cholecalciferol and Psoriasis

Psoriasis is a challenging skin disorder due to its chronicity, high rate of prevalence, disability, comorbidity and disfiguration. It is a multi-system disorder that includes joints and metabolic syndromes. Psoriasis is a condition of pathologic interaction among immune cells, biological signaling molecules and skin cells. Several contributing factors are responsible for the exacerbation and onset of psoriasis, i.e. genetic factors and environmental factors such as medications, infectious diseases and lifestyle.. To study the new insights in the treatment of psoriasis and future prospects.. This review article gives an insight on the current concepts of psoriasis and deals with discussing the initiation and development of the diseases. We described the pathogenetic pathway for psoriasis. The article focuses on the treatment approaches for psoriasis that have arisen from the dissection of the inflammatory psoriatic pathways.. We aimed to highlight the novel therapies and drugs used in the treatment of psoriasis, including food and drug administration (FDA) approved drugs and drugs under clinical trials. The treatment can be initiated for mild to the moderate diseased condition employing vitamin D3 analogues, corticosteroids and a combination of products as first-line therapy.. Psoriasis can be managed by a proper understanding of the immune function. We have also discussed medicinal herbs used for psoriasis based on their ethnopharmacological knowledge and reported work of researchers.

Topics: Adrenal Cortex Hormones; Cholecalciferol; Humans; Plant Preparations; Plants, Medicinal; Psoriasis; Skin

Psoriasis (PsO) requires safe and effective long-term management to reduce the risk of recurrence and decrease the frequency of relapse. Topical PsO therapies are a cornerstone in the management of PsO though safety concerns limit the chronic, continuous use of topical corticosteroids and/or vitamin D

Topics: Administration, Topical; Cholecalciferol; Dermatologic Agents; Glucocorticoids; Humans; Psoriasis

To provide primary care clinicians with an up-to-date and practical overview of the diagnosis and management of psoriasis.. PubMed, MEDLINE, EMBASE, and Cochrane databases were searched for relevant meta-analyses, randomized controlled trials, systematic reviews, and observational studies about the diagnosis and management of psoriasis.. Psoriasis is a chronic, multisystem inflammatory disease with predominantly skin and joint involvement. Beyond the physical dimensions of disease, psoriasis has an extensive emotional and psychosocial effect on patients, affecting social functioning and interpersonal relationships. As a disease of systemic inflammation, psoriasis is associated with multiple comorbidities, including cardiovascular disease and malignancy. The diagnosis is primarily clinical and a skin biopsy is seldom required. Depending on the severity of disease, appropriate treatment can be initiated. For mild to moderate disease, first-line treatment involves topical therapies including corticosteroids, vitamin D3 analogues, and combination products. These topical treatments are efficacious and can be safely initiated and prescribed by primary care physicians. Patients with more severe and refractory symptoms might require further evaluation by a dermatologist for systemic therapy.. Many patients with psoriasis seek initial evaluation and treatment from their primary care providers. Recognition of psoriasis, as well as its associated medical and psychiatric comorbidities, would facilitate timely diagnosis and appropriate management with effective and safe topical therapies and other medical and psychological interventions, as needed. More severe and refractory cases might warrant referral to a dermatologist for further evaluation and possible systemic therapy.

Topics: Administration, Topical; Adrenal Cortex Hormones; Biological Factors; Cholecalciferol; Chronic Disease; Cyclosporine; Dermatologic Agents; Drug Therapy, Combination; Female; Humans; Male; Methotrexate; Phototherapy; Psoriasis; Severity of Illness Index

Relapsing polychondritis (RP) is a rare autoimmune-mediated disease characterized by inflammation involving cartilaginous tissues. We report here a case of RP in a 38-year-old Japanese man with 13-year duration of psoriasis vulgaris treated with topical steroids and vitamin D

Topics: Adalimumab; Administration, Cutaneous; Adult; Antirheumatic Agents; Autoantibodies; Autoimmune Diseases; Biopsy; C-Reactive Protein; Cholecalciferol; Collagen Type II; Ear Cartilage; Glucocorticoids; Humans; Magnetic Resonance Imaging; Male; Matrix Metalloproteinase 3; Polychondritis, Relapsing; Psoriasis; Severity of Illness Index

Topics: Administration, Topical; Adrenal Cortex Hormones; Cholecalciferol; Diagnosis, Differential; Drug Combinations; General Practice; Humans; Nail Diseases; Psoriasis; Skin Care

Topical therapies are the mainstream treatment of psoriasis because most patients have mild disease. First-line treatments are vitamin D derivatives and corticosteroids. These treatments are usually given in combination schedules. For topical treatments the selection of the most appropriate vehicle is of major importance, thus improving adherence to the treatment, which frequently is impaired by the complexities of topical therapeutic choices. Evidence for efficacy and safety of topical treatments is readily available for vitamin D treatments and short-term treatment with corticosteroids. However, the scientific evidence for longer-term treatments is limited. Multiple new small molecules are in various stages of development and are reviewed.

Topics: Administration, Cutaneous; Adrenal Cortex Hormones; Anthralin; Anti-Inflammatory Agents; Cholecalciferol; Coal Tar; Dermatologic Agents; Drug Therapy, Combination; Humans; Protein Kinase Inhibitors; Psoriasis; Retinoids; Severity of Illness Index; Vitamins

In recent years, advances in our understanding of inflammatory mediators and the underlying pathogenesis of psoriasis and psoriatic arthritis have shed light on potential therapeutic targets, which has led to the development of several new promising treatments. In this article, key clinical trials, mechanisms of action, patient outcomes, and relevant safety information for these novel topical medications will be evaluated. This article is the first in a 3-part series on treatments presently in the pipeline for the management of psoriasis and psoriatic arthritis including topical agents, biologic treatments, and systemic therapies in phase 2 and phase 3 clinical trials. With novel approaches to the disease process, these therapies may afford more targeted individualized treatment regimens and offer hope to patients with psoriasis and psoriatic arthritis who have reported a suboptimal therapeutic response to conventional therapies.

Topics: Administration, Topical; Adrenal Cortex Hormones; Anthralin; Biological Factors; Calcineurin Inhibitors; Cholecalciferol; Dermatologic Agents; Humans; Inflammation Mediators; Psoriasis; Retinoids

Chronic plaque psoriasis is the most common type of psoriasis and is characterized by redness, thickness and scaling. First-line management is with topical treatments.. Our objective was to establish the effectiveness, tolerability and safety of topical treatments for people with chronic plaque psoriasis of the scalp, assessing placebo-controlled trials of all treatments and head-to-head trials that assessed vitamin D analogues.. As part of a Cochrane review of topical treatments for psoriasis, we systematically searched electronic databases for randomized controlled trials. The review included 26 randomized controlled trials of treatments for psoriasis of the scalp with 8020 participants. Trials used several measures to assess changes in psoriasis severity: these were combined using the standardized mean difference metric and interpreted by reporting as a six-point global improvement score.. On effectiveness grounds, very potent or potent steroid treatments should be preferred to vitamin D3 analogue with approximately an average 10% additional improvement on a six-point scale. Vitamin D3 analogue combined with potent steroid appears slightly more effective than potent steroid monotherapy (3% additional improvement on a six-point scale). Rates of withdrawal from treatment and adverse events in trials were generally low and similar to those for placebo. There remains uncertainty about the atrophic potential of corticosteroid treatments for scalp psoriasis.. Corticosteroids are more effective than vitamin D analogues and similarly tolerated. However, further research is needed to inform long-term maintenance treatment and provide appropriate safety data.

Topics: Administration, Cutaneous; Adrenal Cortex Hormones; Cholecalciferol; Chronic Disease; Dermatologic Agents; Humans; Psoriasis; Randomized Controlled Trials as Topic; Scalp Dermatoses

One characteristic abnormality of lesional skin in psoriasis is the excessive production of antimicrobial peptides and proteins (AMPs). AMPs typically are small (12-50 amino acids), have positive charge and amphipathic structure, and are found in all living organisms including mammals, insects, plants and invertebrates. These peptides are best known for their integral role in killing pathogenic microorganisms; however, in vertebrates, they are also capable of modifying host inflammatory responses by a variety of mechanisms. In psoriatic lesions, many AMPs are highly expressed, and especially the associations between psoriasis and cathelicidin, β-defensins or S100 proteins have been well studied. Among them, a cathelicidin peptide, LL-37, has been highlighted as a modulator of psoriasis development in recent years. AMPs had been thought to worsen psoriatic lesions but recent evidence has also suggested the possibility that the induction of AMPs expression might improve aspects of the disease. Further investigations are needed to uncover a previously underappreciated role for AMPs in modulating the immune response in psoriasis, and to improve disease without the risks of systemic immunosuppressive approaches.

Topics: Animals; Antimicrobial Cationic Peptides; Cathelicidins; Cholecalciferol; Defensins; Humans; Psoriasis; S100 Proteins

Psoriasis is a chronic immune-mediated disease that appears on the skin. It occurs when the immune system sends out faulty signals that speed up the growth cycle of skin cells. Psoriasis is typically a lifelong condition. There is currently no cure, but various treatments can help to control the symptoms. Activated vitamin D3 is the first-line treatment for psoriasis. Psoriasis is often treated with combination therapy of activated vitamin D3 and other treatment. Depending on the severity and location of outbreaks, individuals may experience significant physical discomfort and some disability. Thus, the goal for the treatment of psoriasis is to control the signs and symptoms over a long period and to ameliorate the quality of life of psoriasis patients.

Topics: Administration, Topical; Cholecalciferol; Clobetasol; Dendritic Cells; Drug Therapy, Combination; Humans; Interleukin-23; Nitric Oxide Synthase Type II; Psoriasis; Quality of Life; Retinoids; Th17 Cells; Tumor Necrosis Factor-alpha

Microvascular abnormalities are a characteristic feature of psoriasis and play a crucial role in its pathogenesis. Investigational studies have shown that activated keratinocytes in lesional skin undergo an accelerated epidermal cell turnover and are a major source of pro-angiogenic cytokines, like as VEGF, ESAF, PDECGE/TP, TNF-alpha, TGF-alpha and PDGF, suggesting that the epidermis is capable of inducing vascular proliferation. On the other hand, microvascular alterations are essential for the development and persistence of the psoriatic lesions as they provide cellular and tissue nutrition to hyperplastic keratinocytes and promote inflammatory cell migration. Also, dilated and slightly tortuous blood vessels within dermal papillae represent one of the earliest detectable histological changes for all stages of lesional development. Videodermatoscopy is a new non invasive imaging technique able to identify modifications of microvascular architecture in vivo and such evaluation will be useful for the dermatologist both for diagnostic and prognostic evaluation, as well as for post-therapeutic follow-up. In this review, the role of microvascular abnormalities in the pathogenesis of psoriasis as well as the mechanisms underlying vascular changes and their primary therapeutic implications will be reviewed and discussed.

Topics: Cell Proliferation; Cholecalciferol; Cyclosporine; Cytokines; Humans; Keratinocytes; Microvessels; Neovascularization, Pathologic; Psoriasis; Razoxane; Retinoids; Skin

Topical vitamin D3 analogues are a mainstay of treatment in mild to moderate plaque psoriasis. Vitamin D3 analogues exert their effect in psoriasis via binding nuclear vitamin D3 receptors on genes involved in cellular proliferation, differentiation and inflammation. Currently available synthetic vitamin D3 analogues include calcipotriol, maxacalcitol, tacalcitol and calcitriol. These agents are only minimally systemically absorbed and therefore have few systemic side effects. Local irritation is the most frequently noted side effect and can be managed by combining vitamin D3 analogues with other topical or systemic therapies, such as topical corticosteroids or narrow-band UVB phototherapy. The use of a vitamin D agent helps improve the efficacy of topical corticosteroids for psoriasis and helps minimize the potential for adverse events associated with topical corticosteroid treatment. Care should be taken when combining with other topical therapies due to potential inactivation of either agent. Topical vitamin D3 analogues can be a cost-effective addition to a psoriasis treatment regimen, especially when compliance is encouraged by the tolerability of these agents and more costly systemic agents are avoided.

Topics: Administration, Cutaneous; Animals; Cholecalciferol; Dermatologic Agents; Drug Interactions; Humans; Medication Adherence; Psoriasis; Skin

Our skin is constantly challenged by microbes but is rarely infected. Cutaneous production of antimicrobial peptides (AMPs) is a primary system for protection, and expression of some AMPs further increases in response to microbial invasion. Cathelicidins are unique AMPs that protect the skin through 2 distinct pathways: (1) direct antimicrobial activity and (2) initiation of a host response resulting in cytokine release, inflammation, angiogenesis, and reepithelialization. Cathelicidin dysfunction emerges as a central factor in the pathogenesis of several cutaneous diseases, including atopic dermatitis, in which cathelicidin is suppressed; rosacea, in which cathelicidin peptides are abnormally processed to forms that induce inflammation; and psoriasis, in which cathelicidin peptide converts self-DNA to a potent stimulus in an autoinflammatory cascade. Recent work identified vitamin D3 as a major factor involved in the regulation of cathelicidin. Therapies targeting control of cathelicidin and other AMPs might provide new approaches in the management of infectious and inflammatory skin diseases.

Topics: Animals; Bacteria; Cathelicidins; Cholecalciferol; Dermatitis, Atopic; Humans; Psoriasis; Rosacea; Skin; Skin Diseases

Topical therapies are the mainstays of treatment for most patients with psoriasis because they relieve symptoms and reduce the size and severity of lesions. The effectiveness of a therapeutic intervention is a function of drug efficacy (determined by randomized clinical trial results) and patient safety and compliance. Alterations in any parameter can have a substantial influence on clinical outcomes. However, topical agents can be associated with unwanted and potentially toxic side effects that make physicians reluctant to prescribe them, and patients intentionally discontinue treatment with these topical agents. To maximize effectiveness and improve patient safety, physicians may prescribe medications in combination, sequential, or rotational therapeutic regimens. This treatment strategy has the potential to improve the overall efficacy and safety of topical therapy; however, the effectiveness of this method may be compromised because the complexity of the therapeutic regimen may decrease patient compliance. Newer topical therapies that have a convenient once-daily dosing schedule are needed and will have important implications for patient compliance.

Topics: Administration, Topical; Adrenal Cortex Hormones; Cholecalciferol; Drug Therapy, Combination; Humans; Patient Compliance; Psoriasis; Safety; Treatment Outcome

Management of psoriasis begins with identification of the extent of cutaneous disease. However, a holistic, contractual approach to treatment is encouraged, with particular reference to psychosocial disability and quality-of-life issues. The presence of psoriasis on palms, soles, body folds, genitals, face, or nails, and concomitant joint disease, are also important when considering treatment options. An evidence-based approach is essential in delineating differences between the many available treatments. However, archaic approaches, especially combinational ones, are routinely used by some clinicians, with inadequate prospective or comparative evidence. Treatments currently available are: topical agents used predominantly for mild disease and for recalcitrant lesions in more severe disease; phototherapy for moderate disease; and systemic agents including photochemotherapy, oral agents, and newer injectable biological agents, which have revolutionised the management of severe psoriasis. Other innovative treatments are undergoing clinical studies, with the aim of maintaining safe, long-term control of the condition.

Topics: Administration, Topical; Adrenal Cortex Hormones; Antibodies, Monoclonal; Cholecalciferol; Dermatologic Agents; Humans; Infliximab; Psoriasis; PUVA Therapy

The scalp is the most common site of disease involvement at the onset and throughout the course of psoriasis. For many patients, psoriasis of the scalp is the most difficult aspect of their disease; yet, despite a wide range of therapy options and an extensive literature base, scalp psoriasis remains difficult to treat, highlighting a long-standing unmet need for the effective treatment of scalp psoriasis. A review of past and current medical literature reveals that a number of interesting therapeutic approaches have been used in the treatment of scalp psoriasis. The diverse and sometimes extreme therapeutic approaches, the marginal benefit of many topical agents, the paucity of controlled studies evaluating the efficacy of topical agents in the treatment of scalp psoriasis and the high level of patient dissatisfaction with currently available treatments for psoriasis all support the need for new, effective and well-tolerated treatment options for scalp psoriasis.

Topics: Administration, Topical; Adrenal Cortex Hormones; Cholecalciferol; Humans; Phototherapy; Psoriasis; Quality of Life; Scalp; X-Ray Therapy; X-Rays

Facial and flexural psoriasis may impair the quality of life of psoriatic patients considerably. For the adequate management of psoriasis it is important to pay attention to lesions at these sensitive sites, which require an approach different to that for lesions on other sites in several respects. An extensive literature search was carried out to collect evidence-based data on facial and flexural psoriasis with respect to epidemiology, clinical aspects, pathogenetic factors and various treatments. Subsequently, a panel of experts, the Copenhagen Psoriasis Working Group (CPWG), discussed these aspects and several recommendations were formulated reconciling the evidence-based data. Facial psoriasis occurs in 17-46% of psoriatics and flexural psoriasis is experienced by 6.8-36% of patients with psoriasis. Therefore, psoriasis at these sites cannot be regarded as a rare manifestation. Facial psoriasis is a prognostic marker indicating a poor prognosis of psoriasis. Facial and flexural psoriasis cannot be regarded as distinct disease entities but rather as site variations. The clinical features of facial psoriasis suggest that there are three subtypes: hairline psoriasis, sebo-psoriasis and true facial psoriasis. Otitis externa and ocular manifestations should not be neglected. Evidence that microbiological factors may be relevant to facial and flexural psoriasis is virtually absent. For facial psoriasis the response to UV radiation is variable. At least 5% of psoriatics have photosensitive psoriasis. In these patients photosensitive diseases such as lupus erythematodes and polymorphic light eruption have to be excluded. Based on the literature assessment and working group discussions the CPWG concluded the following. (1) Low-potency topical corticosteroids, vitamin D3 analogues and calcineurin inhibitors are first choice treatments in facial and flexural psoriasis. Evidence for the efficacy of the first two modalities is at level 3 while it is at level 1 for the third one. An individualized approach is indicated; for example, in case of corticosteroid side effects in the past the other two modalities should be selected and in unstable psoriasis prone to irritation, monotherapy with vitamin D3 analogues should be avoided. (2) Antimicrobial treatments are not indicated for facial and flexural psoriasis. (3) Dithranol and tar treatment are not indicated as first-line treatment but only if the first-line options fail. (4) In case topical therapies are not effect

Topics: Anti-Infective Agents; Calcineurin Inhibitors; Cholecalciferol; Dermatologic Agents; Extremities; Facial Dermatoses; Humans; Immunosuppressive Agents; Phototherapy; Practice Guidelines as Topic; Prognosis; Psoriasis

Psoriasis is a complex disease that requires safe, long-term treatment. Topical steroid therapy, topical non-steroid therapy only, and a combination of various topical therapies in the treatment of mild to moderate forms of psoriasis are presented. Topical therapy includes corticosteroids, vitamin D3 analogs, retinoids, tars, anthralin, keratolytics, and topical immunomodulators. While most medications are approved for use as a single agent in the treatment of psoriasis, some of these drugs are most effective when used in combination with topical corticosteroids. Topical therapy is generally administered for mild and localized forms of psoriasis, whereas phototherapy and systemic therapy are reserved for extensive lesions and more severe forms of the disease. Individual approach is absolutely necessary in each patient with psoriasis.

Topics: Administration, Topical; Adrenal Cortex Hormones; Cholecalciferol; Dermatologic Agents; Humans; Psoriasis; Retinoids; Vitamins

The advent of new topical agents such as topical calcineurin inhibitors, as well as the reformulations of older agents in new vehicles, has broadened the treatment approaches to psoriasis and atopic dermatitis. The clinician must now consider additional novel physiologic pathways and mechanisms of action as well as expanding options for combination therapy. Combination therapy is especially beneficial when the selected agents possess differing mechanisms of action that provide additive or synergistic efficacy, reducing the required doses of the individual agents compared with monotherapy and potentially limiting side effects. Therapeutic approaches also can be rotated or used in various sequences for maintenance therapy. In psoriasis, a number of trials have demonstrated the effectiveness of combination therapy. Although combination therapy has not been extensively studied in atopic dermatitis, many practitioners combine topical corticosteroids and topical calcineurin inhibitors in their clinical practice because the two drug classes have different and possibly complementary mechanisms of action. For both diseases, the decision as to what agents are combined must also be tempered by patient type, disease presentation or severity, and patient preferences.

Topics: Administration, Topical; Adrenal Cortex Hormones; Anti-Inflammatory Agents; Calcineurin Inhibitors; Cell Division; Cholecalciferol; Clinical Trials as Topic; Cytokines; Dermatitis, Atopic; DNA-Binding Proteins; Drug Therapy, Combination; Gene Expression Regulation; Humans; Immunosuppressive Agents; Male; NF-kappa B; NFATC Transcription Factors; Nuclear Proteins; Psoriasis; Receptors, Cytokine; Retinoids; Transcription Factors

Psoriasis is considered as a T-cell-mediated inflammatory skin disease which is characterized by hyperproliferation and poor differentiation of epidermal keratinocytes. While susceptibility to psoriasis is inherited, the disease is influenced by environmental factors such as infections and stress. Diet has been suggested to play a role in the aetiology and pathogenesis of psoriasis. Fasting periods, low-energy diets and vegetarian diets improved psoriasis symptoms in some studies, and diets rich in n-3 polyunsaturated fatty acids from fish oil also showed beneficial effects. All these diets modify the polyunsaturated fatty acid metabolism and influence the eicosanoid profile, so that inflammatory processes are suppressed. Some patients with psoriasis show an elevated sensitivity to gluten. In patients with IgA and/or IgG antigliadin antibodies the symptoms have been shown to improve on a gluten-free diet. The active form of vitamin D, 1,25-dihydroxyvitamin D(3), exhibits antiproliferative and immunoregulatory effects via the vitamin D receptor, and thus is successfully used in the topical treatment of psoriasis. In this review, dietary factors which play a role in psoriasis are assessed and their potential benefit is evaluated. Furthermore, the risk of drug-nutrient interactions in psoriasis therapy is discussed.

Topics: Antioxidants; Cholecalciferol; Diet; Fatty Acids, Unsaturated; Food-Drug Interactions; Glutens; Humans; Oxidative Stress; Psoriasis; Vitamin B 12

Topical treatments are used in first intention for moderate forms. These treatments may be associated if necessary with systemic treatments. Topical steroids, vitamin D3 derivates, and a retinoid (tazarotene) are the most useful treatments. Chlormetine is used sometimes, but a sensitisation occurs quickly. We must know that psoriasic skin is notably permeable and a systemic diffusion must be considered.

Topics: Administration, Topical; Cholecalciferol; Dermatologic Agents; Drug Hypersensitivity; Humans; Nicotinic Acids; Psoriasis; Steroids

Epidermal keratinocytes are the site of both UVB-induced photochemical conversion of 7-dehydrocholesterol to vitamin D(3) (25 OHD(3)) and the enzymatically controlled hydroxylation via 25-hydroxyvitamin D(3) to the biologically active final product 1alpha,25-dihydroxy vitamin D(3) (1alpha,25(OH)(2)D(3), calcitriol). The epidermal synthesis of calcitriol is of fundamental relevance because calcitriol regulates important cellular functions in keratinocytes and dermal immunocompetent cells. Calcitriol and other vitamin D-analogues are effective in the treatment of psoriasis because of their anti-proliferative and pro-differentiation effects. One mechanism for UVB-light therapy in psoriasis could be the induction of calcitriol synthesis. A better understanding of the metabolism of vitamin D(3) in the skin opens new perspectives for potential therapeutic applications of vitamin D analogues in inflammatory skin diseases. Further studies investigating the role of vitamin D(3) metabolism in the prevention of malignant skin disorders are needed.

Topics: Cholecalciferol; Dermatitis; Humans; Psoriasis; Skin Diseases; Ultraviolet Rays; Ultraviolet Therapy

Psoriasis is a complex disease with a spectrum of clinical manifestations. Psoriasis may express as a few coin-sized erythemato-squamous plaques up to widespread disease covering the entire body surface (erythrodermic psoriasis). Psoriasis may present as a few stable plaques or unstable disease, rapidly relapsing after treatment. Some patients may respond excellently to topical treatments whereas other patients may be difficult to manage, showing treatment resistance even to the systemic treatments. Therefore, a spectrum of treatments is available to individualize care of psoriasis. In this chapter the available treatments are presented. The vast majority of patients is treated with topical treatments, with vitamin D(3)analogs and topical corticosteroids as the first line treatments. Tazarotene is an alternative for vitamin D(3) treatment if this treatment fails. In some special cases, dithranol and tar treatment may be used. Phototherapy with UVB and photochemotherapy (PUVA) are indicated in patients not responding sufficiently to topical treatment. However, chronic exposure, in particular to photochemotherapy implies an increased risk for photo- carcinogenicity. Systemic treatments including methotrexate, cyclosporin, acitretin and fumarates are indicated in patients who cannot be managed with topical treatments or phototherapy, either for treatment resistance or cumulative toxicity. In this article the opportunities and limitations of the available treatments are presented.

Topics: Cholecalciferol; Coal Tar; Humans; Nicotinic Acids; Phototherapy; Psoriasis

The active vitamin D(3) regulates proliferation and differentiation of epidermal keratinocytes. Although topical application of steroid has been principal therapy for psoriasis, there occurs some side effects such as skin atropy, telangiectasis, and purpura. Recently topical vitamin D(3), tacalcitol, calcipotriol, and maxacalcitol, which avoid these side effects, are widely used for psoriasis. In this review, we discussed the mechanism, effect, and side effect of topical vitamin D(3) for psoriasis.

Topics: Administration, Topical; Cell Differentiation; Cell Division; Cholecalciferol; Combined Modality Therapy; Cyclosporine; Drug Therapy, Combination; ErbB Receptors; Humans; Keratinocytes; Ointments; Phosphorylation; Protein Precursors; Proto-Oncogene Proteins c-myc; Psoriasis; PUVA Therapy; Transglutaminases

The study of vitamin D(3) topical applications has begun at Osaka University after Morimoto S. reported a patient with senile osteoporosis whose psoriasis was cured after treatment with 1-alpha-hydroxyvitamin D(3) [1 alpha (OH) D(3)]. Another study of the first use of vitamin D(3) for psoriasis was reported in the same year in both Europe and the United States independently. Calcipotriol ointment came first onto the market for the treatment of psoriasis in Denmark in 1990. In Japan, where tacalcitol ointment was first approved in 1993, six kinds of topical vitamin D(3) applications are now available. Now new applications of vitamin D(3) are anticipated to replace therapeutic drugs currently in use for psoriasis and other skin diseases.

Topics: Administration, Topical; Cholecalciferol; Drug Design; History, 20th Century; Humans; Ointments; Osteoporosis; Psoriasis

The review of the literature is devoted to derivatives of calciferol (vitamin D3), representatives of a new group of antiproliferative drugs employed in psoriasis, ichthyosis, rheumatism and some neoplastic processes. Results are submitted of histo- and biochemical, physiological, and clinical trials of the synthetic derivative of vitamin D calcipotriol, a possibility of its combination with physiotheraputic modes of treatment is reported together with recently identified side effects. Novel analogues of the drug are listed, with their merits and demerits pointed out. The authors conclude that further studies are warranted into abnormalities of metabolism of calcium in psoriasis to develop efficacious modes of correction of dermatosis involving the use of representatives of the given group of medicinal agents.

Topics: Calcium; Cholecalciferol; Clinical Trials as Topic; Humans; Psoriasis; Treatment Outcome

Psoriasis is an autoimmune disease affecting 2-4% of the Caucasian population. Inflammatory processes induce the migration of interferon (IFN) gamma producing Th1 lymphocytes into the skin. These play a key role in the pathogenesis of psoriasis. These Th1 lymphocytes are responsible for the pathological reactions in psoriatic skin leading to keratinocyte hyperproliferation, small vessel proliferation and neutrophilic infiltration. Antigen-presenting cells activate dermal CD4+ T lymphocytes, and various signals can support the polarization of Th1 responses. The main signal for Th1 development is interleukin (IL) 12. After binding to their receptors both IL-12 and IFN-gamma promote intracellular IFN-gamma production by activating signal transducer and activator of transcription (STAT) 4 or 1. STAT1 activation by IFN-gamma is followed by T-bet activation, a master transcription factor for Th1 lymphocytes. In experimental models of Th1-mediated autoimmune diseases immune deviation of polarized autoreactive Th1 into anti-inflammatory Th2 responses generally improves the disease. Therefore new therapeutic approaches based on immunomodulating molecules have been developed for psoriasis, a prototypical Th1-mediated autoimmune disorder. Recently IL-4, the most effective Th2-inducing cytokine, has been shown to be safe and efficient for treating psoriasis. Improvement was associated with the induction of a Th2 phenotype of skin infiltrating lymphocytes. This review summarizes the IL-4 inducing potential of various conventional and newer systemic therapies for psoriasis. Many of these were thought to be primarily immunosuppressive. A review of the literature reveals that most of them can induce IL-4 and Th2, and that Th2 induction may be an underestimated mode of action in the therapy of Th1-mediated autoimmune disease. Further studies are needed to determine the central role of IL-4 in the control of Th1-induced autoimmune disease, namely psoriasis.

Topics: Cholecalciferol; Cyclosporine; Cytokines; Fumarates; Humans; Inflammation Mediators; Interleukin-4; Methotrexate; Phototherapy; Psoriasis; Th1 Cells; Th2 Cells; Vitamin A

Topics: Administration, Topical; Alkylating Agents; Cholecalciferol; Humans; Mechlorethamine; Psoriasis; Scalp

Topics: Administration, Topical; Anti-Inflammatory Agents; Cholecalciferol; Clinical Trials as Topic; Glucocorticoids; Humans; Immunosuppressive Agents; Ligands; Methotrexate; Psoriasis; Receptors, Cytoplasmic and Nuclear; Receptors, Steroid; Vitamin A

Scalp psoriasis is a frequent expression of the common skin disease psoriasis, and scaling and itching are the two major complaints. Topical treatments are the mainstay of the treatment of psoriasis of the scalp, with the vehicle as well as the active ingredient relevant to efficacy, tolerability and compliance. Vehicles can be shampoos, lotions, gels, foams, creams and more greasy ointments. Active ingredients are keratolytics, coal tar (liquor carbonis detergens), dithranol, corticosteroids and vitamin D3 analogues. Some effect has also been described from topical or systemic imidazole derivatives. Topical corticosteroids remain the mainstay in the treatment of scalp psoriasis. The effects are rapid, the formulations are patient friendly and the adverse effects seem limited, although no data are available to support safety during prolonged use (more than 4 weeks). Topical vitamin D3 analogues have been available for the treatment of psoriasis since 1992. In the lotion formulation in particular, vitamin D3 analogues are a patient friendly, tolerable and effective alternative to corticosteroids, although the effects are optimal after 8 weeks, in contrast to 2-3 weeks for topical corticosteroids. Facial irritation (often temporary) can also be a disadvantage of vitamin D3 analogues, although only a small proportion of patients stop treatment for this reason. All other treatment options for psoriasis, such as tazarotene, phototherapy and systemic treatment with methotrexate, acitretin and cyclosporin are often not indicated or not suitable for treatment of the scalp. In daily practice, to make a choice from the available therapeutic arsenal for psoriasis, each patient should be examined individually. Deteriorating factors have to be excluded. For scaling, keratolysis is the first step. Subsequently, active treatment can be chosen depending on the clinical picture. When the psoriatic lesions are mainly characterised by inflammation, anti-inflammatory drugs such as topical corticosteroids are indicated. When scaling is the more important clinical feature, vitamin D3 analogues are indicated. Generally, intermittently used topical corticosteroids alternating with vitamin D3 derivatives either combined or not with liquor carbonis detergens containing shampoo is the most suitable treatment for most patients. Because psoriasis capitis is a chronic disease, long term treatment should, in addition to medical advice, also provide patient support and motivation.

Topics: Administration, Topical; Adrenal Cortex Hormones; Cholecalciferol; Guidelines as Topic; Humans; Phototherapy; Psoriasis; Scalp

Within the past decade it has been shown that psoriasis can be treated topically with analogs of vitamin-D3. Impaired differentiation and increased proliferation of keratinocytes are key features in psoriatic lesions together with a local activation of T lymphocytes. Evidence has accumulated showing that analogs of vitamin D3 increase differentiation and inhibit proliferation of keratinocytes. Therefore, analogs of vitamin D3 have been investigated in a number of trials showing improvement of psoriasis. It has been shown that vitamin D analogs are better than their vehicle and show the same potency as potent topical steroids. However, vitamin D analogs have been proven efficacious and without side effects also when used on long term basis. Vitamin D analogs can be used both as monotherapy and in combination topical steroids, UVB, PUVA, retinoids and cysclosporine. The vitamin D3 analog calcipotriol has been investigated in most detail and is available as an ointment, a creme and as a scalp solutation. From clinical studies involving thousands of patients, it can be concluded that calcipotriol is efficacious, safe, well tolerated and can be used on a long term basis. Other analogs are available, however, these analogs have not been studied in greater details yet.

Topics: Calcitriol; Cholecalciferol; Dermatologic Agents; Dihydroxycholecalciferols; Drug Therapy, Combination; Humans; Psoriasis

Psoriasis is one of the most common skin disorders affecting approximately 2% of the population; the disease is recurrent and can be very debilitating. The cause of psoriasis is unknown, although it appears to be an autoimmune disease with a genetic component to its aetiology. Past topical treatments such as emollients, coal tar and dithranol have been messy, cosmetically unacceptable or of low efficacy, while older systemic therapies have suffered from significant side effects. Newer drugs with better therapeutic indexes and new antiproliferative/immunomodulatory therapies based on an increased understanding of the origins of psoriasis have brought us closer to the goal of safely and efficaciously treating the disease. This review will cover the newest topical and systemic drugs currently in use, in clinical trials or preclinical development.

Topics: Antibodies, Monoclonal; Cholecalciferol; Dermatologic Agents; Drugs, Investigational; Humans; Immunosuppressive Agents; Psoriasis; Vitamin A

Topics: Cholecalciferol; Chromosomes, Human, Pair 6; Cyclosporine; Diagnosis, Differential; HLA-C Antigens; Humans; Immunosuppressive Agents; Prognosis; Psoriasis; PUVA Therapy; Retinoids

A spectrum of treatments is available for patients with psoriasis. It is of utmost importance to individualize the selection of treatment for the individual patient at the very moment of consultation. The manifestation of psoriasis, the extent of the lesions and the subjective discomfort of psoriasis are important factors which denominate the selection of treatment. The most important topical treatments are calcipotriol, dithranol, tar and corticosteroids. If topical treatments are unsuccessful, phototherapy with UVB, photochemotherapy (PUVA), methotrexate, cyclosporin and acitretin are the most important therapeutical options. The possibilities and limitations of these treatments will be presented in this review. In particular, the question will be addressed to what extent treatments of psoriasis may have systemic complications.

Topics: Administration, Topical; Adrenal Cortex Hormones; Anthralin; Anti-Inflammatory Agents; Cholecalciferol; Clinical Trials as Topic; Female; Humans; Male; Netherlands; Photochemotherapy; Prognosis; Psoriasis

Psoriasis is common, chronic and currently incurable. First-line therapies consist of topical preparations, the most recent of which include vitamin D3 and retinoid analogues. New approaches to phototherapy include narrow band ultraviolet B and photodynamic therapy. Considerable research is currently focused on immunomodulatory approaches to this disease.

Topics: Cholecalciferol; Humans; Immunotherapy; Laser Therapy; Photochemotherapy; Phototherapy; Psoriasis; Retinoids

Topics: Cholecalciferol; Humans; Phototherapy; Psoriasis; PUVA Therapy

Vitamin D3 analogs have been found to be effective in treating psoriasis.. We attempted to identify the targets and actions of vitamin D3 in the skin and to explore the availability of synthetic vitamin D3 analogs with selective actions on particular cell types or cell functions.. A review of the literature focused on the cellular targets of vitamin D3 in the skin and within the immune system. Furthermore, the use of novel vitamin D3 analogs in skin diseases other than psoriasis was reviewed.. The vitamin D receptor has been detected in most skin cells, which means that keratinization, hair growth, melanogenesis, fibrogenesis, angiogenesis, and immune-mediated processes are potential targets for vitamin D3. Vitamin D3 analogs have been synthesized with a higher therapeutic index or a higher degree of selectivity than the natural form of vitamin D3.. Vitamin D3 analogs with wide-ranging clinical applications may become available for dermatology.

Topics: Adjuvants, Immunologic; Biological Availability; Cholecalciferol; Connective Tissue; Dermatologic Agents; Forecasting; Hair; Humans; Immunity, Cellular; Keratins; Melanins; Neovascularization, Physiologic; Psoriasis; Receptors, Calcitriol; Skin; Skin Diseases

The skin is not only the organ for the photosynthesis of vitamin D3, but also a target tissue for its activated form 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). Vitamin D3 is absolutely essential for the development and maintenance of a healthy skeleton. Without an adequate source of vitamin D, children develop rickets and the elderly develop osteomalacia and exacerbation of osteoporosis. 1,25(OH)2D3 is a potent inhibitor of proliferation of epidermal cells and, with its analogs, it has been developed for the successful treatment of psoriasis. Not all psoriasis patients, however, respond to 1,25(OH)2D3 and its analogs. Evidence suggests that there may be a defect in the regulation of levels of mRNA for the vitamin D receptor in patients who have partial or no response to 1,25(OH)2D3 therapy. The degree of responsiveness to 1,25(OH)2D3 therapy may also be related to the allelic variations in the vitamin D receptor gene. Parathyroid hormone-related peptide is synthesized by the epidermis and is an endogenous antiproliferative factor. Parathyroid hormone-related peptide agonists and 1,25(OH)2D3 inhibit in vitro and in vivo epidermal proliferation, whereas parathyroid hormone-related peptide antagonists stimulate both epidermal proliferation and hair growth in vivo. Therefore, the calciotropic hormones 1,25(OH)2D3 and parathyroid hormone-related peptide have wide-ranging clinical applications in dermatology.

Topics: Calcitriol; Calcium; Cholecalciferol; Drug Resistance; Humans; Parathyroid Hormone-Related Protein; Proteins; Psoriasis; Sunlight

Active vitamin D3 modulates epidermal growth, keratinization and inflammation, and various vitamin D3 analogues have been shown to be effective in the treatment of psoriasis. These analogues now provide a useful addition to the therapeutic modalities available for the treatment of psoriasis. Epidermal hyperproliferation, abnormal keratinization and inflammation are the well-established hallmarks of the psoriatic plaque. The aim of this review is to provide an update of information on the cell biological effects of vitamin D3, and the influence of vitamin D analogues on the pathomechanisms of psoriasis.

Topics: Animals; Cell Division; Cell Line; Cholecalciferol; Humans; Inflammation; Keratinocytes; Mice; Psoriasis; Rats; Receptors, Calcitriol; Signal Transduction

Topics: Administration, Cutaneous; Administration, Topical; Anthralin; Anti-Inflammatory Agents; Cholecalciferol; Dermatologic Agents; Glucocorticoids; Humans; Psoriasis; PUVA Therapy; Tars

Vitamin D is absolutely essential for the maintenance of a healthy skeleton. Without vitamin D, children develop rickets and adults exacerbate their osteoporosis and develop osteomalacia. Casual exposure to sunlight is the major source of vitamin D for most people. During exposure to sunlight, ultraviolet B photons photolyze cutaneous stores of 7-dehydrocholesterol to previtamin D3. Previtamin D3 undergoes a thermal isomerization to form vitamin D3. Increased skin pigmentation, changes in latitude, time of day, sunscreen use, and aging can have a marked influence on the cutaneous production of vitamin D3. Once vitamin D3 is formed in the skin or ingested in the diet, it must be hydroxylated in the liver and kidney to 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. It is now recognized that a wide variety of tissues and cells, both related to calcium metabolism and unrelated to calcium metabolism, are target sites for 1,25(OH)2D3. 1,25(OH)2D3 stimulates intestinal calcium absorption and mobilizes stem cells to mobilize calcium stores from bone. Noncalcemic tissues that possess receptors for 1,25(OH)2D3 respond to the hormone in a variety of ways. Of great interest is that 1,25(OH)2D3 is a potent antiproliferative and prodifferentiation mediator. As a result, 1,25(OH)2D3 and its analogs have wide clinical application in such diverse clinical disorders as rheumatoid and psoriatic arthritis; diabetes mellitus type I; hypertension; cardiac arrhythmias; seizure disorders; cancers of the breast, prostate, and colon; some leukemias and myeloproliferative disorders; chemotherapy-induced hair loss; and skin rejuvenation as well as skin diseases like psoriasis and ichthyosis.

Topics: Binding, Competitive; Calcitriol; Calcium; Cholecalciferol; Heart; Humans; Immune System; Immunohistochemistry; Muscle, Smooth; Psoriasis; Receptors, Calcitriol; Skin; Skin Diseases; Tissue Distribution

The natural form of vitamin D3, 1,25-dihydroxyvitamin D3, modulates epidermal proliferation and differentiation and inhibits immune induction. Calcipotriol (calcipotriene) is a synthetic vitamin D analogue that partially separates the newly identified effects from the classic hypercalcemic effect. Topical treatment with calcipotriene has been shown to be effective, well tolerated, and safe for psoriasis.

Topics: Administration, Cutaneous; Calcitriol; Cell Differentiation; Cell Division; Cholecalciferol; Dermatologic Agents; Epidermis; Humans; Psoriasis

The introduction of this article is devoted to the physiological role of vitamin D3 and its synthesis. The authors refer to the accidental introduction of vitamin D3 into the psoriasis treatment, which later led to the development of a less toxic vitamin D3 analog named calcipotriol, and its administration as a topical antipsoriatic agent. Reviewing the literature the authors discuss the pharmacological and immunological effects of calcipotriol as well as the potential applications of vitamin D3.

Topics: Administration, Topical; Calcitriol; Cholecalciferol; Dermatologic Agents; Humans; Psoriasis

Since the identification of the cholesterol derivative 1,25-dihydroxy-vitamin D3 and its analogues as potent immunomodulatory, proliferation- and differentiation-regulatory molecules, the amount of data available on the effects of these agents on the skin and its appendages has grown exponentially. This review outlines recent progress in the understanding of the molecular biology and pathophysiology of vitamin D, and new strategies for the treatment of skin diseases are discussed. Focusing on psoriasis and preliminary clinical experiences, we discuss possible therapeutic targets and perspectives for these multifunctional steroid hormones in dermatology.

Topics: Animals; Cholecalciferol; Humans; Psoriasis; Skin; Skin Diseases; Structure-Activity Relationship

Cytokines are produced by a variety of cells and have numerous of overlapping activities. There is increasing evidence that cytokines play a crucial role in the pathogenesis of psoriasis and of other dermatologic diseases. This review summarizes current knowledge as to how the altered cytokine network is involved in the accumulation of inflammatory cells in lesional skin, and how the cytokines are involved in epidermal hyperproliferation. The actions of the most important therapeutic compounds, such as corticosteroids, dithranol, cyclosporine, retinoids, vitamin D3 analogues and ultraviolet radiation, on the cytokine system are also discussed. Consideration is given as to how the effects on the production of cytokines and/or cytokine receptors contribute to their therapeutic action.

Topics: Anthralin; Cholecalciferol; Cyclosporine; Cytokines; Glucocorticoids; Humans; Keratinocytes; Psoriasis; Receptors, Cytokine; Retinoids; Ultraviolet Therapy

Topics: Antineoplastic Agents; Cholecalciferol; Female; Health Resorts; Humans; Male; Phototherapy; Psoriasis; PUVA Therapy; Recurrence

Topics: 25-Hydroxyvitamin D3 1-alpha-Hydroxylase; Calcitriol; Cholecalciferol; Dermatologic Agents; Humans; Hydroxycholecalciferols; Psoriasis

The naturally occurring 1,25(OH)2 vitamin D3 and the two synthetic derivatives 1,24(OH)2 vitamin D3 and calcipotriol (Calcipotriol, INN, Calcipotriene, USAN) have a profound effect on keratinocyte proliferation and differentiation. Clinical trials have shown an effect of all three derivatives in psoriasis. The limiting factor for the use of 1,25(OH)2 vitamin D3 is the risk of hypercalcemia, which is 100 to 200 times less for calcipotriol and that may be less also for 1,24(OH)2 vitamin D3. Presently, calcipotriol in an ointment base has been marketed in a number of countries and represents an alternative to treatment with topical glucocorticoids and dithranol.

Topics: Calcitriol; Cholecalciferol; Dermatologic Agents; Humans; Psoriasis

The physiologically active metabolite of vitamin D3, 1 alpha,25-dihydroxycolicalciferol [1,25(OH)2D3, calcitriol] has achieved the status of a hormone. It is believed to mediate its effects by binding to a specific receptor which belongs to the family of nuclear receptors for glucocorticoids, estrogens, thyroxine, and retinoid acid. It has been discovered that 1,25(OH)2D3 has the ability to regulate growth and differentiation in many cell types, including cancer cells, epidermal keratinocytes, and activated lymphocytes. This has set the stage for the development of a new class of compounds with potential usefulness in hyperproliferative and immune-mediated diseases. Ideally, such agents should possess potent effects as regulators of cell proliferation and differentiation at concentrations well below those that may induce side effects related to the classical vitamin D activity on calcium absorption and bone mineralization. In addition to 1,25(OH)2D3, the synthetic vitamin D3 analogues 1 alpha-OH-D3, 1,24(OH)2D3, and calcipotriol have undergone clinical evaluation. Calcipotriol has been studied most extensively. Compared with 1,25(OH)2D3, calcipotriol is about 200 times less potent in its effect on calcium metabolism although similar in receptor affinity. In double-blind, placebo-controlled multicenter studies, topical calcipotriol has been shown to be both efficacious and safe for the short- and long-term treatment of plaque-type psoriasis. Because some of the novel vitamin D analogues are potent regulators of cell growth and immune responses, they may be of potential interest in the treatment of ichthyoses, cancer, and autoimmune diseases.

Topics: Calcitriol; Cholecalciferol; Humans; Psoriasis; Skin; Vitamin D

Vitamin D3 and its active metabolites can be generated within the skin. Their physiological activities encompass the regulation of calcium homeostasis, protooncogene expression and the production of a number of intracellular and secretory molecules from cells in various organs, including keratinocytes, fibroblasts and leukocytes. The major outcome of these activities is a decreased cellular proliferation and the modulation of inflammation and immunity, suggesting that these agents might be effective in the treatment of psoriasis, ichthyosis and allergic dermatitis. Several open and double-blind studies have indeed demonstrated some efficacy in psoriasis, but healing is slow and often incomplete. Higher doses are more effective but increase the potential of calcium deposition in the vascular tree and particularly the kidneys. Clinical results in ichthyosis and allergic dermatitis are disappointing. For the future, therapeutically more effective analogues of vitamin D3 with no calcium liability need to be developed.

Topics: Administration, Topical; Cholecalciferol; Humans; Ichthyosis; Psoriasis

Topics: Animals; Calcitriol; Calcium; Cholecalciferol; Humans; Intracellular Membranes; Osmolar Concentration; Psoriasis; Skin; Skin Physiological Phenomena; Vitamin D

Vitamin D is a hormone, not a vitamin. The skin is responsible for producing vitamin D. During exposure to sunlight, ultraviolet radiation penetrates into the epidermis and photolyzes provitamin D3 to previtamin D3. Previtamin D3 can either isomerize to vitamin D3 or be photolyzed to lymisterol and tachysterol. Vitamin D is also sensitive to sunlight and is photolyzed to 5,6-transvitamin D3, suprasterol I, and suprasterol II. In Boston, solar irradiation only produces previtamin D3 in the skin between the months of March and October. Aging, sunscreens, and melanin all diminish the capacity of the skin to produce previtamin D3. Once formed, vitamin D3 enters the circulation and is sequentially metabolized to 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 (1,25-[OH]2-D3). The epidermis possesses receptors for 1,25-(OH)2-D3. 1,25-(OH)2-D3 inhibits the proliferation of cultured keratinocytes and induces them to terminally differentiate. The topical or oral administration of 1,25-(OH)2-D3 has proved to be effective for the treatment of psoriasis. Therefore, the skin is the site for the synthesis of vitamin D and a target tissue for its active metabolite. The successful use of 1,25-(OH)2-D3 for the treatment of psoriasis heralds a new approach for the treatment of this enigmatic disorder.

Topics: Calcitriol; Cells, Cultured; Cholecalciferol; Humans; Photosynthesis; Psoriasis; Skin; Vitamin D

Topics: Animals; Cholecalciferol; Environment; Erythema; Herpes Simplex; Humans; Lighting; Melatonin; Models, Biological; Psoriasis; Seasons; Spectrum Analysis; Sunlight

Topical vitamin D analogues are routine treatment for psoriasis, but the effect of oral supplementation has not been established.. To examine the effect of vitamin D supplementation on psoriasis severity throughout the winter.. This randomized, double-blind placebo-controlled clinical trial with 2 parallel groups was performed through 2 winter seasons (2017 to 2018 and 2018 to 2019). Randomization was computer generated. All participants, health care clinicians, and outcome assessors were masked to group assignment. Each participant was followed for 4 months. The presented analyses were conducted in May 2022. The trial was conducted at the clinical research unit of the University Hospital of North Norway (Tromsø; Norway). Adults from the general population in Tromsø with active plaque psoriasis and 25-hydroxyvitamin D (25[OH]D) levels of less than 24 ng/mL (to convert to nmol/L, multiply by 2.496) were included.. Vitamin D (cholecalciferol, 100 000 IU, loading dose, followed by 20 000 IU/week) or placebo for 4 months.. Psoriasis Area Severity Index (PASI) (primary outcome), Physician Global Assessment, self-administered PASI, and Dermatology Life Quality Index scores (secondary outcomes).. A total of 122 participants (46 women [37.7%]; mean [SD] age, 53.6 [10.0] years; mean [SD] PASI score, 3.1 [2.0]; mean [SD] serum 25(OH)D, 14.9 [3.9] ng/mL) were included. Of these, 60 (49.2%) were randomized to the vitamin D group and 62 (50.8%) to the placebo group. A total of 120 participants (59 vitamin D [49.2%]/61 placebo [51.8%]) completed the study. By completion, mean (SD) 25(OH)D levels were 29.7 (5.2) ng/mL (vitamin D) and 12.0 (3.8) ng/mL (placebo). There was no significant difference in change in PASI score between the groups (adjusted difference, 0.11; 95% CI, -0.23 to 0.45). There was no significant difference in change in Physician Global Assessment score (adjusted odds ratio, 0.66; 95% CI, 0.27-1.63), self-administered PASI (adjusted difference, -0.60; 95% CI, -1.76 to 0.55) or Dermatology Life Quality Index (adjusted difference, -0.86; 95% CI, -1.9 to 0.19) between the groups. No adverse effects of the intervention were registered.. The results of this randomized clinical trial showed that vitamin D supplementation did not affect psoriasis severity. Low baseline severity scores may explain the lack of measurable effect. Levels of 25(OH)D in the intervention group increased to a less-than-expected degree based on previous experimental data from the same source population, and this may have affected the results.. ClinicalTrials.gov Identifier: NCT03334136.

Topics: Adult; Cholecalciferol; Dietary Supplements; Double-Blind Method; Female; Humans; Middle Aged; Psoriasis; Vitamin D; Vitamins

To investigate the clinical effect of vitamin D. Participants with psoriasis in a large randomized controlled trial examining the effect of vitamin D. Twenty-three were allocated to vitamin D and 42 to placebo. There was no significant difference at baseline between the two groups. Mean (SD) baseline 25-hydroxyvitamin D was 65.7 (25.7) nmol/L. There were no significant differences (p > .05) between the groups in all of the psoriasis outcome measures. Mean scores [95% CI] at 12 months for the Placebo versus Vitamin D groups: PASI 2.2 [1.4, 3.0] versus 2.1 [1.0, 3.2]; PGA 1.4 [1.1, 1.7] versus 1.5 [1.1, 1.9]; PDI 2.1 [0.9, 3.2] versus 1.9 [0.4, 3.4]; and DLQI 2.5 [1.4, 3.6] versus 2.0 [0.5, 3.4].. Vitamin D

Topics: Aged; Aged, 80 and over; Cholecalciferol; Dietary Supplements; Double-Blind Method; Female; Humans; Interleukin-17; Male; Middle Aged; Placebo Effect; Psoriasis; Severity of Illness Index; Treatment Outcome

The management of psoriasis remains a challenge for dermatologist and patient. This study aimed to determine whether vitamin D. PASI did not differ between groups at any time (group F(1, 104) = 0.48, p = .49; group*time F(4, 384) = 0.26, p = .90). However, 25(OH)D increased in both groups, rendering these findings inconclusive. A significant inverse relationship existed between PASI and 25(OH)D, with elevation of 25(OH)D by up to 125 nmol/L associated with mild decreases in PASI (estimated range of decrease 0-2.6; p = .002).. A direct benefit of vitamin D

Topics: Administration, Oral; Adult; Cholecalciferol; Chronic Disease; Dietary Supplements; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Humans; Linear Models; Male; Middle Aged; Placebo Effect; Psoriasis; Severity of Illness Index

Bacterial colonization on skin or tonsil may influence the clinical response of patients with psoriasis to immunosuppressive drugs. However, few studies have investigated the effects of bacterial superantigens on therapy in these patients. Recently, combination therapy with topical glucocorticoids (GC) and vitamin D3 (VD3) appears to be more effective than GC or VD3 monotherapy for psoriasis. We evaluated the suppressive effects of betamethasone butyrate propionate (BBP), three VD3 derivatives (calcipotriol, maxacalcitol and tacalcitol), cyclosporin and BBP plus VD3, on concanavalin A (ConA)- or streptococcal pyrogenic enterotoxin A (SPEA)-stimulated proliferation of peripheral blood mononuclear cells (PBMC) obtained from 35 psoriasis patients. Drug concentrations effecting 50% inhibition concentration of ConA- or SPEA-stimulated PBMC proliferation were estimated. Cytokine levels of tumor necrosis factor-α, γ-interferon, interleukin-1b, -2, -4, -5, -6, -8 -10 and -12p70 in PBMC culture supernatants were measured with bead-array procedures. Suppression of PBMC proliferation by BBP was significantly lower when PBMC were stimulated by SPEA than when stimulated by ConA. In contrast, the suppressive effects of calcipotriol and tacalcitol increased significantly when PBMC were stimulated by SPEA than when stimulated by ConA. The suppressive effect of BBP on SPEA-stimulated PBMC proliferation was improved significantly by adding 1-1000 ng/mL calcipotriol, compared with BBP alone. Cytokine levels in PBMC culture supernatants were not significantly different between ConA- and SPEA-stimulated PBMC. Calcipotriol and BBP in combination markedly suppressed SPEA-stimulated PBMC proliferation. SPEA produced by colonization of hemolytic streptococci may reduce the efficacy of BBP but not VD3 derivatives in the treatment of psoriasis.

Topics: Adult; Aged; Bacterial Toxins; Betamethasone; Cell Proliferation; Cholecalciferol; Cytokines; Female; Glucocorticoids; Humans; Leukocytes, Mononuclear; Male; Middle Aged; Psoriasis

A course of treatment with narrow-band ultraviolet B (NB-UVB) improves psoriasis and increases serum 25-hydroxyvitamin D (25(OH)D). In this study 12 patients with psoriasis who were supplemented with oral cholecalciferol, 20 µg daily, were given a course of NB-UVB and their response measured. At baseline, serum 25(OH)D was 74.14 ± 22.9 nmol/l. At the 9th exposure to NB-UVB 25(OH)D had increased by 13.2 nmol/l (95% confidence interval (95% CI) 7.2-18.4) and at the 18th exposure by 49.4 nmol/l (95% CI 35.9-64.6) above baseline. Psoriasis Area Severity Index score improved from 8.7 ± 3.5 to 4.5 ± 2.0 (p < 0.001). At baseline, psoriasis lesions showed low vitamin D metabolizing enzyme (CYP27A1, CYP27B1) and high human β-defensin-2 mRNA expression levels compared with those of the healthy subjects. In conclusion, NB-UVB treatment significantly increases serum 25(OH)D in patients with psoriasis who are taking oral vitamin D supplementation, and the concentrations remain far from the toxicity level. Healing psoriasis lesions show similar mRNA expression of vitamin D metabolizing enzymes, but higher antimicrobial peptide levels than NB-UVB-treated skin in healthy subjects.

Topics: 25-Hydroxyvitamin D3 1-alpha-Hydroxylase; Administration, Oral; Adult; beta-Defensins; Biopsy; Cholecalciferol; Cholestanetriol 26-Monooxygenase; Female; Humans; Male; Middle Aged; Psoriasis; Real-Time Polymerase Chain Reaction; RNA, Messenger; Skin; Ultraviolet Therapy; Vitamin D; Vitamin D Deficiency; Vitamins

Cyclosporin is used for moderate to severe psoriasis and improves not only the skin lesions but also quality of life of the patients. To improve its safe use, we evaluated a low-dose, intermittent regimen of cyclosporin in the treatment of psoriasis vulgaris. Seventy-three patients received approximately 2.5 mg/kg per day of cyclosporin microemulsion twice daily before breakfast and dinner for 2-12 weeks until 75% reduction was achieved in Psoriasis Area and Severity Index (PASI) score. When the skin lesions relapsed after cessation of cyclosporin and showed less than 50% reduction from baseline in PASI score, cyclosporin was restarted. This cessation and restart cycle was repeated if necessary. Treatment outcomes were assessed at 12, 48 and 96 weeks after initiation of the therapy. The initial dose of cyclosporin was 2.32 ± 0.27 (standard deviation [SD]) mg/kg per day. At baseline, the mean PASI score was 11.3 ± 5.3 (SD). An average of 49.8 ± 23.8 (SD) days of the therapy achieved PASI 75% reduction. In 20 of 73 patients, the second course of cyclosporin was required. The mean interval between the first and second course was 94 days. An average of 60.8 ± 26.9 days was required to achieve PASI 75% reduction in the second course, which was not significantly longer than that in the first course. Only six patients required cyclosporin for 96 weeks. The adverse effects included one case of hypertension. Our study suggests that low-dose, intermittent cyclosporin microemulsion is efficacious for the treatment of moderate to severe psoriasis.

Topics: Adrenal Cortex Hormones; Aged; Cholecalciferol; Cyclosporine; Drug Administration Schedule; Emulsions; Female; Humans; Immunosuppressive Agents; Male; Middle Aged; Prospective Studies; Psoriasis; Severity of Illness Index; Treatment Outcome

Topics: Adult; Aged; Aged, 80 and over; Calcitriol; Cholecalciferol; Dermatologic Agents; Dihydroxycholecalciferols; Female; Humans; Male; Middle Aged; Psoriasis; Treatment Outcome

Combining phototherapy with topical vitamin D3 analogues is a useful therapy for the treatment of psoriasis by reducing the cumulative UV dose required for clearance of lesions. Experimental investigations demonstrated that calcipotriol is degraded by UV radiation, and suggested that calcipotriol should be applied after phototherapy but not immediately before.. Calcipotriol or maxacalcitol ointment was topically applied to psoriatic plaques of six patients immediately before or after phototherapy on the right or left side of the body, respectively.. Topical application of vitamin D3 analogues either before or after irradiation by psoralen and UVA radiation (PUVA) or narrow-band (NB)-UVB showed exactly similar effects in all patients.. Therapeutic effects of vitamin D3 analogues are not clinically inactivated by subsequent irradiation with PUVA or NB-UVB phototherapy.

Topics: Administration, Cutaneous; Adult; Calcitriol; Cholecalciferol; Combined Modality Therapy; Dermatologic Agents; Female; Humans; Male; Middle Aged; Prospective Studies; Psoriasis; Severity of Illness Index; Treatment Outcome; Ultraviolet Therapy

Topics: Adult; Aged; Calcifediol; Calcitriol; Cholecalciferol; Female; Humans; Male; Middle Aged; Psoriasis; Skin

Psoriasis is associated with abnormally exaggerated epidermal cellular turnover. Recent studies showed that calcitriol (1,25-dihydroxyvitamin D3) a calcitrophic hormone, regulates terminal differentiation of basal cells of epidermal keratinocytes. We administered active forms of vitamin D3 in both oral and topical ways in an open-design study to patients with psoriasis vulgaris. Significant improvement was observed at the end of the study periods in these patients, especially in those treated with topical application of calcitriol. We also found a significant negative correlation between the severity of psoriasis and the basal serum level of 1 alpha,25-dihydroxyvitamin D but not with those of other calcium-related parameters in psoriatic patients. These data suggest that exogenous active forms of vitamin D3 are effective for treatment of psoriasis and that the endogenous 1,25-dihydroxyvitamin D level also may be involved in the development of this skin disease.

Topics: Administration, Oral; Administration, Topical; Adult; Calcitriol; Calcium; Cholecalciferol; Female; Humans; Male; Middle Aged; Psoriasis; Random Allocation; Time Factors

Atopic dermatitis and psoriasis are prevalent chronic inflammatory skin diseases that are characterized by dysfunctional skin barriers and substantially impact patients' quality of life. Vitamin D3 regulates immune responses and keratinocyte differentiation and improves psoriasis symptoms; however, its effects on atopic dermatitis remain unclear. Here, we investigated the effects of calcitriol, an active form of vitamin D3, on an NC/Nga mouse model of atopic dermatitis. We observed that the topical application of calcitriol decreased the dermatitis scores and epidermal thickness of NC/Nga mice with atopic dermatitis compared to untreated mice. In addition, both stratum corneum barrier function as assessed by the measurement of transepidermal water loss and tight junction barrier function as evaluated by biotin tracer permeability assay were improved following calcitriol treatment. Moreover, calcitriol treatment reversed the decrease in the expression of skin barrier-related proteins and decreased the expression of inflammatory cytokines such as interleukin (IL)-13 and IL-33 in mice with atopic dermatitis. These findings suggest that the topical application of calcitriol might improve the symptoms of atopic dermatitis by repairing the dysfunctional epidermal and tight junction barriers. Our results suggest that calcitriol might be a viable therapeutic agent for the treatment of atopic dermatitis in addition to psoriasis.

Topics: Animals; Calcitriol; Cholecalciferol; Cytokines; Dermatitis, Atopic; Disease Models, Animal; Interleukin-13; Mice; Psoriasis; Quality of Life; Skin

Topics: Adrenal Cortex Hormones; Basement Membrane; CD8-Positive T-Lymphocytes; Cholecalciferol; Humans; Immunologic Memory; Memory T Cells; Psoriasis

Topics: Animals; Cholecalciferol; Imiquimod; Mice; Nanoparticles; Particle Size; Psoriasis

Topics: Anti-Inflammatory Agents; Antibodies, Monoclonal, Humanized; Cholecalciferol; Dermatologic Agents; Hepatitis; Humans; Male; Middle Aged; Prednisolone; Psoriasis

Recently it has been recognized that there is a need of investigating in detail the vitamin D synthesis and metabolism directly in the skin with respect to its possible autocrine and paracrine actions. The potential effects the active metabolite of vitamin D exerts in pathological skin conditions like psoriasis needs to be clarified. Under ultraviolet B (UVB) irradiation skin can autonomously synthesize, activate and degrade vitamin D. In this pilot case study, we used for the first time Time-of-flight secondary ion mass spectrometry (ToF-SIMS) in the analysis of skin biopsies from a patient with psoriasis before and after UVB phototherapy. We were able to visualize vitamin D

Topics: Aged; Cholecalciferol; Female; Humans; Pilot Projects; Psoriasis; Skin; Spectrometry, Mass, Secondary Ion; Ultraviolet Therapy

The focus was on the development of medicated foam for incorporation of two incompatible active agents for psoriasis treatment; i.e., lipophilic cholecalciferol, and hydrophilic salicylic acid. Emphasis was given to formulation of a propellant-free foam, with sufficient foaming properties, physical and chemical stability, and low irritancy potential to maintain relevance for later translation into clinical practice. Various excipients and concentrations were examined to achieve suitable foam stability parameters, viscoelasticity, and bubble-size, which relate to foamability and spreadability. The major positive impact on these properties was through a combination of surfactants, and by inclusion of a viscosity-modifying polymer. Incorporation of the incompatible drugs was then examined, noting the instability of cholecalciferol in an acidic environment, with the design aim to separate the drug distributions among the different foam phases. Cholecalciferol was stabilized in the emulsion-based foam, with at least a 30-fold lower degradation rate constant compared to its aqueous solution. The composition of the emulsion-based foam itself protected cholecalciferol from degradation, as well as the addition of the radical-scavenging antioxidant tocopheryl acetate to the oil phase. With the patient in mind, the irritancy potential was also examined, which was below the set limit that defines a non-irritant dermal product.

Topics: Cholecalciferol; Emulsions; Excipients; Humans; Psoriasis; Surface-Active Agents; Viscoelastic Substances

The aim of this work is to study the possible mechanisms through which different immune-modulating agents can produce their beneficial effects on treatment of psoriasis and to determine whether the supplementation of these agents for psoriasis patients induces regression of psoriasis.. One hundred fifty participants were included in this study. The participants were divided into five groups: 1. Normal control group, 2. Psoriasis patients not taking any treatment, 3. Psoriasis patients treated with anti-psoriatic treatment (including coal tar, vitamin D3 analogues and corticosteroids). 4. Psoriasis patients treated with anti-psoriatic treatment and oral metformin (850mg twice daily) and 5. Psoriasis patients treated with anti-psoriatic treatment and oral pioglitazone (15mg once a day). Demographic characteristics, diabetic index, lipid profile and liver function tests were monitored. The CD4+ Tcells, CD8+ Tcells, CD4+/CD8+ ratio, interleukin-2 (IL-2), C-reactive protein (CRP) and ceruloplasmin (CP) were assayed.. After treatment of psoriasis patients with a traditional anti-psoriatic drug in combination with metformin and peroxisome proliferator-activated receptor gamma (PPARɤ) agonist (pioglitazone), the CD4+ T cells, IL-2, CRP, CP, ALT and AST levels were statistically significantly decreased compared to psoriasis patients without treatment. Positive and significant correlations between CD4+ % and IL-2, CRP, CP, ALT and AST in psoriasis patients were recorded.. The activation of PPAR-γ receptors by pioglitazone results in reduced formation of the proinflammatory cytokines and infiltration by inflammatory cells. Additionally, metformin acts as a modulator of the immune system in psoriasis patients and has a remarkable effect on the early stages of psoriasis. Therefore, either pioglitazone or metformin in combination with traditional anti-psoriatic drugs provides better results in the treatment of psoriasis than does each alone.

Topics: Adrenal Cortex Hormones; Adult; Cholecalciferol; Coal Tar; Drug Therapy, Combination; Female; Humans; Hypoglycemic Agents; Immunologic Factors; Male; Metformin; Middle Aged; Pioglitazone; Psoriasis; Thiazolidinediones

Topics: Administration, Topical; Adrenal Cortex Hormones; Biological Products; Cholecalciferol; Combined Modality Therapy; Esthetics; Humans; Medication Adherence; Nail Diseases; Psoriasis

Topical combination of a vitamin D3 analogue and corticosteroid is widely used for the treatment of psoriasis, a TH17-mediated disorder, but the underlying mechanism remains unclear.. We investigated the effect of this topical applicant, focusing on skin-infiltrating TH17 cells.. In 10 patients with plaque psoriasis, calcipotriol (Cal), betamethasone dipropionate (Bet), or the calcipotriol and betamethasone dipropionate 2-compound formulation (CB) was applied to 3 different psoriatic plaques with similar severity once a day for 14 days. One nonapplied lesion was used as a control. Four-millimeter biopsy specimens were taken from each site, cut into 2 pieces, and subjected to histologic examination and ex vivo expansion of skin-infiltrating T cells with anti-CD3/CD28 antibodies and IL-2.. Clinical, histologic, and IL-17A(+) cell-infiltrate improvement was found in the following order: CB > Cal > Bet > control or CB > Bet > Cal > control. Numbers of ex vivo expanded T cells were decreased by topical application of Bet and CB, and CB exhibited the most suppressive result. Numbers and frequencies of TH17 cells were significantly reduced by CB and Cal, suggesting that Cal has a capacity to preferentially suppress TH17 cells. When the stocked T cells from control samples were stimulated with anti-CD3 antibodies in the presence of Bet, Cal, or both, Cal downmodulated IL-17 and IFN-γ production and tended to upregulate IL-4 and IL-6 without apoptosis, but Bet inhibited production of these cytokines with apoptosis.. These findings suggest that Cal and Bet have different effects on T cells to normalize psoriatic changes, with decreased TH17 cell expansion in the skin lesions.

Topics: Administration, Topical; Adrenal Cortex Hormones; Apoptosis; Biopsy; Cholecalciferol; Cytokines; Humans; Orphan Nuclear Receptors; Psoriasis; T-Lymphocyte Subsets; Th17 Cells; Treatment Outcome

In relation to Th17 cell actions, interferon (IFN)-α production by plasmacytoid dendritic cells (pDCs) are involved in the pathogenesis of psoriasis. Vitamin D3 analogues are widely used in the treatment of psoriasis, however, their actions on pDCs are not well understood.. To investigate the effects of Vitamin D3 analogue calcipotriol (CAL) on pDCs, focusing on the cytokine production and chemotactic activity.. We compared in mice the effects of CAL, cyclosporine A (CyA), and triamcinolone acetonide (TA) on the cytokine production by pDCs (IFN-α), conventional DCs (TNF-α), and γd T cells (IL-17A). pDCs isolated from mouse spleen cells were stimulated with CpG-ODN in the presence or absence of each drug for 48h. Purified splenic conventional DCs (cDCs) and lymph node γδ T cells were stimulated with CpG-ODN or with anti-CD3/CD28 antibody, respectively. IFN-α, TNF-α and IL-17A in the 48-h culture supernatants were quantified by ELISA. We also studied the ability of CAL to inhibit the chemotaxis of freshly isolated pDCs toward chemerin and VEGF-A, representative chemoattractants of pDCs, by a real-time monitoring method, EZ-Taxiscan. To assess the effect of CAL on pDC accumulation in vivo, we painted CAL ointment to the mouse skin inflamed by topical application of imiquimod cream (IMQ) for 4 consecutive days. In the skin samples, we enumerated 440c. CAL significantly inhibited CpG-enhanced pDC IFN-α production at a comparable level to T cell IL-17A production, whereas its effect on cDC TNF-α production was minimal. Accordingly, CAL suppressed the CpG-augmented expression of TLR9 and MyD88. On the contrary, CyA strongly suppressed the production of TNF-α and IL-17A, but not IFN-α. TA inhibited the production of all the cytokines tested. The effect of CAL on the chemotactic activity of pDCs was also evaluated, demonstrating a significant downmodulation by exposure to the reagent. CAL depressed chemerin receptor CMKLR1 expression in pDCs. The in vivo mouse study showed that simultaneous application of CAL to the imiquimod-applied skin reduce both the recruitment of pDCs and the expression of IFN-α2 in the skin.. Our findings suggest that CAL uniquely downmodulates the cytokine production and chemotactic activity of pDCs. The CAL suppression of the in vivo pDC accumulation to the skin suggests that these actions are therapeutically relevant.

Topics: Animals; Calcitriol; Chemotaxis; Cholecalciferol; CpG Islands; Dendritic Cells; Dermatologic Agents; Down-Regulation; Female; Flow Cytometry; Humans; Immunohistochemistry; Interferon-alpha; Interferon-gamma; Interleukin-17; Mice; Microscopy, Fluorescence; Oligonucleotides; Psoriasis; Receptors, Antigen, T-Cell, gamma-delta; Skin; Spleen; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor A

Current data from daily practice show that vitamin D₃ analogues, corticosteroids and their fixed combination products are used heterogeneously for topical long-term treatment of psoriasis.. To evaluate scientific evidence about topical long-term therapy with vitamin D3 analogues, corticosteroids and their two-compound-products in psoriasis vulgaris and scalp psoriasis and to develop daily practice recommendations.. Systematic literature review via PubMed and Embase and informal expert consensus.. The search strategy identified 21 relevant clinical trials. Best evidence regarding topical long term treatment was available for the two-compound-formulation containing calcipotriene and betamethasone. In a comparative trial in psoriasis vulgaris the two-compound-formulation showed superior tolerability and cost effectiveness compared to monotherapy. In scalp psoriasis the two-compound-gel was superior compared to calcipotriene monotherapy. Standardized and simplified treatment application modes resulted in a better clinical outcome comparing to on-demand therapies.. Patients should be proactively involved in the choice of treatment, formulation and mode of application. Besides long-term treatment with the two-compound-formulation other treatment regimens including calcipotriene monotherapy can also be considered. Due to a favorable risk-benefit ratio in maintenance trials and due to better cost-effectiveness the application of two-compound-products once or twice a week after initial therapy is recommended.

Topics: Administration, Topical; Adrenal Cortex Hormones; Betamethasone; Calcitriol; Cholecalciferol; Clinical Trials as Topic; Drug Combinations; Evidence-Based Medicine; Guideline Adherence; Humans; Long-Term Care; Psoriasis

Vitamin D has important immunomodulatory effects on psoriasis in the Mediterranean region. To measure vitamin D intake in subjects with and without psoriasis, and to find an association with relevant clinical features, a case-control study was performed using cases (n = 50, 50% participation rate) clinically diagnosed with psoriasis and 200 healthy subjects (39.5% participation rate), leaving a final sample of 104 people. A survey was conducted using a food frequency questionnaire and clinical histories. Cases and controls were compared using univariate and multivariate analyses. We observed insufficient intake of cholecalciferol (vitamin D3) or ergocalciferol (vitamin D2) for both cases and controls. Patients with psoriasis were at greater risk of associated pathologies: dyslipidaemia (OR: 3.6, 95% CI: 0.8-15.2); metabolic syndrome (OR: 3.3, 95% CI: 0.2-53.9); hypertension (OR: 1.7, 95% CI: 0.4-7.2). Insufficient vitamin D intake in both psoriasis patients and controls in the Mediterranean population, and cardiovascular comorbility is more frequent in patients with psoriasis.

Topics: Adult; Case-Control Studies; Cholecalciferol; Ergocalciferols; Female; Humans; Male; Middle Aged; Odds Ratio; Psoriasis; Spain; Vitamin D Deficiency; Young Adult

In the UK, referrals to specialists are initiated by general practitioners (GPs). Study objectives were to estimate the incidence of diagnosed psoriasis in the UK and identify factors associated with GP referrals to dermatologists.. Newly diagnosed patients with psoriasis were identified in The Health Improvement Network (THIN) database between 01 July 2007-31 Oct 2009. Incidence of diagnosed psoriasis was calculated using the number of new psoriasis patients in 2008 and the mid-year total patient count for THIN in 2008. A nested case-control design and conditional logistic regression were used to identify factors associated with referral.. Incidence rate of diagnosed adult psoriasis in 2008 was 28/10,000 person-years. Referral rate to dermatologists was 18.1 (17.3-18.9) per 100 person-years. In the referred cohort (N=1,950), 61% were referred within 30 days of diagnosis and their median time to referral was 0 days from diagnosis. For those referred after 30 days (39%, median time to referral: 5.6 months), an increase in the number of GP visits prior to referral increased the likelihood of referral (OR=1.87 95% CI:1.73-2.01). A prescription of topical agents such as vitamin D3 analogues 30 days before referral increased the likelihood of being referred (OR=4.67 95% CI: 2.78-7.84), as did corticosteroids (OR=2.45 95% CI: 1.45-4.07) and tar products (OR=1.95 95% CI: 1.02-3.75).. Estimates of the incidence of diagnosed adult psoriasis, referral rates to dermatologists, and characteristics of referred patients may assist in understanding the burden on the UK healthcare system and managing this population in primary and secondary care.

Topics: Adolescent; Adrenal Cortex Hormones; Adult; Aged; Aged, 80 and over; Case-Control Studies; Cholecalciferol; Family Practice; Female; Humans; Incidence; Logistic Models; Male; Middle Aged; Psoriasis; Referral and Consultation; Retrospective Studies; Risk Factors; United Kingdom; Young Adult

Various therapies have been tried for psoriasis. In Japan, biologics began to be used for psoriasis treatment in January 2010. Their clinical efficacy is well known, but biologics cannot be used in all psoriasis patients for reasons such as side-effects and cost. It is necessary to evaluate the effect of long-term psoriasis treatment, but there have been no reports evaluating long-term treatment. Therefore, the outcomes of patients who had been treated at the Tokai University Hospital for more than 5 years, before biological agents were released, were examined. Three categories, classified by initial severity, changes in severity by method of treatment and background characteristics, were investigated. In conclusion, cases of long-term treatment with a combination of topical corticosteroid and topical vitamin D3 analog or oral cyclosporin were found to be effective therapies. Patients with a history of diabetes mellitus or cardiovascular disease of psoriasis were likely to be treatment resistant.

Topics: Administration, Oral; Administration, Topical; Adolescent; Adult; Aged; Aged, 80 and over; Child; Cholecalciferol; Cyclosporine; Dermatologic Agents; Drug Combinations; Etretinate; Female; Follow-Up Studies; Glucocorticoids; Humans; Japan; Male; Middle Aged; Phototherapy; Psoriasis; Severity of Illness Index; Time Factors; Treatment Outcome; Young Adult

Tumoral necrosis factor alpha blockers are very efficient in the treatment of many inflammatory systemic diseases, including rheumatoid arthritis and psoriasis. However, a paradoxical arouse of psoriasiform lesions may occur in a few patients taking anti-TNFα. The etiology of this rare side effect is still a mystery, and its treatment may be difficult. The authors report the resolution of adalimumab-induced psoriasis in a woman with rheumatoid arthritis after the use of high vitamin D(3) doses for the treatment of vitamin D deficiency. This is the first report of resolution of anti-TNFα-induced psoriasiform lesions by high doses of vitamin D(3) in a patient with rheumatoid arthritis and vitamin D deficiency. This case raises interesting questions on the role of vitamin D deficiency in the pathogenesis of this side effect and on the possible usefulness of high-dose vitamin D(3) in its treatment.

Topics: Adalimumab; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal, Murine-Derived; Antirheumatic Agents; Arthritis, Rheumatoid; Biomarkers; Cholecalciferol; Drug Substitution; Female; Humans; Middle Aged; Psoriasis; Risk Factors; Rituximab; Time Factors; Treatment Outcome; Tumor Necrosis Factor-alpha; Vitamin D; Vitamin D Deficiency; Vitamins

Topics: Blister; Cholecalciferol; Cyclosporine; Dermatologic Agents; Drug Therapy, Combination; Etretinate; Female; Humans; Middle Aged; Psoriasis; Treatment Outcome; Ultraviolet Therapy; Vascular Endothelial Growth Factor A

Psoriasis is a chronic inflammatory skin disease of unknown aetiology, and an active form of vitamin D(3) (1α,25-dihydroxyvitamin D(3)) and its analogues (VD3As) are widely used topical reagents for psoriasis treatment. Besides their well-known calcium homeostasis functions, VD3As have been shown to have various immune-modulating effects including the induction of thymic stromal lymphopoietin (TSLP), a master cytokine for inducing Th2 inflammation, in mouse models, but not yet in human psoriasis. VD3As also have been shown to induce cathelicidin, an antimicrobial peptide and strong inducer of innate immunity. Cathelicidin is overexpressed in psoriatic skin lesions; however, its role in this disease seems as yet inconclusive.. To clarify whether topical VD3As induce TSLP and cathelicidin, and to examine the modulation of expression patterns of related cytokines in human psoriatic lesions.. Skin biopsy samples from psoriatic lesions with or without VD3A treatment were subjected to immunohistochemical staining and quantitative reverse transcription-polymerase chain reaction analyses to measure the expression levels of various cytokines.. Significantly higher levels of TSLP, thymus and activation-related chemokine and CCR4 expression were observed in VD3A+ skin samples than in VD3A- samples. In contrast, significantly lower levels of interleukin (IL)-12/23 p40, IL-1α, IL-1β and tumour necrosis factor (TNF)-α expression were observed in the VD3A+ samples than in the VD3A- samples. Expression of cathelicidin was elevated in VD3A+ samples.. Topical VD3As induce TSLP and cathelicidin in psoriatic lesions, resulting in suppression of IL-12/23 p40, IL-1α, IL-1β and TNF-α, thereby ameliorating psoriatic plaques.

Topics: Administration, Cutaneous; Adult; Aged; Antimicrobial Cationic Peptides; Blotting, Western; Calcitriol; Cathelicidins; Cholecalciferol; Cytokines; Dermatologic Agents; Dihydroxycholecalciferols; Drug Therapy, Combination; Female; Humans; Interleukins; Male; Middle Aged; Psoriasis; Thymic Stromal Lymphopoietin; Tumor Necrosis Factor-alpha

Reduced production of antimicrobial peptides was proposed to contribute to susceptibility for skin infections in atopic dermatitis (AD). Focusing on the human cathelicidin protein, hCAP18, the aim of the present study was to explore whether reduced hCAP18 expression is a constitutive trait in AD and if established inducers affect the expression of hCAP18 in the skin of AD. First, we compared levels of hCAP18 mRNA between lesional skin in AD and psoriasis and verified significantly lower expression of hCAP18 mRNA in AD. In non-lesional skin, however, there was no difference between AD, psoriasis and healthy, indicating that there is no constitutive defect in the production of hCAP18 in AD patients. In healthy skin, hCAP18 was reported to be rapidly induced following wounding and here we verified this pattern in healthy controls and in psoriasis. In AD lesions, however, the expression of hCAP18 mRNA was markedly suppressed following wounding. Obviously, the inflammation in AD lesions neutralizes the expected induction of hCAP18 and even induces suppression. Notably, the mechanism to upregulate hCAP18 following vitamin D treatment was functional in lesional as well as in non-lesional AD indicating that the CAMP gene is normally regulated in this respect. In addition, cultured primary keratinocytes from non-lesional skin of psoriasis, AD and healthy skin, upregulated hCAP18mRNA following treatment with vitamin D. Itching is a hallmark of AD and scratching inevitably injures the skin. Failure to upregulate hCAP18 in eczema following injury is likely to affect antimicrobial protection and tissue repair in AD.

Topics: Adult; Aged; Antimicrobial Cationic Peptides; Cathelicidins; Cells, Cultured; Cholecalciferol; Dermatitis, Atopic; Down-Regulation; Female; Humans; Keratinocytes; Lipopolysaccharide Receptors; Male; Middle Aged; Psoriasis; Skin; Wounds and Injuries; Young Adult

Cathelicidin is strongly expressed in lesional skin in psoriasis and may play an important role as both an antimicrobial peptide and as an autoinflammatory mediator in this chronic skin disease. The mechanism of increased cathelicidin in psoriatic keratinocytes is not known, but recent observations have found that psoriasis has abundant Th17 cells that produce IL-17A and IL-22. We found that human keratinocytes stimulated with supernatants from T cells isolated from lesional psoriatic skin increased expression of cathelicidin when stimulated in the presence of 1,25-dihydroxyvitamin D(3) (1,25D(3)). This increase was signaled through the IL-17RA. In vitro, IL-17A, but not IL-22, enhanced cathelicidin mRNA and peptide expression in keratinocytes dependent on the presence of 1,25D(3). At the same time, coincubation with 1,25D(3) blocked induction of human beta-defensin 2 (HBD2), IL-6, and IL-8, which are other target genes of IL-17A. Act1, an adaptor associated with IL-17RA and essential for IL-17A signaling, mediated cathelicidin induction, as its suppression by small interfering RNA inhibited HBD2 and cathelicidin. Both, 1,25D(3) and IL-17A signaled cathelicidin induction through MEK-ERK. These results suggest that increased IL-17A in psoriatic skin increases cathelicidin through a vitamin D(3)-, Act1-, and MEK-ERK-dependent mechanism. Therapy targeting this cathelicidin-regulating system might be beneficial in patients suffering from psoriasis.

Topics: Adaptor Proteins, Signal Transducing; Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Cathelicidins; Cell Line; Cells, Cultured; Cholecalciferol; Humans; Inflammation Mediators; Interleukin-17; Keratinocytes; MAP Kinase Signaling System; Psoriasis; Tumor Necrosis Factor Receptor-Associated Peptides and Proteins; Up-Regulation

A consensus conference was convened to evaluate the topical treatment of psoriasis.. Members of the International Psoriasis Council (IPC) with broad clinical experience in the treatment of psoriasis and a specialist in meta- and pharmacoeconomic analyses were invited to participate on the consensus panel. Those accepting the invitation convened in Saariselkä, Finland.. An advisory group on topical treatments was nominated by the organizing panel members. All participants reported at the consensus conference on evidence based data with respect to disease severity assessment, the available data on efficacy and safety and on a comparative efficacy/safety analysis.. At the consensus conference, the presentations were discussed and conclusions, which were reached by the group, were recorded. Active participants of the group wrote assigned sections of this consensus document with a majority of participants agreed on the conclusions.

Topics: Administration, Topical; Adrenal Cortex Hormones; Cholecalciferol; Humans; Patient Compliance; Psoriasis; Retinoids; Severity of Illness Index; Vitamins

Bacterial infection might influence the clinical response of patients with immunological disorders including psoriasis to the therapeutic efficacies of immunosuppressive drugs, but few studies have been carried out to investigate the implication of bacterial superantigens. We evaluated the suppressive efficacies of betamethasone butyrate propionate, vitamin D3 derivatives, and cyclosporine against concanavalin A- or superantigen-induced proliferation of peripheral-blood mononuclear cells obtained from 18 healthy subjects. In vitro drug concentrations giving 50% inhibition (IC50s) of peripheral-blood mononuclear cell-proliferation stimulated with concanavalin A or streptococcal pyrogenic enterotoxin A were estimated. Concentrations of tumor necrosis factor-alpha, interferon-gamma, interleukin-2, -4, -5, or -10, in a peripheral-blood mononuclear cell-culture medium were measured with beads-array procedures. The median (range) IC50 value for betamethasone butyrate propionate evaluated in the streptococcal pyrogenic enterotoxin A-stimulated peripheral-blood mononuclear cells was 291.6 (0.001-1171.5) ng/ml, which was significantly higher than the value 0.072 (0.01-222.5) ng/ml found in concanavalin A-stimulated peripheral-blood mononuclear cells (P=0.0245). However, the median (range) IC50 value for calcipotriol in the streptococcal pyrogenic enterotoxin A-stimulated peripheral-blood mononuclear cells was 0.3 (0.24-1357.4) ng/ml, which was significantly lower than the value 128.6 (0.1-776.9) ng/ml found in concanavalin A-stimulated peripheral-blood mononuclear cells (P=0.0323). The IC50 value for cyclosporine was not significantly different between the concanavalin A- and streptococcal pyrogenic enterotoxin A-stimulated PBMCs. Concentration for none of the cytokines was significantly different between concanavalin A- and streptococcal pyrogenic enterotoxin A-stimulated peripheral-blood mononuclear cell cultures. The effects of betamethasone butyrate propionate to suppress these cytokine productions were rather stronger than those of calcipotriol. Streptococcal pyrogenic enterotoxin A induced by hemolytic streptococci colonization is suggested to attenuate the therapeutic efficacy of betamethasone butyrate propionate. While the mechanistic background of calcipotriol to suppress streptococcal pyrogenic enterotoxin A-induced peripheral-blood mononuclear cell-proliferation remains to be elucidated, vitamin D3 derivatives appears to be effective in suppressing anom

Topics: Adult; Betamethasone; Cell Proliferation; Cells, Cultured; Cholecalciferol; Concanavalin A; Cyclosporine; Dose-Response Relationship, Drug; Enterotoxins; Female; Humans; Immunosuppressive Agents; Interferon-gamma; Interleukins; Lymphocyte Activation; Lymphocytes; Male; Mitogens; Psoriasis; Streptococcus; Superantigens; Tumor Necrosis Factor-alpha

Design, synthesis, and in vitro and in vivo evaluation of a series of antipsoriatic antedrugs having 16-en-22-oxa-vitamin D3 are described. Among the seven compounds examined, two are promising: ester 5c and amide 5f, both of which exhibit greater potent antiproliferation activity with lessened calcemic activity than the presently prescribed maxacalcitol (2).

Topics: Animals; Cholecalciferol; Drug Design; Molecular Structure; Psoriasis; Rats; Structure-Activity Relationship

A variety of approaches (in vitro-/ex vivo studies, animal models, human studies and clinical trials) are available to assess compounds with potential antipsoriatic properties. Over the past few years various rodent models that mirror aspects of psoriasis phenotypes and/or pathogenesis have been created (e. g. knockout rodents, xenotransplantation models). Unfortunately these animal models do not reflect the complete pathogenesis of psoriasis. Therefore, screening procedures involving psoriatic lesions in humans are necessary. Even in the era of biologicals, the psoriasis plaque test (PPT) remains an important in vivo tool. In addition to screening potential antipsoriatic substances, the PPT can help answer other questions (frequency of use, dose-response relationship). A prerequisite for correct performance of PPT is knowledge of the toxicological and pharmacological data of the investigational compounds. The PPT is relatively simple, not time-consuming and allows the simultaneous testing of multiple substance. All the results from PPT must be confirmed by controlled clinical trials.

Topics: Administration, Topical; Animals; Anti-Inflammatory Agents; Biological Products; Calcineurin Inhibitors; Calcitriol; Cholecalciferol; Dermatologic Agents; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Evaluation, Preclinical; Humans; Psoriasis; Rodentia; Skin

Topics: Adult; Cholecalciferol; Diagnosis, Differential; Humans; Male; Nurse's Role; Patient Education as Topic; Psoriasis; Skin Care; Streptococcal Infections; Streptococcus pyogenes; Tonsillitis; Ultraviolet Therapy

The goals of the experiments reported in this paper were to explore skin bioavailability and cell growth inhibitory activity of new vitamin D3-based conjugates studied as a potential drug complex for psoriasis.. Conjugation was made between polyunsaturated fatty acids (PUFAs), such as linolenic acid or gamma-linolenic acid, and calcipotriol--a vitamin D3 analogue clinically used for topical treatment of psoriasis. These complexes were prepared by coupling the corresponding fatty acid with calcipotriol in the presence of dicyclohexyl-carbodiimide (DCC) and 4-(dimethylamino)-pyridine (DMAP) to obtain an ester bond.. The conjugates were capable of enhancing the penetration of the vitamin into the skin as well as inhibiting proliferation of keratinocytes in cultures. The antiproliferative activity even increased after simulating the full hydrolysis of the conjugates. In vitro skin penetration studies revealed that the conjugates penetrated into the skin at higher levels relative to calcipotriol alone. It was also demonstrated that the conjugate containing n-3 fatty acid penetrated into the skin at higher levels as compared to the conjugate containing n-6 PUFA. High-performance liquid chromatography analysis has shown that after penetration, a major portion of calcipotriol-PUFA conjugate was first converted mainly into another isomer form, presumably by transesterification, and only then it was hydrolyzed to form apparently high local concentrations of both calcipotriol and PUFA.. The unique biotransformation that occurred after penetration into the skin indicates that these conjugates are mutual prodrugs that are able to be bioprocessed in the skin and fully converted to the parent therapeutic agents.

Topics: Administration, Topical; Animals; Cell Proliferation; Cholecalciferol; Growth Inhibitors; In Vitro Techniques; Psoriasis; Skin Absorption; Swine

The treatment of hyperkeratotic palmoplantar eczema is notoriously difficult. A considerable number of patients do not or only partially respond to the current treatments such as topical corticosteroids, topical keratolytics, or PUVA therapy. The purpose of this pilot study was to look for an alternative treatment for hyperkeratotic palmoplantar eczema. We treated five patients with topical vitamin D3 derivatives (calcipotriol 50 microg/g and maxacalcitol 25 microg/g ointments). The lesions almost disappeared after 2 to 8 weeks of treatment in four patients and extremely improved with a seven week treatment in one patient. No adverse effect was observed during or after the treatment, and routine laboratory investigations were within normal ranges. When relapses occurred, they responded well to retreatment. Although the study is preliminary, the results suggest that vitamin D3 derivatives offer a safe, effective alternative form of treatment for recalcitrant hyperkeratotic palmoplantar eczema.

Topics: Administration, Topical; Aged; Biopsy, Needle; Cholecalciferol; Eczema; Female; Follow-Up Studies; Hand Dermatoses; Humans; Immunohistochemistry; Keratosis; Middle Aged; Psoriasis; Risk Assessment; Sampling Studies; Severity of Illness Index; Treatment Outcome

Caspase-14 is a nonapoptotic caspase family member whose expression in the epidermis is confined to the suprabasal layers, which consist of differentiating keratinocytes. Proteolytic activation of this caspase is observed in the later stages of epidermal differentiation. In psoriatic skin, a dramatic decrease in caspase-14 expression in the parakeratotic plugs was observed. Topical treatment of psoriatic lesions with a vitamin D3 analogue resulted in a decrease of the psoriatic phenotype and an increase in caspase-14 expression in the parakeratotic plugs. To investigate whether vitamin D3 directly affects caspase-14 expression levels, we used keratinocyte cell cultures. 1alpha,25-Dihydroxycholecalciferol, the biologically active form of vitamin D3, increased caspase-14 expression, whereas retinoic acid inhibited it. Moreover, retinoic acid repressed the vitamin D3-induced caspase-14 expression level. In addition, the use of organotypic skin cultures demonstrated that 1alpha,25-dihydroxycholecalciferol enhanced epidermal differentiation and caspase-14 activation, whereas retinoic acid completely blocked caspase-14 processing. Our data indicate that caspase-14 plays an important role in terminal epidermal differentiation, and its absence may contribute to the psoriatic phenotype.

Topics: Adolescent; Adult; Aged; Apoptosis; Caspase 14; Caspase Inhibitors; Caspases; Cell Differentiation; Cholecalciferol; Enzyme Activation; Epidermis; Female; Humans; Keratinocytes; Male; Middle Aged; Organ Culture Techniques; Phenotype; Psoriasis; Thymidine; Tretinoin

The Japanese Society for Psoriasis Research has conducted an annual survey of psoriasis patients in Japan from 1982 to 2001.. To perform the epidemiological study about a survey of psoriasis patients conducted in Japan for twenty years.. A sample of 28628 cases was collected from 148 dermatology centers throughout Japan. The reports from each center were analyzed.. Males (65.8%) were predominant over females (34.2%) in number. The vast majority of cases (86.0%) had plaque-form of psoriasis vulgaris, and 812 cases (2.8%) showed guttate psoriasis. Psoriatic erythroderma (0.8%), generalized pustular psoriasis (0.9%), and localized pustular psoriasis (0.5%) were rare. Three hundred of the patients (1.0%) manifested psoriatic arthritis. Local corticosteroids (67.8%) were the most used modalities, whereas local vitamin D(3) preparations (2.4%) were rarely used. For photo-therapeutic treatments, topical (12.1%) and systemic (7.5%) PUVA were predominant over UVB therapy (0.5%). In systemic treatments, drugs from the herbal medicine was the first (14.2%), followed by etretinate (7.6%), nonsteroidal anti-inflammatory drugs (4.4%), oral corticosteroids (4.1%), methotrexate (2.8%), cyclosporine (1.6%), and anti-cancer drugs (1.4%).. This survey was the first epidemiological study throughout Japan.

Topics: Administration, Topical; Adrenal Cortex Hormones; Adult; Age Distribution; Age of Onset; Cholecalciferol; Female; Health Surveys; Humans; Japan; Male; Middle Aged; Psoriasis; Sex Distribution

Psoriasis is a disease characterized by inflammation and increased population of hyperproliferative keratinocytes. It is well known that chemokines and chemokine receptors, such as interleukin-8 and its receptors (CXCR1 and CXCR2), play important roles in the pathogenesis of psoriasis. So far, examination of CXCR2 expression in psoriatic lesional keratinocytes by FACS calibur has not been reported and whether VitD3 inhibits psoriatic lesional keratinocyte proliferation through down-regulation of CXCR2 expression has not been elucidated. In the present study, CXCR2 expression in psoriatic lesional keratinocytes and HACAT treated with VitD3 was detected by flow cytometry. The proliferative capacity of HACAT treated with VitD3 was assayed by MTT assay. The results showed that CXCR2 expression in psoriatic lesional keratinocytes was higher than that in normal human keratinocytes. At the correct concentration VitD3 could inhibit human keratinocyte proliferation and down-regulate CXCR2 expression in HACAT. The data demonstrate that the inhibitory effect of VitD3 on keratinocyte proliferation might be mediated by down-regulation of CXCR2 expression.

Topics: Administration, Topical; Anti-Inflammatory Agents; Cell Culture Techniques; Cholecalciferol; Down-Regulation; Humans; Keratinocytes; Psoriasis; Receptors, Interleukin-8B

The association between psoriasis and hypoparathyroidism has been reported by several authors, and it has been suggested that abnormalities in calcium homeostasis may be involved in the development or exacerbation of psoriasis. However, so far there have only been two reports of pseudohypoparathyroidism associated with psoriasis.. To describe the familial occurrence of this association for the first time.. Two siblings with psoriasis associated with pseudohypoparathyroidism were presented. The first patient was a 24-year-old white male with disseminated erythrodermic pustular psoriasis that began 2 months before admission. He had had a history of mental retardation, recurrent otitis, seizures and arthralgia from the age of 11 years onwards. He presented the characteristic phenotype of Albright osteodystrophy: short stature, obesity, round facies, broad forehead, short neck and brachydactylia. He adopted a position of flexed limbs and showed proximal muscle weakness and a positive Trousseau sign. He had clinical signs of hypocalcemia (0.69 mmol/l ionized calcium and 3.2 mg/dl total calcium), hyperphosphatemia (6.6 mg/dl), hypomagnesemia (1.0 mEq/l), hypoalbuminemia (3.1 g/dl), normal serum intact PTH levels (45.1 pg/ml), primary hypothyroidism (13.2 mU/ml TSH, and 4.7 mg/dl total T(4)), hypergonadotrophic hypogonadism (116.0 ng/ml LH, 13.2 mU/ml FSH and 325.0 ng/dl testosterone), osteoporosis, and diffuse calcifications in soft tissues and in the central nervous system. The second case was a 14-year-old white girl with a history of psoriasis vulgaris from the age of five years onwards, and antecedents of mental retardation. She presented signs of Albright osteodystrophy (short stature, round facies, obesity, short neck, brachydactylia), hypocalcemia (ionized calcium of 1.08 mmol/l and total calcium of 6.7 mg/dl) hyperphosphatemia (9.4 mg/dl), elevated serum PTH levels (223.0 pg/ml), osteoporosis, and hypergonadotrophic hypogonadism (7.0 mU/ml LH, 9.3 mU/ml FSH and undetectable estradiol levels).

Topics: Abnormalities, Multiple; Adolescent; Adult; Calcium Carbonate; Cholecalciferol; Female; Humans; Male; Nuclear Family; Pseudohypoparathyroidism; Psoriasis

Psoriasis is a chronic skin disease characterized by epidermal hyperproliferation, which may be regulated by several mechanisms including apoptosis. In this study, we detected DNA fragmentation by the terminal deoxynucleotide transferase-mediated dUTP nick-end labeling (TUNEL) method and immunohistochemically examined the expression of Bcl-x and Bax in psoriasis. We determined the expression of bcl-xL mRNA by RT-PCR, and also determined the effect of vitamin D(3) (VD3) on bcl-xL mRNA expression in cultured normal human keratinocytes by RT-PCR, and the expression of Bcl-xL in psoriatic lesions before and after topical application of VD3. A large number of TUNEL-positive cells as well as Bcl-xL - and Bax-positive cells were observed throughout the epidermis in psoriatic lesions. Whereas, in nonlesional and normal skin, only a few TUNEL-positive cells were observed and only the lower epidermis showed positive staining for Bcl-x and Bax. We also observed higher expression of bcl-xL mRNA in psoriatic lesions than in nonlesional and normal skin. The expression of bcl-xL mRNA in cultured normal human keratinocytes stimulated or not with IFN-gamma and PMA was suppressed by VD3 in a dose-dependent manner, and the expression of Bcl-xL, but not Bax, in psoriatic lesional skin decreased after topical application of VD3 for 4 weeks. In conclusion, it is suggested that the apoptotic process in psoriatic lesions is in part regulated by Bcl-xL, and decreasing the expression of Bcl-xL by treatment with VD3 might ameliorate psoriatic lesions by contributing to the completion of the apoptotic process.

Topics: Administration, Topical; Adult; Aged; bcl-X Protein; Cells, Cultured; Cholecalciferol; Female; Humans; Immunohistochemistry; In Situ Nick-End Labeling; Keratinocytes; Male; Middle Aged; Proto-Oncogene Proteins c-bcl-2; Psoriasis; RNA, Messenger

Topics: Antibodies, Monoclonal; Cholecalciferol; Clinical Trials as Topic; Combined Modality Therapy; Fumarates; Humans; Prognosis; Psoriasis; PUVA Therapy; Tumor Necrosis Factor-alpha

Recently, there have been many vitamin D3 analogues synthesized and tried in the treatment of psoriasis. In the experiments reported here we observed and compared their effects on normal and psoriatic epidermis in organ culture in vitro. We employed a new vitamin D3 analogue, 22-oxa-calcitriol (OCT), the effect of which was compared with that of calcitriol (1,25-D3). Both caused suppression of proliferation of normal and psoriatic epidermis, dependent upon concentration and culture time. Histologically, in the presence of the agents, degeneration started from the top of the epidermis downwards. This is the first report of cell degeneration as a direct effect of vitamin D. The nature of the degeneration was evaluated by electron microscopy (EM) and by the in situ nick end labeling technique (TUNEL), and these studies revealed that the degeneration involved necrosis rather than apoptosis. This in vitro method may be useful to assess the effectiveness of newly synthesized vitamin D3 analogues in the treatment of psoriasis.

Topics: Apoptosis; Bromodeoxyuridine; Calcitriol; Cholecalciferol; Dermatologic Agents; Dose-Response Relationship, Drug; Epidermis; Humans; Microscopy, Electron; Organ Culture Techniques; Psoriasis

The aim of treatment in psoriasis is to reduce the degree of extension to a point compatible with the patients social, occupational and personal lifestyle. The patient should be informed that there is no curative treatment. A good patient-doctor relationship is required for the patient to understand that the proposed treatment can provide symptomatic relief but must take into account an optimal balance between treatment benefit and risk. Therapeutic abstention must be recognized as a possibility. In all cases, efforts must be made to recognize and eliminate if possible any favoring factors. A TWO-PHASE TREATMENT: Initially, the aim of the treatment is to induce an involution of the active lesions. A second phase is aimed at avoiding subsequent fiare-ups. Local treatments: Local care should always be preferred in patients with limited lesions. Keratolytic agents, dermocorticoids and vitamin D3 derivatives can be used. Topical retinoids, particularly tazarotene are in the development stage.. Systemic treatments should be reserved for extensive psoriasis and for failure after well-conducted local care. Photoherapy, particularly PUVA-therapy and more recently narrow-spectrum UVB-therapy play an important role. Systemic retinoids can be used alone or in combination with PUVA-therapy. The risks of methrotrexate and cyclosporin impose their use exclusively in specialized centers. Several other treatments are still in the experimental stage, particularly promising highly selective immunotherapy.

Topics: Administration, Topical; Anti-Inflammatory Agents, Non-Steroidal; Cholecalciferol; Humans; Keratolytic Agents; Psoriasis; PUVA Therapy; Retinoids

Topics: Cholecalciferol; Cortisone; Crohn Disease; Drug Therapy, Combination; Female; Humans; Middle Aged; Osteoporosis; Psoriasis; Risk Factors; Treatment Outcome

SM-10193 (26,26,26,27,27,27-hexafluoro-1 alpha,23(S),25-trihydroxyvitamin D3; F6-1,23(S),25-(OH)3D3) is one of the active vitamin D3 analogues, which is under exploration as a new therapeutic agent for psoriasis. In this paper, we present that SM-10193 induces the growth inhibition and differentiation of cultured normal human keratinocytes more effectively than 1,25(OH)2D3. The growth of keratinocytes was inhibited in the presence of 10(-11), 10(-10), 10(-9), 10(-8), 10(-7) and 10(-6) M of SM-10193 by 36.8, 42.1, 48.5, 47.6, 66.0 and 85.9% respectively. SM-10193 increased the number of involucrin positive cells (the marker for keratinocyte differentiation) from 4.9 +/- 0.1 to 12.5 +/- 0.8, 20.1 +/- 1.6 and 42.8 +/- 1.0% (P < 0.01) at 10(-8), 10(-7) and 10(-6) M, respectively. To elucidate the mechanism of SM-10193-induced growth inhibition, we analyzed cell cycle related distribution and the alteration of hyperphosphorylated and hypophosphorylated state of retinoblastoma protein (pRB). SM-10193 induces growth arrest in G1/G0 and G2 + M phases and an increase of the hypophosphorylated form of pRB more remarkably than 1,25(OH)2D3 does.

Topics: Calcitriol; Cell Cycle; Cell Differentiation; Cell Division; Cholecalciferol; Dose-Response Relationship, Drug; Humans; Keratinocytes; Psoriasis; Retinoblastoma Protein

Calcipotriol, 1,25(OH)2D3 and 1,24(OH)2D3 are potent drugs for the treatment of psoriasis. It has recently been published that these compounds induce epidermal hyperproliferation in hairless mouse skin.. The aim of our study was to examine the effect of vitamin D3 derivatives on epidermal growth, keratinization and permeability barrier function in vivo.. Calcipotriol, 1,25(OH)2D3 and 1,24(OH)2D3 in isopropanol or in an ointment formula were applied to normal hairless mouse skin. Transepidermal water loss (TEWL), a marker of cutaneous barrier function, and epidermal proliferation were determined at different time points 0-264 h after treatment. In addition, light and electron microscopy studies were performed.. A single treatment in solution led to a transient (2- to 3-fold) increase in TEWL after application of calcipotriol or 1,25(OH)2D3 and to a 3- to 6-fold increase in epidermal proliferation after application of each of the compounds. Repeated applications also resulted in an up to 3-fold increase in TEWL which persisted for 3 days after the end of the treatment. By light microscopy an increase in epidermal thickness was observed. There was no sign of inflammation. Electron microscopy studies showed the formation of a transitional cell zone as a sign of a premature keratinization.. These results demonstrate that in normal mouse skin vitamin D3 and its analogues disrupt the epidermal permeability barrier by induction of epidermal proliferation and premature keratinization but without morphological signs of inflammation.

Topics: 1-Propanol; Administration, Cutaneous; Animals; Calcitriol; Cell Division; Cholecalciferol; Dermatologic Agents; Dihydroxycholecalciferols; Epidermis; Keratins; Male; Mice; Mice, Hairless; Microscopy, Electron; Ointments; Permeability; Psoriasis; Skin; Time Factors; Water Loss, Insensible

Topics: 24,25-Dihydroxyvitamin D 3; Baths; Calcifediol; Calcitriol; Calcium; Cholecalciferol; Climate; Humans; Israel; Oceans and Seas; Parathyroid Hormone; Phosphorus; Prospective Studies; Psoriasis; Seawater; Sunlight; Tars; Ultraviolet Rays

Topics: Calcitriol; Cholecalciferol; Dermatologic Agents; Humans; Psoriasis

The efficacy of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and the new analogue calcipotriene (MC 903) in the treatment of psoriasis was investigated. Eight patients with psoriasis were enrolled in a pilot study with systemically administered vitamin D3 and were given 1,25(OH)2D3 (Rocaltrol; Hoffmann-La Roche) in dosages from 0.5 microgram to 2 micrograms/day for a 6-month trial. In one patient, the psoriatic plaques resolved within 2 months after treatment (0.5 microgram/day) was initiated. Moderate improvement was noted in one other patient (1 microgram/day). The serum level of 1,25(OH)2D before treatment was not less than the normal range of the adult population. Side effects of systemically administered 1,25(OH)2D3 included a dose-dependent increase in the 24-hour urinary calcium excretion and a decrease in the total number of platelets. Seven patients with symmetric plaque-type psoriasis were treated topically with 2 micrograms/g of 1,25(OH)2D3 in petrolatum. During 3 months of follow-up, mild improvement was noted in three patients. Five patients in the calcipotriene study were part of a nationwide double-blind placebo-controlled trial by Bristol-Myers Squibb. Moderate to marked improvement was noted in the two patients who received 50 micrograms/g of calcipotriene topically. The three patients who received placebo showed no response. We conclude that a subset of patients with psoriasis responds well to 1,25(OH)2D3. Calcipotriene is efficacious and an excellent alternative to topically applied corticosteroids.

Topics: Administration, Oral; Administration, Topical; Adult; Aged; Calcitriol; Cholecalciferol; Dermatologic Agents; Female; Humans; Male; Middle Aged; Pilot Projects; Psoriasis

Topics: Administration, Topical; Anthralin; Anti-Inflammatory Agents; Cholecalciferol; Coal Tar; Dermatologic Agents; Glucocorticoids; Humans; Psoriasis

The inhibitory effects of 1 alpha,25-(OH)2D3 and synthetic oxa-derivatives of vitamin D3 on growth of normal and psoriatic fibroblasts in culture were compared. Proliferation of normal fibroblasts was strongly inhibited by these new compounds in the following order: 22-oxa-1 alpha,25-(OH)2D3 greater than 22-oxa-1 alpha-(OH)D3 greater than 1 alpha,25-(OH)2D3 greater than 20-oxa-1 alpha,25-(OH)2D3. 22-Oxa-1 alpha,25-(OH)2D3 was about 10-times more inhibitory than 1 alpha,25-(OH)2D3. Proliferation of psoriatic fibroblasts was not inhibited by 1 alpha,25-(OH)2D3 at concentrations of up to 10(-6) M, but was suppressed by 10(-8)-10(-6) M 22-oxa-1 alpha,25-(OH)2D3 and 10(-6) M 22-oxa-1 alpha-(OH)D3. These results suggest that oxa-derivatives of vitamin D3, especially 22-oxa-1 alpha,25-(OH)2D3, should be useful in further studies on the cause and treatment of psoriasis.

Topics: Calcitriol; Cell Division; Cells, Cultured; Cholecalciferol; Dose-Response Relationship, Drug; Fibroblasts; Humans; In Vitro Techniques; Psoriasis; Time Factors

Active forms of vitamin D3, 1 alpha-hydroxyvitamin D3 and 1 alpha,25-dihydroxyvitamin D3, were administered in an open-design study to 40 patients with psoriasis vulgaris in three ways: to 17 patients 1 alpha-hydroxyvitamin D3 was given orally at a dose of 1.0 micrograms/day for 6 months, to four patients 1 alpha,25-dihydroxyvitamin D3 was given orally at a dose of 0.5 microgram/day for 6 months, and 19 patients were given 1 alpha,25-dihydroxyvitamin D3 applied topically at concentration of 0.5 microgram/g of base for 8 weeks. Improvement was observed at the end of the individual study periods in 13 (76%) patients in Group 1 with a mean period of treatment (+/- SD) of 2.7 +/- 0.6 months, in one patient in Group 2 at 3 months after the start of treatment, and in 16 (84%) patients in Group 3 when the chemical was applied for 3.3 +/- 1.2 weeks. No side-effects were observed in any of these trials. These data suggest that psoriasis may respond to active metabolites of vitamin D3 and that abnormalities in vitamin D metabolism or in responsiveness of the skin cells to active metabolites of vitamin D may be involved in the pathogenesis of this skin disease.

Topics: Adolescent; Adult; Aged; Calcitonin; Cholecalciferol; Dihydroxycholecalciferols; Female; Humans; Hydroxycholecalciferols; Male; Middle Aged; Parathyroid Hormone; Psoriasis