. The maximum modified score for each side was 64.8 (vs. 72 in the standard PASI scoring system). Clinical evaluations were comple

Topics: Administration, Topical; Adolescent; Adult; Aged; Ambulatory Care Facilities; Anthralin; Anti-Inflammatory Agents; Body Surface Area; Calcitriol; Chronic Disease; Day Care, Medical; Dermatitis, Irritant; Dermatologic Agents; Dose-Response Relationship, Drug; Drug Therapy, Combination; Erythema; Humans; Middle Aged; Psoriasis; PUVA Therapy; Severity of Illness Index; Time Factors; Treatment Outcome

Calcipotriol is widely used in the treatment of psoriasis. Adverse lesional and perilesional irritation may occur. Allergy may occasionally be suspected. Allergy patch testing with calcipotriol may be difficult or impossible because calcipotriol is a local irritant. The aim of the present study was to assess the calcipotriol dose-irritation relationship, and establish a non-irritant patch test concentration for calcipotriol allergy patch testing. The study was a prospective, double-blind, randomized, dose titration evaluation in 180 healthy volunteers never previously exposed to calcipotriol. All individuals were patch tested with a calcipotriol dilution series (range 0.016-250 micrograms/mL). Clinical reading of test sites and measurement of erythema using a Minolta ChromaMeter were performed on days 2 and 3. Laser Doppler perfusion imaging of cutaneous blood flow was performed on day 3. Doubtful reactions (score 1/2) and weak reactions (score 1) were frequent and observed even at low dose exposure. Reactions declined in strength between the readings on day 2 and day 3. Only score 2 reactions with moderate erythema and some infiltration showed a threshold of no irritation. This threshold was confirmed by colorimetry and flowmetry. Cases of suspected allergy to calcipotriol may to avoid irritant reaction and false positive readings, be patch tested with calcipotriol 2 micrograms/mL citrate-buffered isopropanol solution applied under occlusion for 48 h using small Finn Chambers. Score 1/2 and 1 reactions are likely to reflect irritation. A positive test should be repeated after a minimum period of 3 months to ensure its consistency over time. A repeated open application test may be indicated.

Topics: Adolescent; Adult; Aged; Calcitriol; Dermatitis, Irritant; Dermatologic Agents; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Prospective Studies; Skin; Skin Tests

Although potent, topical corticosteroids offer effective and rapid healing of psoriatic lesions. Their long term use is limited because of the risk of side effects. Calcipotriol is safe for long-term treatment, but its initial efficacy is lower than with topical corticosteroids.. To investigate whether 2 weeks of treatment with clobetasol propionate 0.05% ointment bd followed by 4 weeks of treatment with calcipotriol 50 microg/g bd would offer therapeutic advantages over 6 weeks of continuous treatment with calcipotriol.. Forty-nine patients with moderate to severe plaque psoriasis were recruited from five centres in Norway. In a randomised, double-blind, right- versus left-side comparison, ointments were applied to two symmetrically-located areas.. Two weeks of treatment with clobetasol propionate produced a significantly greater decrease in total symptom score (combined scores of erythema, induration and scaling) than calcipotriol treatment (P < 0.0001). This improvement on the clobetasol propionate-treated side of the body was maintained throughout a subsequent 4-week treatment period when calcipotriol was applied to both sides of the body (P < 0.0001). The superiority of the clobetasol propionate followed by calcipotriol treatment was maintained during a 4-week, treatment-free, observation period. Treatments were well tolerated with no rebound effect.. Clobetasol propionate ointment bd for 2 weeks followed by treatment with calcipotriol ointment bd for 4 weeks was superior to calcipotriol ointment alone in the treatment of plaque psoriasis.

Topics: Administration, Topical; Adolescent; Adult; Aged; Anti-Inflammatory Agents; Calcitriol; Clobetasol; Dermatitis, Irritant; Dermatologic Agents; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; Glucocorticoids; Humans; Male; Middle Aged; Patient Satisfaction; Physician's Role; Program Evaluation; Pruritus; Psoriasis; Purpura; Severity of Illness Index; Skin; Treatment Outcome

Topics: Administration, Topical; Calcitriol; Combined Modality Therapy; Dermatitis, Irritant; Dermatologic Agents; Double-Blind Method; Drug Administration Schedule; Follow-Up Studies; Humans; Ointments; Prognosis; Psoriasis; Risk Assessment; Ultraviolet Therapy

Reports of purported sensitization reactions to widely used prescription dermatologicals have raised questions concerning the clinical significance of these reports. The current study was designed to compare irritant and sensitization potentials of such marketed products and to evaluate the risks involved in their usage.. One hundred and eight healthy adult volunteers were evaluated for primary irritation and hypersensitivity following application under a double-blind paradigm of eight leading prescription dermatologic products and the vehicle cream of one product according to an intensified version of the Shelanski and Shelanski "Repeated Insult Patch Test.". No clinically significant irritant or sensitization reactions were associated with applications of topical formulations containing clobetasol propionate, doxepin hydrochloride, metronidazole, mupirocin, oxiconazole nitrate, and terbinafine hydrochloride. The doxepin hydrochloride cream vehicle was also found to be nonirritating and nonsensitizing. Both calcipotriene and ketoconazole were moderate irritants and possible sensitization reactions were also associated with ketoconazole.. Although every topically applied chemical has the potential to cause an adverse response in some individuals, the data obtained in this study for eight commercially available prescription dermatologic products indicate that most are quite safe and have very low risks of clinically significant irritation or sensitization.

Topics: Adult; Aged; Aged, 80 and over; Allergens; Antifungal Agents; Calcitriol; Clobetasol; Dermatitis, Irritant; Dermatologic Agents; Double-Blind Method; Doxepin; Drug Prescriptions; Female; Humans; Hypersensitivity; Imidazoles; Irritants; Ketoconazole; Male; Metronidazole; Middle Aged; Mupirocin; Naphthalenes; Patch Tests; Pharmaceutical Vehicles; Placebos; Risk Factors; Skin; Terbinafine

The irritant potential of calcipotriol, 1 alpha,24-dihydroxyvitamin D3 (tacalcitol) and 1 alpha,25-dihydroxy-vitamin D3 (calcitriol) was compared in a hairless guinea pig model, Randomized, occlusive patch testing for 2 days was used. Each group of 8 animals was tested simultaneously with the 3 substances and a placebo vehicle. 3 dose levels i.e. 500 micrograms/ml, 50 micrograms/ml and 5 micrograms/ml were used. Test sites were evaluated at day 2 (2 h after removal of the patches) and again at day 3. Evaluation was blinded and based on a multiple parameter assessment of skin irritancy, comparing clinical scoring, skin perfusion using high resolution laser Doppler image scanning, skin colour (a*, Minolta ChromaMeter) and skin thickening (20 MHz ultrasound) indicating oedema. Skin biopsies were taken for histological preparation and assessment of epidermal hyperplasia. No difference was observed between the irritant potential for calcipotriol, tacalcitol and calcitriol based on clinical scoring as well as objective non-invasive measuring techniques. All 3 substances showed a dose-dependent and equal increase in clinical irritation score, cutaneous blood flow, skin colour and epidermal hyperplasia. The cutaneous inflammatory reaction was dominated by vasodilation and increased cutaneous perfusion. Oedema formation was only seen at the highest dosages tested. Skin barrier damage was not induced as TEWL remained unaffected. The hairless guinea pig appears a valid model to test irritancy of topical D-vitamins since the same profile of irritancy was previously established in humans for 2 of the compounds tested, calcitriol and calcipotriol.

Topics: Administration, Topical; Analysis of Variance; Animals; Calcitriol; Dermatitis, Irritant; Dermatologic Agents; Dihydroxycholecalciferols; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Guinea Pigs; Laser-Doppler Flowmetry; Patch Tests; Random Allocation; Reference Values; Skin; Ultrasonography

Exposure of the skin to sodium dodecyl sulfate (SDS) leads to disruption of barrier and skin irritation. We used repetitive short exposure to a low molarity SDS solution as an in vivo model to mimic the development of irritant contact dermatitis. In this model, we studied clinical (erythema), functional (transepidermal water loss(TEWL)) and cell biological changes. 24 healthy volunteers were patch tested with SDS (0.2%) for 4 h a day for 5 consecutive days. After removal of the patches, the exposed sites were treated 1 X daily either with a topical corticosteroid (triamcinolon acetonide cream 0.05%), a retinoid (tretinoin cream 0.025%), or a vitamin D3 derivative (calcipotriol ointment 50 micrograms/g). Irritant reactions were assessed by erythema scoring and measurement of barrier function with TEWL up to 14 days after the first challenge. Skin biopsies were taken for cell biological changes at day 4. Vehicle-treated sites served as controls. Repetitive exposure of human skin to SDS resulted in a gradual increase in erythema scoring and TEWL associated with the upregulation of proliferative cells as measured by the expression of Ki-67-antigen and of differentiation markers, visualized by increased expression of involucrin and epidermal-fatty-acid binding protein (E-FABP). Skin irritation as assessed by erythema scoring and TEWL was not significantly suppressed by triamcinolone cream. However, a significant reduction of the number of cycling keratinocytes and a decrease in involucrin positive cell layers was observed in this group. Neither treatment with calcipotriol ointment nor with tretinoin cream induced improvement of skin irritation as judged by visual scoring and TEWL. In contrast to steroid treatment, no significant effect of calcipotriol ointment or tretinoin cream treatment was observed with regard to the number of cycling cells and differentiation markers. Further studies are needed to assess whether treatment with topical corticosteroids is an effective modality in skin irritation and irritant contact dermatitis.

Topics: Administration, Topical; Adult; Anti-Inflammatory Agents; Biopsy, Needle; Calcitriol; Cell Division; Dermatitis, Irritant; Dermatologic Agents; Female; Glucocorticoids; Humans; Irritants; Keratolytic Agents; Male; Middle Aged; Ointments; Skin; Sodium Dodecyl Sulfate; Surface-Active Agents; Tretinoin; Triamcinolone Acetonide; Water Loss, Insensible

Topics: Administration, Topical; Aged; Calcitriol; Dermatitis, Irritant; Dermatologic Agents; Drug Eruptions; Humans; Male; Psoriasis; Ultraviolet Therapy

Topics: Administration, Cutaneous; Adult; Calcitriol; Dermatitis, Irritant; Dermatologic Agents; Female; Humans; Irritants; Male; Middle Aged; Occlusive Dressings; Patch Tests; Skin