tacrolimus and Dermatitis--Irritant

Alternatives to corticosteroids in the treatment of irritant contact dermatitis (ICD) are needed and may include glycerol and topical immunomodulators like tacrolimus. Because the efficacy of different treatments in experimentally induced ICD may vary depending on the irritant applied, we tested the efficacy of four anti-irritant compounds using the two different irritants sodium lauryl sulfate (SLS) and nonanoic acid (NON).. In a randomized, double-blind, controlled trial, healthy volunteers were exposed to 5% SLS and 50% NON (the right and the left forearm, respectively) in a cumulative wash test. Induction of ICD was obtained by three daily washings for 7 days, followed by a maintenance phase with two daily washings for 12 days. Treatment (triamcinolone acetonide, clobetasol propionate, tacrolimus and glycerol ointment) was started at day 7 and applied immediately after washing. Vehicle and no treatment served as the control. Reactions were evaluated clinically and instrumentally.. No treatments were significantly better than the other treatments and controls. There was a tendency toward a dose-dependent response to corticoid treatment, and a trend toward worsened irritancy by tacrolimus on SLS-irritated skin. Explained variance in the experiment by anova revealed a very small effect of treatments compared with an immense and significant subject effect.. No claims of effective anti-irritant properties for any of the ointments can be maintained. Application of the present wash test as a tool for anti-irritant efficacy testing may be complicated by the small observed variance explained by treatment.

Topics: Administration, Topical; Adrenal Cortex Hormones; Adult; Dermatitis, Irritant; Dose-Response Relationship, Drug; Fatty Acids; Female; Forearm; Glycerol; Humans; Immunosuppressive Agents; Irritants; Male; Reproducibility of Results; Sodium Dodecyl Sulfate; Tacrolimus; Water; Young Adult

The skin barrier, located in the stratum corneum, is influenced mainly by the lipid and protein composition of this layer. In eczematous diseases impairment of the skin barrier is thought to be of prime importance. Topical anti-inflammatory drugs and emollients are the most widely used eczema treatments. The aim of this study was to examine the effects of topically applied corticosteroid, tacrolimus and emollient on stratum corneum lipids and barrier parameters. Nineteen healthy volunteers participated in the study. Both forearms of the subjects were divided into four areas, which were treated twice daily for one week with betamethasone, tacrolimus, emollient, or left untreated, respectively. After one week each area was challenged with a 24 h sodium lauryl sulphate patch test. The lipids were collected using the cyanoacrylate method and evaluated by high performance thin layer chromatography. For evaluation of the skin barrier, transepidermal water loss, erythema and electrical capacitance were measured. The ceramide/cholesterol ratio was increased in betamethasone- (p = 0.008) and tacrolimus-treated (p = 0.025) skin compared with emollient-treated skin. No differences in ceramide subgroups were found between treatment regimes. Pretreatment with betamethasone (p = 0.01) or with tacrolimus (p = 0.001) causes a decreased inflammatory response to sodium lauryl sulphate compared with emollient. In conclusion, treatment with betamethasone and tacrolimus has a positive effect on the ceramide/cholesterol ratio and susceptibility to irritant reaction compared with an emollient.

Topics: Administration, Topical; Adolescent; Adrenal Cortex Hormones; Adult; Betamethasone; Ceramides; Cholesterol; Chromatography, High Pressure Liquid; Denmark; Dermatitis, Irritant; Electric Capacitance; Emollients; Erythema; Female; Forearm; Humans; Immunosuppressive Agents; Male; Middle Aged; Skin; Skin Irritancy Tests; Sodium Dodecyl Sulfate; Tacrolimus; Time Factors; Water Loss, Insensible; Young Adult

Pimecrolimus is a calcineurin inhibitor used for the topical treatment of inflammatory skin diseases. We have shown previously that pimecrolimus cream is not effective on intact skin in the ultraviolet erythema test.. To test the anti-inflammatory effect of pimecrolimus cream after damage of the skin barrier by sodium lauryl sulphate (SLS) in a randomised, placebo-controlled, observer-blinded study.. SLS (3% v/v) was applied under occlusion on the back of 36 healthy volunteers for 24 h. Subsequently, the test areas were treated for 24 h with pimecrolimus cream, 1% hydrocortisone in a hydrophilic ointment, and the vehicle alone over three consecutive days. One control area remained untreated. The erythema index and the transepidermal water loss (TEWL) served as readout parameters to assess the SLS-induced skin irritation.. Pimecrolimus cream and 1% hydrocortisone cream significantly reduced the SLS-induced erythema. The two test preparations did not have a significant effect on the TEWL.. After damage to the skin barrier by SLS, pimecrolimus seems to penetrate into the skin as shown by a reduction of the irritation-induced erythma. These data further support the notion that pimecrolimus is selectively effective in the treatment of skin disorders with an impaired function of the epidermal barrier.

Topics: Adolescent; Adult; Analysis of Variance; Back; Dermatitis, Irritant; Dermatologic Agents; Female; Humans; Hydrocortisone; Male; Middle Aged; Ointments; Sodium Dodecyl Sulfate; Surface-Active Agents; Tacrolimus; Treatment Outcome; Water Loss, Insensible

Atopic dermatis (AD) is a chronic disease that often requires long-term treatment. Topical corticosteroids are the usual therapy for patients with AD, but prolonged usage can result in skin atrophy and other side-effects.. In a randomized, double-blind, comparative study, to compare the efficacy and safety of a 6-month treatment period with 0.1% tacrolimus ointment vs. a corticosteroid ointment regimen in adults with moderate to severe AD.. Treatment was applied twice daily for a maximum of 6 months. Patients in the tacrolimus treatment group (n = 487) applied 0.1% tacrolimus ointment to all affected areas over the whole body. The patients treated with the corticosteroid regimen (n = 485) applied 0.1% hydrocortisone butyrate ointment to affected areas on the trunk and extremities and 1% hydrocortisone acetate ointment to affected areas on the face and neck. The study primary endpoint was the response rate, i.e. the proportion of patients with at least 60% improvement in the modified Eczema Area and Severity Index (mEASI) between baseline and month 3.. By month 3, more patients in the 0.1% tacrolimus group responded to treatment (72.6% vs. 52.3% in the corticosteroid group, P < 0.001). The patients treated with 0.1% tacrolimus also showed greater improvement in mEASI, EASI, affected body surface area and physician and patient assessments of global response. Patients applying 0.1% tacrolimus ointment experienced more skin burning (52.4% vs. 13.8% in the corticosteroid group; P < 0.001). In most patients, skin burning was mild to moderate in severity and decreased rapidly after the first week of treatment. There was no increase in the incidence of infections or malignancies over time in either treatment group.. Long-term treatment with 0.1% tacrolimus ointment is significantly more efficacious than a corticosteroid ointment regimen in adults with moderate to severe AD.

Topics: Adult; Chi-Square Distribution; Dermatitis, Atopic; Dermatitis, Irritant; Double-Blind Method; Drug Administration Schedule; Female; Glucocorticoids; Herpes Simplex; Humans; Hydrocortisone; Immunosuppressive Agents; Male; Ointments; Sample Size; Statistics, Nonparametric; Tacrolimus; Time Factors; Treatment Outcome

To evaluate pimecrolimus cream 1% and tacrolimus ointment 0.03% in pediatric patients with moderate atopic dermatitis (AD).. 141 patients (aged 2-17 years) were randomized to treatment with pimecrolimus cream 1% (n=71) or tacrolimus ointment 0.03% (n=70) twice daily for 6 weeks.. At day 4, local, application-site reactions were less common and of shorter duration with pimecrolimus than with tacrolimus. Incidence of erythema/irritation was 8% (6/71) with pimecrolimus compared with 19% (13/70) with tacrolimus (P=.039). Fewer patients receiving pimecrolimus (0%, 0/6) experienced erythema/irritation lasting >30 minutes, compared with those receiving tacrolimus (85%, 11/13; P <.001). Fewer patients reported itching with pimecrolimus (8%; 6/71) than with tacrolimus (20%; 14/70; P=.073). Incidence of warmth, stinging, and burning was similar in both groups; however, reactions lasting >30 minutes were fewer with pimecrolimus (0%, 0/14) than with tacrolimus (67%, 8/12; P <.001). More patients receiving pimecrolimus rated ease of application as 'excellent' or 'very good', compared with tacrolimus (76% vs 59%, respectively; P <.020). Efficacy was similar in both groups at day 43. Both treatments were generally well tolerated with no unexpected adverse events.. Pimecrolimus cream 1% had better formulation attributes and local tolerability than tacrolimus ointment 0.03% while providing similar efficacy and overall safety in pediatric patients with moderate AD.

Topics: Adolescent; Child; Child, Preschool; Dermatitis, Atopic; Dermatitis, Irritant; Dermatologic Agents; Drug Administration Schedule; Drug Combinations; Erythema; Female; Humans; Male; Ointments; Patient Satisfaction; Pruritus; Tacrolimus

Topics: Adolescent; Bandages, Hydrocolloid; Dermatitis, Irritant; Humans; Immunosuppressive Agents; Male; Occlusive Dressings; Skin Pigmentation; Tacrolimus; Vitiligo

Irritant dermatitis of the face and neck is particularly prevalent in women > or = 30 years old, who typically present with periocular cutaneous symptoms. Current therapies are limited, indicating a need for rapid, effective alternatives. Pimecrolimus cream 1%, a nonsteroid, cell-selective inhibitor of inflammatory-cytokine release, is effective in the treatment of inflammatory skin diseases, such as chronic irritant dermatitis of the hands, and thus offers a potential therapeutic option for this indication. This study reports on the safety and efficacy of pimecrolimus treatment in patients with irritant periocular dermatitis, extending to the face and neck in some patients.. Twenty-seven patients with periocular irritant dermatitis (extending onto the face and neck in eight) were treated twice daily with pimecrolimus cream 1% for 7 d, followed by once-daily application for a further 7 d. Erythema, swelling, and pruritus were assessed at baseline, weeks 1-4 using a 4-point clinical score (0, absent; 1, mild; 2, moderate; and 3, severe).. All patients showed marked improvement within 2-3 d of treatment with disease clearance in 23 of 27 patients within 14 d. In the remaining four patients, mild relapse occurred at weeks 3-4, but improvement was observed following a further 10-d treatment. Side-effects were mild and transient.. Pimecrolimus cream 1% provides a new potential option for treatment of irritant dermatitis of the periocular region, head and neck. Further double-blind, controlled studies are required to confirm the efficacy and safety of pimecrolimus cream 1% for this indication.

Topics: Administration, Topical; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Biopsy, Needle; Dermatitis, Irritant; Dose-Response Relationship, Drug; Drug Administration Schedule; Facial Dermatoses; Female; Follow-Up Studies; Humans; Immunohistochemistry; Male; Middle Aged; Neck; Ointments; Patient Satisfaction; Prospective Studies; Tacrolimus; Treatment Outcome

Topics: Case-Control Studies; Catechols; Dermatitis, Allergic Contact; Dermatitis, Contact; Dermatitis, Irritant; Dermatitis, Toxicodendron; Humans; Immunosuppressive Agents; Ointments; Pilot Projects; Single-Blind Method; Sodium Dodecyl Sulfate; Surface-Active Agents; Tacrolimus; Toxicodendron

Tacrolimus (FK 506) is a macrolide discovered in 1984 as a metabolic product of Streptomyces tsukabaensis. It has been used successfully in treating atopic dermatitis, allergic contact dermatitis, lichen planus mucosae and pyoderma gangrenosum. In the present study, we evaluated the anti-inflammatory activity of FK 506 in 2 human skin inflammation models. FK 506 as Protopic(R) cream was tested (i) in a 4-day repetitive irritation test with 2 x daily application of sodium lauryl sulphate (SLS), and (ii) in a UVB erythema model. The effect was evaluated visually and quantified by non-invasive bioengineering methods, namely chromametry and tewametry (TEWL). When FK 506 was applied 30 min after SLS irritation, an increased inflammation in comparison to controls was observed with all 3 methods, with only the TEWL data reaching statistical significance. 1 x daily application of FK 506 for 5 days, starting at the end of the 4-day irritation period, was without any effect. Similarly, no effect of FK 506 was seen in the UVB model. In conclusion, FK 506 was shown to enhance experimentally induced irritant contact dermatitis and not to accelerate healing of irritant contact dermatitis and UVB erythema.

Topics: Adult; Dermatitis, Irritant; Female; Humans; Immunosuppressive Agents; Male; Statistics, Nonparametric; Tacrolimus; Water Loss, Insensible

Topical FK506 has recently been shown to have an anti-inflammatory effect in vivo in humans. In this study its effects in contact dermatitis were studied in the guinea pig model. Topical FK506 suppressed both irritant and allergic patch-test reactions. The most prominent suppressive effect was seen when skin sites were pretreated with FK506. Topical FK506 did not impair the induction of contact allergy as assessed by challenges, although it suppressed local lymph node cell accumulation during contact allergy induction. Topical FK506 may hold promise as a treatment for skin disorders that respond to oral FK506 or cyclosporin A.

Topics: Administration, Topical; Animals; Cell Division; Cyclosporine; Dermatitis, Allergic Contact; Dermatitis, Irritant; Guinea Pigs; Lymph Nodes; Tacrolimus