tacrolimus and Psoriasis

Topics: Administration, Topical; Biopsy, Needle; Blood Chemical Analysis; Crohn Disease; Facial Dermatoses; Follow-Up Studies; Humans; Immunohistochemistry; Infliximab; Male; Photosensitivity Disorders; Psoriasis; Risk Assessment; Tacrolimus; Treatment Outcome; Tumor Necrosis Factor-alpha; Young Adult

Inverse psoriasis commonly involves skin fold areas including the axillae, perianal skin, intergluteal cleft, inframammary, genital/inguinal, abdominal, and retroauricular folds. Topical calcineurin inhibitors are indicated for the treatment of atopic dermatitis but have also been studied in the treatment of psoriasis. The object of the present study is to define the efficacy of topical calcineurin inhibitors in the treatment of psoriasis. We checked for English-vernacular articles conveyed since 1990 in PubMed, Ovid/Cochrane, and Embase using "tacrolimus," "pimecrolimus," or "topical calcineurin inhibitors," and "psoriasis" as keywords. Eight double-blind studies and seven open studies displayed the ampleness of topical tacrolimus in psoriasis. Included studies demonstrated a considerable efficacy of topical administration of tacrolimus and pimecrolimus in the treatment of psoriasis, especially for facial, genital, and intertriginous areas. The role of topical tacrolimus and pimecrolimus in the treatment of psoriasis seems to be promising as shown by the results of double-blind and open studies. Because these agents do not cause cutaneous atrophy, they have a special role in facial, genital, and intertriginous psoriatic lesions. Both agents await additional investigation to determine their roles.

Topics: Administration, Cutaneous; Calcineurin Inhibitors; Dermatologic Agents; Humans; Immunosuppressive Agents; Psoriasis; Skin; Tacrolimus; Treatment Outcome

The largest proportion of psoriasis patients are candidates for topical treatment rather than treatment paradigms encompassing systemic, biologic and apremilast, and phototherapy, making skillfulness with topical therapy of paramount importance. As such, numerous studies have been conducted to demonstrate the benefits of using topical therapy in combination with other therapies. In addition, innovative uses of otherwise conventional methods, such as proactive use to minimize flare, have been developed. This article reviews five types of strategies for improved efficacy from topical agents beyond monotherapy. These strategies include proactive use, rotational therapy, sequential therapy, using topical agents to shorten the onset of therapeutic action for slower internal agents or phototherapy, and combination use for added efficacy. Each of these is reviewed in detail.

Topics: Administration, Topical; Calcitriol; Clobetasol; Databases, Factual; Dermatologic Agents; Humans; Nicotinic Acids; Phototherapy; Psoriasis; Tacrolimus

Psoriasis is a chronic disease that has a substantial effect on quality of life of patients and often needs long-term treatment. Topical treatments for psoriasis include corticosteroids, vitamin D derivatives, tazarotene, anthralin, tacrolimus, pimecrolimus, and newer formulations of tar. Although many of these treatments are effective, they must be prescribed appropriately and used consistently for a period of weeks to months before clinical evidence of improvement can be seen and patients perceive that the treatment is working. As such, medication dosage/schedule, choice of vehicle, and especially patient adherence to medication are key factors for a treatment to be effective. Addressing patient preferences about treatments and concerns about treatment-related toxicities and managing their expectations represent additional aspects of patient care. Therapies such as calcipotriene and betamethasone dipropionate (Cal/BD) fixed combination foam and new drugs and vehicles continuously enhance the treatment landscape for psoriasis. Because adherence to topical treatment can be a major difficulty, keeping the treatment regimen simple and using new and sophisticated treatment vehicles that are acceptable to patients can likely improve treatment outcomes.

Topics: Administration, Cutaneous; Anthralin; Betamethasone; Calcitriol; Dermatologic Agents; Drug Combinations; Drug Therapy, Combination; Evidence-Based Medicine; Glucocorticoids; Humans; Nicotinic Acids; Patient Compliance; Pharmaceutical Vehicles; Practice Guidelines as Topic; Psoriasis; Quality of Life; Severity of Illness Index; Tacrolimus; Treatment Outcome; Vitamin D

Inverse psoriasis is clinically defined by chronic inflammatory lesions in intertrigineous areas. Colonisation or infection with Candida ssp. or bacteria is common. The disease-related quality of life is significantly reduced especially regarding sexual behavior. After the exclusion of relevant differential diagnoses, therapy should be adapted to the clinical outcome and potential comorbidities. Substances which are efficacious in psoriasis vulgaris are generally efficacious in inverse psoriasis, but have to be used off-label. Controlled clinical studies are only available for topical ascomycin.

Topics: Bacterial Infections; Candidiasis; Diagnosis, Differential; Female; Humans; Male; Off-Label Use; Psoriasis; Superinfection; Tacrolimus

Topics: Administration, Topical; Adult; Biopsy; Cheilitis; Drug Therapy, Combination; Female; Hashimoto Disease; Humans; Immunosuppressive Agents; Male; Psoriasis; Recurrence; Salicylic Acid; Tacrolimus; Young Adult

Pimecrolimus is a calcineurin inhibitor which has a role in the treatment of psoriasis. However, it remains an off-license treatment, despite its potential use in patients with treatment-resistant psoriasis or in those who have had multiple adverse effects to other therapies.. This review covers the efficacy and role of both topical and oral Pimecrolimus in the management of psoriasis and compares them to other available treatments. The paper provides a comprehensive review of the literature on topical and oral Pimecrolimus and its utility in the treatment of patients with psoriasis following literature searches via PubMed and Embase.. Topical Pimecrolimus is an effective, off-license treatment option particularly for facial and intertriginous psoriasis. Oral Pimecrolimus shows great promise as an alternative systemic treatment option, but Phase III trials are required before further recommendations can be made.

Topics: Administration, Cutaneous; Administration, Oral; Animals; Calcineurin Inhibitors; Dermatologic Agents; Humans; Psoriasis; Tacrolimus

Treating psoriasis in pregnant and lactating women presents a special challenge. For ethical reasons, prospective randomized control trials have not been conducted in this patient population although these patients do encounter new-onset psoriasis in addition to flares and may require treatment throughout their pregnancies.. Our aim was to arrive at consensus recommendations on treatment options for psoriasis in pregnant and lactating women.. The literature was reviewed regarding all psoriasis therapies in pregnant and lactating women.. Topical therapies including emollients and low- to moderate-potency topical steroids are first-line therapy for patients with limited psoriasis who are pregnant or breast-feeding. The consensus was that second-line treatment for pregnant women is narrowband ultraviolet B phototherapy or broadband ultraviolet B, if narrowband ultraviolet B is not available. Lastly, tumor necrosis factor-α inhibitors including adalimumab, etanercept, and infliximab may be used with caution as may cyclosporine and systemic steroids (in second and third trimesters). Some specific strategies may be used to minimize risk and exposure.. There are few evidence-based studies on treating psoriasis in pregnant and lactating women.. Because there will always be a question of ethical concerns placing pregnant and lactating women in prospective clinical trials, investigation of both conventional and biologic agents are unlikely to ever be performed. Some of these medications used to treat psoriasis are known abortifacients, mutagens, or teratogens and must be clearly avoided but others can be used with relative confidence in select patients with appropriate counseling of risks and benefits.

Topics: Administration, Topical; Female; Glucocorticoids; Humans; Immunosuppressive Agents; Pregnancy; Pregnancy Complications; Psoriasis; Tacrolimus; Tumor Necrosis Factor-alpha; Ultraviolet Therapy

There have been many new developments in therapeutic modalities for the treatment of pediatric dermatological diseases in the past year. Advances in the treatment of atopic dermatitis, psoriasis, infantile hemangiomas and dystrophic epidermolysis bullosa will be discussed. The following review will update the reader on these exciting new possibilities for patient care and future directions for research to improve the lives of children suffering from skin diseases.. This review will discuss recent articles describing the use of topical tacrolimus for maintenance of remission in atopic dermatitis, utility of nurse educators in atopic dermatitis, safety and efficacy of etanercept for the treatment of psoriasis in children, narrow band ultraviolet B phototherapy for atopic dermatitis and psoriasis, use of topical timolol for infantile hemangiomas and bone marrow transplantation for dystrophic epidermolysis bullosa.. There are many new interesting, potentially useful therapeutic modalities emerging in pediatric dermatology. New treatments for atopic dermatitis, psoriasis, infantile hemangiomas and dystrophic epidermolysis bullosa are reviewed.

Topics: Adrenergic beta-Antagonists; Child; Dermatitis, Atopic; Epidermolysis Bullosa Dystrophica; Etanercept; Hemangioma; Humans; Immunoglobulin G; Immunosuppressive Agents; Pediatrics; Psoriasis; Receptors, Tumor Necrosis Factor; Skin Diseases; Skin Neoplasms; Tacrolimus; Timolol; Ultraviolet Therapy; Vitamin D; Vitamins

Topical tacrolimus and pimecrolimus are indicated for treatment of atopic dermatitis, but they have been studied in many off-label uses. Double-blind and open studies have shown favorable results with topical tacrolimus and pimecrolimus in oral lichen planus. In 1 study of oral lichen planus, blood tacrolimus was detected in 54% of patients, but there were no signs of systemic toxicity. Double-blind and open studies of vitiligo have shown favorable results with tacrolimus in combination with excimer laser, especially for lesions over bony prominences and on extremities. Similarly, double-blind studies of vitiligo have shown favorable results when pimecrolimus is combined with narrow-band UVB, especially for facial lesions. Double-blind and open studies of psoriasis have shown favorable results for tacrolimus and pimecrolimus, especially for inverse psoriasis. Topical calcineurin inhibitors have been effective in many other cutaneous disorders, and further studies would help clarify their roles.

Topics: Administration, Cutaneous; Calcineurin Inhibitors; Child; Child, Preschool; Crohn Disease; Dermatitis, Atopic; Dermatologic Agents; Double-Blind Method; Female; Humans; Lichen Planus, Oral; Lupus Erythematosus, Cutaneous; Male; Off-Label Use; Psoriasis; Rosacea; Skin Diseases; Tacrolimus; Therapies, Investigational; Vitiligo

Psoriasis is a chronic inflammatory disease causing important physical and psychological morbidity. Topical treatments are the first choice therapeutic alternatives for mild and moderate psoriasis. We review the different topical treatment options for this common skin disease.

Topics: Administration, Cutaneous; Anthralin; Calcitriol; Dermatologic Agents; Drug Administration Schedule; Drug Therapy, Combination; Emollients; Humans; Keratolytic Agents; Nicotinic Acids; Ointments; Psoriasis; PUVA Therapy; Quality of Life; Tacrolimus; Treatment Outcome; Vitamins

Pimecrolimus is a non-steroidal immunosuppressant derived from ascomycin. This drug inhibits the action of calcineurin phosphatase and blocks the production of inflammatory substances that are thought to be important in causing skin lesions in inflammatory diseases. Pimecrolimus 1% cream (Elidel, Novartis Pharma, East Hanover, NJ, USA) was approved in the European Union, the United States and Japan as second-line therapy for the short- term and non-continuous chronic treatment of mild to moderate atopic dermatitis in non-immunocompromised adults and children aged 2 years and older, who have failed to respond adequately to other topical prescription treatments, or when those treatments are not advisable. This topical immunomodulator has also an enormous potential as topical treatment for numerous inflammatory skin diseases like psoriasis and vitiligo. Recently, some authors reported its efficacy in the treatment of skin manifestations of Lupus erytematosus.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Calcineurin Inhibitors; Dermatitis, Atopic; Dermatologic Agents; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Lymphocyte Activation; Molecular Structure; Pain; Psoriasis; T-Lymphocytes; Tacrolimus; Vitiligo

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

There are numerous possibilities for specific antiinflammatory therapy of psoriasis. One option is the use of calcineurin inhibitors. To date, only systemic administration of cyclosporine A is approved for this indication. Nonetheless cyclosporine A, tacrolimus and pimecrolimus can all be classed as effective anti-inflammatory agents for the therapy of psoriasis. Unfortunately, the vehicles currently available do not insure adequate topical delivery of these substances. Clinical efficacy of the preparations can be proven only when additional penetration-promoting measures are used or penetration-facilitating conditions exist. The entire group can be expected to play a greater role in the topical therapy of psoriasis if advances in vehicles and delivery systems are made.

Topics: Administration, Topical; Calcineurin Inhibitors; Cell Division; Cyclosporine; Cytokines; Dermatologic Agents; Gene Expression Regulation; Granulocytes; Humans; Interleukin-2; Lymphocyte Activation; Mast Cells; Pilot Projects; Psoriasis; T-Lymphocytes; Tacrolimus

Psoriasis is a chronic skin disorder that affects approximately 2% of the US and European population. Over the last several years, one of the major focuses in psoriasis research has been the development of biologic therapies for this disease. The aim of these therapies is to provide selective, immunologically directed intervention with fewer side effects than traditional therapies. The goal of this article is to review the progress of the biologic agents which are available, or under investigation for clinical use: infliximab, etanercept, efalizumab, alefacept, and adalimumab. In addition, two other investigational therapies, oral tazarotene and oral pimecrolimus will be discussed. Clinical data for these agents, including the most recent phase II and/or III study results, will be discussed, as well as the most recent safety data.

Topics: Adalimumab; Administration, Oral; Alefacept; Animals; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Etanercept; Humans; Immunoglobulin G; Infliximab; Meta-Analysis as Topic; Nicotinic Acids; Psoriasis; Receptors, Tumor Necrosis Factor; Recombinant Fusion Proteins; Tacrolimus; Treatment Outcome

Topics: Adalimumab; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Biological Products; Cyclosporine; Dermatologic Agents; Forecasting; Fumarates; Humans; Infliximab; Nicotinic Acids; Psoriasis; Receptors, Tumor Necrosis Factor; Receptors, Tumor Necrosis Factor, Type I; Tacrolimus; Tumor Necrosis Factor Decoy Receptors; Ustekinumab

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

Pimecrolimus (SDZ ASM 981, Elidel ) is an ascomycin macrolactam derivative and a cell-selective inhibitor of inflammatory cytokines specifically developed to treat inflammatory skin diseases. Pimecrolimus combines high anti-inflammatory activity in the skin with a low potential to impair systemic immune reactions. Multi-centre studies have proved the efficacy and safety of pimecrolimus cream in patients with atopic dermatitis (AD) and confirmed that it is suitable for short-term treatment and long-term management of AD in adults, children and infants as young as 3 months. Topical application in humans is not associated with the atrophogenic side effects observed with corticosteroids. Pimecrolimus blood levels remained consistently low after repeated topical application and no clinically relevant drug-related systemic adverse events have been reported among the 8000 patients treated in clinical trials so far. Short-term, Phase I/II and Phase II trials of pimecrolimus administered orally in psoriasis and AD have shown that this drug is highly effective in a dose-dependent manner in patients with these diseases and has high safety profile. This finding is confirmed by pharmacogenomic blood analysis. Available data thus indicates that pimecrolimus, in both the cream and oral formulations, may represent a new option for the treatment of inflammatory skin diseases.

Topics: Administration, Cutaneous; Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Clinical Trials as Topic; Dermatitis, Atopic; Disease Models, Animal; Humans; Psoriasis; Tacrolimus

Biopharmaceuticals that target specific disease-mediating molecules have advanced our understanding of the pathogenesis of psoriasis. The traditional paradigm that psoriasis is primarily a disease of epidermal cells has been replaced with a model that now includes keratinocyte-derived factors, inflammatory mediators and angiogenic mechanisms. Recent studies have highlighted some of the key molecules involved in all of these pathogenic processes. Several have already been evaluated as putative targets in in vitro and in vivo studies, whereas other molecules are significantly upregulated in psoriasis and require further study to elucidate their role and contribution to disease. Although not all these molecules will eventually qualify as drug targets, data from similar experimental strategies are predicted to underpin the next generation of candidate targets and novel therapeutic approaches.

Topics: Angiogenesis Inhibitors; Animals; Dermatologic Agents; Humans; Keratinocytes; Psoriasis; Tacrolimus; Vascular Endothelial Growth Factors

Tacrolimus ointment and pimecrolimus cream are approved in the United States for treatment of atopic dermatitis. Tacrolimus and pimecrolimus are both calcineurin inhibitors and function as immunosuppressants. Their mechanisms have been discussed elsewhere. This article will discuss their utility in treating psoriasis.

Topics: Administration, Cutaneous; Animals; Calcineurin Inhibitors; Chemistry, Pharmaceutical; Double-Blind Method; Drug Evaluation, Preclinical; Facial Dermatoses; Female; Humans; Immunosuppressive Agents; Liposomes; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Middle Aged; Occlusive Dressings; Ointments; Psoriasis; Randomized Controlled Trials as Topic; Skin Absorption; Tacrolimus; Treatment Outcome

The ascomycine macrolactam derivative pimecrolimus has a gene profile of broad anti-inflammatory activity without evidence of toxicity. It exhibits excellent clinical tolerability after 4 weeks and 12 weeks, respectively, of oral treatment, and it is highly effective in a concentration-dependent manner in patients with moderate to severe plaque psoriasis. Although not yet approved, oral pimecrolimus promises to be a novel, highly effective, and well-tolerated drug in the systemic treatment of psoriasis and other T-cell-mediated skin diseases.

Topics: Administration, Oral; Administration, Topical; Animals; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Follow-Up Studies; Humans; Immunosuppressive Agents; Maximum Tolerated Dose; Psoriasis; Randomized Controlled Trials as Topic; Rats; Risk Assessment; Severity of Illness Index; Tacrolimus; Treatment Outcome

Immune response modifiers (IRMs) are agents that target the body's immune system (i.e., cytokines, receptors, and inflammatory cells) to combat disease. Topical IRM therapies, which encompass both proinflammatory and immunosuppressive therapeutics, have been used to successfully treat a number of dermatologic conditions. Proinflammatory treatments include Toll-like receptor agonists (e.g., imiquimod 5% cream) and interferon (e.g., interferon-alpha) therapies, which have been used in the treatment of external genital warts, basal cell carcinoma, and other dermatologic diseases. Immunosuppressive therapies include topical and intralesional corticosteroids, anti-tumor necrosis factor agents (e.g., infliximab and etanercept), and anti-CD4+ T-cell agents, including calcineurin inhibitors and mycophenolate. These agents have been used to treat a number of conditions, including atopic and seborrheic dermatitis and psoriasis. This article reviews the mechanism of action of IRMs and the application of IRMs in several dermatologic diseases.

Topics: Adjuvants, Immunologic; Alefacept; Aminoquinolines; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Calcineurin Inhibitors; CD11 Antigens; Dermatitis, Atopic; Glucocorticoids; Humans; Imiquimod; Interferons; Membrane Glycoproteins; Mycophenolic Acid; Psoriasis; Receptors, Cell Surface; Recombinant Fusion Proteins; Skin Diseases; Tacrolimus; Toll-Like Receptors

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

Topical corticosteroids (TCC) have significantly shaped dermatological therapy for five decades. A few months ago the TCC were joined by competition, the topical inhibitors of calcineurin (TIC), wrongly termed topical immunomodulators. The present paper reviews the pharmacological effects and clinical efficacy of TIC, compares the risks, benefits and costs of those two groups of topical drugs and develops a position on the use of TIC. While TIC have ushered in a new era of topical anti-inflammatory therapy, the age of TCC is far from over.

Topics: Acute Disease; Administration, Topical; Anti-Inflammatory Agents; Calcineurin Inhibitors; Cyclosporins; Dermatitis, Atopic; Eczema; Facial Dermatoses; Glucocorticoids; Humans; Immunosuppressive Agents; Neurodermatitis; Psoriasis; Pyoderma Gangrenosum; Risk Factors; Skin Diseases; Tacrolimus

Pimecrolimus (SDZ ASM 981), an ascomycin derivative, is one of the new classes of immunomodulating macrolactams and was specifically developed for the treatment of inflammatory skin diseases. The interest in pimecrolimus has been substantial because of its significant anti-inflammatory activity and immunomodulatory capabilities and its low systemic immunosuppressive potential. The mechanism of action of pimecrolimus is the blockage of T cell activation. Pimecrolimus (like all ascomycins) is an immunophilin ligand, which binds specifically to the cytosolic receptor, immunophilin macrophilin-12. This pimecrolimus-macrophilin complex effectively inhibits the protein phosphatase calcineurin, by preventing calcineurin from dephosphorylating the nuclear factor of activated T cells (NF-AT), a transcription factor. This results in the blockage of signal transduction pathways in T cells and the inhibition of the synthesis of inflammatory cytokines, specifically Th1- and Th2-type cytokines. Pimecrolimus has also been shown to prevent the release of cytokines and pro-inflammatory mediators from mast cells. Several studies have evaluated the effectiveness of pimecrolimus as a treatment for skin diseases. In animal models of allergic contact dermatitis, topical pimecrolimus was found to be effective. In human studies of allergic contact dermatitis pimecrolimus demonstrated significantly more efficacy than the control treatment. As well, the effectiveness of pimecrolimus 0.6% cream was comparable to 0.1% betamethasone-17-valerate; however, pimecrolimus was not associated with any of the side effects characteristic of a topical steroid. Topical application of pimecrolimus is not associated with skin atrophy. Pimecrolimus is effective and safe in both children and adults with atopic dermatitis. When pimecrolimus 1% cream has been applied to adult atopics, improvement has been observed as early as the first week, with a 72% reduction in severity after 3 weeks. Pharmacokinetic studies have shown very low blood levels of pimecrolimus following topical application, with no accumulation after repeated applications. Following application of pimecrolimus cream occasional transient irritation may be experienced at the application site. Similar results have also been found in children aged 3 months and older following application of pimecrolimus 1% cream. Topical pimecrolimus in psoriasis appears to exhibit a dose-dependent therapeutic effect under semi-occlusive conditions. Pime

Topics: Administration, Oral; Administration, Topical; Adult; Animals; Child, Preschool; Controlled Clinical Trials as Topic; Dermatitis, Allergic Contact; Dermatitis, Atopic; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Middle Aged; Psoriasis; Swine; Tacrolimus; Treatment Outcome

There is a paucity of randomized, controlled therapy studies of the extraintestinal manifestations of inflammatory bowel disease (IBD). Most current therapeutic approaches are empiric or based on approaches to therapy in other settings. In the past year anecdotal evidence has emerged for the use of therapies that neutralize tumor necrosis factor-a in both ankylosing spondylitis and the dermatologic extraintestinal manifestations. Topical tacrolimus has also emerged as a potentially useful therapy for dermatologic manifestations. Finally, patients with IBD occasionally become transplant recipients. One study reported worsening IBD after orthotopic liver transplantation for primary sclerosing cholangitis, and another reported the benefit of renal transplantation in amyloidosis-induced renal failure.

Topics: Antibodies, Monoclonal; Cholangitis, Sclerosing; Dermatitis, Atopic; Drug Combinations; Gastrointestinal Agents; Humans; Immunosuppressive Agents; Inflammatory Bowel Diseases; Infliximab; Myocarditis; Osteoporosis; Psoriasis; Pyoderma Gangrenosum; Tacrolimus; Treatment Outcome; Tumor Necrosis Factor-alpha; Vitamin D

The newly developed immunomodulator tacrolimus (FK506) is the first of a new class of agents that have enormous potential to change the way that dermatoses are treated and managed. Tacrolimus has been found to be active in a topical formulation with the latter exerting its effects by acting on the signal transduction pathways inside T cells and inhibiting gene transcription. The result is decreased responsiveness of T cells to antigens. Percutaneous absorption of tacrolimus is higher in diseased skin as opposed to healthy skin and, therefore, the drug will be taken in at progressively lower quantities as lesions heal. There is limited systemic absorption of tacrolimus over the course of therapy. The most extensive experience with tacrolimus has been in treating atopic dermatitis. In numerous trials, tacrolimus ointment 0.03-0.3% has shown to be effective in reducing the symptoms and severity of atopic dermatitis in adults and the paediatric population. Furthermore, there have been no significant toxic effects associated with topical therapy with tacrolimus. The most common complaint is that of local irritation after applying the ointment. This is generally transient and the patient is able to continue with therapy. The other dermatoses where tacrolimus has been used include contact dermatitis, psoriasis and pyoderma gangrenosum.

Topics: Administration, Oral; Administration, Topical; Clinical Trials as Topic; Dermatitis, Atopic; Dermatitis, Contact; Female; Humans; Immunosuppressive Agents; Male; Prognosis; Psoriasis; Skin Absorption; Skin Diseases; Tacrolimus; Treatment Outcome

Tacrolimus and cyclosporin A are potent immunosuppressants that are used systemically to treat several inflammatory skin conditions successfully. They differ in their structure and tacrolimus is 10-100 times more potent than cyclosporin A. They have similar side-effects. They have been used topically in various clinical studies. Topical cyclosporin A is largely ineffective whereas topical tacrolimus is effective in treating atopic dermatitis. Topical tacrolimus has not been studied sufficiently in treating psoriasis although it has been used successfully in allergic contact dermatitis, erosive mucosal lichen planus and pyoderma gangrenosum.

Topics: Adult; Animals; Child; Cytokines; Dermatitis, Atopic; Female; Forecasting; Guinea Pigs; Humans; Immunosuppressive Agents; Male; Mice; Psoriasis; Tacrolimus

Tacrolimus has been shown to be a powerful suppressor of the immune system. It was introduced into clinical use to prevent allograft rejection and is now routinely used in kidney, liver, and heart transplantation. Recently, 2 double-blind multicenter studies demonstrated the therapeutic efficacy of topical and systemic tacrolimus in the inflammatory skin diseases atopic dermatitis and psoriasis.. MEDLINE was searched for relevant publications and combined with our own clinical, in vitro, and in vivo studies.. All studies dealing with tacrolimus and dermatology were reviewed.. Publications with clinically relevant data were included in this review.. Topical tacrolimus is a safe and effective therapeutic agent that may open a new era in the treatment of inflammatory skin diseases, particularly for patients with atopic dermatitis. Before its full potential in dermatology can be assessed, more clinical experience in treating children and comparison with the criterion standard of anti-inflammatory therapy, glucocorticosteroids, are needed.

Topics: Dermatitis, Atopic; Humans; Immunosuppressive Agents; Psoriasis; Skin Diseases; Tacrolimus

Psoriasis is a heterogeneous disorder not only in regard to its variability in clinical expression and age at onset, but also in the degree to which genetic and immunological factors such as T cells and cytokines contribute. A Psoriasis Treatment Index' is proposed according to clinical severity and hence suggested treatment regimens. Recent and new treatments include FK 506, cyclosporin, a fusion protein of human interleukin 2 with fragments of diphtheria toxin, topical tumour necrosis factor inhibitors, topical retinoids, T cell receptor peptide vaccines and intercellular adhesion molecule 1 (ICAM-1) antisense oligonucleotides.

Topics: Clinical Trials as Topic; Cyclosporine; Humans; Immunosuppressive Agents; Photochemotherapy; Prognosis; Psoriasis; Tacrolimus

Treatment of psoriasis is rapidly changing with improved understanding of the pathogenesis of the disease. Newer topical preparations such as calcipotriol and immunosuppressive agents such as cyclosporin A and FK506 are having a major impact on the therapy of psoriasis. This article reviews the conventional therapies and newer agents used in the treatment of this common dermatosis.

Topics: Administration, Topical; Adrenal Cortex Hormones; Anthralin; Calcitriol; Coal Tar; Combined Modality Therapy; Cyclosporine; Dermatologic Agents; Emollients; Humans; Immunosuppressive Agents; Methotrexate; Phototherapy; Psoriasis; Retinoids; Tacrolimus; United Kingdom

Topics: Adult; Animals; Autoimmune Diseases; CD4-Positive T-Lymphocytes; Cholangitis; Cyclosporine; Diabetes Mellitus, Type 1; Digestive System Diseases; Disease Models, Animal; Drug Evaluation; Drug Evaluation, Preclinical; Female; Humans; Kidney Diseases; Male; Mice; Multiple Sclerosis; Nephrotic Syndrome; Psoriasis; Rats; Swine; Tacrolimus

FK 506 is a superior immunosuppressive agent that should improve patient survival after the commonly performed transplant procedures, make feasible transplantations that have been previously impractical, allow immune intervention for serious autoimmune diseases, and create a better spin-off understanding of basic biologic processes including signal transduction.

Topics: Autoimmune Diseases; Bone Marrow Transplantation; Female; Graft Rejection; Graft vs Host Disease; Heart Transplantation; Humans; Kidney Transplantation; Liver Transplantation; Male; Nephrotic Syndrome; Psoriasis; Tacrolimus

Atopic dermatitis (AD) presents a large unmet need for treatments with better safety and efficacy. To facilitate development of topical therapeutics, we need an efficient model for assessing different formulations and concentrations. The "plaque model" has been successfully implemented in patients with psoriasis, another common inflammatory disease, to assess the efficacy of topical treatments. This model has not been validated for AD, which has higher placebo responses and less stable lesions than psoriasis.. We aimed to assess changes in molecular signatures of intrapatient target lesions treated with topical therapeutics.. We enrolled 30 patients with mild-to-moderate AD in a randomized, double-blind, intraindividual comparison of 3 approved agents applied blindly at the investigator site daily for 14 days: pimecrolimus, betamethasone dipropionate, clobetasol propionate, and a vehicle/emollient control. Changes in total sign scores (TSSs), transepidermal water loss, and tissue biomarkers (determined by using RT-PCR and immunohistochemistry) were evaluated.. TSSs showed improvements of 30%, 40%, 68%, and 76% at 2 weeks with vehicle, pimecrolimus, betamethasone, and clobetasol, respectively, with parallel changes in transepidermal water loss (P < .05). Significant differences versus vehicle values were limited to steroids (P < .0001). Steroids (particularly clobetasol) restored epidermal hyperplasia and terminal differentiation versus minimal changes with vehicle or pimecrolimus (P < .001). Levels of cellular infiltrates and cytokines (IL-13, IL-22, and S100As) were similarly reduced only by steroids (P < .001). TSS improvement correlated with changes in hyperplasia, infiltrates, and differentiation markers.. We detected significant clinical and tissue differences between agents, providing a novel approach to study the differential effects of topical formulations using a limited sample size.

Topics: Administration, Topical; Adult; Aged; Anti-Inflammatory Agents; Betamethasone; Biomarkers; Cell Differentiation; Clobetasol; Cytokines; Dermatitis, Atopic; Female; Humans; Hyperplasia; Male; Middle Aged; Placebo Effect; Psoriasis; Skin; Tacrolimus; Young Adult

Despite recent advances in the treatment of psoriasis, the therapeutic options for nail psoriasis are very limited, particularly when this is the only manifestation of the disease.. We performed a randomized controlled open-label study to assess the efficacy and safety of a topical treatment with tacrolimus 0.1% ointment in nail psoriasis.. In each patient, tacrolimus 0.1% ointment was prescribed for application only on the affected nails of a randomly selected hand for 12 weeks, whereas nails of the other hand did not receive any treatment. Severity of nail psoriasis was evaluated using the Nail Psoriasis Severity Index (NAPSI) score.. We enrolled 21 consecutive psoriatic patients. At week 12, a statistically significant (P < 0.001) improvement was obtained in the treated hands with respect to the hands used as control (NAPSI score absolute change 13.0 and 3.0 respectively). Each of the enrolled patients concluded the period of treatment, but one patient was withdrawn from tacrolimus application after 9 weeks because of the appearance of acute paronychia.. Our study showed that tacrolimus 0.1% ointment may be an efficacious and safe therapeutic opportunity in the treatment of nail psoriasis. Our data should be confirmed by a double-blind study with a larger sample of patients.

Topics: Humans; Immunosuppressive Agents; Nail Diseases; Ointments; Psoriasis; Tacrolimus

Calcipotriene ointment is widely used in the topical treatment of psoriasis, with tacrolimus ointment as an effective alternative in controlling stable plaque psoriasis. The efficacy of the combination of both products on stable plaque psoriasis has not been assessed in the literature consulted. We evaluated the efficacy of calcipotriene ointment 0.005% applied twice daily, tacrolimus ointment 0.1% applied twice daily, or a morning application of calcipotriene and an evening application of tacrolimus in 27 participants with stable plaque psoriasis over an 8-week treatment period. The mean reduction in the sum of the scores between baseline and week 8 was significant (P = .001) for calcipotriene alone (39.5%), tacrolimus alone (38.2%), and the combination of calcipotriene and tacrolimus (60.7%). Combination therapy was statistically more effective than tacrolimus alone (P = .043) but not statistically superior to calcipotriene alone (P=.056). Most adverse events (AEs) were related to skin irritation and pruritus; however, no AEs were evident in participants given the combination therapy.

Topics: Adolescent; Adult; Aged; Calcitriol; Dermatologic Agents; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Ointments; Pilot Projects; Psoriasis; Tacrolimus; Treatment Outcome; Young Adult

Despite new treatment options with systemic disease modifiers, topical therapy - especially as combination therapy - plays an important role in psoriasis treatment.. Antipsoriatic efficacy of methylprednisolone aceponate ointment (MPA), tacrolimus 0.1% ointment (FK506) and their combination (MPA+FK506) were investigated in a double-blind randomized pilot study using the psoriasis plaque test. Agents and corresponding placebos were applied once daily under occlusion for 11 days. Test sites were evaluated by sum score (erythema, scaling, infiltration), objective assessment by 20-MHz-sonography and optical coherence tomography (OCT).. After 11 days, the sum score significantly improved from baseline value in FK506-treated skin (9.6 vs. 2.9, p < 0.0001). MPA led to a significant improvement of the sum score (9.4 vs. 0.6, p < 0.0001). Combination therapy showed results similar to MPA monotherapy (9.4 vs. 0.4, p < 0.0001). These findings were confirmed by 20-MHz-sonography and OCT data.. FK506 is moderately effective in chronic plaque-type psoriasis in our model. Combination therapy with FK506+MPA has no additive effect compared to MPA alone.

Topics: Adult; Aged; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Methylprednisolone; Middle Aged; Psoriasis; Tacrolimus; Tomography, Optical Coherence; Ultrasonography

Facial psoriasis requires a treatment approach other than topical corticosteroids which bear the risk of skin atrophy. Topical pimecrolimus has been shown to be effective in atopic eczema and recently in psoriasis.. The aim of this open-label single-center investigator-initiated study was to evaluate the efficacy and safety of pimecrolimus 1% cream in patients with facial psoriasis.. 20 adults with facial psoriasis were enrolled. Pimecrolimus 1% cream was applied twice daily to psoriatic lesions of the face over an 8-week period. An 8-week follow-up was added.. All clinical parameters showed a significant improvement after 8 and 16 weeks compared to baseline. Pimecrolimus 1% cream was effective and well tolerated.. This is the first clinical study with a larger patient cohort reporting a relevant therapeutic effect and favorable safety profile of pimecrolimus 1% cream in facial psoriasis.

Topics: Administration, Topical; Adult; Aged; Calcineurin Inhibitors; Dermatologic Agents; Dose-Response Relationship, Drug; Face; Female; Follow-Up Studies; Humans; Male; Middle Aged; Ointments; Prospective Studies; Psoriasis; Tacrolimus; Treatment Outcome

Tacrolimus gel 0.3% and tacrolimus cream 0.5% were studied and compared with calcipotriol ointment 0.005%, as topical treatment for mild to moderate plaque psoriasis. Tacrolimus is able to inhibit several cellular processes thought to be important in the pathogenesis of psoriasis, e.g. the transcription of proinflammatory cytokines, keratinocyte hyperproliferation and the expression of HLA-DR in lesional psoriatic skin.. In the present study we investigated the effects of preparations of tacrolimus and calcipotriol ointment on SUM score, hyperproliferation (Ki67-positive keratinocytes), keratinization (percentage keratin 10 (K10)-positive epidermal surface), T-cell subsets (CD4, CD8, CD45RO, CD45RA, CD2, CD25), cells expressing natural killer receptors and HLA-DR expression. The following three topical treatments were studied in chronic plaque psoriasis over a 12-week treatment period: calcipotriol ointment 0.005% twice daily, tacrolimus gel 0.3% twice daily and tacrolimus cream 0.5% twice daily.. The mean reductions in SUM score between day 0 and week 12 for calcipotriol ointment, tacrolimus gel and cream were significant. Calcipotriol ointment, and tacrolimus gel and cream had a comparable effect on epidermal proliferation (Ki67-positive cells), but calcipotriol is significantly more effective in normalizing differentiation (K10-positive epidermal surface). Calcipotriol and tacrolimus gel both reduced several lesional T-cell subsets significantly, whereas the effect induced by tacrolimus cream was modest.. Calcipotriol and tacrolimus gel are comparable in reducing the SUM score, the number of Ki67-positive cells and T-cell subsets and HLA-DR expression, although calcipotriol induces a more substantial improvement of keratinization.

Topics: Calcitriol; Dermatologic Agents; Drug Administration Routes; Gels; HLA-DR Antigens; Humans; Immunohistochemistry; Immunosuppressive Agents; Keratinocytes; Psoriasis; Severity of Illness Index; Skin Physiological Phenomena; T-Lymphocyte Subsets; Tacrolimus; Treatment Outcome

Two nonsteroidal topical agents, calcitriol and tacrolimus, have been reported to be effective and safe for psoriatic lesions on sensitive areas. However, no comparative studies between calcitriol and tacrolimus have been reported.. To compare the tolerability and efficacy of calcitriol 3 microg g(-1) and tacrolimus 0.3 mg g(-1) ointment in chronic plaque psoriasis affecting facial and genitofemoral regions.. This is a double-blind, parallel, 6-week study of 50 patients who were randomized in a 1 : 1 ratio to apply calcitriol or tacrolimus twice daily. The primary efficacy variable was the mean reduction of the target area score (TAS), and the secondary efficacy variable was the percentage of patients with the Physician's Global Assessment (PGA) score of 5 (clear) and 4 (almost clear) at the end of the study.. Both calcitriol and tacrolimus were well tolerated. Although calcitriol induced perilesional erythema in a statistically significant higher proportion of patients than tacrolimus (55% vs. 16% at week 6; P < 0.05), it did not necessitate treatment discontinuation. At the end of the study, tacrolimus was significantly more effective than calcitriol based on a significant reduction of mean TAS (67% vs. 51%; P < 0.05) as well as more patients achieving complete or almost complete clearance by PGA (60% vs. 33%; P < 0.05).. Both calcitriol 3 microg g(-1) and tacrolimus 0.3 mg g(-1) are safe and well-tolerated therapeutic agents in the treatment of psoriasis in sensitive areas. Tacrolimus demonstrated a more effective clinical outcome compared with calcitriol.

Topics: Administration, Cutaneous; Adult; Aged; Calcitriol; Dermatologic Agents; Double-Blind Method; Facial Dermatoses; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Ointments; Psoriasis; Tacrolimus; Treatment Outcome; Vitamins

The efficacy and safety of 0.3% tacrolimus gel and 0.5% tacrolimus cream compared with calcipotriol ointment were evaluated in adults (n = 124) with mild to moderate plaque psoriasis. Treatment was twice daily for a maximum of 12 weeks. Clinical efficacy was assessed by the percentage change in the local psoriasis severity index of a target lesion between baseline and week 12. By week 12, the median percentage changes in local psoriasis severity index of the target lesions in the tacrolimus gel, tacrolimus cream and calcipotriol groups were 55.6%, 50.0% and 58.6%, respectively (no statistically significant differences). Clinical improvement was observed after one week and increased throughout the study. Tacrolimus-treated patients experienced more application site skin burning (tacrolimus gel and cream both 31.0% versus 7.5% for calcipotriol; p = 0.011). Skin burning was mostly mild in intensity and decreased substantially after 1 week of treatment. There were no differences in the nature and incidence of infections and no clinically relevant changes in laboratory values.

Topics: Administration, Topical; Adolescent; Adult; Aged; Aged, 80 and over; Calcitriol; Dermatologic Agents; Dose-Response Relationship, Drug; Female; Gels; Humans; Immunosuppressive Agents; Male; Middle Aged; Ointments; Psoriasis; Severity of Illness Index; Tacrolimus; Treatment Outcome

Tacrolimus is an immunosuppressive drug that has proved effective in the treatment of psoriasis when administered systemically. Topically, it seems only useful in thin psoriasis plaques located on the face, genitalia, and intertriginous areas. We present an open-label clinical trial to test the efficacy of 0.1% tacrolimus ointment in patients with psoriasis on the face, intertriginous areas, both, and in corporal plaques. Efficacy was assessed with the evaluation of erythema, desquamation, infiltration, reduction of the PASI, and reduction of itching. A total of 15 patients were enrolled in the study. In all the localizations evaluated, each of the signs (erythema, desquamation, and infiltration) showed a statistically significant improvement when compared to the baseline (p < .001). Itching also improved rapidly. PASI was also reduced from a mean of 12 at baseline to 2.2 at the end of the study. Of the 15 patients, only 2 experienced an adverse effect (13%), which was described as a warm sensation in facial lesions which was transient and self-limited. In conclusion, tacrolimus ointment may be an alternative to classical options for the treatment of psoriasis, not only for intertriginous, genital, and facial areas, but also for corporal plaques without occlusion, with good tolerance.

Topics: Adult; Aged; Aged, 80 and over; Elbow; Erythema; Facial Dermatoses; Female; Genitalia; Humans; Immunosuppressive Agents; Intertrigo; Lumbosacral Region; Male; Middle Aged; Ointments; Psoriasis; Severity of Illness Index; Skin; Tacrolimus; Treatment Outcome

Psoriasis is a common skin condition affecting approximately 2.6% of the population in the US. The most effective current therapies for psoriasis have suppressive activity against T lymphocytes directly or by modulating the biologic effects of inflammatory cytokines. Tacrolimus has been used successfully to treat a number of T cell-mediated diseases. UVA1 has been shown to induce T lymphocyte apoptosis. Combination treatment is commonly used in the management of psoriasis. Therefore, this pilot study was performed to evaluate if the combination of medium-dose UVA1 (50 J/cm2) and tacrolimus ointment is effective for the treatment of palmar plantar psoriasis. A total of 5 patients completed the study of 30 UVA1 treatments, and another patient completed half of the treatments. No dramatic changes in plaque thickness or scaling were seen with either tacrolimus alone or with the combination of tacrolimus and medium dose UVA1 on palmar or plantar psoriasis.

Topics: Dermatologic Agents; Humans; Immunosuppressive Agents; Ointments; Psoriasis; Severity of Illness Index; Tacrolimus; Treatment Outcome; Ultraviolet Therapy

During the last decades, management of intertriginous psoriasis (IP) has been unsatisfactory because of the adverse effects associated with long-term corticosteroid application and the lack of alternatives. Recently, both pimecrolimus and tacrolimus have been investigated for this indication and shown to be safe and effective. So far, to our knowledge, a comparison of one of these drugs with standard regimens for IP has not been performed.. A single-center, 4-week, double-blind, randomized, vehicle-controlled comparison study to assess the safety and efficacy of 1% pimecrolimus, 0.005% calcipotriol, and 0.1% betamethasone valerate in the treatment of IP.. Dermatologic hospital at Ruhr University of Bochum.. Eighty adults with IP.. Treatment of IP with 1% pimecrolimus, 0.005% calcipotriol, 0.1% betamethasone, or the vehicle once daily for 28 days.. Mean reduction of the Modified Psoriasis Area and Severity Index (M-PASI) score after 28 days of treatment was considered the primary outcome measure, which was analyzed on an intention-to-treat basis. The secondary outcome was a visual analog scale score for itching.. After 4 weeks of treatment, the 3 active compounds and the vehicle resulted in a significant decrease in mean M-PASI score (86.4% for 0.1% betamethasone, 62.4% for 0.005% calcipotriol, 39.7% for 1% pimecrolimus, and 21.1% for vehicle). The 0.1% betamethasone was significantly more effective than 1% pimecrolimus during the study period (P<.05). No significant difference was found between 0.005% calcipotriol and 0.1% betamethasone and between 0.005% calcipotriol and 1% pimecrolimus. The visual analog scale score for pruritus decreased by 78% for 0.1% betamethasone, 57% for 0.005% calcipotriol, 35% for 1% pimecrolimus, and 43% for the vehicle, again demonstrating a clear advantage for the corticosteroid (P<.05).. The 1% pimecrolimus was shown to be less potent than 0.1% betamethasone in the treatment of IP. Considering the adverse-effect profile of long-term application of corticosteroids, occasional or intermittent rescue therapy with short-term topical corticosteroids and maintenance with a less potent agent, such as 1% pimecrolimus or 0.005% calcipotriol, might be appropriate for patients with IP in general practice.

Topics: Administration, Cutaneous; Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents; Betamethasone; Calcineurin Inhibitors; Calcitriol; Double-Blind Method; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Peptidylprolyl Isomerase; Psoriasis; Severity of Illness Index; Tacrolimus; Treatment Outcome

While oral tacrolimus is effective for the treatment of psoriasis, tacrolimus ointment has shown only spotty efficacy in the treatment of plaque psoriasis. The efficacy of tacrolimus ointment for the treatment of facial and intertriginous psoriasis suggests that if tacrolimus penetration can be increased, the ointment could be used for effective treatment of plaque psoriasis.. To assess whether tacrolimus ointment is an effective psoriasis treatment when used in a combination regimen with the penetration-enhancer salicylic acid.. A total of 30 adult subjects with generally symmetrical plaque-type psoriasis were randomized to treatment with 6% salicylic acid gel plus vehicle or 6% salicylic acid gel plus 0.1% tacrolimus ointment in a 12-week left-right comparison study. The primary outcome was the difference between tacrolimus- and vehicle-treated target lesions in the change in the sum of erythema, scale, and thickness scores from baseline to end of treatment.. A total of 24 subjects completed the trial. Combination treatment with tacrolimus ointment or vehicle plus salicylic acid gel was well tolerated. There was greater improvement of the sum score in the tacrolimus plus salicylic acid-treated target plaques than in the vehicle plus salicylic acid-treated plaques at weeks 1, 2, and 8 (P<.05). The efficacy of this regimen was confirmed by investigator and subject global assessments of plaque severity.. The combination of 0.1% tacrolimus ointment and 6% salicylic acid gel is an effective treatment for psoriasis. Although the results reported herein are from a small exploratory study, the magnitude of the effect was sufficiently large as to be detectable with statistical significance (P<.05).

Topics: Administration, Topical; Adult; Aged; Drug Therapy, Combination; Female; Gels; Humans; Immunosuppressive Agents; Male; Middle Aged; Psoriasis; Salicylic Acid; Severity of Illness Index; Tacrolimus; Treatment Outcome

There is a need for safe and effective alternative treatments for patients with moderate to severe psoriasis.. Pimecrolimus is a calcineurin inhibitor that is being investigated in oral form for the treatment of psoriasis.. A double-blind, randomized, parallel-group, dose-finding study was performed. Healthy adult outpatients with moderate to severe chronic plaque-type psoriasis (n = 143) were randomized to receive oral placebo or pimecrolimus 10 mg, 20 mg or 30 mg twice daily (b.d.) for 12 weeks.. The Psoriasis Area and Severity Index (PASI) was used to assess clinical severity of psoriasis. Results were analysed at weeks 7 (primary endpoint) and 13. Safety was assessed by monitoring all adverse events, laboratory investigations (blood chemistry, urinalysis, haematology) and physical examinations.. The change from baseline in PASI at week 7 showed a dose-dependent effect. The differences between each of the two higher doses of pimecrolimus and placebo were statistically significant (P < 0.001; ANOVA). The mean percentage decreases from baseline in PASI in the placebo group and pimecrolimus 10 mg, 20 mg and 30 mg b.d. groups at week 7 were 3.1%, 22.2%, 51.3% and 54.0%, respectively. Most adverse events were of mild or moderate severity. The only adverse event to show a dose-response relationship was a transient feeling of warmth. No clinically relevant effects on laboratory parameters were observed, and no increase in skin infection with pimecrolimus was seen.. Oral pimecrolimus produces a dose-dependent reduction in psoriasis severity, with doses of 20 mg and 30 mg b.d. being the most effective and well tolerated.

Topics: Abdominal Pain; Adult; Aged; Blood Glucose; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Middle Aged; Psoriasis; Severity of Illness Index; Skin; Sleep Initiation and Maintenance Disorders; Statistics as Topic; Tacrolimus; Treatment Outcome

Tacrolimus is an immunomodulatory agent that inhibits the activation and maturation of T-cells and blocks transcriptional activation of several cytokine genes. It also interferes with the function of Langerhans cells, basophil cells and mast cells. Recent studies have demonstrated the efficacy of topical tacrolimus in inflammatory skin disorders. Our objective was to assess the efficacy of topical treatment with tacrolimus ointment 0.1% in patients with psoriasis on the anogenital region and the face. Included in the study were 10 patients with a long-standing history of genital and facial psoriasis, partially controlled with periodic use of topical corticosteroids. Tacrolimus ointment 0.1% was applied twice daily for 10 days. The patients were followed-up every 3 weeks for a total period of 12 weeks. The severity of psoriasis was evaluated in all patients at baseline (day 0) and at the end of weeks 3, 6, 9 and 12. Clinical severity of erythema, scaling, infiltration and lesional extent were graded using a 0-3 scale indicating none, mild, moderate and severe expression, at baseline and at follow-ups. An overall severity score of 0 (clear), 1-4 (mild), 5-8 (moderate) or 9-12 (severe) was then assigned to each patient by adding the scores for the above parameters. On each visit, every patient was evaluated clinically. The decision to reapply the drug was determined by the clinical response of each patient at each visit. At the end of the study, patients also assessed efficacy, safety and tolerance after topical application of tacrolimus ointment using a 0-5 scale for each parameter: A marked improvement was noticed in all patients at the end of the first week without drug-related adverse effects. There were 15 recurrences during the 12-week period in all patients. In conclusion, tacrolimus ointment 0.1% seems to represent a safe new option for the treatment of genital and facial psoriasis. Further studies are probably needed to specify the therapeutic dosage and maintenance therapy

Topics: Adult; Face; Female; Genital Diseases, Male; Humans; Immunosuppressive Agents; Male; Psoriasis; Tacrolimus

Biopharmaceuticals that target specific disease-mediating molecules have advanced our understanding of the pathogenesis of psoriasis. The traditional paradigm that psoriasis is primarily a disease of epidermal cells has been replaced with a model that now includes keratinocyte-derived factors, inflammatory mediators and angiogenic mechanisms. Recent studies have highlighted some of the key molecules involved in all of these pathogenic processes. Several have already been evaluated as putative targets in in vitro and in vivo studies, whereas other molecules are significantly upregulated in psoriasis and require further study to elucidate their role and contribution to disease. Although not all these molecules will eventually qualify as drug targets, data from similar experimental strategies are predicted to underpin the next generation of candidate targets and novel therapeutic approaches.

Topics: Angiogenesis Inhibitors; Animals; Dermatologic Agents; Humans; Keratinocytes; Psoriasis; Tacrolimus; Vascular Endothelial Growth Factors

Patients are commonly nonadherent to medication regimens. In dermatology, there has been little study of the effect of nonadherence on outcomes.. To test the association between adherence behaviour and changes in severity of psoriasis.. Twenty-four subjects with psoriasis were enrolled in an 8-week, left/right, controlled trial of salicylic acid plus topical tacrolimus ointment vs. salicylic acid plus placebo. Subjects were given salicylic acid to apply to all lesions. The salicylic acid was supplied in a bottle with a medication event monitoring system cap in order to assess adherence to the salicylic acid. The primary outcome for this study was the relationship between the change in the disease severity (change in sum score of erythema, scale and thickness scores for a target plaque) and medication adherence.. The mean initial disease severity was 5.8 on a nine-point sum score scale. For the topical tacrolimus-treated side, a decrease in adherence rate of 10% was associated with a 1-point increase in severity (P < 0.05). For the placebo-treated side, adherence was not significantly correlated with changes in severity.. Nonadherence may have a significant role in altering clinical trial data, skewing it towards ineffectiveness. Improved outcomes in psoriasis may be achievable through interventions that improve patients' adherence to treatment.

Topics: Adolescent; Adult; Aged; Drug Monitoring; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents; Keratolytic Agents; Male; Middle Aged; North Carolina; Patient Compliance; Psoriasis; Salicylic Acid; Severity of Illness Index; Tacrolimus; Treatment Outcome

Intertriginous and facial involvement are manifestations of psoriasis that require a different approach than is used for typical plaque psoriasis on other skin areas. Topical corticosteroids are the primary treatment for psoriasis; however, the side effects of corticosteroids are magnified on intertriginous and facial skin. Topical tacrolimus offers the potential for anti-inflammatory effect without the atrophy or other local side effects associated with the use of topical corticosteroids.. To determine the efficacy and tolerability of 0.1% tacrolimus ointment for the treatment of facial or intertriginous psoriasis.. One hundred sixty-seven patients 16 years or older were evaluated in an 8-week, randomized, double-blind, vehicle-controlled, multi-center study. Upon entry into the study, patients were randomized 2:1 to apply the tacrolimus ointment 0.1% or vehicle twice daily to all psoriatic lesions of the face or intertriginous areas for 8 weeks. The physician's global assessment was used to assess improvement from baseline. The inverse psoriasis severity for patients was measured using a 6-point scale from clear to very severe.. As early as day 8, more patients ( P = .004) had cleared or achieved excellent improvement in the 0.1% tacrolimus ointment group compared to the vehicle group (24.8% vs 5.8%). At the end of the 8-week treatment period 65.2% of the tacrolimus ointment group and 31.5% of the vehicle were clear or almost clear ( P < .0001) based on a Static Severity Score. Adverse events were similar in the 0.1% tacrolimus ointment and vehicle groups. Conclusion Tacrolimus ointment is an effective treatment for psoriasis of the face or intertriginous areas.

Topics: Adolescent; Adult; Dermatologic Agents; Double-Blind Method; Facial Dermatoses; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Ointments; Psoriasis; Tacrolimus

Inverse psoriasis can be difficult to treat because of the high sensitivity of intertriginous areas to cutaneous side effects, such as irritation and striae. Pimecrolimus, a well-tolerated, nonatrophogenic, skin-selective inflammatory cytokine inhibitor, has been shown to be effective in the treatment of psoriasis when applied topically under occlusion.. This study evaluated the efficacy and safety of pimecrolimus cream 1% versus vehicle twice a day in the treatment of inverse psoriasis. Methods This was a double-blind, randomized, vehicle-controlled study in 57 patients with moderate to severe inverse psoriasis. Patients were evaluated using Investigator's Global Assessment of overall severity, Target Area Score, and Patient Self-Assessment.. A significant between-group difference was observed early on, with 54% of the pimecrolimus group versus 21% of the vehicle group having an Investigator's Global Assessment score of 0 or 1 (clear or almost clear) at week 2 ( P = .0169). By week 8, 71% of the pimecrolimus group had an Investigator's Global Assessment score of 0 or 1. Change from baseline in Target Area Score was -2.4 (pimecrolimus group) compared with -0.7 (vehicle) at day 3 ( P < .0001). By week 8, 82% of patients using pimecrolimus scored their disease as well or completely controlled versus 41% of the vehicle group ( P = .0007). Adverse events were similar between groups.. Pimecrolimus cream 1% is an effective treatment for inverse psoriasis with a rapid onset of action, and is safe and well-tolerated.

Topics: Administration, Topical; Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Dermatologic Agents; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Ointments; Psoriasis; Tacrolimus; Treatment Outcome

The safety and efficacy of 0.1% tacrolimus ointment for the treatment of psoriasis on the face, intertriginous areas, or both were evaluated in an open-label, clinical trial of 21 patients with psoriasis. Patients applied 0.1% tacrolimus ointment twice daily for 8 weeks. Efficacy was assessed through the investigator's evaluation of the individual signs and symptoms of psoriasis, and the physician's global evaluation of change in disease status. Assessments of cutaneous atrophy and other adverse events were made throughout the study to evaluate the safety of tacrolimus ointment. A total of 21 patients were enrolled in the study; 21 patients at least 18 years of age received study medication. Statistically significant improvement in the physician's assessment of the individual signs and symptoms was observed during the study. A total of 81% of patients (17 of 21) experienced complete clearance at day 57 (end of treatment). Only 2 patients reported adverse events, which were limited to itching and the feeling of warmth at the application site. None of the patients had atrophy, telangiectasia, or striae develop during the study. In summary, tacrolimus 0.1% ointment may be a safe and effective treatment option for patients with psoriasis on the face, intertriginous areas, or both.

Topics: Administration, Topical; Adult; Aged; Aged, 80 and over; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Ointments; Psoriasis; Tacrolimus

Pimecrolimus (Elidel, SDZ ASM 981), a new macrolactam ascomycin derivative, was highly effective in treating plaque-type psoriasis when applied under Finn-chamber occlusion. A two-centre, randomized, double-blind, vehicle- and positive-controlled within-patient study was therefore conducted in 23 adult psoriasis patients. Pimecrolimus 1% was applied, twice daily, in an experimental ointment formulation, along with the corresponding vehicle, 0.005% calcipotriol ointment and 0.05% clobetasol-17-propionate ointment to test sites without occlusion for 21 days. Erythema, induration and scaling (score: 0 [absent] to 4 [severe]) were evaluated. The total sign score was defined as the sum of the erythema, induration and scaling scores (range 0-12). Pimecrolimus 1% ointment was significantly (p = 0.03) more effective than the corresponding vehicle, with an improvement in total sign score of 51.4% compared with 36.7% for the corresponding vehicle. Improvements with calcipotriol and clobetasol-17-propionate were 71.5% and 88.3%, respectively. No local or systemic drug-related side effects were observed in the study. We conclude that pimecrolimus 1% in the experimental ointment formulation was significantly more effective than its corresponding vehicle, but less effective than calcipotriol and clobetasol ointment. This is the first study reporting a significant therapeutic effect of pimecrolimus in an ointment formulation applied without occlusion to psoriatic plaques.

Topics: Administration, Topical; Adult; Double-Blind Method; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Occlusive Dressings; Ointments; Pharmaceutical Vehicles; Psoriasis; Tacrolimus; Treatment Outcome

The ascomycin macrolactam pimecrolimus is a novel inflammatory cytokine release inhibitor that so far has not been administered systemically to humans. In this phase I/II randomized double-blind, placebo-controlled, multiple rising dose proof of concept study psoriasis patients were treated with oral pimecrolimus or placebo. Gene profiling identified a common genomic profile with a downregulation of genes associated with inflammation but no changes in gene expression linked to drug-related side-effects. A steady state of pimecrolimus was reached after 5-10 d, Cmax, and area under the curve (0-24) was 54.5 ng per ml and 589.9 ng h per ml, respectively, at steady state at the highest dose. There was clear clinical efficacy in patients receiving 20 mg pimecrolimus twice daily and 30 mg twice daily with a reduction of Psoriasis Area and Severity Index by 60% and 75%, respectively. Histopatho logically and immunopathologically there was a reversion of the psoriatic phenotype towards normal. There were no notable clinical, laboratory, kidney function, or immunologic side-effects. We conclude that pimecrolimus taken orally is highly effective in a concentration-dependent manner in patients with psoriasis and on a short-term basis it is well tolerated and this is confirmed by its pharmacogenomic profile. The latter also indicates that pimecrolimus should be equally effective in other inflammatory skin diseases.

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follow-Up Studies; Gene Expression Profiling; Humans; Male; Middle Aged; Psoriasis; Recurrence; Tacrolimus

Tacrolimus (FK506) is an effective and well tolerated immunosuppressant used to prevent allograft rejection. We describe the evaluation of two tacrolimus ointment formulations for treatment of chronic plaque-type psoriasis. This was a microplaque assay with randomized, double-blind design. Sixteen patients (15 men, one woman, all white and 28-69 years old) with chronic plaque-type psoriasis participated. Six different ointments were applied to discrete microplaques, 17 mm in diameter, on a descaled psoriasis lesion: these were tacrolimus ointment with diisopropyl adipate as penetration enhancer, tacrolimus ointment without diisopropyl adipate, 0.1% betamethasone 17alpha-valerate ointment, 0.005% calcipotriol ointment and, as controls, the ointment bases for tacrolimus and betamethasone. Ointments were reapplied and the area was sealed every 2-3 days during the 14-day treatment period. After 7 and 14 days, erythema and infiltration were graded on a scale of 0-4, and superficial blood flow was measured with a laser Doppler flowmeter. Epidermal thickness was measured histologically at the end of treatment. Compared with the vehicle controls, sites treated with tacrolimus ointment (with or without penetration enhancer) showed a significant reduction in erythema and infiltration (P < 0. 001), a significant reduction in superficial blood flow (P < 0.01) and a significant decrease in epidermal thickness (P < or = 0.001). Results for betamethasone and calcipotriol, when compared with the vehicle controls, were similar. These results suggest that, under conditions of descaling and occlusion, tacrolimus ointment is effective in the treatment of psoriasis.

Topics: Administration, Topical; Adult; Aged; Anti-Inflammatory Agents; Betamethasone; Calcitriol; Dermatologic Agents; Double-Blind Method; Female; Glucocorticoids; Humans; Immunosuppressive Agents; Male; Middle Aged; Ointments; Psoriasis; Skin Tests; Statistics, Nonparametric; Tacrolimus

Cyclosporine for the treatment of psoriasis constitutes a new approach. Alternative systemic cyclosporine derivatives have been studied to find an immunosuppressive drug with fewer adverse effects. Tacrolimus is one of these new immunosuppressive drugs. Systematically, it has been proven effective in treating psoriasis. A topical formulation of tacrolimus is attractive because it has fewer adverse effects and is useful for a large group of patients. We report for the first time on the efficacy of nonocclusive topical tacrolimus in the treatment of psoriasis.. After a washout phase of 2 weeks, patients were randomized to receive 0.005% calcipotriol ointment twice daily, placebo ointment once daily, or 0.3% tacrolimus ointment once daily. One psoriatic plaque was treated with a surface area of 40 to 200 cm2. Efficacy was estimated using the local psoriasis severity index. The reduction in the local psoriasis severity index score after 6 weeks was 62.5% in the calcipotriol group, 33.3% in the tacrolimus group, and 42.9% in the placebo group.. There was no statistically significant difference between the efficacy of tacrolimus and placebo ointment (P = .77). Calcipotriol ointment, applied twice daily, had a better effect than tacrolimus ointment and placebo ointment once daily.

Topics: Administration, Cutaneous; Chronic Disease; Humans; Immunosuppressive Agents; Pilot Projects; Psoriasis; Tacrolimus

Topical SDZ ASM 981 has been found to be highly effective in preclinical models of T-cell-mediated skin disease. T cell activation is crucial in the pathogenesis of psoriasis. It has been hypothesized that SDZ ASM 981 may prove to be an effective treatment for chronic plaque psoriasis. Therefore, the study objective was to determine the efficacy, tolerability and safety of the new topical macrolactam, SDZ ASM 981, for chronic plaque psoriasis. Ten patients with chronic plaque-type psoriasis were treated with SDZ ASM 981 (0.3% and 1.0%), the corresponding ointment base (placebo) and open-labelled clobetasol-17-propionate ointment (0.05%) in a randomized, double-blind, within-subject comparison for 2 weeks using the microplaque assay. Evaluation was performed by daily determination of clinical scores for erythema and induration. The results of the study showed that, after 2 weeks of treatment, total scores described by 92% for clobetasol, by 82% for 1 SDZ ASM 981, by 63% for 0.3% SDZ ASM 981 and by 18% for the ointment base (placebo). No adverse drug effects were seen in any patient throughout the study. We conclude from our results that the new macrolactam SDZ ASM 981 (1%) is similar to clobetasol-17-propionate (0.05%) in plaque-type psoriasis when applied topically under occlusion for 2 weeks using the microplaque assay.

Topics: Administration, Topical; Adult; Aged; Dermatologic Agents; Double-Blind Method; Female; Humans; Male; Middle Aged; Ointments; Psoriasis; Tacrolimus; Treatment Outcome

Accumulating evidence suggests that psoriasis may be a genetically determined immunogenic, inflammatory disorder based on an ongoing autoreactive Th-1 response. Systemic immunosuppressive therapy is highly effective but fraught with longterm side effects. Our research therefore focuses on therapeutic strategies that induce local immunosuppression in the skin by topical, transepidermal delivery of immunosuppressive drugs. SDZ 281-240 is a newly developed macrolide of the ascomycin type. It is immunosuppressive by mechanism of action similar to that of FK506 but has no antiproliferative activity against keratinocytes in vitro. To evaluate whether SDZ 281-240 exhibits antipsoriatic activity when applied topically, we tested 15 patients with severe, recalcitrant psoriasis, using a microplaque assay in randomized, double-blind, placebo-controlled study, comparing the therapeutic efficacy of the macrolide with a potent halogenated corticosteroid and vehicle. All patients showed a significant improvement of psoriatic lesions treated with two concentrations of the macrolide and, as expected, with the corticosteroid but not with placebo. Both concentrations of the macrolide led to clearing of psoriasis after 10 days of treatment and biopsies confirmed a reversal of the histopathological and immunopathological phenotype of psoriasis to that of normal skin. Thus, an immunosuppressive agent that interferes with early T cell activation can be designed to penetrate into psoriatic lesions when applied topically and to be functionally active within the skin to suppress the ongoing psoriatic process.

Topics: Administration, Topical; Aged; Animals; Double-Blind Method; Humans; Immunosuppressive Agents; Mice; Mice, Inbred BALB C; Mice, Inbred CBA; Psoriasis; Tacrolimus

Fifty patients with severe recalcitrant plaque-type psoriasis were randomized to receive treatment with either oral tacrolimus (FK 506) (n=27) or placebo (n=23) for 9 weeks. The two treatment groups were comparable with respect to baseline demographic data. The initial dose was 0.05 mg/kg per day and, in cases of insufficient efficacy, could be increased to 0.10 and 0.15 mg/kg per day at the end of weeks 3 and 6, respectively. Treatment efficacy was based on the percentage reduction in the Psoriasis Area and Severity Index compared with baseline data. Patients were defined as responding to therapy if the percentage change in the Psoriasis Area and Severity Index from baseline after 3, 6, and 9 weeks was 20% or greater, 45% or greater, and 70% or greater, respectively. Safety was assessed on the basis of all adverse events reported.. At the end of week 9, tacrolimus+-treated patients had a significantly greater reduction in the Psoriasis Area and Severity Index than did placebo-treated patients (tacrolimus, -83; placebo, -47; P<.02). Similar numbers of patients in both groups responded to therapy at the end of week 3, but at the end of weeks 6 and 9, more tacrolimus-treated patients responded to therapy (week 6 ,12 tacrolimus- and six placebo-treated patients; week 9, 12 tacrolimus- and three placebo-treated patients). Diarrhea, paresthesia, and insomnia were the most frequently reported causally related adverse events in the tacrolimus-treated group. All of the reported adverse events were mild or moderate in severity, and all resolved without a change in study medication.. Compared with placebo, tacrolimus is efficacious in the treatment of recalcitrant plaque-type psoriasis.

Topics: Adolescent; Adult; Aged; Double-Blind Method; Europe; Female; Humans; Male; Middle Aged; Placebos; Prospective Studies; Psoriasis; Tacrolimus

Recently, the keratinocyte IL-8/IL-8 receptor (IL-8R) pathway has been implicated in the pathogenesis of psoriasis, and there is evidence that the potent macrolide immune suppressant tacrolimus (formerly FK506) can inhibit this pathway in vitro. In this study, determination of the expression of cytokine mRNAs in lesional skin of patients with active disease by reverse transcriptase polymerase chain reaction revealed transcripts for IL-1 beta, tumour necrosis factor-alpha (TNF-alpha), IL-6, IL-8, IL-8R, IL-10, interferon-gamma (IFN-gamma), IL-2R and transforming growth factor-beta (TGF-beta), but not IL-2 or IL-4. IL-8 was the only cytokine expressed in affected skin of all patients but not in clinically normal skin of healthy subjects. In seven CD4+ T cell clones propagated from the lesional skin of an untreated psoriasis patient, IL-8 was expressed by the skin-derived T lymphocytes and not by feeder cells (irradiated autologous blood lymphocytes); IL-1 beta, IL-2, IL-6 and IL-10 were also expressed by some or all of the T cell clones. IL-8 mRNA was not detected in the skin of any patient after the start of systemic tacrolimus therapy; IL-1 beta, IL-6 and IFN-gamma transcripts were also reduced. By 12 weeks, the mean psoriasis area and severity index (PASI) had decreased from 18.8 to 3.8, a reduction of 80%. In the same post-treatment biopsies, however, message for IL-8R persisted. Estimation of circulating IL-8 levels by enzyme immunoassay showed that all patients with detectable IL-8 before treatment had decreased levels in response to treatment with tacrolimus; reductions in PASI scores were accompanied by decreases in IL-8 levels, that varied both in rate and extent. Partial relapse, which in a minority of patients followed the initial period of remission, and was precipitated by drug dose reduction, was accompanied by an increase in circulating IL-8. These findings add credence to the view that the IL-8/IL-8R autocrine/paracrine pathway may be important in the pathogenesis of psoriasis. They further suggest that interference with IL-8 production and/or that of other key chemokines may be an important mechanism underlying the therapeutic efficacy of tacrolimus, and other agents such as cyclosporin A, with similar molecular actions.

Topics: Adolescent; Adult; Cytokines; Female; Gene Expression; Humans; Interleukin-8; Male; Middle Aged; Polymerase Chain Reaction; Psoriasis; Receptors, Interleukin; Receptors, Interleukin-8A; RNA, Messenger; T-Lymphocytes; Tacrolimus

FK506 is a local drug that is commonly used in the treatment of psoriasis. Its clinical application, however, is limited by its transdermal drug delivery rate, the time-consuming, and the greasy therapy. In this study, which was inspired by local block injection used in the clinical treatment for keloid, a hyaluronic acid (HA) based system to transport FK506 into the skin to treat psoriasis, named blocking patch (BP) was developed. BP has a complete appearance, sufficient puncture strength, and is virtually non-irritating in vivo. By confocal fluorescence microscopy, BP loaded with FK506 (FK506-BP) showed satisfactory transdermal release ability in vivo. Further animal studies revealed that FK506-BP showed a good anti-inflammatory ability in the imiquimod (IMQ)-induced mouse psoriasis-like dermatitis and inhibited the activation of associated immune cells. This study indicates that BP as a novel delivery system, realizes an efficient local delivery of FK506 in psoriasis and holds great potential in transdermal delivery.

Topics: Administration, Cutaneous; Animals; Imiquimod; Mice; Mice, Inbred BALB C; Psoriasis; Skin; Tacrolimus

Psoriasis is an autoimmune disorder disease with abnormally activated T lymphocytes and thickening of the epidermis. The mechanism of the action of tacrolimus and paclitaxel are matched with the two only known pathogenesis of psoriasis. However, there has been no report on tacrolimus combined with paclitaxel in the treatment of psoriasis until now. The O/O ointment was prepared for the topical application to overcome poor solubility, poor skin penetration, and erratic absorption of the two drugs. A high-speed shearing method was adopted to prepare the ointment, in which propylene carbonate was used to solve tacrolimus and paclitaxel completely. The ointment showed excellent stability, slow release of the drugs, better retention in psoriatic skin, and good skin tolerance. The therapeutic efficacy of ointment was evaluated with imiquimod induced psoriatic model, and the level of expression of psoriatic biochemical markers was evaluated using the PASI score and immunohistochemistry. The cumulative PASI score was 10.8 for the imiquimod induced group, 7.8 for the tacrolimus ointment group, 8.3 for the paclitaxel ointment and 5.3 for the tacrolimus-paclitaxel (1:1) ointment group, respectively. Ointment group with tacrolimus and paclitaxel indicated a significant improvement in the phenotypic features of the psoriatic skin treated. Compared with the imiquimod group, tacrolimus-paclitaxel (1:1) ointment group was significantly reduced the level of IL-17. The results confirm that tacrolimus and paclitaxel co-loaded ointment can be an effective strategy for the treatment of psoriasis.

Topics: Humans; Imiquimod; Ointments; Paclitaxel; Psoriasis; Pulmonary Surfactants; Surface-Active Agents; Tacrolimus

Cutaneous immune-related adverse events (cirAEs) remain a prevalent and common sequelae of immune checkpoint inhibitor (ICI) therapy, often necessitating treatment interruption and prolonged immune suppression. Treatment algorithms are still poorly defined, based on single-institution case reports without adequate safety assessments, and subject to publication bias.. Data in this registry were collected through a standardized REDCap form distributed to dermatologists via email listserv.. Ninety-seven cirAEs were reported from 13 institutions in this registry. Topical and systemic steroids were the most common treatments used; however, targeted treatment matched to disease morphology was identified at numerous sites. Novel cirAE therapy uses that to our knowledge have not been previously described were captured including tacrolimus for the treatment of follicular, bullous, and eczematous eruptions and phototherapy for eczematous eruptions. Moreover, further evidence of cirAE treatment applications sparsely described in literature were also captured in this study including dupilumab and rituximab for bullous eruptions, phototherapy for lichenoid and psoriasiform eruptions, and acitretin for psoriasiform eruptions, among others. No serious adverse events were reported. Numerous targeted therapeutics including dupilumab, rituximab, and psoriasis biologics, among others, were associated with a cirAE grade improvement of ≥2 grades in every patient treated.. This study suggests that a multi-institutional registry of cirAEs and management is not only feasible but that the information collected can be used to detect, evaluate, and rigorously assess targeted treatments for cirAEs. Further expansion and modification to include treatment progression may allow for sufficient data for specific treatment recommendations to be made.

Topics: Exanthema; Humans; Psoriasis; Rituximab; Skin; Tacrolimus

Psoriasis is an auto-immune condition with high keratinocyte hyperproliferation due to lower p53 and p22 levels. Tacrolimus, an immune suppressor, is considered one of the most effective drugs in suppressing psoriasis. Systematic administration of tacrolimus often leads to challenging side effects, namely increased infection risk, renal toxicity, neurological symptoms such as tremors and headaches, gastrointestinal disturbances, hypertension, skin-related problems, etc. To address this, a nanocarrier-based formulation of tacrolimus along with inclusion of hyaluronic acid was developed. The optimization and formulation of ethosomes via the ethanol injection technique were done based on the Box-Behnken experimental design. The results revealed hyaluronic acid-based tacrolimus ethosomes (HA-TAC-ETH) had nanometric vesicle size (315.7 ± 2.2 nm), polydispersity index (PDI) (0.472 ± 0.07), and high entrapment efficiency (88.3 ± 2.52%). The findings of drug release and skin permeation showed sustained drug release with increased dermal flux and enhancement ratio. The effectiveness of HA-TAC-ETH was confirmed in an imiquimod (5%)-prompted psoriasis model. The skin irritation score and Psoriasis Area and Severity Index (PASI) score indicated that HA-TAC-ETH gel has validated a decline in the entire factors (erythema, edema, and thickness) in the imiquimod-induced psoriasis model in contrast with TAC-ETH gel and TAC ointment. The fabricated HA-TAC-ETH opt gel proved to be safe and effective in in vivo studies and could be employed to treat psoriasis further.

Topics: Administration, Cutaneous; Humans; Hyaluronic Acid; Imiquimod; Psoriasis; Skin; Tacrolimus

Gold nanoparticles are a promising drug delivery system for treatment of inflammatory skin conditions, including psoriasis, due to their small size and anti-inflammatory properties. The aim of this study was to conjugate gold nanoparticles with anti-psoriatic formulations that previously showed successful results in the treatment of psoriasis (tacrolimus-loaded chitosan nanoparticles and lecithin-chitosan nanoparticles) by virtue of their surface charges, then examine whether the hybridization with gold nanoparticles would enhance the anti-psoriatic efficacy

Topics: Animals; Anti-Inflammatory Agents; Chitosan; Gold; Lecithins; Metal Nanoparticles; Mice; Psoriasis; Tacrolimus

Preclinical safety and proof of concept studies for a topical ointment comprising of concentrated tetrahydrocurcumin loaded lipidic nanoparticles (THC-LNs) and tacrolimus ointment (TTO) is proposed in the present investigation. The skin irritation potential and acute dermal toxicity were performed in rats in compliance with the Organization for Economic Cooperation and Development (OECD) guidelines (402, 404 and 410) while the cytotoxic potential was performed in HaCaT cells. Finally, in vivo evaluation was performed in Imiquimod mice model of psoriasis. In primary skin irritation assessment, TTO formulation, marketed formulation (Tacroz® Forte), THC-LNs, and blank LNs were topically applied on intact skin sites in rats while another group served as a negative control group for 72 h. TTO did not induce any adverse reactions. Repeated 28 days dermal toxicity followed by biochemical and histopathological assessment showed negligible alternations and skin lesions. THC-LNs revealed negligible cytotoxic potential in HaCaT cells. TTO showed significantly high anti-psoriatic activity in comparison to marketed ointment. This was also confirmed via histopathological evaluation. Based on these findings, it can be ascertained that TTO showed minimal toxicity and has ample potential for further clinical analysis. The above studies affirm the potential of TTO as an alternative for psoriasis.

Topics: Animals; Curcumin; Mice; Mice, Inbred BALB C; Nanoparticles; Ointments; Psoriasis; Rats; Tacrolimus

Other than single-center case studies, little is known about generalized pustular psoriasis (GPP) flares.. To assess GPP flares and their treatment, as well as differences between patients with and patients without flares documented in US electronic health records (EHRs).. This retrospective cohort study included adult patients with GPP (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision code L40.1) identified in Optum deidentified EHR data between July 1, 2015, and June 30, 2020. The index GPP diagnosis was the first occurrence in the EHR, with no coded history of GPP for at least 6 months prior. Flare episodes were identified using an algorithm based on diagnosis coding, care setting, type of clinician, GPP disease terms, and flare terms and attributes in the EHR.. Flare episodes were characterized by the frequency of occurrence per patient, the care setting in which they were identified, the type of specialist managing the episode, associated symptoms, and the type of treatment before, during, and after the episode. Patients were divided into groups based on whether or not they had a flare episode documented in their EHR. Comparisons were made between the groups based on demographic characteristics, comorbidity burden, health care use, and treatments.. Of 1535 patients with GPP (1018 women [66.3%]; mean [SD] age, 53.4 [14.7] years), 271 had 513 flares documented. Compared with patients without flares, patients with flares had a 34% higher mean (SD) Charlson Comorbidity Index score (2.80 [3.11] vs 2.09 [2.52]), were almost 3 times more likely to have inpatient visits (119 of 271 [44%] vs 194 of 1264 [15%]), were more than twice as likely to have emergency department (ED) visits (126 of 271 [47%] vs 299 of 1264 [24%]), and had higher use of almost all treatment classes. Flares were identified in outpatient (271 of 513 [53%]), inpatient (186 of 513 [36%]), and ED (48 of 513 [9%]) settings. The most common treatments during flares were topical corticosteroids (35% of episodes [178 of 513]), opioids (21% [106 of 513]), other oral treatments, (eg, methotrexate, cyclosporine, tacrolimus; 13% [67 of 513]), and oral corticosteroids (11% [54 of 513]). Almost one-fourth of flare episodes (24% [122 of 513]) had no dermatologic treatment 30 days before, during, or 30 days after a flare episode.. This cohort study suggests that there is significant unmet need for the treatment of GPP and its flares, as evidenced by patients seeking treatment in inpatient and ED settings, as well as the lack of advanced treatments.

Topics: Acute Disease; Adult; Chronic Disease; Cohort Studies; Cyclosporine; Electronic Health Records; Female; Humans; Methotrexate; Middle Aged; Psoriasis; Retrospective Studies; Skin Diseases, Vesiculobullous; Tacrolimus

Lecithin-chitosan hybrid nanoparticles are emerging as a promising nanocarrier for topical drug delivery. They could achieve a maximized encapsulation of hydrophobic drugs due to the lipophilic nature of lecithin that comprises the core while enhancing retention in the upper skin layers using the positively charged polymeric coat of chitosan. The aim of this study is to incorporate tacrolimus; a hydrophobic anti-proliferative agent into lecithin chitosan hybrid nanoparticles by ethanolic injection technique using a suitable co-solvent to enhance encapsulation of the drug and allow a satisfactory release profile in the upper skin layers. Tacrolimus was successfully incorporated into the synthesized particles using olive oil and Tween 80 as co-solvents, with particle size (160.9 nm ± 15.9 and 118.7 nm ± 13.3, respectively) and EE (88.27% ± 4.3 and 66.72% ± 1.8, respectively). The in vitro drug release profile showed a faster release pattern for the Tween 80-containing particles over a 48-hour period (79.98% vs. 35.57%), hence, were selected for further investigation. The hybrid nanoparticles achieved significantly higher skin deposition than the marketed product (63.51% vs. 34.07%) through a 24-hour time interval, particularly, to the stratum corneum and epidermis skin layers. The in vivo results on IMQ-mouse models revealed superior anti-psoriatic efficacy of the synthesized nanoparticles in comparison to the marketed product in terms of visual observation of the skin condition, PASI score and histopathological examination of autopsy skin samples. Additionally, the in vivo drug deposition showed superior skin deposition of the nanoparticles compared to the marketed product (74.9% vs. 13.4%).

Topics: Animals; Chitosan; Drug Carriers; Lecithins; Mice; Nanoparticles; Particle Size; Psoriasis; Tacrolimus

Topics: Adrenal Cortex Hormones; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; COVID-19; Dermatitis, Atopic; Female; Humans; Immunosuppressive Agents; Lichen Planus; Male; Middle Aged; Pemphigus; Psoriasis; SARS-CoV-2; Tacrolimus

Tacrolimus is a natural macrolide that exhibits an anti-proliferative action by T-lymphocytic cells inhibition. Hence, it was tested as a potential topical treatment to improve and control psoriatic plaques. In this study, for the first time the lipophilic tacrolimus in chitosan nanoparticles was used to achieve the desired response and dermal retention of the drug using a modified ionic gelation technique. The hydrophobic drug, tacrolimus, was successfully encapsulated into the synthesized positively-charged particles (140.8 nm ± 50.0) and EE of (65.5% ± 1.3). Local skin deposition of the drug was significantly enhanced with 82.0% ± 0.6 of the drug retained in the skin compared to 34.0% ± 0.9 from tarolimus® ointment. An outstanding response to the prepared formula was the enhanced hair growth rate in the treated animals, which can be considered an excellent sign of the skin recovery from the induced psoriatic plaques after only three days of treatment.

Topics: Administration, Cutaneous; Animals; Chitosan; Drug Carriers; Drug Liberation; Ear; Imiquimod; Immunosuppressive Agents; Mice, Inbred C57BL; Nanoparticles; Particle Size; Psoriasis; Rats, Sprague-Dawley; Skin; Tacrolimus

Since psoriasis is an immuno-mediated skin disease, long-term therapies are necessary for its treatment. In clinical investigations, tacrolimus (TAC), a macrolide immunosuppressive inhibitor of calcineurin, arises as an alternative for the treatment of psoriasis, acting in some cytokines involved in the pathogenesis of the disease. Here, we aim to study the psoriasis treatment with TAC and siRNA for one of most cytokines expressed in psoriasis, the TNF-α. A multifunctional nanostructure lipid carrier (NLC) was developed to co-delivery TAC and siRNA. Results showed that the particle size and zeta potential were around 230 nm and + 10 mV, respectively. The release study demonstrated a controlled release of TAC, and the permeation and retention profile in the skin tissue show to be promising for topical application. The cell viability and uptake in murine fibroblast presented low toxicity associated to uptake of NLC in 4 h, and finally, the in vivo animal model demonstrates the efficiency of the NLC multifunctional, exhibiting a reduction of the cytokine TNF-α expression about 7-fold and presenting a synergic effect between the TAC and TNF-α siRNA. The developed system was successfully to treat in vivo psoriatic animal model induced by imiquimod and the synergic combination was reported here for the first time. Graphical abstract.

Topics: Administration, Cutaneous; Animals; Delayed-Action Preparations; Disease Models, Animal; Down-Regulation; Drug Synergism; Female; Imiquimod; Liposomes; Male; Mice; Mice, Inbred BALB C; Nanoparticles; NIH 3T3 Cells; Particle Size; Psoriasis; RNA, Small Interfering; Tacrolimus; Tumor Necrosis Factor-alpha

Psoriasis is a chronic relapsing inflammatory and hyperproliferative skin disease affecting quality of life. It affects an estimated 8 million Americans and more than 125 million people worldwide. The estimated cost to treat psoriasis in USA is over 13 billion US dollars per year. Treatment of psoriasis may include topical steroid-sparing agent, topical corticosteroids, phototherapy or biologics. Tacrolimus has 10-fold greater immunosuppressive activity than the ciclosporin A which has been recommended for effective treatment of psoriasis. However, it has been widely investigated using conventional formulation approaches which limit its clinical outcomes. It has poor cutaneous bioavailability when administered topically using conventional delivery approach, thus it has poor efficacy against the psoriasis. Low aqueous solubility and high degradation of Tacrolimus make it difficult to formulate as a liquid preparation. Moreover, Tacrolimus has narrow therapeutic index and thus it is essential to prevent its possible toxic effects when a modified release dosage form is administered. The present hypothesis aims to put forward to incorporate Tacrolimus into a novel lipid based nanocarrier system, which would be further loaded into a hydrogel base and evaluated for its target specific topic delivery. Due to the structural similarity of the lipid nanocarriers and skin, these vesicles would target the skin tissues effectively and treat psoriasis with minimum or no side effects. Thus, the proposed formulation would be a considerable value addition to the current therapeutic approaches used for psoriasis management.

Topics: Administration, Cutaneous; Humans; Immunosuppressive Agents; Liposomes; Psoriasis; Quality of Life; Tacrolimus

Although tacrolimus (FK-506) has been shown to be an effective monotherapy for psoriasis, it does not always work well. Currently, combination therapy is frequently used to manage psoriasis because clinical trials have shown it may provide additive or synergistic benefits and reduce risks of adverse effects. Myeloid-derived suppressor cells (MDSCs) have potent immunomodulatory and anti-inflammatory properties in autoimmune diseases. We previously reported that MDSCs had protective effects in a murine model of imiquimod (IMQ)-induced psoriasis. The present study was undertaken to investigate the systemic immunomodulatory and therapeutic efficacy effects of MDSC plus FK-506 in an IMQ-induced mouse model of psoriasis and to investigate the immunomodulatory mechanisms involved. Systemic MDSC plus FK-506 therapy was found to have a significant anti-psoriatic effect in the murine model, to reduce levels of pro-inflammatory cytokines Th1 cytokines (TNF-α and IFN-γ) and Th17 cytokines (IL-17A and IL-23) in serum and skin. However, treatment with MDSCs or FK-506 alone had little impact. Furthermore, the anti-psoriatic effects of MDSC plus FK-506 were associated with histopathological reductions in inflammatory infiltration, epidermal hyperplasia, and hyperkeratosis. In addition, this combined treatment also attenuated IMQ-induced splenomegaly, and increased the proportion of CD4

Topics: Animals; Cytokines; Disease Models, Animal; Drug Therapy, Combination; Female; Imiquimod; Immunomodulation; Immunosuppressive Agents; Mice, Inbred C57BL; Myeloid-Derived Suppressor Cells; Psoriasis; Skin; Spleen; T-Lymphocytes, Regulatory; Tacrolimus; Th1 Cells; Th17 Cells

The present work reports the development, optimization and characterization of novel lipid based nanoformulations viz., Liquid crystalline nanoparticles (LCNP), solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) and liposomes loaded with Tacrolimus (Tac) for topical delivery. Different nanoformulations were developed after screening lipids and suitable surfactants depending upon emulsification ability. The various nanoformulations were then optimized (to achieve higher entrapment efficacy, lower particle size, PDI and zeta potential), characterized and loaded into gel. The gels loaded with nanoformulations were also characterized depending upon rheology and viscosity. The gels were analyzed for in vitro drug release, HaCaT cell lines studies and skin permeation studies. The in vivo efficacy studies were carried out using mouse tail model and skin irritation studies using Draize patch test and measurement of TEWL. The developed nanoformulations showed optimum particle size (<200 nm), polydispersity index (PDI < 0.3), zeta potential (≥-10 mV) and higher entrapment efficiency (>85%). The nanoformulations showed higher penetration of Tac into skin. Tac-LCNP, Tac-SLN, Tac-NLC and Tac-liposomes loaded gels showed 14, 11.5, 12.5 and 3.7 folds increment in dermal bioavailability respectively, in comparison to free Tac loaded gel and 2.5, 2 and ∼2 folds augmentation in dermal bioavailability respectively as compared to Tacroz™ Forte. In case of Tac-liposomes, the dermal bioavailability was lower as compared with the marketed formulation, Tacroz™ Forte. Despite, the increased bioavailability into the skin, the developed nanoformulations showed no significant skin irritation. The above mentioned nanoformulations were able to achieve greater penetration of Tac into the skin as compared to marketed ointment of Tac, Tacroz™ Forte.

Topics: Administration, Cutaneous; Animals; Cell Line; Drug Carriers; Drug Liberation; Humans; Immunosuppressive Agents; Lipids; Liquid Crystals; Mice, Inbred BALB C; Nanoparticles; Psoriasis; Skin; Skin Irritancy Tests; Swine; Tacrolimus; Treatment Outcome

Severe dermatitis, multiple allergies and metabolic wasting (SAM) syndrome is a recently recognized syndrome caused by mutations in the desmoglein 1 (DSG1) and desmoplakin (DSP) genes. Only two cases of SAM-DSP have been reported. We report on a 2-year-old girl presenting with pustular lakes within areas of erythema and large accumulations of intraepidermal neutrophils, which initially led to our misdiagnosis of generalized pustular psoriasis. No mutation was found in either the IL36RN or CARD14 genes by Sanger sequencing. The distinctive manifestations of erythroderma with severe itching, hypotrichosis, enamel defects, onychodystrophy, palmoplantar keratoderma and the crucial result of de novo missense mutation in exon 14 of the DSP gene (c.1828T>C, p.S610P) discovered by next-generation sequencing finally confirmed the diagnosis of SAM syndrome. The eruptions significantly improved after a 4-week treatment with oral acitretin and topical pimecrolimus. Oral gabapentin was prescribed simultaneously for 4 months, relieving her skin pruritus and suggesting that early treatment with pimecrolimus, acitretin and gabapentin for SAM-DSP syndrome is effective. It may even inhibit multiple allergies induced by skin barrier injury. In this work we also review the clinical features, differential diagnoses and pathological manifestations of SAM-DSP syndrome.

Topics: Acitretin; Administration, Cutaneous; Administration, Oral; Child, Preschool; Dermatitis, Exfoliative; Desmoplakins; Diagnosis, Differential; Diagnostic Errors; DNA Mutational Analysis; Female; Gabapentin; Humans; Hypersensitivity; Mutation, Missense; Psoriasis; Severity of Illness Index; Skin; Syndrome; Tacrolimus; Treatment Outcome; Wasting Syndrome

Topics: Adult; Aged; Baths; Child; Combined Modality Therapy; Female; Humans; Male; Middle Aged; Psoriasis; Tacrolimus

Topics: Administration, Cutaneous; Animals; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Imiquimod; Immunosuppressive Agents; Male; Mice; Mice, Hairless; Mice, Inbred BALB C; Psoriasis; Skin; Tacrolimus; Treatment Outcome

Topics: Adult; Humans; Immunosuppressive Agents; Male; Ointments; Penis; Psoriasis; Tacrolimus; Treatment Outcome

The current study is emphasized on development of a nanoemulsion system that simultaneously delivers two antipsoriatic agents viz. Tacrolimus and Kalonji oil (functional excepient) topically.. A nanoemulsion was characterized for quality attributes; a nanoemulsion gel was evaluated for spreadability, viscosity, dermal bioavailability, and in vitro efficacy in A-431 cell line, and so forth. In vivo performance was evaluated on psoriasis model in BALB/c mice.. Nanoemulsion depicted droplet size: 93.37 ± 2.58 nm with PDI (Polydispersity Index) 0.330 ± 0.025. The nanoemulsion gel exhibited desirable spreadability with sustained release pattern (biphasic). Dermal bioavailability enhancement (4.33-fold) accompanied significant in vitro results. A significant reduction in serum cytokines and improvement in psoriatic condition was achieved in vivo, indicating formulation efficacy compared with marketed formulation (Tacroz Forte, Glenmark Pharmaceuticals Ltd, Maharashtra, India).. Nanoemulsion gel thus provides an effective alternative for psoriasis treatment.

Topics: Administration, Cutaneous; Cell Line, Tumor; Emulsions; Humans; Nanoparticles; Psoriasis; Skin Absorption; Tacrolimus

In this study, we demonstrate for the first time the dual roles of Tocopheryl Polyethylene Glycol 1000 Succinate (TPGS) based microemulsion (ME) for tacrolimus (TAC) to enhance TAC percutaneous delivery and anti-psoriatic efficacy. The ME formulation was developed and optimized based on pseudo-ternary phase diagrams combined with in vitro permeation. The result of Fourier transform infrared spectroscopy (FTIR) demonstrated that TAC was completely solubilized in the TPGS-ME. In vitro permeation studies showed that TPGS-ME enhanced TAC permeation through and into the skin, and the enhanced deposition of TAC in the normal or psoriatic skin was further confirmed in vivo. The cellular uptake performed with HaCaT cells presented more pronounced uptake of TPGS-ME. Topical TAC-TPGS-ME treated imiquimod-induced psoriasis in mice more efficaciously than the commercial formulation of TAC (Protopic

Topics: Animals; Cell Line; Drug Carriers; Humans; Male; Mice; Mice, Inbred BALB C; Polyethylene Glycols; Psoriasis; Rats, Sprague-Dawley; Skin Absorption; Tacrolimus; Vitamin E

Psoriasis is a common chronic inflammatory skin disease. Ocular manifestations, which occur in 10% to 20% of cases of psoriasis, are usually bilateral and often present during an exacerbation of the psoriasis. Serious corneal involvement is rare but can be devastating.. Two cases of sterile corneal infiltrates secondary to an exacerbation of psoriasis are presented. Treatment involved the use of 0.02% topical tacrolimus ointment, which resulted in resolution of the symptoms and infiltrates.. Topical tacrolimus may be considered as an alternative treatment option to corticosteroids in sterile corneal infiltrates.

Topics: Administration, Topical; Adult; Corneal Diseases; Humans; Immunosuppressive Agents; Male; Ointments; Psoriasis; Tacrolimus

Tacrolimus, a congener of cyclosporine, has replaced cyclosporine as a first-line treatment for most transplant patients due to its superior efficacy and safety. Tacrolimus has not been extensively studied for the treatment of psoriasis.. To study the efficacy and safety of oral tacrolimus in adult patients with severe refractory plaque psoriasis.. This was an open-label pilot study. Patients with severe plaque type psoriasis who were unresponsive to at least 1 systemic treatment were treated with oral tacrolimus.. Thirty patients were treated. After 12 weeks, improvement in mean Psoriasis Area Severity Index (PASI) score was 80.37% (P < .001), PASI 75 was observed in 19 of 26 (73.1%) patients, and PASI 90 was observed in 11 of 26 (42.3%) patients. No severe side effects were noted.. Oral tacrolimus is an effective and safe option for the short-term treatment of severe plaque psoriasis.

Topics: Administration, Oral; Adult; Humans; Immunosuppressive Agents; Middle Aged; Pilot Projects; Prospective Studies; Psoriasis; Retreatment; Severity of Illness Index; Tacrolimus

Cases are presented of 4 patients suffering from severe symptoms due to ocular psoriasis and who were treated with off-label 0.03% tacrolimus once a day.. All four patients had a mixed blepharitis and keratitis. Pseudopterygium and corneal opacities were present in three of them. All of them experienced an improvement of their itching and ocular surface. They all referred to a marked improvement of their quality of life in a follow-up period ranging from six months to two years. Therefore, topical tacrolimus could be considered an option in the treatment of ocular psoriasis.

Topics: Administration, Topical; Aged; Eye Diseases; Female; Humans; Male; Psoriasis; Tacrolimus

Topics: Aged; Erythema; Female; Humans; Immunosuppressive Agents; Lichen Planus; Lichen Planus, Oral; Middle Aged; Psoriasis; Scalp; Tacrolimus; Treatment Outcome; Vulva

We have developed a composite hydrogel for improved topical delivery of the poorly soluble drug Tacrolimus (TAC) to psoriasis lesions. TAC is efficiently solubilized in methoxy poly- (ethylene glycol) hexyl substituted poly-(lactic acid) (mPEGhexPLA) based nanocarriers. For convenient and patient-friendly topical administration, TAC loaded polymeric nanocarriers were incorporated in a Carbopol® based hydrogel, to yield a composite hydrogel formulation (TAC composite hydrogel). TAC composite hydrogel was designed to have superior pharmaceutical formulation properties, delivery efficiency and local bioavailability, compared to currently available paraffin-based TAC ointments. Composite hydrogel formulations had good local tolerance and showed no signs of immediate toxicity after repeated topical administration in healthy mice. Skin delivery of TAC composite hydrogel in an imiquimod-induced psoriasis mouse model was found to be twice as high as for the commercial formulation Protopic™, used as benchmark. TAC composite hydrogel showed significant improvement in the in vivo and histopathological features of the imiquimod-induced psoriasis model.

Topics: Administration, Cutaneous; Aminoquinolines; Animals; Biological Availability; Chemistry, Pharmaceutical; Disease Models, Animal; Drug Carriers; Drug Delivery Systems; Hydrogels; Imiquimod; Immunosuppressive Agents; Mice; Mice, Inbred C57BL; Polymers; Psoriasis; Skin; Skin Absorption; Solubility; Tacrolimus

Psoriasis is an autoimmune skin disorder characterized by hyper proliferation and poor differentiation of keratinocytes. It significantly affects patient's quality of life. This study reports the anti-psoriatic efficacy of tacrolimus and curcumin loaded liposphere gel formulation. Poor solubility, poor skin penetration and erratic absorption are some problems associated with the topical delivery of these drugs. To overcome these problems, lipospheres containing combination of tacrolimus and curcumin was prepared with a particle size of nearly 50nm and incorporated into a gel for topical application. Liposphere gel showed slow release of both the drugs and shear thinning behaviour that is desirable property of topical formulation. Further, dermal distribution study using dye loaded formulation suggested penetration of dye into skin layers. The therapeutic efficacy of tacrolimus and curcumin loaded liposphere gel was assessed on imiquimod induced psoriatic plaque model, and the level of expression of psoriatic biochemical markers was evaluated using enzyme-linked immunosorbent assay. Results indicated improvement in the phenotypic and histopathological features of psoriatic skin treated with tacrolimus and curcumin loaded liposphere gel. There was reduction in the level of TNF-α, IL-17 and IL-22 compared to imiquimod group. These results corroborate the premise that liposphere gel containing combination of tacrolimus and curcumin can be an effective strategy for the treatment of psoriasis.

Topics: Administration, Cutaneous; Aminoquinolines; Animals; Chemistry, Pharmaceutical; Curcumin; Delayed-Action Preparations; Dermatologic Agents; Drug Synergism; Enzyme-Linked Immunosorbent Assay; Gels; Imiquimod; Immunosuppressive Agents; Lipids; Male; Mice; Mice, Inbred BALB C; Particle Size; Psoriasis; Tacrolimus; Tissue Distribution

Psoriasis is a chronic inflammatory skin disease and topical therapy remains a key role for treatment. The aim of this study is to evaluate the influence of psoriasis-like lesions on the cutaneous permeation of anti-psoriatic drugs.. We first set up imiquimod-induced dermatitis in mice that closely resembles human psoriasis lesions. The development of the lesions is based on the IL-23/IL17A axis for phenotypical and histological characteristics. Four drugs, 5-aminolevulinic acid (ALA), tacrolimus, calcipotriol, and retinoic acid, were used to evaluate percutaneous absorption.. The most hydrophilic molecule, ALA, revealed the greatest enhancement on skin absorption after imiquimod treatment. Imiquimod increased the skin deposition and flux of ALA by 5.6 to 14.4-fold, respectively, compared to normal skin. The follicular accumulation of ALA was also increased 3.8-fold. The extremely lipophilic drug retinoic acid showed a 1.7- and 3.8-fold increase in skin deposition and flux, respectively. Tacrolimus flux was enhanced from 2 to 21 μg/cm2/h by imiquimod intervention. However, imiquimod did not promote skin deposition of this macrolide. The lipophilicity, but not the molecular size, dominated drug permeation enhancement by psoriatic lesions. The in vivo percutaneous absorption of ALA and rhodamine B examined by confocal microscopy confirmed the deficient resistance of epidermal barrier for facilitating cutaneous delivery of drugs via psoriasis-like skin.. We established the topical delivery profiles of anti-psoriatic drugs via imiquimod-treated psoriasis-like skin.

Topics: Aminolevulinic Acid; Aminoquinolines; Animals; Cytokines; Disease Models, Animal; Female; Imiquimod; Mice; Psoriasis; Skin; Skin Absorption; Tacrolimus; Tretinoin

Topical immunosuppressant therapy is widely used in the treatment of inflammatory skin diseases, such as atopic dermatitis and psoriasis. Besides its beneficial therapeutic effects, application of topical anti-inflammatory drugs may render the epidermis more vulnerable to invading pathogens by suppressing innate immune responses in keratinocytes (KCs). Cytokines, chemokines and antimicrobial peptides (AMPs) produced by epithelial cells enable them to participate in innate and acquired immune responses. The aim of the present work was to study the influence of tacrolimus (FK506) on KCs infected with Malassezia furfur (M. furfur), evaluating the expression of pro-inflammatory cytokines IL-1α and IL-6, chemokine IL-8, anti-inflammatory cytokines transforming growth factor beta1 (TGF-β1) and IL-10 and AMP β-defensin-2. Human KCs were obtained from surgical specimens of normal adult skin. The expression of mRNAs in KCs: FK506-treated, FK506-treated and M. furfur-infected as well as only M. furfur-infected was quantified by real-time quantitative polymerase chain reaction. Next, the production of the AMP β-defensin-2 and of the above-mentioned pro-inflammatory and anti-inflammatory cytokines was evaluated using enzyme-linked immunosorbent assay. In this study, FK506 did not alter cytokine and AMP production by KCs; this led us to hypothesise that it may not enhance the risk of mycotic skin infections.

Topics: Antimicrobial Cationic Peptides; beta-Defensins; Cell Survival; Cytokines; Enzyme-Linked Immunosorbent Assay; Humans; Interleukin-10; Interleukin-1alpha; Interleukin-6; Interleukin-8; Keratinocytes; Malassezia; Psoriasis; RNA, Messenger; Skin; Tacrolimus; Transforming Growth Factor beta1

Tacrolimus (TAC) suffers from poor cutaneous bioavailability when administered topically using conventional vehicles with the consequence that although it is indicated for the treatment of atopic dermatitis, it has poor efficacy against psoriasis. The aim of this work was to formulate TAC loaded polymeric micelles using the biodegradable and biocompatible methoxy-poly(ethylene glycol)-dihexyl substituted polylactide (MPEG-dihexPLA) diblock copolymer and to investigate their potential for targeted delivery of TAC into the epidermis and upper dermis. Micelle formulations were characterized with respect to drug content, stability, and size. An optimal 0.1% micelle formulation was developed and shown to be stable over a period of 7 months at 4 °C; micelle diameters ranged from 10 to 50 nm. Delivery experiments using human skin and involving quantification by UHPLC-MS/MS demonstrated that this formulation resulted in significantly greater TAC deposition in skin than that with Protopic (0.1% w/w; TAC ointment), (1.50 ± 0.59 and 0.47 ± 0.20 μg/cm(2), respectively). The cutaneous biodistribution profile of TAC in the upper 400 μm of tissue (at a resolution of 20 μm) demonstrated that the increase in cutaneous drug levels was due to improved TAC deposition in the stratum corneum, viable epidermis, and upper dermis. Given that there was no increase in the amount of TAC in deeper skin layers or any transdermal permeation, the results suggested that it would be possible to increase TAC levels selectively in the target tissue without increasing systemic absorption and the risk of side effects in vivo. Micelle distribution and molecular penetration pathways were subsequently visualized with confocal laser scanning microscopy (CLSM) using a fluorescently labeled copolymer and fluorescent dyes. The CLSM study indicated that the copolymer was unable to cross the stratum corneum and that release of the micelle "payload" was dependent on the molecular properties of the "cargo" as evidenced by the different behaviors of DiO and fluorescein. A preferential deposition of micelles into the hair follicle was also confirmed by CLSM. Overall, the results indicate that MPEG-dihexPLA micelles are highly efficient nanocarriers for the selective cutaneous delivery of tacrolimus, superior to the marketed formulation (Protopic). Furthermore, they may also have significant potential for targeted delivery to the hair follicle.

Topics: Administration, Cutaneous; Animals; Biological Availability; Chemistry, Pharmaceutical; Drug Carriers; Drug Delivery Systems; Hair Follicle; Humans; Micelles; Nanoparticles; Polymers; Psoriasis; Skin Absorption; Swine; Tacrolimus; Tissue Distribution

To detect the expression level of macrophage inflammatory protein-1 (MIP-1)α, MIP-1β and monocyte chemoattractant protein-1 (MCP-1) in with psoriasis vulgaris and explore the role in the pathogenesis of psoriasis vulgaris.. The level of MIP-1α, MIP-1β and MCP-1 in peripheral blood from 50 patients with psoriasis vulgaris and 50 normal controls were measured by enzyme linked immunosorbent assay. The correlation with psoriasis area and severity index (PASI) was analyzed. The level of MIP-1α, MIP-1β and MCP-1 was compared between psoriasis vulgaris patients at active stage and resting stage. And the change in MIP-1α, MIP-1β and MCP-1 before and after therapy was also observed.. The content of MIP-1α, MIP-1β and MCP-1 in patients with psoriasis vulgaris was (1342.78 ± 210.30), (175.28 ± 28.18) and (266.86 ± 32.75) ng/L, respectively, significantly higher than those in control group (P<0.05). The expression level of MIP-1α, MIP-1β and MCP-1 in peripheral blood of patients with psoriasis vulgaris was positively correlated with PASI (P<0.01). After acitretin therapy, expression level of MIP-1α, MIP-1β and MCP-1 in peripheral blood of patients with psoriasis vulgaris was significantly decreased.. Chemokine factor MIP-1α, MIP-1β and MCP-1 may be involved in the pathogenesis of psoriasis vulgaris.

Topics: Acitretin; Adult; Case-Control Studies; Chemokine CCL2; Enzyme-Linked Immunosorbent Assay; Female; Humans; Immunosuppressive Agents; Keratolytic Agents; Macrophage Inflammatory Proteins; Male; Middle Aged; Psoriasis; Tacrolimus; Young Adult

Psoriasis (PS) is one of the most frequent dermatologic diseases and occurs in approximately 2% of the population. It is believed to be an autoimmune disease (AID) that is potentially mediated by pro-inflammatory cytokines produced by lesional T cells. Infections are considered a key factor for triggering or even inducing PS flare-ups. Liver transplant recipients (LTR) with co-existing PS are unique to follow because their T cells are subject to long-term immunosuppression (IS) and they experience infections more frequently than the general population.. Our 7.6 ± 3.5-year follow-up aimed to determine the clinical course of PS in 10 patients out of 591 LTR (1.69%). Demographic data, IS protocols, signs of infections, and viral status were analyzed. The PS clinical course was assessed retrospectively by measuring the PS area and severity index.. Remission was observed in all patients 2-6 weeks after liver transplantation (LT). Three patients had PS flare-ups within 2 years. Multivariant analysis did not reveal any correlations between recurrent PS (rPS) and cytomegalovirus (CMV), Epstein-Barr, human papilloma, hepatitis B and C viral status, or interferon treatment. rPS was only observed in LTR with co-existing AID. Response to therapy was variable, but cyclosporine (CsA) seemed to have a better effect than tacrolimus (TAC).. PS may relapse after LT despite IS, concomitant AID may be the main predisposing factor to disease relapses, and CsA seems to be more potent than TAC for treating rPS in LTR.

Topics: Adult; Cyclosporine; End Stage Liver Disease; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Liver Transplantation; Male; Middle Aged; Psoriasis; Recurrence; Risk Factors; Tacrolimus; Transplant Recipients; Treatment Outcome

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: Acitretin; Aged; Animals; Anti-Inflammatory Agents; Humans; Immunosuppressive Agents; Keratolytic Agents; Male; Middle Aged; Mite Infestations; Mites; Psoriasis; PUVA Therapy; Steroids; Tacrolimus

Topics: Child, Preschool; Dermatology; Diagnosis, Differential; Humans; Male; Nevus, Sebaceous of Jadassohn; Psoriasis; Skin Pigmentation; Tacrolimus

The imbalance between regulatory T cells (Treg) and effector T cells is important for maintaining of psoriasis vulgaris. FOXP3 is a master control transcription factor for the development and function of Tregs and is critical for transcriptional repression. Tacrolimus is effective in treatment of psoriasis vulgaris. Data show that tacrolimus has multiple impacts on FOXP3, but the exact pharmacological mechanism of tacrolimus on FOXP3 have yet to be elucidated. We herein suggest the bidirectional immunoregulation of tacrolimus on FOXP3. High concentration of tacrolimus renders the cooperation of NFAT with STAT6 and NF-κB to activate GATA3 transcription. On the contrary, low concentration of tacrolimus results in higher nucleus level of NFAT, which directly binds to FOXP3 enhancer and/or cooperates with Smad3 to activate FOXP3 transcription. Further studies using loss of function and over-expression methods are needed to determine the detailed molecules involved in this bidirectional immunoregulation of tacrolimus on FOXP3.

Topics: Animals; Calcineurin Inhibitors; Cell Nucleus; Dose-Response Relationship, Drug; Forkhead Transcription Factors; GATA3 Transcription Factor; Gene Expression Regulation; Humans; Immunosuppressive Agents; NFATC Transcription Factors; Psoriasis; STAT6 Transcription Factor; T-Lymphocytes, Regulatory; Tacrolimus; Transcription Factors

Topics: Acitretin; Adalimumab; Adrenal Cortex Hormones; Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Calcitriol; Cyclosporine; Dermatologic Agents; Drug Therapy, Combination; Etanercept; Female; Humans; Immunoglobulin G; Infliximab; Methotrexate; Psoriasis; Receptors, Tumor Necrosis Factor; Tacrolimus; Treatment Outcome; Ustekinumab

Topics: Dermatologic Agents; Female; Humans; Immunosuppressive Agents; Middle Aged; Psoriasis; Tacrolimus; Thermography; Video Recording

Although clinical trials for new drugs are often limited in children because of safety concerns or restrictions, new therapies or novel strategies with old drugs have recently expanded dermatologic armamentarium for pediatric patients. Oral propranolol is currently the first choice in the treatment of alarming infantile hemangiomas. In atopic dermatitis, proactive strategy with topical calcineurin inhibitors can safely prevent disease exacerbation. Tacrolimus, in particular, is also useful for the treatment of vitiligo occurring in sensitive areas such as the eyelids. Among biologic drugs, use of etanercept is safe and efficient in children and adolescents with moderate-to-severe plaque psoriasis. Engineered tissues with special antimicrobial properties (silver-coated fabrics or engineered silk) are now used to treat eczema and fungal diseases in children. In athlete's foot, the use of 5-finger socks can also be helpful.

Topics: Adolescent; Adrenal Cortex Hormones; Alopecia Areata; Autoimmune Diseases; Child; Child, Preschool; Dermatitis, Atopic; Eczema; Female; Hemangioma; Humans; Immunosuppressive Agents; Male; Propranolol; Psoriasis; Randomized Controlled Trials as Topic; Skin Diseases; Tacrolimus; Therapies, Investigational; Vitiligo

Ciclosporin A (CsA) is widely utilized for the treatment of inflammatory skin diseases such as psoriasis.The therapeutic effects of CsA are thought to be mediated via its immunosuppressive action on infiltrating lymphocytes in skin lesions. CsA and tacrolimus block T cell activation by inhibiting the phosphatase calcineurin and preventing translocation from the cytoplasm to the nucleus of the transcription factor Nuclear Factor of Activated T cells (NFAT).. RT-PCR and Western Analysis were used to investigate the presence of NFAT-3 mRNA and protein in human keratocytes. Tissue culture of human keratocytes and immunostaining of cells on coverslips and confocal microscopy were used to assess the degree of nuclear localisation of NFAT-3 in cultured cells. Keratome biopsies were taken from patients with psoriasis (lesional and non-lesional skin) and normal skin and immunohistochemistry was used to assess the NFAT-3 localisation in these biopsies using a well characterized anti-NFAT-3 antibody.. The NFAT-3 mRNA and protein expression was demonstrated using RT-PCR and Western blotting. The expression of NFAT-3 in human keratocytes and response to different agonists provides perhaps a unique opportunity to examine the regulation, subcellular localization and kinetics of translocation of different NFATs in primary cultured human cells. As with NFAT 1, NFAT 2 and recently NFAT 5, differentiation-promoting agents that increase intracellular calcium concentration induced nuclear translocation of NFAT-3 in cultured keratocytes but with different kinetics.. These data provide the first evidence of that NFAT-3 is expressed in normal skin, psoriasis and that NFAT-3 functionally active in human keratocytes and that nuclear translocation of NFAT-3 in human skin cells has different kinetics than NFAT 1 suggesting that NFAT-3 may play an important role in regulation of keratocytes proliferation and differentiation at a different stage. Inhibition of this pathway in human epidermal keratocytes many account, in part for the therapeutic effects of CsA and tacrolimus in skin disorders such as psoriasis.

Topics: Calcineurin Inhibitors; Calcium Signaling; Cell Nucleus; Cells, Cultured; Cyclosporine; Dermis; Fibroblasts; Gene Expression; Humans; Immunosuppressive Agents; Keratinocytes; Microscopy, Confocal; NFATC Transcription Factors; Psoriasis; RNA, Messenger; Skin; Tacrolimus

Topics: Betamethasone; Chickenpox; Child, Preschool; Erythromycin; Humans; Male; Psoriasis; Tacrolimus; Treatment Outcome

Topics: Acitretin; Acute Disease; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Body Surface Area; Calcitriol; Dermatologic Agents; Diagnosis, Differential; Drug Monitoring; Female; Humans; Immunosuppressive Agents; Keratolytic Agents; Middle Aged; Nurse Practitioners; Nursing Assessment; Patient Education as Topic; Phototherapy; Physical Examination; Primary Health Care; Psoriasis; Tacrolimus

A 58-year-old, obese, male, army officer was presented with tinea incognito of the groin masking intertriginous psoriasis. According to his history, he had pruritic, symmetrical erythematous eruption of the groin of 2-month duration that he treated himself by using topical pimecrolimus 1%. This medication had been prescribed for his 8-year son's atopic dermatitis by the paediatrician. Direct examination with potassium hydroxide preparation showed fungal hyphae and Trichophyton rubrum was isolated in culture. This is the second case of topical pimecrolimus induced tinea incognito. We also review the cutaneous disorders that tinea incognito may mimic.

Topics: Diagnosis, Differential; Erythema; Groin; Humans; Immunosuppressive Agents; Male; Middle Aged; Psoriasis; Tacrolimus; Tinea; Trichophyton

Topics: Administration, Topical; Combined Modality Therapy; Female; Humans; Immunosuppressive Agents; Laser Therapy; Middle Aged; Psoriasis; Retreatment; Tacrolimus

This case report describes the successful treatment of severe plaque psoriasis with etanercept in a patient who underwent a liver transplant. It also addresses the concerns that arise in the treatment of chronic inflammatory dermatologic disease accompanied by multiple organ disorders.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Diabetes Mellitus, Type 1; Etanercept; Graft Rejection; Humans; Immunocompromised Host; Immunoglobulin G; Immunosuppressive Agents; Liver Transplantation; Male; Middle Aged; Psoriasis; Receptors, Tumor Necrosis Factor; Renal Insufficiency; Sirolimus; Tacrolimus

Psoriasis is a chronic inflammatory skin disorder of multifactorial etiology. Because of the potential side effects of repeated topical application of potent corticosteroids, equally-effective, safer therapeutic options are required, especially in the treatment of children. We report on the efficacy of twice daily application of pimecrolimus 1 percent cream in a girl who suffered from psoriasis involving the eyelids and anogenital region. After 20 days of application of pimecrolimus cream the plaques completely resolved. No significant side effects have been observed. Topical pimecrolimus appears to be an effective and safe treatment for children with psoriasis. Our case observations provide further evidence for the beneficial effects of topical pimecrolimus in the treatment of psoriasis. Vehicle-controlled studies on a larger number of patients are now needed to investigate long-term efficacy and safety of topical pimecrolimus in the treatments of a variety of types of psoriasis in children.

Topics: Administration, Topical; Child; Dermatologic Agents; Female; Humans; Psoriasis; Tacrolimus

Topics: Adolescent; Coccidioidomycosis; Humans; Immunosuppressive Agents; Male; Ointments; Psoriasis; Severity of Illness Index; Tacrolimus

Topics: Acquired Immunodeficiency Syndrome; Administration, Topical; Adult; Dermatitis, Seborrheic; Humans; Immunosuppressive Agents; Male; Psoriasis; Sarcoma, Kaposi; Skin Neoplasms; Tacrolimus

Topics: Administration, Topical; Adult; Erythema; Humans; Immunosuppressive Agents; Male; Mouth Diseases; Phototherapy; Psoriasis; Severity of Illness Index; Tacrolimus

Atopic dermatitis (AD) is a recurrent inflammatory skin disease characterized by high serum levels of IgE and Th2-type cytokines such as IL-4, IL-5 or IL-13. Chemokines attract leukocytes in inflamed tissues. We have previously found that thymus and activation regulated chemokine (TARC)/CCL17 and macrophage-derived chemokine (MDC)/CCL22 are highly secreted in the plasma levels of AD patients. Dendritic cells (DCs) are antigen-presenting cells that are divided into two subgroups including monocyte derived DCs (MoDCs) and plasmacytoid DCs (pDCs).. The aim of the study was to elucidate CCL17 and CCL22 production by MoDCs in AD patients, psoriasis vulgaris (PsV) patients and healthy controls (HC).. MoDCs were obtained from AD patients, PsV patients or HC and were cultured. In addition, the chemokine levels were measured in the supernatants.. We found that the CCL22 levels produced by MoDCs in AD patients to be significantly higher than those of PsV patients and HC. There was a significant correlation between the CCL22 levels produced by MoDCs and the SCORAD index. No significant difference in the CCL17 levels produced by MoDCs was detected among AD patients, PsV patients or HC. Immunosuppressive drugs such as dexamethasone (Dex), tacrolimus and cyclosporine (Cys) inhibited the CCL22 production by MoDCs in the AD patients.. These data suggest that the CCL22 level produced by MoDCs thus reflects the disease activity of AD and it may also play an important role regarding the production of CCL22 in the pathogenesis of AD.

Topics: Adolescent; Adult; Anti-Inflammatory Agents; Chemokine CCL17; Chemokine CCL22; Chemokines, CC; Cyclosporine; Dendritic Cells; Dermatitis, Atopic; Dermatologic Agents; Dexamethasone; Female; Gene Expression Regulation; Humans; Immunosuppressive Agents; Interleukin-12; Interleukin-18; Male; Middle Aged; Monocytes; Psoriasis; Severity of Illness Index; Tacrolimus

Topics: Administration, Topical; Ainhum; Dermatologic Agents; Female; Hand Dermatoses; Humans; Infant; Psoriasis; Tacrolimus; Ultraviolet Therapy

Recently, tacrolimus ointment has proved to be effective and well tolerated in patients with facial psoriasis. A few months ago we had the opportunity to treat a patient with tacrolimus ointment who had severe and recalcitrant plaque psoriasis of the face. This present case illustrates the impressive improvement of facial plaque psoriasis following 5 months of treatment with tacrolimus 0.1% ointment twice a day. Significant improvement of facial plaque psoriasis was seen after 1 month and complete clearance after 5 months of therapy. Based on the available literature and illustrated by the present case we may conclude that tacrolimus ointment 0.1% can be recommended as a first-line treatment for facial psoriasis.

Topics: Administration, Topical; Facial Dermatoses; Humans; Immunosuppressive Agents; Male; Middle Aged; Ointments; Psoriasis; Tacrolimus

Topics: Administration, Cutaneous; Adult; Female; Humans; Immunosuppressive Agents; Psoriasis; Tacrolimus

Pimecrolimus (SDZ ASM 981), an ascomycin derivative, as one of the new classes of immunomodulating macrolactams, is specifically effective in the treatment of inflammatory skin diseases. The interest in pimecrolimus is highly important for its significant anti-inflammatory activity, cell-selective inhibition of inflammatory cytokines, immunomodulatory capabilities, and low systemic immunosuppressive potential. The mechanism of action of pimecrolimus is the blockage of T cell activation, blocking signal transduction pathways in T cells, and inhibition of the synthesis of inflammatory cytokines, specifically Th1- and Th2-type cytokines. Several studies have evaluated the effectiveness of pimecrolimus as the treatment of choice for inflammatory skin diseases.

Topics: Chronic Disease; Dermatitis, Atopic; Eczema; Immunologic Factors; Immunosuppressive Agents; Inflammation; Psoriasis; Skin Diseases; Tacrolimus

Topics: Administration, Topical; Dermatologic Agents; Facial Dermatoses; Humans; Immunosuppressive Agents; Psoriasis; Tacrolimus; Treatment Outcome

Inverse psoriasis is a chronic disease frequently treated with topical corticosteroids. This retrospective case study evaluated the efficacy of tacrolimus 0.1% ointment to treat inverse psoriasis in children. Twelve of 13 patients had complete clearance of their psoriatic lesions within 2 weeks after initiating treatment with topical tacrolimus 0.1%.

Topics: Administration, Topical; Adolescent; Child; Child, Preschool; Diagnosis, Differential; Humans; Immunosuppressive Agents; Psoriasis; Retrospective Studies; Tacrolimus

Acrodermatitis continua of Hallopeau (ACH) is a rare type of pustular psoriasis affecting the digits. We report on a 43-year-old female patient who had been suffering from ACH for more than 20 years. Despite the fact that the disease was localized on one finger during the whole period, several topical and systemic treatments resulted in only temporary or partial improvement of the lesion. Although the monotherapies with calcipotriol and tacrolimus ointments gave no satisfying results in the long-term management of the disease, the combination of both agents led to a continuous improvement of the patient's skin condition.

Topics: Acrodermatitis; Administration, Cutaneous; Adult; Calcitriol; Dermatologic Agents; Drug Combinations; Female; Hand Dermatoses; Humans; Immunosuppressive Agents; Ointments; Psoriasis; Tacrolimus

Topics: Administration, Cutaneous; Anti-Inflammatory Agents, Non-Steroidal; Child; Diagnosis, Differential; Humans; Male; Penile Diseases; Psoriasis; Tacrolimus

Topics: Administration, Cutaneous; Dermatomycoses; Diagnosis, Differential; Facial Dermatoses; Humans; Immunosuppressive Agents; Male; Middle Aged; Psoriasis; Tacrolimus

Topics: Adult; Aged; Child; Facial Dermatoses; Female; Humans; Immunosuppressive Agents; Male; Psoriasis; Tacrolimus

Topics: Administration, Topical; Calcitriol; Dermatologic Agents; Female; Humans; Immunosuppressive Agents; Middle Aged; Psoriasis; Tacrolimus

Systemic cyclosporin A and tacrolimus are effective treatments for psoriasis. Cyclosporin A and tacrolimus block T cell activation by inhibiting the phosphatase calcineurin and preventing translocation from the cytoplasm to the nucleus of the transcription factor nuclear factor of activated T cells (NFAT). Inhibition of T cell activation is thought to account for their therapeutic action in psoriasis. We investigated whether nonimmune cells in human skin express calcineurin and NFAT1 and whether cyclosporin A and tacrolimus block activation of calcineurin/NFAT in epidermal keratinocytes. The expression patterns of the principal components of calcineurin/NFAT signaling pathway in normal human skin and psoriasis were determined by immunohistochemistry. We assessed calcineurin/NFAT activation in cultured keratinocytes by measuring the degree of nuclear localization of calcineurin and NFAT1 using immunofluorescence/confocal microscopy and assessed if cyclosporin A and tacrolimus blocked nuclear translocation of these proteins. A variety of cell types in normal and psoriatic skin expressed calcineurin and NFAT1, but expression was particularly prominent in keratinocytes. The principal cyclosporin A and tacrolimus binding proteins cyclophilin A and FKBP12 were also expressed by keratinocytes and nonimmune cells in skin. NFAT1 was predominantly nuclear in normal basal epidermal keratinocytes. Increased nuclear localization of NFAT1 was observed in suprabasal keratinocytes within lesional and to a lesser extent nonlesional psoriatic epidermis compared to normal skin (p = 0.001 and p = 0.03, respectively), suggesting increased activation of calcineurin in psoriatic epidermal keratinocytes. Agonists that induce keratinocyte differentiation, specifically 12-0-tetradecanoyl-phorbol-13-acetate (TPA) plus ionomycin, TPA, and raised extracellular calcium, induced nuclear translocation of NFAT1 and calcineurin in keratinocytes that was inhibited by pretreatment with cyclosporin A or tacrolimus. In contrast in human dermal fibroblasts, TPA plus ionomycin or TPA did not significantly alter the proportion of nuclear-associated NFAT1. These data provide the first evidence that calcineurin is functionally active in human keratinocytes inducing nuclear translocation of NFAT1 and also indicate that regulation of NFAT1 nuclear translocation in skin is cell type specific. Inhibition of this pathway in epidermal keratinocytes may account, in part, for the therapeutic effect of cyc

Topics: Biological Transport; Calcineurin; Calcineurin Inhibitors; Carcinogens; Cell Differentiation; Cell Membrane; Cell Nucleus; Cells, Cultured; Cyclophilin A; Cyclosporine; DNA-Binding Proteins; Enzyme Inhibitors; Fibroblasts; Humans; Immunosuppressive Agents; Ionomycin; Ionophores; Keratinocytes; NFATC Transcription Factors; Nuclear Proteins; Psoriasis; Signal Transduction; Skin; Tacrolimus; Tacrolimus Binding Protein 1A; Tetradecanoylphorbol Acetate; Transcription Factors

Systemic but not topical tacrolimus (TAC) is effective against psoriasis. Mechanical methods that enhance skin penetration by TAC increase its topical antipsoriatic effect. Liposomal delivery of TAC would increase its penetration of skin, allow for slow release and diminish its toxicity.. To test a liposomal TAC (LTAC) formulation in a murine model.. Drug penetration was assessed using radiolabelled LTAC, and the effect of TAC and LTAC on Balb/c skin graft survival and on ovalbumin-induced delayed-type hypersensitivity reactions was tested in C57BL/6 mice.. Radiotracer studies showed that topical application of LTAC achieved nine times the concentration of TAC at a target site than did systemic administration of TAC. Combination of systemic and topical LTAC significantly increased mean +/- SD skin graft survival (14.8 +/- 1.5 days) compared with systemic TAC (8.0 +/- 0.7 days) and control mice (8.4 +/- 1.2 days). LTAC was more effective systemically than TAC in the prevention of delayed-type hypersensitivity reactions. Topical LTAC also prevented this response.. Topical LTAC was effective in this model of immune-mediated skin disease. Because LTAC achieves higher skin concentrations than systemic TAC it may be an effective delivery system for TAC in the treatment of psoriasis.

Topics: Administration, Cutaneous; Animals; Graft Survival; Hypersensitivity, Delayed; Immunosuppressive Agents; Liposomes; Mice; Mice, Inbred C57BL; Models, Animal; Ovalbumin; Psoriasis; Skin Transplantation; Tacrolimus

The immunosuppressive macrolides are a novel class of antiinflammatory substances, which could supplant glucocorticosteroids for the topical treatment of some chronic inflammatory skin diseases. Cyclosporine A (CyA), well known from transplantation medicine for years, is licensed in Germany for oral treatment of psoriasis and atopic dermatitis but is not suitable for topical therapy. Tacrolimus (FK506) penetrates the inflamed epidermis and is regarded as the key immunosuppressive macrolide. Clinical trials have demonstrated the efficacy of FK506 ointment for atopic dermatitis, many case reports have been published regarding other inflammatory skin diseases. The ascomycin derivative ASM 981 has many of the properties of FK506 but less data is available at present. Sirolimus (Rapamycin) is structurally related to FK506 but has other biological effects since its molecular actions involve different biochemical pathways. A review of the biochemical and cellular properties, mode of action, therapeutic efficacy and unwanted side effects, as well as data from clinical trials and status of licensing, is given for the respective drugs.

Topics: Administration, Topical; Clinical Trials as Topic; Cyclosporine; Dermatitis, Atopic; Humans; Immunosuppressive Agents; Psoriasis; Sirolimus; Tacrolimus

Topics: Adult; Chronic Disease; Demyelinating Diseases; Electromyography; Female; Humans; Immunosuppressive Agents; Polyneuropathies; Prednisolone; Psoriasis; Recurrence; Tacrolimus

The influence of the immunosuppressants, cyclosporin A (CsA) and FK506, on cAMP formation was studied in T cells from healthy controls and patients with psoriasis. While basal cAMP levels were not affected, CsA (1 microM) and FK506 (2 nM) prevented the isoprenaline (0.1 microM)-induced increase in cAMP formation. Half-maximal inhibition by FK506 and CsA was observed at about 0.2 nM and 20 nM, respectively. In addition, both agents significantly reduced (by about 50%) the forskolin (8 microM)-stimulated cAMP formation. No differences were noted in cAMP responses (basal, stimulation by isoprenaline, inhibition by CsA and FK506) of T cells from healthy controls and psoriatic patients. We conclude that CsA and FK506 potently and efficiently interfere with the stimulatory adenylyl cyclase pathway in T cells and that regulation of T cell cAMP formation is apparently not altered in psoriasis.

Topics: Adult; Aged; Colforsin; Cyclic AMP; Cyclosporine; Dose-Response Relationship, Drug; Female; Humans; Immunosuppressive Agents; Isoproterenol; Male; Middle Aged; Psoriasis; T-Lymphocytes; Tacrolimus

Uncontrolled proliferation of epidermal cells is the most prominent characteristic of psoriasis. This widespread skin disease can be effectively treated with the microbial substance FK506, which acts by modulating gene expression. We, therefore, asked if the drug changes the expression of genes involved in growth regulation (the mitogenic cytokine interleukin-8 (IL-8) and p53, a negative cell cycle regulator) and signal transduction (protooncogenes c-ras, c-raf, and HER-2). Gene expression was monitored by semiquantitative mRNA-PCR and for p53 by immunocytochemistry in cultured primary keratinocytes (KC). In addition, p53 expression was analysed in skin biopsies of psoriatic patients. After 1-3 hr, IL-8 mRNA levels were dose-dependently decreased in tacrolimus (FK506)-treated cells. Protooncogene expression was not significantly altered. Interestingly, p53 transcription was clearly induced by FK506 treatment. This tendency could be verified on the protein level by immunocytochemistry. In contrast, p53 expression was decreased in lesional psoriatic as compared to normal skin, providing evidence that not only posttranslational modification of the p53 protein, but also transcriptional modulation of the p53 gene, are involved in pathological processes and pharmacological drug action in skin. Together with earlier results showing downmodulation for IL-8 receptor type A expression in cultured KC treated with FK506, these results suggest that both the mitogenic IL-8/IL-8R system and the cell cycle inhibitor p53 represent potential targets for the antipsoriatic action of the drug, whereas protooncogenes acting downstream in mitogenic signal transduction cascades are unaffected. The differential modulation of an entire set of genes provides evidence for the specificity of the drug effects and rules out nonspecific toxic effects on KC.

Topics: Dose-Response Relationship, Drug; Gene Expression; Genes, Tumor Suppressor; Humans; Immunohistochemistry; Interleukin-8; Polymerase Chain Reaction; Psoriasis; Skin; Tacrolimus

Psoriasis is a T-cell-mediated inflammatory skin disease which can be treated successfully with immunosuppressive drugs. Our purpose was to evaluate disease activity of psoriasis and the effect of immunosuppressive treatment by monitoring the soluble T-cell products sIL-2R, sCD27, sCD4, sCD8 and sICAM-1. Twenty-two patients were treated orally with escalating dosages of cyclosporin A (n = 17)(3-5 mg/kg/day) or FK506 (n = 5)(0.05-0.15 mg/kg/day). The Psoriasis Area and Severity Index (PASI) was used to monitor clinical activity of psoriasis. Serum samples were analyzed by ELISA. sIL-2R levels showed the highest correlation with psoriasis disease activity (rs = 0.89; p < 0.05). The longitudinal part of this study showed that levels of sIL-2R and sCD27 decreased during immunosuppressive treatment but remained above normal even in patients successfully treated. Our data indicate that sIL-2R levels are well correlated with disease activity in patients with psoriasis. sIL-2R levels closely follow the decrease of disease activity during immunosuppressive treatment.

Topics: Adolescent; Adult; Aged; Biomarkers; CD4 Antigens; CD8 Antigens; Cyclosporine; Humans; Immunosuppressive Agents; Intercellular Adhesion Molecule-1; Middle Aged; Monitoring, Physiologic; Psoriasis; Receptors, Interleukin-2; Severity of Illness Index; Tacrolimus; Tumor Necrosis Factor Receptor Superfamily, Member 7

FK 506 and cyclosporin A (CyA) are two immunosuppressive drugs which are known to be effective in the treatment of psoriasis by inhibiting the activation of T cells. In contrast, their influence on the proliferation of keratinocytes is discussed controversially. The second messenger cyclic adenosine monophosphate (cAMP) has been regarded as a regulator for cell growth and proliferation for 20 years. Hyperproliferation of many cells and particularly of psoriatic keratinocytes was speculated to be due to a decrease in cAMP levels in the psoriatic epidermis, whereas new findings could not confirm these observations. To clarify this discussion we determined the intracellular cAMP content in isoprenaline-stimulated keratinocytes from psoriatics and controls after treatment with CyA or FK 506. Ethanol and the beta-blocking drug propranolol served as controls. The basal level of cAMP and the response to isoprenaline in psoriatic keratinocytes did not differ from those of controls. CyA dramatically reduced the cAMP level and FK 506 just slightly diminished it in a dose-dependent manner. Both drugs diminished the cAMP level more effectively in the keratinocytes from lesional psoriatic skin than in keratinocytes from controls. These data provide evidence that CyA influences early signal transduction pathways by depressing the intracellular cAMP in keratinocytes. This supports the view of other groups that CyA and perhaps also FK 506 influence not only immuno-competent cells but also keratinocytes in the treatment of psoriasis. Furthermore, it is doubtful that a low cAMP level is a positive regulator for cell growth and the hyperproliferation of psoriatic keratinocytes.

Topics: Adult; Aged; Cyclic AMP; Cyclosporine; Female; Humans; Keratinocytes; Male; Middle Aged; Psoriasis; Signal Transduction; Tacrolimus

Protein tyrosine kinases (PTKs) are closely related to cell growth, proliferation and differentiation. In keratinocytes, various growth factor receptors and cytosolic proteins, including the EGF and IGF receptors, the proteins of the src family and others, exhibit PTK activity. In psoriatic epidermis an increased level of EGF receptors and their ligand TGF-alpha has been found, and this is thought to be one reason for the pathological hyperproliferation of keratinocytes in this disease. Oral treatment with cyclosporin A (CsA) and FK506 or topical treatment with dithranol lead to an improvement in psoriasis. In the present study we examined the effect of these three drugs on the cellular content of phosphorylated tyrosines in highly proliferative HaCaT keratinocytes. HaCaT keratinocytes can be used as a model for highly proliferative epidermis, e.g. psoriatic epidermis. CsA had no effect whereas FK506 and dithranol reduced the phosphorylation of tyrosine residues in HaCaT keratinocytes. The activation of serine/threonine protein kinase C (PKC) is known to downregulate PTKs. Therefore we incubated keratinocytes with the selective PKC inhibitor Ro 31-8220 in addition to the other drugs. Only after the addition of Ro 31-8220 to FK506-treated keratinocytes was the phosphotyrosine (p-tyr) level elevated, but this was only one-third of the increase measured without additional therapeutic drugs. We assume that an induction of PKC alone is not responsible for the reduced p-tyr level after treatment with dithranol and FK506.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Anthralin; Cell Line; Cyclosporine; Humans; Immunohistochemistry; Indoles; Intracellular Fluid; Keratinocytes; Organ Culture Techniques; Phosphorylation; Phosphotyrosine; Protein Kinase C; Protein-Tyrosine Kinases; Proteins; Psoriasis; Signal Transduction; Skin; Tacrolimus; Tyrosine

The induction of protein tyrosine kinases (PTKs) is known to be a key element in the activation of lymphocytes.. Because immunologic mechanisms are important in the pathogenesis of psoriasis, we examined the time course of tyrosine-phosphorylated proteins (p-tyr) as a marker for cellular PTK activity in phytohemagglutinin (PHA)-stimulated T cells of psoriatic patients and healthy controls.. PHA-stimulated T cells from both groups expressed peaks of p-tyr after 15 min and 4 h. In T cells from psoriatics, the 15-min peak was smaller but the 4-hour peak reached an enormous maximum, which was 270% higher than the basic p-tyr value. PHA-stimulated T cells were additionally treated with psoriasis-provoking drugs (lithium, chloroquine, propranolol and ethanol) and the two immunosuppressive drugs cyclosporin A and FK 506. Lithium and propranolol were able to increase the p-tyr level after 15 min in PHA-stimulated T cells from psoriatics in contrast to controls. Chloroquine and ethanol did not have a significant effect on T cells of both groups. CsA markedly diminished the phosphorylation of intracellular tyrosines in T cells of psoriatics and controls, whereas FK 506 diminished the p-tyr level in controls only slightly.. We have characterized important differences in p-tyr phosphorylation activities of psoriatic T cells compared to controls. This could be a hint to explain the known abnormalities of psoriatic T cells.

Topics: Adolescent; Adult; Aged; Case-Control Studies; Cells, Cultured; Chloroquine; Cyclosporine; Ethanol; Female; Humans; Immunosuppressive Agents; Irritants; Lithium; Lymphocyte Activation; Male; Middle Aged; Phosphorylation; Phytohemagglutinins; Propranolol; Protein-Tyrosine Kinases; Psoriasis; T-Lymphocytes; Tacrolimus; Time Factors; Tyrosine

FK 506 is a new immunosuppressive agent with a similar molecular action to cyclosporin A. We have investigated immunohistochemical changes in lesional biopsies of seven patients with severe recalcitrant chronic plaque psoriasis receiving systemic FK 506 therapy. Within 4 weeks of start of treatment, there was a striking reduction in psoriasis area and severity index (mean reduction 87.4%), accompanied by marked reductions in dermal and epidermal CD4+ and CD8+ cells. Investigation of biopsies obtained 4-8 weeks after start of treatment revealed a significant fall in the numbers of activated mononuclear cells expressing CD25 (IL-2 receptor alpha-chain), HLA-DR, or CD11a (lymphocyte function-associated antigen-1, LFA-1 alpha chain). In contrast, the number of epidermal CD1+ (Langerhans) cells increased in response to FK 506 therapy. Study of leukocyte adhesion-related epitopes in active disease revealed strong expression of CD54 (intercellular adhesion molecule-1, ICAM-1) and E-selectin (previously known as endothelial leukocyte adhesion molecule-1) both on microvascular endothelial cells and of ICAM-1 on infiltrating mononuclear cells; ICAM-1 was also expressed weakly on epidermal keratinocytes. Vascular cell adhesion molecule-1 (VCAM-1) was either absent or expressed rarely on vascular endothelium. In response to FK 506 treatment, both ICAM-1 and E-selectin expression on blood vessels was reduced consistently but nevertheless persisted, even in individuals exhibiting total clearance of psoriatic lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Antigens, CD; Cell Adhesion Molecules; E-Selectin; Female; HLA-DR Antigens; Humans; Immunohistochemistry; Intercellular Adhesion Molecule-1; Lymphocyte Function-Associated Antigen-1; Male; Middle Aged; Psoriasis; Receptors, Interleukin-2; Tacrolimus; Vascular Cell Adhesion Molecule-1

Topics: Adult; Cell Adhesion Molecules; Cytokines; E-Selectin; Female; Gene Expression; Humans; Intercellular Adhesion Molecule-1; Male; Middle Aged; Psoriasis; Skin; Tacrolimus

IL-8 is a chemotactic cytokine with proinflammatory and growth-promoting activities. Recently it has been shown to influence several functions of keratinocytes, including HLA-DR expression, chemotaxis, and proliferation by binding to a specific receptor. Because psoriasis vulgaris is characterized by epidermal hyperproliferation and infiltration of inflammatory cells, we investigated the expression of IL-8 and its receptor in normal and psoriatic epidermis using semiquantitative reverse-transcriptase-polymerase chain reaction. In addition the mRNA levels of the proto-oncogenes c-ras, c-raf, c-myc, and HER-2 were also investigated as potential growth-promoting stimuli in psoriatic epidermis. IL-8 mRNA was only detected in lesional psoriatic epidermis, and IL-8R-specific mRNA was found to be 10 times increased in lesional psoriatic epidermis. There was no significant difference in the protooncogene mRNA levels. In order to test the relevance of the massively increased IL-8R levels in psoriatic epidermis, we investigated the effect of the antipsoriatic drug FK-506 on specific IL-8 and IL-8R mRNA expression. FK-506 dose dependently inhibited IL-8R expression and function. Our data suggest that in psoriatic skin, elevated IL-8 levels and markedly increased IL-8R expression may act in concert to induce the cardinal signs of psoriasis--epidermal hyperproliferation and leukocyte infiltration. IL-8R may prove a molecular target for antipsoriatic drugs such as FK-506.

Topics: Adult; Aged; Amino Acid Sequence; Cells, Cultured; Down-Regulation; Female; Gene Expression Regulation; Humans; Interleukin-8; Male; Middle Aged; Molecular Sequence Data; Proto-Oncogenes; Psoriasis; Receptors, Interleukin; Receptors, Interleukin-8A; RNA, Messenger; Skin; Tacrolimus

Psoriasis, a disease of unknown etiology, is in some patients severe, extremely debilitating, and unresponsive to conventional therapies, including UV-B, oral psoralen with long-wave UV radiation in the A range (PUVA), oral retinoids, and methotrexate. We report the results from our study of seven patients with refractory psoriasis who were treated with the new immunosuppressive drug, tacrolimus (FK 506).. All seven patients showed a dramatic resolution of psoriasis that remained in remission as long as they received full-dose therapy. Serial skin biopsy specimens demonstrated a rapid disappearance of the inflammatory infiltrate and a slower resolution of the epidermal changes. Tacrolimus was well tolerated during the 5.5 to 14 months of observation. Side effects, including nephrotoxicity and hypertension, were controlled by appropriate modification of drug dosage.. Tacrolimus, a new immunosuppressive agent, is effective in treating patients with severe recalcitrant psoriasis. The mechanism of its action in psoriasis is unknown, but it may be related to its ability to modulate immune function. Further studies will establish criteria for patient selection and drug dosage, to maximize efficacy of this agent in psoriasis, while minimizing its toxicity.

Topics: Administration, Oral; Adult; Arthritis, Psoriatic; Blood Urea Nitrogen; Creatinine; Female; Follow-Up Studies; Heart Transplantation; Humans; Liver Transplantation; Male; Middle Aged; Psoriasis; Remission Induction; Severity of Illness Index; Tacrolimus

Topics: Adult; Female; Heart Transplantation; Humans; Liver Transplantation; Male; Psoriasis; Tacrolimus

Topics: Adult; Blood Glucose; Blood Pressure; Blood Urea Nitrogen; Cholesterol; Creatinine; Female; Follow-Up Studies; Humans; Kidney Function Tests; Male; Psoriasis; Tacrolimus; Uric Acid

Topics: Antigens, CD; Biopsy; Cell Adhesion Molecules; E-Selectin; Female; Humans; Langerhans Cells; Psoriasis; Receptors, Interleukin-2; T-Lymphocytes; Tacrolimus