tacrolimus and Dermatitis

Topical steroid-sparing agents (SSA), such as tacrolimus, pimecrolimus, and crisaborole, represent an important therapeutic option in the treatment of inflammatory dermatoses such as atopic dermatitis. While these agents lack the common side effects associated with topical corticosteroids, they all share application site pain as an important adverse effect.. Based on the available evidence and our experience, we suggest the following 7 practical strategies for decreasing the pain associated with SSA use. (1) Use a topical corticosteroid for a few days to reduce inflammation before starting the SSA treatment. (2) Use SSAs strategically. (3) Apply moisturizer before applying SSAs. (4) Store moisturizers in the refrigerator. (5) Ask the patient to apply the SSA on a small test area before broader application. (6) Apply the SSA on dry rather than on damp skin. (7) Consider using aspirin when appropriate for the patient.

Topics: Administration, Cutaneous; Adrenal Cortex Hormones; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Boron Compounds; Dermatitis; Dermatologic Agents; Humans; Pain; Skin Cream; Tacrolimus

FK506-binding protein 12 (FKBP12) is an endogenous protein with peptidyl-prolyl isomerase (PPIase) activity. Natural compounds FK506, rapamycin and ascomycin, are FKBP12 ligands used for treating organ transplant rejection and other diseases. Small ligands that also interact with FKBP12 are designed and synthetized based on the natural ligands. This suggests that targeting FKBP12 has potential in the treatment of multiple diseases.. This article describes the features of FKBP12 and the therapeutic actions of agents targeting FKBP12 reported in the published articles and patents.. The multiple functions of FKBP12 cause side effects during therapy with FKBP12 ligands. The interaction between FKBP12 and other receptors should be explored to guide their use as drugs in the clinical setting. In addition, the neuroprotective mechanism of small-molecule FKBP12 ligands needs further study in order to develop them as novel drugs for treating neurological disorders.

Topics: Animals; Antineoplastic Agents; Dermatitis; Humans; Immunosuppressive Agents; Ligands; Neuroprotective Agents; Patents as Topic; Sirolimus; Small Molecule Libraries; Tacrolimus; Tacrolimus Binding Protein 1A; Vision Disorders

Topical tacrolimus is an immunosuppressant that acts through the inhibition of calcineurin and thus of the T cells. This causes a decrease in the production of interleukins, the granulocyte colony stimulating factor, alpha interferon and tumor necrosis factor. Although the use of topical tacrolimus is only indicated for the treatment of moderate or severe atopic dermatitis, its immunosuppressant effect and fewer side effects regarding topical corticosteroids have lead to the increase of its use in other types of inflammatory skin diseases. The purpose of this article is to review the use of tacrolimus in this group of diseases other than atopic dermatitis, this use not being authorized within the data sheet of the drug.

Topics: Adult; Autoimmune Diseases; Child; Clinical Trials as Topic; Dermatitis; Graft vs Host Disease; Humans; Immunosuppressive Agents; Lichenoid Eruptions; Multicenter Studies as Topic; Off-Label Use; Pruritus; Psoriasis; Pyoderma Gangrenosum; Skin Diseases; Tacrolimus; Uremia; Vitiligo

Pimecrolimus is an ascomycin macrolactam derivative with anti-inflammatory and immunomodulatory activity that belongs to the class of calcineurin inhibitors. It was developed after the attempt to discover alternatives to corticosteroids for the treatment of inflammatory skin diseases. Although pimecrolimus has been only approved for the treatment of atopic dermatitis, many clinical reports have proved its efficacy in a variety of skin conditions. However, corticosteroids remain the treatment of choice in inflammatory skin diseases. The possibility that pimecrolimus deserves a greater role in the long-term treatment of skin diseases is discussed herein by reviewing the published clinical studies that compare pimecrolimus and corticosteroids.

Topics: Administration, Cutaneous; Adrenal Cortex Hormones; Anti-Inflammatory Agents; Dermatitis; Dermatologic Agents; Dermatology; Drug Administration Schedule; Drug Labeling; Humans; Practice Guidelines as Topic; Tacrolimus; Treatment Outcome

Pimecrolimus is a calcineurin inhibitor developed for the topical therapy of inflammatory skin diseases, particularly atopic dermatitis (AD). Pimecrolimus selectively targets T cells and mast cells. Pimecrolimus inhibits T-cell proliferation, as well as production and release of interleukin-2 (IL-2), IL-4, interferon-gamma and tumour necrosis factor-alpha. Moreover, pimecrolimus inhibits mast cell degranulation. In contrast to tacrolimus, pimecrolimus has no effects on the differentiation, maturation and functions of dendritic cells. In contrast to corticosteroids, pimecrolimus does not affect endothelial cells and fibroblasts and does not induce skin atrophy. Given the low capacity of pimecrolimus to permeate through the skin, it has a very low risk of systemic exposure and subsequent systemic side-effects. In different randomised controlled trials, topical pimecrolimus as cream 1% (Elidel) has been shown to be effective, well tolerated and safe in both adults and children with mild to moderate AD. In addition, pimecrolimus has been successfully used in inflammatory skin diseases other than AD, including seborrheic dermatitis, intertriginous psoriasis, lichen planus and cutaneous lupus erythematosus.

Topics: Dermatitis; Dermatitis, Atopic; Hand Dermatoses; Humans; Immunosuppressive Agents; Ointments; Psoriasis; Skin Absorption; Tacrolimus

Topics: Cellulitis; Dermatitis; Dermatomyositis; Facial Dermatoses; Humans; Immunosuppressive Agents; Impetigo; Lupus Erythematosus, Discoid; Ointments; Psoriasis; Rosacea; Tacrolimus

Chronic inflammatory skin disorders, such as atopic eczema, can cause considerable impairment of life quality. Their treatment is mainly driven by systemic or topical glucocorticosteroids which have the risk of many side effects. Recently, immunosuppressive macrolides which act via the inhibition of cytokine expression in T-lymphocytes have been shown to exert good therapeutic potency in inflammatory skin disorders. Cyclosporin, widely used in transplantation medicine, is also effective in psoriasis and atopic eczema but is not suitable for topical treatment. Tacrolimus (FK506) has been found to be 10-100 times more potent than cyclosporin and to penetrate skin much better due to a lower molecular weight. Initial clinical investigations have shown efficacy of topical tacrolimus in patients with atopic eczema. Large multi-centre studies have proven that long-term therapy with 0.03% and 0.1% tacrolimus ointment reveals effectiveness and safety both in adults and in children with severe atopic eczema. A burning sensation at the site of application is the most frequently observed local side effect. Relevant systemic adverse events were not detected. In Japan and the US, the drug is already licensed for the treatment of atopic eczema. The European admission for the pharmaceutical market is expected in the year 2002. Tacrolimus represents a milestone in topical therapy of inflammatory skin disorders which has so far been dominated by corticosteroid formulations and gives hope for the development of further topical immunosuppressive agents of its class in the future.

Topics: Administration, Oral; Administration, Topical; Adult; Child; Chronic Disease; Clinical Trials as Topic; Contraindications; Dermatitis; Drug Interactions; Drug Tolerance; Eczema; Humans; Immunosuppressive Agents; Molecular Structure; Tacrolimus

Drug therapy for the major inflammatory skin diseases, which include atopic dermatitis, psoriasis and allergic contact dermatitis, is often inadequate due to poor efficacy, toxicity, or both. Much research has focused on the macrolactam T cell inhibitors as a promising new class of agents for immunotherapy, and medicinal chemistry efforts to design novel ascomycin analogs have produced clinically promising agents. A synthetic program to modify the ascomycin nucleus to alter its physicochemical properties and promote systemic clearance is described. A biologic screening strategy to identify analogs with reduced systemic activity and rapid pharmacokinetic elimination led to identification of the clinical candidate, ABT-281. A swine contact hypersensitivity model was used as a stringent indicator of skin penetration as human doses of topical corticosteroids produced inhibition only in the 50% range and ED50 values were 100-fold less potent than in rat. Also, cyclosporine was confirmed to be topically inactive in swine, as seen in human. ABT-281 had topical potency equal to tacrolimus (FK506) despite a severalfold lower potency for inhibiting swine T cells in vitro, consistent with superior skin penetration. ABT-281 was found to have a shorter duration of action after i.v. dosing in monkeys using an ex vivo whole blood IL-2 production assay. Systemic potency was reduced by 30-fold or more in rat popliteal lymph node hyperplasia and contact hypersensitivity assays. Following i.v. or i.p. administration in the swine contact hypersensitivity model, ABT-281 was 19- and 61-fold less potent, respectively, than FK506. Pharmacokinetic studies showed that ABT-281 had a shorter half life and higher rate of clearance than FK506 in all three species. The potent topical activity and reduced systemic exposure of ABT-281 may thus provide both efficacy and a greater margin of safety for topical therapy of skin diseases.

Topics: Administration, Topical; Animals; Anti-Inflammatory Agents; Cyclosporine; Dermatitis; Drug Design; Humans; Immunosuppressive Agents; Inflammation; Interleukin-2; Skin Diseases; T-Lymphocytes; Tacrolimus

The immunosuppressive macrolide drug FK506 is currently gaining increasing importance in dermatopharmacology. Here, Gunter Michel and colleagues summarize the current state of research into the molecular mechanisms responsible for the functional modulation of cell types other than T cells, particularly epidermal cells, by this drug.

Topics: Animals; Dermatitis; Humans; Immunosuppressive Agents; Skin; T-Lymphocytes; Tacrolimus

Cyclosporine A (CsA) is an immunosuppressant that is efficacious in several inflammatory skin disorders. Its use is, however, limited due to systemic side-effects. Topical forms of CsA have been tried but they do not seem to be effective presumably due to insufficient penetration to skin. Tacrolimus (FK506) is another immunosuppressant that has almost similar effects on the cellular level as CsA. FK506 is 10-100 times more potent than CsA and it has lower molecular weight. Recent studies suggest that topical FK506 penetrates human skin in amounts exceeding those of topical CsA. Topical FK506 also seems to suppress skin inflammation in man. These findings prompt for further clinical studies of efficacy and safety of topical FK506.

Topics: Administration, Cutaneous; Administration, Oral; Animals; Cell Division; Clinical Trials as Topic; Cyclosporine; Dermatitis; Guinea Pigs; Humans; Keratinocytes; Lymphocyte Activation; Male; Skin Absorption; T-Lymphocytes; Tacrolimus

To investigate the antipruritic mechanisms of pimecrolimus cream for women facial dermatitis.. Topical pimecrolimus cream 1% was applied in 52 women patients with facial dermatitis. The Investigators Global Assessment (IGA) score, severity of pruritus (SP) scores, and a basic syntax and molecular substrate (molecular psychophysics) of nociception and pruriception established by temperature-sensitive transient receptor potential (TRP) channels were used to evaluate the clinical signs, severity of pruritus, and skin sensory phenomenon.. The IGA scores at day 1 and 4 of treatment and the SP score at day 1, 4, and 11 of treatment were significantly lower than the baseline scores before treatment (P < 0.05). Among these 52 patients, 28 (53.8%) showed positive capsaicin-like response (i.e., burning with consequent rapid amelioration of pruritus) at the application sites, 12 (23.1%) showed camphor-like response (i.e., warming with consequent rapid amelioration of pruritus), and 12 (23.1%) showed negative capsaicin-like response or negative camphor-like response.. Treatment with pimecrolimus cream 1% can rapidly and effectively improve the signs and symptoms of facial dermatitis in adult women patients. Pimecrolimus cream 1% may act on the transient potential vanilloid 1 (TRPV1) receptor in the skin sensory afferents to induce capsaicin-like response or camphor-like response and then desensitizes TRPV1 and rapidly inhibits or alleviate itching.

Topics: Administration, Topical; Adolescent; Adult; Antipruritics; Dermatitis; Face; Female; Humans; Middle Aged; Pruritus; Tacrolimus; Young Adult

Refractory periorbital dermatitis has a chronic course with exacerbations leading to discomfort and cosmetic issues, yet characterization of treatment options is limited.. The objective was to present comprehensive demographic data and medical management of a series of patients with refractory periorbital dermatitis.. Retrospective review identified patients treated at a single institution from January 2010 to August 2020.. Descriptive analyses were performed. Demographic data and treatment history were reviewed and data including medication, use, date of use and discontinued use, reason for discontinuation (if applicable), refractory status, formulation, concentration, and dose frequency were extracted.. Descriptive analyses.. Forty-five patients were included. The average age at first diagnosis was 60.3 years (sd 14.9). 82.2% were women and 84.4% identified as Caucasian. Triamcinolone cream was most frequently used followed by tobramycin-dexamethasone, tacrolimus, and neomycin-polymyxin-dexamethasone. Less than 30% of patients on triamcinolone were refractory. 13.3% of patients used topical hydrocortisone, with over 80% of these patients experiencing refractory episodes of persistent irritation and erythema. Most patients were refractory during initial use or the first recurrence of periorbital dermatitis flare.. By better characterizing the diverse treatment regimens in a unique subset of refractory patients, we hope to better inform potential courses of medical management for periorbital dermatitis.

Topics: Administration, Topical; Cosmetics; Dermatitis; Dexamethasone; Female; Humans; Male; Middle Aged; Tacrolimus; Triamcinolone

This study was designed to establish quality standards of Burnet gels and investigate the effects and mechanism of Burnet gels on steroid-dependent dermatitis (HDD) in guinea pigs.. HPLC was used to determine the content of gallic acid, Gentiopicrin, and paeonol. A total of 48 male guinea pigs were recruited and randomly divided into control group, model group, tacrolimus ointment group, and Burnet gel group (Low, medium, and high concentration). The HDD guinea pig model was established by the 0.5% clobetasol propionate tincture. After HDD model establishment, control group and model group smeared normal saline and the rest of the group with corresponding drugs for three weeks. The contents of IFN-. The content of gallic acid, Gentiopicrin, and paeonol was 0.30 mg/g, 1.06 mg/g, and 0.56 mg/g. Compared with the normal group, the IFN-. Burnet gels can improve guinea pig HDD model, and the mechanism may be related to inhibiting skin inflammation and promoting the formation of epidermal skin barrier.

Topics: Acetophenones; Animals; Caspase 14; Clobetasol; Dermatitis; Gallic Acid; Gels; Guinea Pigs; Immunoglobulin E; Interleukin-4; Iridoid Glucosides; Male; Ointments; Saline Solution; Sanguisorba; Tacrolimus

Data regarding the treatment of periorificial dermatitis with topical calcineurin inhibitors (TCI) in the pediatric population are limited.. To assess the clinical utility of TCI in pediatric patients with periorificial dermatitis.. A retrospective medical record review of all pediatric patients with periorificial dermatitis treated with TCIs was performed. Follow-up via telephone was performed to capture missing data.. A total of 132 patients met the inclusion criteria. The median age at diagnosis was 4.2 years (interquartile range, 2.3-8.2). The median follow-up was 5.2 months (interquartile range, 2.1-11.7). Seventy-two patients had evaluable follow-up data. Of these, 48 (67%) patients were treated with TCI alone, 12 (16.7%) were treated with a combination of TCI and topical metronidazole, and 9 (12.5%) were treated with a combination of TCI and a systemic antibiotic. Complete response was noted in 68.8% of patients treated with TCI alone, in 75% of patients treated with TCI and metronidazole, and in 77.8% of patients treated with TCI and a systemic antibiotic. Adverse events were rare and mild in severity.. Topical calcineurin inhibitors are an effective therapeutic option for pediatric patients with periorificial dermatitis and were well tolerated in this cohort.

Topics: Administration, Topical; Calcineurin Inhibitors; Child; Child, Preschool; Dermatitis; Eye; Female; Humans; Male; Mouth; Nose; Retrospective Studies; Tacrolimus

Topics: Adolescent; Adult; Clobetasol; Dermatitis; Diagnosis, Differential; Female; Humans; Lichenoid Eruptions; Male; Tacrolimus

Topics: Dermatitis; Humans; Immunosuppressive Agents; Male; Middle Aged; Tacrolimus

Topics: Adenocarcinoma; Aged; Colonic Neoplasms; Colostomy; Dermatitis; Diagnosis, Differential; Humans; Male; Postoperative Complications; Prednisone; Pyoderma Gangrenosum; Skin Neoplasms; Skin Ulcer; Surgical Stomas; Tacrolimus

Psoriasis is a chronic relapsing inflammatory skin disorder affecting 2-3% of world population. In present context, a novel topical formulation that could effectively deliver tacrolimus for psoriasis treatment would be of great interest. Liquid crystalline nanoparticle (LCN) is one of the potential drug delivery systems for topical drug delivery. Herein, the effects of tacrolimus-loaded LCNs on in vitro skin permeation and retention as well as on in vivo psoriasis-like skin inflammation are studied. Characterization of nanoparticles included particle size and entrapment efficiency analysis that presented nanoparticles of 149.1 nm for monoolein-based and 204.3 nm for oleic acid added monoolein-based nanoparticles with entrapment efficiency of tacrolimus above 99%. Skin permeation and retention study has revealed a significant increase in the amount of tacrolimus permeated and retained by the use of LCNs. Tacrolimus-loaded LCNs are more effective in the treatment of psoriasis-like skin inflammation as compared to tacrolimus dissolved in propylene glycol. Hence, this study provides a basis for possible applicability of tacrolimus-loaded LCNs in the treatment of psoriasis.

Topics: Animals; Chemistry, Pharmaceutical; Dermatitis; Drug Delivery Systems; Glycerides; Inflammation; Mice; Nanoparticles; Oleic Acid; Particle Size; Psoriasis; Skin; Skin Absorption; Tacrolimus

Topics: Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Delayed Diagnosis; Dermatitis; Diagnostic Errors; Drug Substitution; Humans; Immunocompromised Host; Immunosuppressive Agents; Kidney Transplantation; Mycophenolic Acid; Postoperative Complications; Postoperative Period; Prednisone; Sarcoma, Kaposi; Sirolimus; Skin Neoplasms; Tacrolimus; Vinblastine

Effects of probiotics on the prevention of atopic diseases have been proposed recently. Although we have already reported the suppressive effects of the probiotic, ImmuBalance™, on a mouse model for peanuts allergy, its influence on atopic diseases remains unclear.. Potential efficacy of ImmuBalance™, which is the fermented soy product, on treatment of atopic dermatitis (AD) was investigated using a mouse model for human AD, NC/Tnd mice.. For in vivo study, ImmuBalance containing chow or a control diet were fed to NC/Tnd mice with moderate dermatitis for 2 weeks. Topical application of FK506 ointment was used as a positive control. Clinical skin severity scores, scratching behaviors, trans-epidermal water loss (TEWL), and histological features were analyzed. For in vitro study, suppressive effect of ImmuBalance™ on nerve growth factor (NGF)-activated neurite outgrowth of PC12 cells was examined.. Clinical skin severity scores of the mice fed with ImmuBalance containing chow were gradually reduced as well as the mice treated with FK506. Feeding with ImmuBalance completely inhibited the increase in scratching behavior of NC/Tnd mice. The value of TEWL of NC/Tnd mice fed with ImmuBalance was significantly decreased. In addition, histological examination revealed that application of ImmuBalance decreased the number of PGP9.5-positive neuronal fibers in the lesional skin. When ImmuBalance extract was added to the culture, NGF-activated neurite outgrowth of PC12 cells was diminished through the inhibition of the phosphatidylinositol 3-kinase phosphorylation.. ImmuBalance could exhibit favorable alterations on AD symptoms, particularly through down regulation of the itch sensation.

Topics: Administration, Oral; Administration, Topical; Animals; Dermatitis; Dermatitis, Atopic; Down-Regulation; Fermentation; Glycine max; Hydrolysis; Male; Mice; Nerve Growth Factor; PC12 Cells; Phosphatidylinositol 3-Kinases; Phosphorylation; Pruritus; Rats; Skin; Tacrolimus; Time Factors; Water

Phospholipase Cε (PLCε) is an effector of Ras and Rap small GTPases. We showed previously using PLCε-deficient mice that PLCε plays a critical role in activation of cytokine production in non-immune skin cells in a variety of inflammatory reactions. For further investigation of its role in inflammation, we created transgenic mice overexpressing PLCε in epidermal keratinocytes. The resulting transgenic mice spontaneously developed skin inflammation as characterized by formation of adherent silvery scales, excessive growth of keratinocytes, and aberrant infiltration of immune cells such as T cells and DC. Development of the skin symptoms correlated well with increased expression of factors implicated in human inflammatory skin diseases, such as IL-23, in keratinocytes, and with the accumulation of CD4(+) T cells producing IL-22, a potent inducer of keratinocyte proliferation. Intradermal injection of a blocking antibody against IL-23 as well as treatment with the immunosuppressant FK506 reversed these skin phenotypes, which was accompanied by suppression of the IL-22-producing T-cell infiltration. These results reveal a crucial role of PLCε in the development of skin inflammation and suggest a mechanism in which PLCε induces the production of cytokines including IL-23 from keratinocytes, leading to the activation of IL-22-producing T cells.

Topics: Animals; Antibodies, Blocking; Cytokines; Dendritic Cells; Dermatitis; Female; Humans; Immunosuppressive Agents; Interleukin-22; Interleukin-23; Interleukins; Keratinocytes; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Phosphoinositide Phospholipase C; T-Lymphocytes; Tacrolimus; Up-Regulation

A case of childhood granulomatous perioral dermatitis (CGPD)/facial Afro-Caribbean childhood eruption (FACE) in a three year old boy from Madagascar is described. This disorder occurs predominantly in black children until puberty. It is a relatively uncommon condition of unknown aetiology characterized by a monomorphic, papular eruption around the mouth, nose and eyes. The disorder looks like sarcoidosis, but it is benign and self-limited and not associated with any systemic manifestations. In our case we treated the patient with Elidel (pimecrolimus) with an excellent result.

Topics: Child, Preschool; Dermatitis; Dermatologic Agents; Granuloma; Humans; Male; Mouth; Tacrolimus

Topics: Administration, Topical; Child; Dermatitis; Face; Granuloma; Humans; Immunosuppressive Agents; Male; Tacrolimus

Topics: Cell Survival; Cells, Cultured; Dermatitis; Dose-Response Relationship, Drug; Humans; Immunosuppressive Agents; Interleukin-6; Interleukin-8; Keratinocytes; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Tacrolimus; Ultraviolet Rays

Topics: Bites and Stings; Child, Preschool; Cnidarian Venoms; Dermatitis; Female; Humans; Immunosuppressive Agents; Ointments; Recurrence; Tacrolimus

Autoimmunity results from loss of mechanisms controlling self-reactivity. Autoimmune disorders play an increasingly important role and CD40-CD40 ligand (CD40L) interaction on immunocompentent cells is able to break established immunotolerance. To study the effects of the calcineurin-inhibitor FK506 on CD40L-induced systemic autoimmunity, CD40L transgenic (tg) mice, which spontaneously develop a mixed connective tissue-like disease, were treated with FK506 after onset of overt autoimmunity. Interestingly, FK506-treated CD40L tg mice showed significantly reduced autoimmune dermatitis scores and markedly decreased numbers of lesional infiltrating leukocytes. This finding was associated with diminished lymphadenopathy induced by FK506 treatment. Furthermore, FK506 suppressed the development of cytotoxic/autoreactive CD8(+) T cells as evidenced by the reduced expression of T cell activation markers in treated CD40L tg mice. Importantly, FK506 induced a significant reduction in autoantibody titers in the serum of CD40L tg animals. As CD40L tg mice develop nephritis leading to loss of renal function proteinuria was determined after FK506 injections. Notably, FK506 treatment re-established renal function as indicated by significantly reduced uric protein concentrations of treated CD40L tg mice. Together, these findings show the beneficial therapeutic effects of FK506 for the treatment of CD40L-induced autoimmunity. Additionally, these results demonstrate that FK506 is able to suppress ongoing severe autoimmune responses.

Topics: Animals; Autoantibodies; Autoimmune Diseases; Autoimmunity; Calcineurin Inhibitors; CD40 Ligand; Cell Nucleus; Dermatitis; Female; Immunosuppressive Agents; Mice; Mice, Transgenic; T-Lymphocytes, Cytotoxic; Tacrolimus

Patients with stomas face a variety of problems, such as skin breakdown or ulceration at the peristomal site, that can complicate care. Topical steroids are frequently used to treat various inflammatory conditions that affect peristomal skin with good results, but chronic use can lead to undesirable side effects. Tacrolimus ointment 0.1%, a nonsteroidal immunosuppressant, could offer a more favorable alternative to topical steroids. We present 3 cases of peristomal skin disease that were successfully treated with tacrolimus ointment 0.1%.

Topics: Administration, Topical; Aged; Aged, 80 and over; Colonic Neoplasms; Dermatitis; Female; Humans; Immunosuppressive Agents; Male; Ointments; Surgical Stomas; Tacrolimus; Treatment Outcome; Urinary Bladder Neoplasms

Stasis dermatitis is a common dermatologic disorder as a consequence of impaired venous drainage and often accompanied by chronic leg ulcers. Until today the standard in acute therapy represents the topical administration of highly potent corticosteroids and if possible a consequent long-term compression therapy. The macrolide tacrolimus represents a new selective inflammatory cytokine release inhibitor by binding to macrophilin-12 and inhibiting calcineurin. Beside the resulting anti-inflammation and immunosuppression an antipruritic effect have been discussed as further clinical benefits of tacrolimus. Here we report for the first time about a 81-year old patient suffering from an ulcus cruris mixtum and stasis dermatitis treated with topical 0.1% tacrolimus ointment twice daily for 5 days. Until now tacrolimus is available for topical treatment as a fatty ointment only. Although we would have preferred a more hydrophilic base for treatment of acute stasis dermatitis we achieved complete healing. As this is only a case report about one single patient further clinical investigations are needed to confirm this observation in more individuals with stasis dermatitis.

Topics: Administration, Topical; Aged; Aged, 80 and over; Dermatitis; Humans; Immunosuppressive Agents; Leg Dermatoses; Male; Tacrolimus; Treatment Outcome; Varicose Ulcer

We investigated the effects of 1-4% ointments of metronidazole and tinidazole (derivatives of nitroimidazole) on models of inflammatory dermatitis evoked by antigen, hapten and monoclonal anti-dinitrophenol (DNP) IgE antibody in mice. Metronidazole and tinidazole ointments (1) suppressed the late-phase reaction (LPR) of biphasic ear edema in mice sensitized with ovalbumin (OA), (2) suppressed trinitrochlorobenzene-induced inflammatory dermatitis, (3) suppressed the immediate phase reactions and LPR in mice passively sensitized with anti-DNP IgE mAb, and (4) enhanced vascular permeability and the number of scratching reactions, presumably due to itching, in passively sensitized mice. These results strongly indicate that metronidazole and tinidazole 1-4% ointments possess antiinflammatory, immunosuppressive and anti-itching effects, and have the potential for clinical use in the treatment of human inflammatory skin diseases including atopic dermatitis in addition to rosacea and acne vulgaris.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antigens; Antipruritics; Capillary Permeability; Dermatitis; Dermatologic Agents; Disease Models, Animal; Edema; Humans; Immunosuppressive Agents; Male; Metronidazole; Mice; Ointments; Ovalbumin; Picryl Chloride; Pruritus; Tacrolimus; Tinidazole

Topics: Advertising; Dermatitis; Dermatologic Agents; Drug Industry; Humans; Ointments; Tacrolimus

Pimecrolimus, an ascomycin macrolactam derivative, is an inhibitor of T-cell and mast-cell activation, developed and launched by Novartis for the potential treatment of psoriasis and allergic, irritant and atopic dermatitis. The topical formulation had been launched in the US by February 2002 for mild-to-moderate atopic dermatitis in patients aged two years and older. At that time, an oral formulation was in development for which launch was anticipated for 2006. In March 2002, pimecrolimus was approved in Denmark, becoming the first non-steroid prescription cream approved for patients from as young as 3 months of age through to adulthood. At this time, Novartis planned to seek approvals in other European countries during 2002 under the Mutual Recognition Procedure, and elsewhere around the globe. In December 2000, Merrill Lynch predicted sales of SFr 100 million in 2002, rising to SFr 330 million in 2004, and in February 2001, the analysts predicted sales of SFr 120 million in 2002, rising to SFr 574 million in 2005. Later in August 2001, Deutsche Bank estimated sales of SFr 150 million in 2002, rising to SFr 550 million in 2005. Following FDA approval in 2002, Morgan Stanley Dean Witter cautiously predicted sales of SFr 60 million rising to SFr 860 million by 2007.

Topics: Administration, Topical; Animals; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Clinical Trials as Topic; Dermatitis; Humans; Tacrolimus

Tacrolimus, available for intravenous, oral and now topical administration, is a potent immunosuppressive agent with the ability to block the production of Interleukin-2 (IL-2) and inhibit T-cell proliferation. Originally developed for use in organ transplantation, it is currently being studied for the treatment of inflammatory dermatoses. The US FDA recently approved tacrolimus ointment (Protopic (R), Fujisawa) for the treatment of atopic dermatitis.

Topics: Administration, Topical; Clinical Trials as Topic; Dermatitis; Drug Interactions; Humans; Immunosuppressive Agents; Tacrolimus; United States

Topics: Adjuvants, Immunologic; Aminoquinolines; Condylomata Acuminata; Dermatitis; Dermatology; Humans; Imiquimod; Interferon Inducers; Keratolytic Agents; Stevens-Johnson Syndrome; Tacrolimus

Weaned hairless rats were fed a diet deficient in fat, magnesium and folacin. After approximately 1 week, an erythematous dermatitis developed which was associated with extreme generalized pruritus. Scratching led to excoriations and hemorrhagic crusting. The acute stage (pruritic rash) resolved after several days and was followed by sporadic non-itching relapses. Subsequent to the onset of symptoms, rats were treated orally, once daily for 3 days with CyA, CyH or FK506. The immunosuppressants CyA and FK506 caused a dose-dependent inhibition of symptoms in contrast to CyH. The immediate clinical response was associated with changes in blood histamine, white blood cell counts and histological parameters. Since CyH is known to lack immunosuppressive activity, these results may indicate that the cutaneous changes induced by the nutritional deficiency are associated with immunological abnormalities. The results may also indicate mechanisms influenced by CyA and FK506 but not by CyH; for example, release of chemical mediators from inflammatory cells.

Topics: Animals; Cyclosporine; Dermatitis; Diet; Dose-Response Relationship, Drug; Hair; Histamine; Leukocyte Count; Male; Rats; Rats, Inbred Strains; Skin; Tacrolimus