Goździalska, Anna; Lipko-Godlewska, Sylwia; Obtułowicz, Aleksander; Sułowicz, Joanna; Podolec, Katarzyna; Wojas-Pelc, Anna
Introduction The tumor necrosis factor (TNF-α) was initially described as lymphotoxin or cachectin. The discovery of therapies blocking the action of TNF-α, in 1988, started a new era in the therapy. One of often reported adverse effects related to the use of TNF-α antagonists is induction of the formation of autologous antibodies and antibodies neutralizing anti-TNF drugs. The development of anti-TNF-induced lupus or classical drug-induced lupus is more rarely reported. Aim To evaluate the presence and the level of anti-nuclear antibodies in patients with psoriasis and psoriatic arthritis and the influence of anti-TNF therapy used on the concentration of antinuclear antibody (ANA). Material and methods A total of 28 subjects were included in the study. 71.4% of subjects were diagnosed with psoriatic arthritis and 28.6% with plaque psoriasis. Results Among the patients with plaque psoriasis, the antinuclear antibodies were found in 25% of subjects and in 80% of patients with psoriatic arthritis. After the treatment an increase in the titer or appearance of antibodies was found in 66.7% in the infliximab group, 18.2% in the etanercept group and 54.7% in the adalimumab group. No subjects developed symptoms of drug-induced systemic lupus. Conclusions Our findings have shown that all anti-TNF therapies induced ANA in psoriatic arthritis and psoriatic patients. Considering a mild course of lupus induced by anti-TNF treatment and, usually intrinsic, resolution of symptoms, the biological therapy still appears as a safe treatment for patients. PMID:26366147
Torsekar, R.; Gautam, Manjyot M.
Topical therapy as monotherapy is useful in psoriasis patients with mild disease. Topical agents are also used as adjuvant for moderate-to-severe disease who are being concurrently treated with either ultraviolet light or systemic medications. Emollients are useful adjuncts to the treatment of psoriasis. Use of older topical agents such as anthralin and coal tar has declined over the years. However, they are cheaper and can still be used for the treatment of difficult psoriasis refractory to conventional treatment. Salicylic acid can be used in combination with other topical therapies such as topical corticosteroids (TCS) and calcineurin inhibitors for the treatment of thick limited plaques to increase the absorption of the latter into the psoriatic plaques. Low- to mid-potent TCS are used in facial/flexural psoriasis and high potent over palmoplantar/thick psoriasis lesions. The addition of noncorticosteroid treatment can also facilitate the avoidance of long-term daily TCS. Tacrolimus and pimecrolimus can be used for the treatment of facial and intertriginous psoriasis. Tazarotene is indicated for stable plaque psoriasis usually in combination with other therapies such as TCS. Vitamin D analogs alone in combination with TCS are useful in stable plaques over limbs and palmoplantar psoriasis. Topical therapies for scalp psoriasis include TCS, Vitamin D analogs, salicylic acid, coal tar, and anthralin in various formulations such as solutions, foams, and shampoos. TCS, vitamin D analogs, and tazarotene can be used in the treatment of nail psoriasis. PMID:28761838
Protic, Marijana; Schoepfer, Alain; Yawalkar, Nikhil; Vavricka, Stephan; Seibold, Frank
The cause of anti-TNF-induced psoriasis is still unknown. We aimed to evaluate if the appearance of psoriasis under anti-TNF therapy is associated with anti-TNF antibody levels and TNF-antagonist trough levels. In this case-control study we identified 23 patients (21 with Crohn's disease [CD], two with ulcerative colitis [UC]) who developed psoriasis under infliximab (IFX, n = 20), adalimumab (ADA, n = 2), and certolizumab pegol (CZP, n= 1) and compared them regarding the anti-TNF-antagonist antibody levels with 85 IBD patients (72 with CD, 13 with UC) on anti-TNF therapy without psoriasis. Median disease duration was not different between the two groups (7 years in the group with psoriasis under TNF-antagonists vs. 10 years in the control group, p = 0.072). No patient from the psoriasis group had antibodies against TNF-antagonists compared to 10.6% in the control group (p = 0.103). No difference was found in IFX trough levels in the group of patients with psoriasis compared to the control group (2.6 μg/mL [IQR 0.9-5.5] vs. 3.4 μg/mL [IQR 1.4-8.1], p = 0.573). TNF-antagonist therapy could be continued in 91.3% of patients with TNF-antagonist related psoriasis and most patients responded to topical therapies. Anti-TNF-induced psoriasis seems to be independent of anti-TNF antibodies and trough levels. Interruption of Anti-TNF therapy is rarely necessary.
Cohen Barak, Eran; Kerner, Miryam; Rozenman, Dganit; Ziv, Michael
Combination therapy has become important in treating psoriasis, using synergism between different mechanisms to maximize efficacy and minimize toxicity. Little has been published on the combination of cyclosporine and anti-tumor necrosis factor (TNF) α agents. In this study, a retrospective chart review was made of the effects of this combination therapy in 10 patients with recalcitrant psoriasis. Treatment included a conditioning phase with cyclosporine, 3.14 ± 0.37 mg/kg for 4.6 ± 2 weeks, and a combination phase during which etanercept/adalimumab were initiated and cyclosporine was tapered over 10.2 ± 3.7 weeks. Treatment success, evaluated after each phase, was classified as complete recovery (CR, more than 75% improvement), partial response (PR, 25-75% improvement), and no response (NR, less than 25% improvement). All patients reached CR at the end of the combination therapy. Two were still on combination therapy after 12 and 20 weeks. Adverse event occurred in three cases, all in the conditioning phase. We conclude that combination therapy with cyclosporine and anti-TNF α appears to offer an effective and safe approach to treatment of psoriasis.
Guerra, Iván; Pérez-Jeldres, Tamara; Iborra, Marisa; Algaba, Alicia; Monfort, David; Calvet, Xavier; Chaparro, María; Mañosa, Miriam; Hinojosa, Esther; Minguez, Miguel; Ortiz de Zarate, Jone; Márquez, Lucía; Prieto, Vanessa; García-Sánchez, Valle; Guardiola, Jordi; Rodriguez, G Esther; Martín-Arranz, María Dolores; García-Tercero, Iván; Sicilia, Beatriz; Masedo, Ángeles; Lorente, Rufo; Rivero, Montserrat; Fernández-Salazar, Luis; Gutiérrez, Ana; Van Domselaar, Manuel; López-SanRomán, Antonio; Ber, Yolanda; García-Sepulcre, Marifé; Ramos, Laura; Bermejo, Fernando; Gisbert, Javier P
Psoriasis induced by anti-tumor necrosis factor-α (TNF) therapy has been described as a paradoxical side effect. To determine the incidence, clinical characteristics, and management of psoriasis induced by anti-TNF therapy in a large nationwide cohort of inflammatory bowel disease patients. Patients with inflammatory bowel disease were identified from the Spanish prospectively maintained Estudio Nacional en Enfermedad Inflamatoria Intestinal sobre Determinantes genéticos y Ambientales registry of Grupo Español de Trabajo en Enfermedad de Croh y Colitis Ulcerosa. Patients who developed psoriasis by anti-TNF drugs were the cases, whereas patients treated with anti-TNFs without psoriasis were controls. Cox regression analysis was performed to identify predictive factors. Anti-TNF-induced psoriasis was reported in 125 of 7415 patients treated with anti-TNFs (1.7%; 95% CI, 1.4-2). The incidence rate of psoriasis is 0.5% (95% CI, 0.4-0.6) per patient-year. In the multivariate analysis, the female sex (HR 1.9; 95% CI, 1.3-2.9) and being a smoker/former smoker (HR 2.1; 95% CI, 1.4-3.3) were associated with an increased risk of psoriasis. The age at start of anti-TNF therapy, type of inflammatory bowel disease, Montreal Classification, and first anti-TNF drug used were not associated with the risk of psoriasis. Topical steroids were the most frequent treatment (70%), achieving clinical response in 78% of patients. Patients switching to another anti-TNF agent resulted in 60% presenting recurrence of psoriasis. In 45 patients (37%), the anti-TNF therapy had to be definitely withdrawn. The incidence rate of psoriasis induced by anti-TNF therapy is higher in women and in smokers/former smokers. In most patients, skin lesions were controlled with topical steroids. More than half of patients switching to another anti-TNF agent had recurrence of psoriasis. In most patients, the anti-TNF therapy could be maintained.
Lebwohl, M; Ting, P; Koo, J
Even before the recent development of biological agents, a long list of effective treatments has been available for patients with psoriasis. Topical therapies such as corticosteroids, vitamin D analogues, and retinoids are used for localised disease. Phototherapy including broadband ultraviolet B (UVB), narrowband UVB, PUVA, and climatotherapy are effective for more extensive disease. Systemic therapies such as methotrexate, retinoids, and ciclosporin are effective for patients with refractory or extensive cutaneous disease. PMID:15708945
Lowe, N J; Lazarus, V; Matt, L
Retinoids are potent therapuetic agents that have been found to be effective in a variety of skin diseases. They are of benefit in various forms of severe psoriasis. With severe plaque psoriasis, they are used most effectively in combination with other forms of therapy, such as phototherapy. With generalized pustular psoriasis, they are effective monotherapy and are frequently helpful for the control of exfoliative psoriasis. A variety of new retinoid analogs have been studied in clinical investigations. This article discusses important aspects of the use of etretinate, isotretinoin, acitretin, and arotinoid ethyl ester in the treatment of severe forms of psoriasis.
Gold, Linda F Stein
The topical vitamin D3 modulator calcitriol, the naturally occurring active form of vitamin D3, has long been used for topical psoriasis therapy in Europe and other countries and was recently approved in the United States (U.S.) for the treatment of plaque psoriasis. In vehicle-controlled clinical trials, calcitriol 3 microg/g ointment has been shown to significantly improve the symptoms of psoriasis with a low incidence of adverse effects and without affecting calcium homeostasis, even when applied continuously for up to one year. A number of studies have examined the efficacy and safety of calcitriol ointment in combination therapy regimens that also included topical corticosteroid therapy or ultraviolet B (UVB) phototherapy. Calcitriol 3 microg/g ointment is a new option that provides flexibility for use in a variety of psoriasis treatment regimens. According to guidelines developed by the American Academy of Dermatology (AAD), the goals of psoriasis treatment are to produce durable remission of psoriasis symptoms, to achieve "substantial" clearing with the possibility of complete clearing, to maintain the initial benefits of therapy, and to minimize the risk of adverse events. Topical medications are the most commonly used treatments for psoriasis in the U.S. and are important in meeting the goals of psoriasis therapy. These agents offer high response rates with generally favorable safety and tolerability profiles and are useful for both acute treatment and long-term maintenance. Topical medications are used by approximately 85% of patients with psoriasis.
Ritchlin, Christopher T; Krueger, James G
Over the last several years, novel immunologic pathways pivotal in the development of the pathobiology of psoriasis and psoriatic arthritis (PsA) have been revealed. These discoveries catalyzed a search for new treatment targets resulting in many new therapies that are now available for patients with psoriatic disease. Helper T cells that secrete interleukin-17 (TH17) along with CD8+ cells, innate lymphocyte cells, and gamma delta T cells are important in the pathogenesis of psoriasis and PsA. Recently, agents that target interleukin-17, the interleukin-17 receptor, and interleukin-23 (antip19) have been approved or are in clinical trials. Apremilast, a new oral agent, was approved for the treatment of psoriasis and PsA. Secukinumab, an interleukin-17A antibody, has been approved for treatment of psoriasis and PsA in the United States. It is effective with a good safety profile. Ixekizumab, another anti-interleukin-17A antibody, is currently in clinical trials and brodalumab, an interleukin-17 receptor antagonist, was removed from clinical trials because of safety concerns despite demonstrated efficacy in psoriasis and PsA. Targeting interleukin-23 with antibodies to p19 is another approach with encouraging results in psoriasis. Apremilast, an oral agent, approved to treat psoriasis and PsA demonstrates moderate efficacy with an excellent safety record. The role of tofacitinib in psoriatic disease remains to be determined pending a safety review in psoriasis and completion of PsA trials.
Lowe, Nicholas J.
Psoriasis is a common papulosquamous skin disease which frequently presents a therapeutic challenge to physicians. Topical therapy with steroids, coal tars and anthralin are effective when used properly for many patients. More severely affected patients may require phototherapy using coal tars and anthralin plus ultraviolet radiation. Systemic methotrexate administration is indicated for some patients with severe skin and arthropathic psoriasis. Treatment using psoralen and long-wavelength ultraviolet phototherapy has recently been approved and is effective in many patients, but long-term safety remains a question. Synthetic retinoids are experimental drugs currently being evaluated for severe forms of psoriasis. PMID:6195826
Pina, Trinitario; Corrales, Alfonso; Lopez-Mejias, Raquel; Armesto, Susana; Gonzalez-Lopez, Marcos A; Gómez-Acebo, Ines; Ubilla, Begoña; Remuzgo-Martínez, Sara; Gonzalez-Vela, M Carmen; Blanco, Ricardo; Hernández, Jose L; Llorca, Javier; Gonzalez-Gay, Miguel A
The aim of the present study was to determine if the use of the anti-tumor necrosis factor (TNF)-α monoclonal antibody adalimumab could improve endothelial function and arterial stiffness in patients with moderate to severe psoriasis. This was a prospective study on a series of consecutive patients with moderate to severe psoriasis who completed 6 months of therapy with adalimumab. Patients with history of cardiovascular events, diabetes mellitus, kidney disease, hypertension or body mass index of 35 kg/m(2) or more were excluded. Assessment of endothelial function by brachial artery reactivity measuring flow-mediated endothelial dependent vasodilatation (FMD%), and carotid arterial stiffness by pulse wave velocity (PWV) was performed at the onset of treatment (time 0) and at month 6. Twenty-nine patients were studied. Anti-TNF-α adalimumab therapy yielded a significant improvement of endothelial function. The mean ± standard deviation (SD) FMD% values increased from 6.19 ± 2.44% at the onset of adalimumab to 7.46 ± 2.43% after 6 months of treatment with this biologic agent (P = 0.008). Likewise, following the use of adalimumab, PWV levels decreased from 6.28 ± 1.04 m/s at the onset of adalimumab to 5.69 ± 1.31 m/s at 6 months (P = 0.03). In conclusion, patients with moderate to severe psoriasis exhibit improvement of endothelial function and arterial stiffness following anti-TNF-α therapy. These findings are of potential relevance due to increased risk of cardiovascular disease in patients with severe psoriasis.
Pina, Trinitario; Genre, Fernanda; Lopez-Mejias, Raquel; Armesto, Susana; Ubilla, Begoña; Mijares, Veronica; Dierssen-Sotos, Trinidad; Corrales, Alfonso; Gonzalez-Lopez, Marcos A; Gonzalez-Vela, Maria C; Blanco, Ricardo; Hernández, Jose L; Llorca, Javier; Gonzalez-Gay, Miguel A
Patients with psoriasis, in particular those with severe disease, have an increased risk of cardiovascular (CV) events compared with the general population. The aim of the present study is to determine whether correlation between asymmetric dimethylarginine (ADMA) and osteoprotegerin (OPG), two biomarkers associated with CV disease, and disease severity may exist in patients with moderate-to-severe psoriasis. We also aimed to establish if baseline serum levels of these two biomarkers could correlate with the degree of change in the clinical parameters of disease severity following the use of anti-tumor necrosis factor (TNF)-α therapy in these patients. This was a prospective study on a series of consecutive non-diabetic patients with moderate-to-severe psoriasis who completed 6 months of therapy with anti-TNF-α-adalimumab. Patients with kidney disease, hypertension or body mass index of 35 kg/m(2) or more were excluded. Metabolic and clinical evaluation was performed immediately prior to the onset of treatment and at month 6. Twenty-nine patients were assessed. Unlike OPG, a significant positive correlation between ADMA and resistin serum levels was found at the onset of adalimumab and also after 6 months of biologic therapy. We also observed a positive correlation between the percent of body surface area affected (BSA) and ADMA levels obtained before the onset of adalimumab and a negative correlation between baseline ADMA levels and a 6-month BSA change compared with baseline results. In patients with moderate-to-severe psoriasis, ADMA levels correlate with clinical markers of disease severity.
Guenther, Lyn C
Although biologics are very efficacious as monotherapy in patients with psoriasis, combination treatment with traditional systemic and topical therapies may increase the speed of onset and enhance efficacy without significant additional toxicity. In contrast, in psoriatic arthritis, the addition of methotrexate to anti-tumour necrosis factor-alpha therapy does not enhance efficacy in either the skin or joints.
Selective UV-Phototherapy with lambda 300-320 nm (SUP) as well as oral photochemotherapy with 8-methoxy-psoralene plus UVA-radiation (PUVA intern) are very effective in clearing the lesions of th generalized psoriasis and those of the chronic forms of parapsoriasis. Being treated with 4 suberythemal doses per week psoriasis patients are free or nearly free of symptoms after averaging 6.3 weeks of SUP-therapy or after 5.3 weeks of PUVA orally. The PUVA-therapy is mainly indicated in pustular, inverse and erythrodermic psoriasis as well as in parapsoriasis in plaques and variegata. In all other forms of psoriasis and in pityriasis lichenoides chronica, we prefer the SUP-therapy because of less acute or chronic side effects, and because of its better practicability. X-rays are indicated in psoriasis of nails, grenz-rays in superficial psoriatic lesions of the face, the armpits, the genitals and the anal region.
Pinto, G M; Gonçalo, M M; Resende, C; Pereira, A
The purpose of these Guidelines is to summarize the most relevant features of the pathogenesis, clinical presentation and treatment of psoriasis. Patient education should include the deleterious effects that some drugs, trauma, alcohol, infection and stress may have on psoriasis; the beneficial action of careful sunlight exposure should also be emphasized. Topical treatment--emollients, keratolytics, coal tar preparations, anthralin, corticosteroids, calcipotriol--is essential for the control of plaque-type psoriasis and is also an important adjuvant therapy in more severe cases; the relative strength and the potential adverse effects of topical steroids are also referred. UV therapy (phototherapy and photochemotherapy) is recommended for psoriasis with generalized plaque, guttate or palmoplantar psoriasis refractory to topical therapies. Systemic therapy--retinoids, methotrexate, cyclosporine--is limited to severe plaque psoriasis unresponsive to topical or UV therapy, erythrodermic, pustular or arthropatic psoriasis. Combination and rotational therapies are likely to reduce the risks of each individual therapy and should be encouraged. Finally, a few diagrams are included, pointing out the scientific validity of the therapies currently available to help clinicians to optimize their management of psoriasis.
Levin, Ethan C; Debbaneh, Maya; Koo, John; Liao, Wilson
The efficacy of biologic therapy in treating plaque-type psoriasis is well documented. However, there is less data for use in other psoriasis subtypes, such as erythrodermic and generalized pustular psoriasis. We sought to review the safety and efficacy of biologic medications in the treatment of these severe subtypes of psoriasis and to identify strategies to help clinicians optimally manage these patients. We searched Pubmed for English language literature that assessed the use of biologic medication to treat erythrodermic or generalized pustular psoriasis. The primary literature included cases reports, cases series, and open-label, uncontrolled trials. There were no head-to-head studies or other controlled trials. In both erythrodermic and generalized pustular psoriasis, infliximab was used to treat over half of the reported cases. Other biologic medications that were successfully used included etanercept, ustekinumab, adalimumab, and anakinra. Most cases reported improvement with biologic therapy. Serious adverse events were reported in 10-12% of the patients. Although the evidence is limited, biologic therapy appears to be effective in treating erythrodermic and generalized pustular psoriasis. In order to assess the comparative efficacy and safety of the biologic medications, larger controlled studies are needed.
Vincent, Nitha; Ramya, Devi D; Vedha, Hari Bn
Psoriasis is a lifelong condition which is caused by the negative signals produced by immune system, which leads to hyper proliferation and other inflammatory reactions on the skin. In this case, keratinocytes which are the outermost layer of skin possess shortened life cycle and results in the alteration of desquamation process where the cytokines will come out through lesions of affected patients and as a result, scaling marks appears on the skin. These conditions may negatively affect the patient's quality of life and lead to psychosocial stress. Psoriasis can be categorized as mild, moderate and severe conditions. Mild psoriasis leads to the formation of rashes, and when it becomes moderate, the skin turns into scaly. In severe conditions, red patches may be present on skin surface and becomes itchy. Topical therapy continues to be one of the pillars for psoriasis management. Drug molecules with target effect on the skin tissues and other inflammations should be selected for the treatment of psoriasis. Most of the existing drugs lead to systemic intoxication and dryness when applied in higher dose. Different scientific approaches for topical delivery are being explored by researches including emollient, modified gelling system, transdermal delivery, spray, nanogels, hydrogels, micro/nano emulsion, liposomes, nano capsules etc. These topical dosage forms are evaluated for various physico chemical properties such as drug content, viscosity, pH, extrudability, spreadability, toxicity, irritancy, permeability and drug release mechanism. This review paper focus attention to the impact of these formulation approaches on various anti-psoriasis drugs for their successful treatment.
Leonardi, Craig L; Gordon, Kenneth B
This article discusses the scientific rationale for the use of cytokine inhibitors, including ustekinumab, an inhibitor of the interleukin (IL)-12 and IL-23 pathways in psoriasis. Also addressed are the efficacy and safety data for this agent, as well as for several emerging therapies that target other cytokine pathways in psoriasis: the IL-17 inhibitors secukinumab, ixekizumab, and brodalumab, the IL-23 blocker tildrakizumab, and the small-molecule kinase inhibitors apremilast (a phosphodiesterase-4 blocker) and tofacitinib (a Janus kinase inhibitor).
... short period of time, like when symptoms flare.Sunlight can help psoriasis, but be careful not to ... to your doctor about how to safely use sunlight exposure as a form of treatment. Light therapy ...
Campanati, Anna; Ganzetti, Giulia; Giuliodori, K; Molinelli, Elisa; Offidani, A
This review focuses on the emerging concepts concerning the efficacy profile of biological drugs in psoriasis ranging from moderate to severe, and attempts to provide the most recent individual positioning of biologics in treating psoriasis. Biologic agents targeting towards specific immune mediators have emerged as treatment options for patients with moderate to-severe plaque psoriasis unresponsive or intolerant to traditional systemic agents. Data on the safety of biologics are available for up to 5 years in psoriasis and are on the whole reassuring. National registries are still evolving and will provide data on safety, to help the long-term monitoring of patients with psoriasis ongoing biological treatment. Although several biologics have demonstrated good efficacy and tolerability in short-term trials, treatment guidelines recommend them as third line therapies due to relative lack of long-term safety data, especially for those who have been commercialized recently. Here, we have reviewed the long-term safety data obtained from National Registries, randomized controlled trials, open-label extension studies and meta-analyses on etanercept, infliximab, adalimumab, and ustekinumab in the treatment of adults with moderate to severe plaque psoriasis.
Tsianakas, A; Mrowietz, U
Psoriasis is a common chronic inflammatory disease with an incidence of about 0.5-3 %. Previously psoriasis was not primarily regarded to be associated with pruritus; however, this perception has changed in recent years. Meanwhile data conclusively show that between 64 and 97 % of patients report about pruritus that can be severe in a number of cases. Apart from suffering from psoriasis, the presence of pruritus causes additional stress and leads to a significant impairment of health-related quality of life. Neurogenic inflammation at least in part contributes to the development of pruritus in psoriasis skin lesions. A number of neuropeptides including substance P and calcitonin gene related peptide can act as pro-inflammatory mediators. There is evidence for a dysbalance between κ‑ and µ‑opioid receptors in lesional skin favoring inflammation and pruritus. After clearing of psoriasis lesions, pruritus is relieved as well. Therefore, specific treatment of pruritus is not necessary in general. In cases where severe pruritus is a prominent symptom, targeted therapy with mirtazapin or doxepin or neuroleptic compounds such as pregabalin or gabapentin or drugs affecting the κ‑ und µ‑opioid receptor balance can be administered. Today the importance of pruritus as a prominent symptom of psoriasis lesions has been widely accepted. In recent and running clinical trials with new drugs, pruritus at baseline and the effect of these drugs on pruritus is always assessed. This awareness also fuels basic research about pruritus in psoriasis.
Di Meglio, Paola; Villanova, Federica; Nestle, Frank O.
Psoriasis is a common chronic inflammatory skin disease with a spectrum of clinical phenotypes and results from the interplay of genetic, environmental, and immunological factors. Four decades of clinical and basic research on psoriasis have elucidated many of the pathogenic mechanisms underlying disease and paved the way to effective targeted therapies. Here, we review this progress and identify future directions of study that are supported by a more integrative research approach and aim at further improving the patients' life. PMID:25085957
Vincent, Nitha; Ramya, Devi D; Vedha, Hari BN
Psoriasis is a lifelong condition which is caused by the negative signals produced by immune system, which leads to hyper proliferation and other inflammatory reactions on the skin. In this case, keratinocytes which are the outermost layer of skin possess shortened life cycle and results in the alteration of desquamation process where the cytokines will come out through lesions of affected patients and as a result, scaling marks appears on the skin. These conditions may negatively affect the patient’s quality of life and lead to psychosocial stress. Psoriasis can be categorized as mild, moderate and severe conditions. Mild psoriasis leads to the formation of rashes, and when it becomes moderate, the skin turns into scaly. In severe conditions, red patches may be present on skin surface and becomes itchy. Topical therapy continues to be one of the pillars for psoriasis management. Drug molecules with target effect on the skin tissues and other inflammations should be selected for the treatment of psoriasis. Most of the existing drugs lead to systemic intoxication and dryness when applied in higher dose. Different scientific approaches for topical delivery are being explored by researches including emollient, modified gelling system, transdermal delivery, spray, nanogels, hydrogels, micro/nano emulsion, liposomes, nano capsules etc. These topical dosage forms are evaluated for various physico chemical properties such as drug content, viscosity, pH, extrudability, spreadability, toxicity, irritancy, permeability and drug release mechanism. This review paper focus attention to the impact of these formulation approaches on various anti-psoriasis drugs for their successful treatment. PMID:25386329
Sharma, Vinod Kumar; Dutta, Bornali; Ramam, M
Methotrexate is the drug of choice in extensive psoriasis in developing countries. In patients who can not take methotrexate either due to intolerance or concomitant liver disease, there is an urgent need for an alternative affordable and accessible drug. To evaluate the therapeutic efficacy and safety of hydroxyurea as an alternative in the management of patients with extensive psoriasis. A prospective study was carried out over 16 months on 34 patients with chronic plaque psoriasis (>20% body surface area involvement), erythrodermic or generalized pustular psoriasis who were partially responsive or non-responsive to the conventional topical and systemic modalities of therapy. Besides doing a baseline hemogram, liver and renal function tests, and urine analysis, these tests were frequently repeated during the course of therapy. Hydroxyurea was started at 1 g daily and increased to 1.5 g, if required. The therapeutic response was evaluated by a global assessment made by the patient and physician and regular PASI scoring. Good to excellent response was observed in 25 (73.5%) patients, less than 50% response in 7 (20.6%) patients, while 2 (5.9%) patients were lost to follow up. The mean PASI score was reduced by 76% at 10-12 weeks. Therapy was discontinued in 3 patients due to leukopenia that recovered on discontinuation of hydroxyurea. Patients were followed up to 1 year and relapse was observed in 5 patients. The duration of remission varied from 6 months to 1 year. Hydroxyurea is an effective and reasonably safe second line agent for psoriasis.
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Skarmoutsou, Evangelia; Trovato, Chiara; Granata, Mariagrazia; Rossi, Giulio A; Mosca, Ambra; Longo, Valentina; Gangemi, Pietro; Pettinato, Maurizio; D'Amico, Fabio; Mazzarino, Maria Clorinda
Psoriasis is a chronic inflammatory skin disease, characterized by hyperproliferation of keratinocytes and by skin infiltration of activated T cells. To date, the pathophysiology of psoriasis has not yet been fully elucidated. The Notch pathway plays a determinant role in cell fate determination, proliferation, differentiation, immune cell development and function. Many biological agents, used in the treatment of psoriasis, include TFN-α inhibitors, such as etanercept, adalimumab, and anti IL-12/IL-23 p40 antibody, such as ustekinumab. This study aimed to determine mRNA expression levels by real-time RT-PCR, and protein expression levels, analysed by Western blot and immunohistochemistry, of some components of the Notch pathway, such as NOTCH1, NOTCH2, JAGGED1, and HES1 after biological treatments in psoriatic patients. mRNA and protein levels of NOTCH1, NOTCH2, JAGGED1 and HES1 were upregulated in skin samples from untreated psoriatic patients compared with normal controls. Biological therapy showed to downregulate differently the protein expression levels of the molecules under study. Our study suggests that Notch pathway components might be a potential therapeutic target against psoriasis.
Navarini, Alexander A; Trüeb, Ralph M
Psoriasis is a skin disease typically presenting with sharply demarcated, inflammatory, erythematous plaques with characteristic silver-white scaling due to epidermal hyperproliferation and parakeratosis secondary to the inflammation. The name derives from pisigmaomicronrhoalpha (mange or scabies), and in ancient times the disease was confused with leprosy resulting in expulsion from society. Hence, both itching and social stigmatization are major problems affecting patients with psoriasis. Today, psoriasis is recognized as a genetically determined, autoimmune, T cell mediated systemic disease manifesting on the skin, nails and joints and associated with a number of co-morbidities. Accordingly, therapeutic strategies are antiinflammatory, antiproliferative and keratolytic. The extent and severity of disease (PASI), impairment of life quality (DLQI), and affected anatomic regions (inverse, palmoplantar, nails) as well as co-morbidities (arthritis, metabolic syndrome, cardiovascular disease, depression) determine the therapy. In 80 % of cases psoriasis is mild or moderate and sufficiently treated with topical corticosteroids, vitamin D-analogues, and phototherapy. 20 % of patients suffer from severe psoriasis, necessitating systemic drugs such as acitretin, methotrexate, ciclosporin A or the newer biologic agents. Especially in severe psoriasis, psychological strain, co-morbidities, and medico-economic aspects must be taken into account.
Kempter, W; Stein, A; Bauer, A; Wozel, G
A 61-year-old patient had a 25-year history of erythematous scaling lesions, diagnosed and treated as psoriasis vulgaris. He presented with a growing nodule within the erythematous plaque. Biopsy shows epithelioid cell granulomas with prominent Langhans giant cells. There was no sign of a squamous cell carcinoma. The tuberculin test was strongly positive and M. tuberculosis complex was detected in the biopsy material by PCR. He was diagnosed with lupus vulgaris, the most frequent form of cutaneous tuberculosis. Other types include tuberculosis verrucosa cutis, tuberculosis cutis orificialis and disseminated military tuberculosis. The patient was treated with rifampicin, isoniazid, pyrazinamide and ethambutol for two months, following a four month treatment with rifampicin and isoniazid. The skin lesions rapidly resolved under antituberculotic treatment.
Jin, Yiguang; Zhang, Xiaohan; Zhang, Baolei; Kang, Hongxiang; Du, Lina; Li, Miao
Psoriasis is a chronic inflammatory skin disease affecting 2-5% of the population worldwide and it severely affects patient quality of life. In this study, an amphiphilic zinc phthalocyanine polymer conjugate (ZPB) was synthesized, in which zinc phthalocyanine (ZnPc) was conjugated with the poly(ethylene glycol) (PEG) chain of Brij 58. ZPB showed two maximum UV-vis absorption wavelengths, 348 nm and 678 nm. A monomolecular micelle of ZPB formed in water with a mean size of 25 nm and zeta potential of -15 mV. The nanostructures aggregated into cloudy precipitates, which were easily dispersed. The nanostructure showed the shell-core structure with the ZnPc segments as the core and the PEG chains as the shell. The anti-psoriasis effect of the ZPB nanostructure was explored using a guinea pig psoriasis model. After comparing the anti-psoriasis effects of saline, light alone, ZPB alone, and the combination of light and ZPB, the combination of light and ZPB showed the best photodynamic therapy of psoriasis based on the light excitation of the photosensitizer ZPB and the psoriasis was nearly cured according to the histopathological investigation. The ZPB nanostructure is a promising anti-psoriasis nanomedicine based on photodynamic therapy.
Greb, Jacqueline E; Goldminz, Ari M; Elder, James T; Lebwohl, Mark G; Gladman, Dafna D; Wu, Jashin J; Mehta, Nehal N; Finlay, Andrew Y; Gottlieb, Alice B
Psoriasis is a chronic, immune-mediated disorder with cutaneous and systemic manifestations and substantial negative effects on patient quality of life. Psoriasis has a strong, albeit polygenic, genetic basis. Whereas approximately half of the accountable genetic effect of psoriasis maps to the major histocompatibility complex, >70 other loci have been identified, many of which implicate nuclear factor-κB, interferon signalling and the IL-23-IL-23 receptor axis. Psoriasis pathophysiology is characterized by abnormal keratinocyte proliferation and immune cell infiltration in the dermis and epidermis involving the innate and adaptive immune systems, with important roles for dendritic cells and T cells, among other cells. Frequent comorbidities are rheumatological and cardiovascular in nature, in particular, psoriatic arthritis. Current treatments for psoriasis include topical agents, photo-based therapies, traditional systemic drugs and biologic agents. Treatments can be used in combination or as monotherapy. Biologic therapies that target specific disease mediators have become a mainstay in the treatment of moderate-to-severe disease, whereas advances in the treatment of mild-to-moderate disease have been limited.
Foulkes, Amy C; Warren, Richard B
Psoriasis is a model disease for the development of pharmacogenomic markers of treatment response, with ready access to diseased tissue and objective validated outcome measures. With the application of state-of-the-art technologies and investment in careful experimental design, the goal of stratified medicine in psoriasis may be possible. Current pharmacogenomic studies in psoriasis show excellence in many areas, including the investigation of a broad range of psoriasis therapies. To facilitate the advent of stratified medicine in psoriasis, uniformity of study design is required, with high quality, consistent phenotyping strategies for participants; definitions of outcome; and the publication of reproducible methodologies.
Canavan, Theresa N; Elmets, Craig A; Cantrell, Wendy L; Evans, John M; Elewski, Boni E
Our ability to successfully treat patients with moderate to severe psoriasis has improved significantly over the last several years with the development of more targeted therapies. IL-17A, a member of the IL-17 family of interleukins, is involved in regulating the innate and adaptive immune systems and has been identified as a key cytokine involved in the pathogenesis of psoriasis and psoriatic arthritis. In this review, we summarize our understanding of IL-17 and its role in psoriasis and psoriatic arthritis, as well as key findings from clinical trials using anti-IL-17 medications for the treatment of the aforementioned diseases. Secukinumab, ixekizumab, and brodalumab are three anti-IL-17 medications used for treating psoriasis, of which only secukinumab is FDA approved; ixekizumab and brodalumab remain under clinical development. Results from clinical trials show that these three medications are highly effective in treating psoriasis and appear to be as safe as other biologic treatments that are FDA approved.
Yamauchi, Paul S; Bissonnette, Robert; Teixeira, Henrique D; Valdecantos, Wendell C
Tumor necrosis factor (TNF) antagonists have improved outcomes for patients with psoriasis, but some patients are unresponsive to treatment (primary failure) or lose an initially effective response (secondary failure). We sought to systematically investigate the efficacy and safety of a second TNF antagonist after failure of a first TNF antagonist. Published primary studies evaluating the efficacy of switching TNF antagonists after failure were systematically extracted. Fifteen studies were included. Although response rates to a second TNF antagonist were lower than for a first, a substantial proportion of patients in every study achieved treatment success. Week-24 response rates for a second antagonist were 30% to 74% for a 75% improvement in Psoriasis Area and Severity Index score and 20% to 70% for achieving a Physician Global Assessment score of 0/1; mean improvements in Dermatology Life Quality Index ranged from -3.5 to -13. In general, patients who experienced secondary failure achieved better responses than patients with primary failure. Adverse event incidences ranged from 20% to 71%, without unexpected adverse events; 0% to 11% of patients experienced serious adverse events. There was no common definition of treatment failure across these studies of varied design. Some patients benefit from switching to a second TNF antagonist after failure of a first TNF antagonist, with improved quality of life. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.
Georgala, S; Katoulis, A C; Kanelleas, A; Befon, A; Georgala, C
Biological therapy for psoriasis exerts its action via an immunomodulatory and eventually immunosuppressive mode. Immunosuppression is linked to HPV flares. Our purpose is to investigate a possible relationship between infliximab therapy for psoriasis and human papilloma virus and molluscum (HPV/MC) infections. We report a case series of three patients with psoriasis on infliximab, who developed HPV/MC lesions following their treatment. Our patients developed HPV/MC lesions within a few months after the initiation of infliximab infusions for psoriasis. Immunosuppresion is related to HPV/MC flares. Biological therapy and in particular infliximab treatment acts by immunomodulation and eventually a degree of immunosuppression. Anti-TNF treatment could be associated with HPV and/or MC flares. For this reason, we suggest the consideration of obtaining a routine cervical PAP smear before the commencement and during treatment with anti-TNF agents for psoriasis.
The approval of substantial numbers of targeted biologic therapies (e.g., monoclonal antibodies, fusion proteins) for treatment of inflammatory diseases has positioned these drugs as important to fight chronic disorders such as psoriasis, rheumatoid arthritis and Crohn's disease. One of the concerns raised with the administration of biologic therapies is that because most of them are immunogenic glycoproteins they induce undesirable immune response leading to the generation of specific anti-drug antibodies (ADA). The development of "self" derived protein therapeutics (comprised of human germline sequence), such as recombinant "human" antibodies, helped to reduce the production of ADA but did not avoid all immunogenicity. Reduced efficacy and safety issues such as anaphylaxis or vasculitis accompany the development of ADA. In addition to immune reactions directed against the biologic therapies as a whole, some of them such as anti-TNFα are able to induce auto-immune response, notably antinuclear antibody (ANA). ANA development was associated with induced lupus and in psoriasis it was suggested that it may act as a marker of treatment failure to anti-TNFα. With a focus on psoriasis, this paper makes a current point on the consequences and challenges of the development of anti-drug antibodies and auto-immunity in patients who receive biologic therapies.
Bale, Jessica; Chee, Paul
Infliximab is a high-affinity recombinant chimeric immunoglobulin-1 monoclonal antibody directed against tumour necrosis factor-alpha. It is used to treat a range of inflammatory disorders including psoriatic joint and skin changes. Acute interstitial lung disease is a rare but potentially fatal complication of therapy. We report the case of a 67-year-old man with severe psoriasis who presented with acute alveolitis shortly after his third infusion of infliximab. The infliximab was discontinued and investigations did not reveal an infective cause. His respiratory signs and symptoms improved quickly with corticosteroid therapy. Clinicians should be aware of this uncommon but potentially serious complication. © 2012 The Authors Australasian Journal of Dermatology © 2012 The Australasian College of Dermatologists.
Eppinga, Hester; Thio, H Bing; Schreurs, Marco W J; Blakaj, Blerdi; Tahitu, Ruena I; Konstantinov, Sergey R; Peppelenbosch, Maikel P; Fuhler, Gwenny M
Psoriasis and inflammatory bowel disease (IBD) are chronic inflammatory diseases sharing similar pathogenic pathways. Intestinal microbial changes such as a decrease of bakers' yeast Saccharomyces cerevisiae have been reported in IBD, suggesting the presence of a gut-skin axis. To investigate whether the S. cerevisiae abundance was altered in psoriasis patients versus healthy controls, and whether dimethylfumarate (DMF) interacted with this yeast. Using qPCR, faecal samples were compared between psoriasis patients without DMF (n = 30), psoriasis patients with DMF (n = 28), and healthy controls (n = 32). Faecal S. cerevisiae abundance was decreased in psoriasis compared to healthy controls (p<0.001). Interestingly, DMF use raised S. cerevisiae levels (p<0.001). Gastrointestinal adverse-effects of DMF were correlated with a higher S. cerevisiae abundance (p = 0.010). In vitro, a direct effect of DMF on S. cerevisiae growth was observed. In addition, anti-Saccharomyces cerevisiae antibodies were not elevated in psoriasis. The abundance of baker's yeast S. cerevisiae is decreased in psoriasis patients, but appears to be restored upon DMF use. S. cerevisiae is generally classified as a yeast with beneficial immunomodulatory properties, but may also be involved in the occurrence of DMF's gastrointestinal adverse-effects. Potentially, DMF might be a new therapy for IBD.
Sukarovska, Biljana Gorgievska; Lipozencić, Jasna; Vrzogić, Pero
Psoriasis is a chronic, recurrent, genetically determined, inflammatory dermatosis that affects the skin, scalp and joints. Psoriasis is caused by various triggers (infections, drugs, physical and emotional factors). It ranges in severity from mild to severe, and patients with moderate to severe disease suffer significant deterioration in the quality of life. Clinical types of psoriasis are psoriasis guttata, nummular psoriasis, plaque, generalized and erythrodermic psoriasis. Skin changes affect intertriginous regions (inverse psoriasis), and there also are special forms of pustular psoriasis and arthropathic psoriasis. The goals of psoriasis treatment are to gain initial and rapid control of the disease; to decrease plaque lesions and percentage of body surface area involved, to achieve long-term remission; and to minimize adverse events. Topical treatment for mild psoriasis includes topical corticosteroids, calcipotriene, tazarotene, topical tars, anthralin and keratolytics, and immunomodulators (pimecrolimus, tacrolimus). The treatment of moderate to severe psoriasis includes systemic therapies such as methotrexate, acitretin, cyclosporine, hydroxurea and biologicals. Topical treatment can be effective using combination, rotational or sequential regimens for patients with more severe disease. The aim of successful treatment of psoriasis is fast control of the disease and regression of lesions in a short period, prolonged remission and minimal adverse reaction. Local therapy with various topicals is administered for mild and localized forms of the disease, with or without phototherapy (UVB). Topical corticosteroids are used in a variety of formulations, with a potential ranging from superpotent to least potent (class 1-7), which decrease symptoms in tne first two weeks of treatment with improvement in subsequent weeks; D3 vitamin analog (effective in 6-8 weeks), retinoids (effective in 1-2 weeks), tars (2-4 weeks), anthralin (2-4 weeks), and keratolytics (most
Constantin, M M; Poenaru, E; Constantin, T; Poenaru, C; Purcarea, V L; Mateescu, B R
An inflammatory, proliferative condition with chronic evolution and systemic response, psoriasis, is positioned today among the most common inflammatory skin diseases affecting the Caucasian population worldwide. With a significant incidence, psoriasis has been increasingly defined as a disease with a major impact on the patient's life and the society to which he/she belongs. This paper conducts an analysis of the currently available therapies for the treatment of moderate and severe psoriasis, therapies with biological agents obtained through sophisticated genetic engineering technologies. Recent research and the increasing interest in therapeutic methods as complete and efficient as possible make us optimistic and confident in the future.
Constantin, MM; Poenaru, E; Constantin, T; Poenaru, C; Purcarea, VL; Mateescu, BR
An inflammatory, proliferative condition with chronic evolution and systemic response, psoriasis, is positioned today among the most common inflammatory skin diseases affecting the Caucasian population worldwide. With a significant incidence, psoriasis has been increasingly defined as a disease with a major impact on the patient's life and the society to which he/she belongs. This paper conducts an analysis of the currently available therapies for the treatment of moderate and severe psoriasis, therapies with biological agents obtained through sophisticated genetic engineering technologies. Recent research and the increasing interest in therapeutic methods as complete and efficient as possible make us optimistic and confident in the future. PMID:25870666
Chen, Qian; Zhou, Hui; Yang, Yinxue; Chi, Mingwei; Xie, Nan; Zhang, Hong; Deng, Xingwang; Leavesley, David; Shi, Huijuan; Xie, Yan
Psoriasis vulgaris is a chronic inflammatory skin disease, stubbornly intractable, with substantial consequences for patient physical and mental welfare. Approaches currently available to treat psoriasis are not satisfactory due to undesirable side-effects or expense. Psoriasis is characterized by hyperproliferation and inflammation. Oxymatrine, an active component extracted from Sophora flavescens, has been demonstrated to possess anti-proliferation, anti-inflammatory, anti-tumorigenic, immune regulation and pro-apoptotic properties. This investigation presents a detailed retrospective review examining the effect of Oxymatrine on psoriasis and investigates the mechanisms underlying patient responses to Oxymatrine. We confirm that Oxymatrine administration significantly reduced the Psoriasis Area Severity Index score, with high efficacy compared to the control group. In addition, we have found that Oxymatrine significantly inhibits the viability, proliferation and differentiation of human keratinocyte in vitro. Immunohistochemical analysis indicates Oxymatrine significantly suppresses the expression of Pan-Cytokeratin, p63 and keratin 10. The results indicate that the suppression of p63 expression may lead to the anti-proliferation effect of Oxymatrine on human skin keratinocytes. Oxymatrine does not affect the formation of basement membrane, which is very important to maintain the normal function of human skin keratinocytes. In summary, Oxymatrine offers an effective, economical, and safe treatment for patients presenting with intractable psoriasis vulgaris. Copyright © 2017 Elsevier B.V. All rights reserved.
Risk of serious infections, cutaneous bacterial infections, and granulomatous infections in patients with psoriasis treated with anti-tumor necrosis factor agents versus classic therapies: Prospective meta-analysis of Psonet registries.
Garcia-Doval, Ignacio; Cohen, Arnon D; Cazzaniga, Simone; Feldhamer, Ilan; Addis, Antonio; Carretero, Gregorio; Ferrándiz, Carlos; Stern, Robert S; Naldi, Luigi
Anti-tumor necrosis factor (TNF) therapy in psoriasis has been associated with an increased risk of serious infections compared with nonbiologic systemic therapies. We sought to quantify the risk of: (1) serious infections (leading to hospitalization, sequelae, or death); and (2) "any infection," bacterial cutaneous infections, and granulomatous infections among patients receiving anti-TNF therapy compared with nonbiologics (acitretin, methotrexate, cyclosporine). We used prospective meta-analysis to combine data from the Psocare registry (Italy), Biobadaderm registry (Spain), and Clalit Health Services database (Israel), including 17,739 patients and 23,357.5 person-years of follow-up. For serious infections, age, gender, and Charlson morbidity index adjusted hazard ratio of exposure to anti-TNFs compared with nonbiologics was 0.98 (95% confidence interval 0.80-1.19), for bacterial cutaneous infections it was 1.00 (95% confidence interval 0.62-1.61), and for granulomatous infections it was 1.23 (95% confidence interval 0.82-1.84). Using methotrexate as comparator and comparing first year of exposure with later exposure did not modify the results. For any infectious episode, risks and relative risks were heterogeneous among registries, probably because of different definitions of outcome. There was lack of power to describe risk of single drugs. In current clinical practice, treatment with anti-TNF drugs was not associated with a higher risk of serious infections than treatment with nonbiologic systemic therapy. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.
Chang, Ting; Sun, Linchao; Wang, Yan; Wang, Datai; Li, Wei; Li, Chunying; Gao, Tianwen; Liu, Yufeng; Wang, Gang
Psoriasis is now considered to be a chronic, immune-mediated and inflammatory skin disease. As the precise cause of psoriasis remains unknown, its treatment is challenging for dermatologists. Keratin 17 (K17), an intermediate filament protein, is highly expressed in psoriatic lesions, while not normally expressed in healthy epidermis. Studies have suggested that K17 plays a role in the pathogenesis of psoriasis. However, no study has been performed to determine the potential application of K17 down-regulation as a treatment option for psoriatic lesions. We hypothesized that anti-K17 interference may suppress the development and progression of psoriasis and potentially serve as a novel strategy for the treatment of psoriasis. Therefore, we down-regulated and silenced K17 gene expression in keratinocytes (KCs) using antisense and RNA interference (RNAi) techniques. We found that K17-specific antisense oligonucleotides (ASODN) or siRNAs inhibited proliferation and induced apoptosis in KCs as well as down-regulated K17 expression at both mRNA and protein levels. For our in vivo study, we constructed the SCID-hu xenogeneic transplantation psoriasis mouse model by grafting psoriatic lesions onto SCID mice and topically applied K17-specific ASODN and liposome-encapsulated siRNA to the grafts. We observed morphological and histological improvement in the treated psoriatic grafts. As a result, K17 mRNA and protein expression was significantly decreased in the grafts of the mouse model. Taken together, we conclude that anti-K17 therapy is an effective treatment option for psoriasis, and the K17 molecule, as a new target, may hold tremendous potential for the treatment of psoriasis in the future.
Kurian, A; Barankin, B
Topical therapy forms the cornerstone of treatment in the management of psoriasis. It plays a significant role as monotherapy in mild to moderate psoriasis, and it is used predominantly as adjunctive therapy in moderate to severe forms of the disease. Over the past decade, the topical treatment of psoriasis has evolved from the age-old applications, such as coal tar, to the more cosmetically acceptable and efficacious options containing topical corticosteroids, vitamin D analogues, and combined agents. With the advent of topical therapies in tailored vehicles and sophisticated delivery modes, the outlook for effectively managing psoriasis with topical approaches appears promising. To ensure therapeutic success, patient education about the disease, treatment options, proper administration, and adverse effects is essential, which will alleviate the common problem of poor patient adherence and promote more optimal clinical outcomes.
... Health Gynecology Medical Conditions Nutrition & Fitness Emotional Health Psoriasis Posted under Health Guides . Updated 26 January 2016. + ... who has it. What are the symptoms of psoriasis? Skin patches with raised edges that are red ...
Psoriasis is a partly inflammatory hyperproliferative skin disease. Its origin has not been clarified yet, but numerous immunologic, bioregulatory, and biochemical changes accompanying this disease are known. Many cell types and a number of immunity system factors forming a perfectly interlinked network are involved in the immunity processes in the psoriasis-affected skin. This network is a common place where antipsoriatics operate. There is no therapeutic means known which guarantees permanent elimination of psoriasis symptoms. External as well as internal therapeutic methods having effect on the pathogenetic processes at various levels are combined. UV radiation treatment (SUP), sometimes combined with psoralens (PUVA), tar, and dithranol are some of the classical methods of psoriasis treatment. Topical medicamentous treatment with corticoids, vitamin D derivatives, salicylic acid, urea, and tar plays an important part here.
Psoriasis is a common, chronic, immune mediated, inflammatory disease of skin characterized by red patches enclosed with white scales and affects 2-3% of people in the world. Topical therapy, phototherapy, and systemic therapy were employed for management of disease from many last decades. However, long term uses of these agents are associated with unwanted effects and toxicities. Recently, Itolizumab has been developed as world's first anti-CD6 humanized monoclonal IgG1 antibody for the management of moderate-to-severe chronic plaque psoriasis in India. Here we are presenting the response indicated by Itolizumab in 7 Indian patients having moderate-to-severe psoriasis with severe comorbidities and who were intolerant/nonresponding to conventional therapies. PMID:27885324
Psoriasis is a common, chronic, immune mediated, inflammatory disease of skin characterized by red patches enclosed with white scales and affects 2-3% of people in the world. Topical therapy, phototherapy, and systemic therapy were employed for management of disease from many last decades. However, long term uses of these agents are associated with unwanted effects and toxicities. Recently, Itolizumab has been developed as world's first anti-CD6 humanized monoclonal IgG1 antibody for the management of moderate-to-severe chronic plaque psoriasis in India. Here we are presenting the response indicated by Itolizumab in 7 Indian patients having moderate-to-severe psoriasis with severe comorbidities and who were intolerant/nonresponding to conventional therapies.
At any point in time, psoriasis affects 2-3% of the world's population and has one of the biggest impacts on quality of life of any dermatological disorder. Treatment is extremely costly and prevention of disease progression in severity and extent is crucial. Psoriasis treatment should include skin hydration (regular use of moisturizers and emollients), careful, gentle skin cleansing, and identification and avoidance of Koebner phenomenon triggers (excoriation, maceration) and infectious foci (Streptococcus pyogenes). Moisturizers have been shown to significantly improve skin conditions and quality of life for psoriasis patients. They are a valuable first-line treatment, as dry skin is common and adds to the irritability of the diseased skin. Most patients respond well to topical treatment with topical corticosteroids, emollients, coal tar, anthralin (dithranol) or calcipotriol. Emollients are the most prescribed products, providing transient relief from irritation and some possessing anti-inflammatory properties. Moisturizers and emollients should be used in the following cases: minimal psoriasis, napkin psoriasis, psoriasis of the folds, psoriatic skin damaged by previous local treatments, and in pregnancy or women of childbearing age.
Psoriasis is a chronic immune-mediated inflammatory skin disease in which the alteration of the interleukin-23 (IL-23)/IL-17 cytokine axis appears to be crucial from a pathogenetic perspective. This has been confirmed by the efficacy of monoclonal antibodies blocking IL-17A, such as secukinumab and ixekizumab. Brodalumab is a human anti-IL-17 receptor A (IL-17RA) monoclonal antibody that inhibits the biological activity of IL-17A, IL-17F and other IL-17 isoforms, and has been approved (210 mg s.c. at weeks 0, 1, 2 and every 2 weeks thereafter) for the treatment of psoriasis vulgaris, psoriatic arthritis, pustular psoriasis and psoriatic erythroderma in Japan (Lumicef). The U.S. Food and Drug Administration has also recently approved brodalumab (Siliq) for the treatment of moderate to severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy and have failed to respond or have lost response to other systemic therapies. Regulatory applications are under review in the E.U. and Canada. The phase III clinical trials in moderate to severe plaque psoriasis met their primary endpoints after 12 weeks' treatment, with PASI 75 (75% improvement in the Psoriasis Area and Severity Index) response rates ranging between 83% and 86% (210 mg) and PASI 100 response rates ranging between 37% and 44%, significantly higher than those achieved with ustekinumab in the head-to-head trials AMAGINE-1 and AMAGINE-2. The most frequently reported adverse events in brodalumab clinical trials consisted of nasopharyngitis, headache, upper respiratory tract infection and arthralgia. In the head-to-head trials, rates of neutropenia were higher with both active drugs than with placebo, and mild or moderate Candida infections were more frequent with brodalumab than with ustekinumab or placebo. Clinical development was terminated by Amgen after adverse events of suicidal ideation and behavior were observed ls involving several indications, but data are
Caca Biljanovska, N; V'lckova Laskoska, M
Psoriasis is a chronic, systemic T-cell mediated autoimmune skin disease, potentially associated with arthritis. The new understanding of immunopathogenesis and inflammatory cytokine pathways was actually the rationale for developing and introducing biological drugs in the treatment of moderate to severe psoriasis and psoriatic arthritis. Different from the traditional systemic drugs that impact the entire immune system, bio-logics target only specific points of the immune system. This review focuses on five biologics which target either T-cells (alefacept) or TNF-alpha (etanercept, adalimumab and infliximab) or interleukin IL-12/IL-23 (ustekinumab)--their efficacy, safety, patient monitoring and recommended dosage. The purpose of the treatment guidelines presented here is to provide a high standard of continuing care of psoriasis and psoriatic arthritis patients.
Perego, S; Sansoni, V; Diani, M; Banfi, G; Altomare, G
Objective Adalimumab has proven effective in psoriasis; however, secondary failure may result from the drug's immunogenicity. Prevalence data on the immunogenicity of biologicals, and of adalimumab in particular, are highly variable. We investigated the prevalence of anti-adalimumab antibodies and the association with clinical indexes and tumour necrosis factor α (TNFα) serum levels in psoriatic patients. Design Case–control, longitudinal. Setting Single centre. Participants Patient groups: I (n=20) receiving biological therapies after switching from adalimumab; II (n=30) ongoing adalimumab therapy; III (n=30) novel adalimumab therapy; IV (n=15) biological therapies other than adalimumab. Healthy subjects: (group V; n=15) never treated with immunosuppressants or biologicals. Interventions All groups were tested at enrolment. Group II was also tested at 12 months, and group III at 1, 3, and 6 months. Primary and secondary outcome measures Standard clinical evaluations (Psoriasis Area Severity Index (PASI)), blood samples and two-site ELISA-based measurement of serum adalimumab trough levels, anti-adalimumab antibodies and TNFα. Results The false-positive rate was 23% for adalimumab detection and 22% for anti-adalimumab antibodies in patients naïve to adalimumab. Spurious positivity for anti-adalimumab antibodies (one-time-point positivity in group III during follow-up) accounted for 33% of the total. The prevalence of anti-drug antibodies was highest (87%) in group I patients. No correlations were found between the presence of anti-adalimumab antibodies or adalimumab levels and changes in PASI scores. Conclusions High variability of results, high prevalence of false-positives and lack of association between anti-adalimumab antibodies and TNFα level/PASI score limit this assay's usefulness. Accurate clinical evaluation is key to early identification of treatment failures. PMID:27940624
Shenenberger, Donald W
Psoriasis, a T-cell-mediated disorder, affects 1% to 3% of the world's population. The characteristic lesions occur in many different forms, can cause significant discomfort and social distress, and in some instances, lead to dehydration and metabolic derangement. A chronic, unpredictable course and the necessity of periodically switching drugs or classes of drugs make psoriasis frustrating to treat. However, topical and systemic drug therapies and phototherapy can help minimize the exacerbations and prolong remissions. In this article, Dr Shenenberger outlines treatment approaches and discusses research into the use of immunomodulatory agents.
Background: Although various therapies used for the treatment of psoriasis are able to produce remission, yet relapses, a common problem, remains frequent. It was observed that treatment with intermittent high dose (IHD) and continuous low dose (CLD) azathioprine can produce prolonged and durable remission in psoriasis. Aims: To see the long term effect of azathioprine pulse therapy (APT) in psoriasis. Methods: Ten patients with psoriasis who has completed more than 5 years in remission with azathioprine pulse therapy are being taken in the study. They were given IHD azathioprine (500 mg on 3 consecutive days which is repeated every month) with CLD azathioprine (100 mg orally) daily in between IHD. The entire treatment schedule was divided into four phases. During phase I, treatment with IHD and CLD azathioprine was started and continued till complete clearance of lesions after which, patients proceeded to Phase II. In phase II, they continued to get treatment with IHD and CLD. After continued remission for a period of nine months, they entered into phase III, when the treatment with IHD was stopped, but CLD continued. If there was no recurrence after nine months of phase III treatment, CLD was also withdrawn, and patients were followed-up without any treatment (Phase IV). Results: All 10 patients completed treatment and are in remission for more than five years without any treatment. Conclusions: Out of 60 patients in phase IV, 10 patients were in continuous remission for more than five years, after all treatment had been stopped. Thus, azathioprine pulse therapy regimen produces prolonged remission in psoriasis. PMID:26288403
Wolf, Joel; Ferris, Laura Korb
The IL-36 family of cytokines and receptors seems to play a role in the pathogenesis of both pustular psoriasis, and the much more common variant, plaque-type psoriasis. Human skin biopsies from patients with psoriasis show overexpression of IL-36 and mice that lack the inhibitory IL-36 receptor (IL-36Ra) antagonist develop psoriasis, suggesting that signaling through the IL-36R may drive the skin lesions of psoriasis. Currently, no drugs targeting IL-36 are used in the treatment of psoriasis. The patent WO2013074569 describes an antibody to the IL-36R that is proposed as a potential therapy for psoriasis.
Corrales Padilla, H
Oral 4, 5', 8 trimethoxypsoralen (TMP) or 8-M-methoxypsoralen (8 MP) plus black light therapy of psoriasis produced disappearing of lesions in 6 out of 8 pacients treated with TMP and in 6 out of 7 treated with 8 MP. In three patients treated with the first drug, a paired comparision demonstrated that the ingestion of it, when followed of black exposure, is more effective than the exposure to conventional ultraviolet light. Parrish et al. have shown this for oral methoxalen and long wave ultraviolet light. Combined TMP or 8-MP and black light therapy inhibits epidermal DNA synthesis and this is the scientific base of its application in the therapy of psoriasis, disease in which an accelerated celular cicle and DNA synthesis has been postulated.
Sachsman, Suzanne M; Madkan, Vandana; Yamauchi, Paul S
The adverse effects of laser procedures performed in patients with psoriasis have not been reported to date. The authors report the incidence of koebnerization in patients with psoriasis who underwent laser treatment with different devices over the past 12 years. The medical records of 38 patients with psoriasis treated with laser therapy were reviewed. Patient characteristics, including duration and severity of psoriasis, baseline psoriasis treatment, laser modality and settings, facial areas treated, and number of sessions, were collected. The primary outcome of interest was incidence of koebnerization. None of the 38 patients with psoriasis treated with laser therapy experienced subsequent koebnerization. Seven patients were on oral systemic medications, 14 were on biologic agents, and 3 were on combination therapy. None of the patients experienced skin infections, delayed healing, or scarring, irrespective of their psoriasis therapy. Koebnerization did not occur on the face, neck, or scalp of patients with psoriasis who underwent laser therapy, irrespective of psoriasis severity or types of psoriasis medications they were receiving. Although these results are encouraging, the risk of koebnerization should be discussed with patients with psoriasis who wish to undergo laser procedures.
Julià, A; Ferrándiz, C; Dauden, E; Fonseca, E; Fernández-López, E; Sanchez-Carazo, J L; Vanaclocha, F; Puig, L; Moreno-Ramírez, D; Lopez-Estebaranz, J L; Herrera, E; de la Cueva, P; Ávila, G; Alonso, A; Tortosa, R; López-Lasanta, M; Marsal, S
Psoriasis is a prevalent autoimmune disease of the skin that causes significant psychological and physical disability. Tumor necrosis factor (TNF)-blocking agents have proven to be highly efficacious in the management of moderate-to-severe psoriasis. However, a significant percentage of patients do not respond to this treatment. Recently, variation at the PDE3A-SLCO1C1 (phosphodiesterase 3A-SoLute Carrier Organic anion transporter family member 1C1) locus has been robustly associated with anti-TNF response in rheumatoid arthritis. Using a cohort of 130 psoriasis patients treated with anti-TNF therapy, we sought to analyze the association of this locus with treatment response in psoriasis. We found a highly significant association between PDE3A-SLCO1C1 and the clinical response to TNF blockers (P=0.0031). Importantly, the allele that was previously associated with the lack of response to rheumatoid arthritis (G allele, single-nucleotide polymorphism rs3794271) was associated with a higher anti-TNF efficacy in psoriasis. The results of this study are an important step in the characterization of the pharmacogenetic profile associated with anti-TNF response in psoriasis.
Kumar, B; Handa, S; Kaur, I
Data on 82 psoriatics (62 males and 20 females) with either chronic recalcitrant, erythrodermic, generalized pustular or severe palmoplantar psoriasis treated with methotrexate (MTX) have been reviewed. MTX was given in a single oral weekly dose of 3.75-30 mg based on body weight. Seven patients with a relative contraindication for MTX use were also treated safely with MTX. An attempt was made to withdraw MTX as quickly as possible with the intention of providing drug free period of 4-6 months coinciding this period with the seasonal remissions in disease activity. MTX could be withdrawn in up to 90 per cent patients within an average of 25 wk. The total cumulative dose could also be reduced by this method as also the need to repeat liver biopsies.
Carrascosa, J M; López-Estebaranz, J L; Carretero, G; Daudén, E; Ferrándiz, C; Vidal, D; Belinchón, I; Sánchez-Regaña, M; Puig, L
Novel treatment strategies and new information concerning the management of moderate to severe psoriasis justify a reassessment of the role of the classic therapies in this setting. This consensus statement evaluates narrowband UV-B therapy, which is currently considered the phototherapy option of choice in psoriasis because of its risk-to-benefit ratio. The role of excimer laser and photodynamic therapies are also discussed. These targeted therapies are still only available in a small number of centers in Spain and are used principally in the treatment of localized and recalcitrant forms of psoriasis. We discuss the efficacy and safety of phototherapy as well as treatment regimens, combination therapy, and clinical considerations relating to the characteristics of the patient or the disease. Copyright © 2010 Elsevier España, S.L. y AEDV. All rights reserved.
Checa, Antonio; Xu, Ning; Sar, Daniel G.; Haeggström, Jesper Z.; Ståhle, Mona; Wheelock, Craig E.
Sphingolipids are bioactive molecules with a putative role in inflammation. Alterations in sphingolipids, in particular ceramides, have been consistently observed in psoriatic skin. Herein, we quantified the circulating sphingolipid profile in individuals with mild or severe psoriasis as well as healthy controls. In addition, the effects of anti-TNF-α treatment were determined. Levels of sphingoid bases, including sphingosine-1-phosphate (S1P), increased in severe (P < 0.001 n = 32), but not in mild (n = 32), psoriasis relative to healthy controls (n = 32). These alterations were not reversed in severe patients (n = 16) after anti-TNF-α treatment despite significant improvement in psoriasis lesions. Circulating levels of sphingomyelins and ceramides shifted in a fatty acid chain length-dependent manner. These alterations were also observed in psoriasis skin lesions and were associated with changes in mRNA levels of ceramide synthases. The lack of S1P response to treatment may have pathobiological implications due to its close relation to the vascular and immune systems. In particular, increased levels of sphingolipids and especially S1P in severe psoriasis patients requiring biological treatment may potentially be associated with cardiovascular comorbidities. The fact that shifts in S1P levels were not ameliorated by anti-TNF-α treatment, despite improvements in the skin lesions, further supports targeting S1P receptors as therapy for severe psoriasis.
Checa, Antonio; Xu, Ning; Sar, Daniel G.; Haeggström, Jesper Z.; Ståhle, Mona; Wheelock, Craig E.
Sphingolipids are bioactive molecules with a putative role in inflammation. Alterations in sphingolipids, in particular ceramides, have been consistently observed in psoriatic skin. Herein, we quantified the circulating sphingolipid profile in individuals with mild or severe psoriasis as well as healthy controls. In addition, the effects of anti-TNF-α treatment were determined. Levels of sphingoid bases, including sphingosine-1-phosphate (S1P), increased in severe (P < 0.001; n = 32), but not in mild (n = 32), psoriasis relative to healthy controls (n = 32). These alterations were not reversed in severe patients (n = 16) after anti-TNF-α treatment despite significant improvement in psoriasis lesions. Circulating levels of sphingomyelins and ceramides shifted in a fatty acid chain length-dependent manner. These alterations were also observed in psoriasis skin lesions and were associated with changes in mRNA levels of ceramide synthases. The lack of S1P response to treatment may have pathobiological implications due to its close relation to the vascular and immune systems. In particular, increased levels of sphingolipids and especially S1P in severe psoriasis patients requiring biological treatment may potentially be associated with cardiovascular comorbidities. The fact that shifts in S1P levels were not ameliorated by anti-TNF-α treatment, despite improvements in the skin lesions, further supports targeting S1P receptors as therapy for severe psoriasis. PMID:26174087
Seité, S; Khemis, A; Rougier, A; Ortonne, J P
Emollients or moisturizers can act as an important adjunctive therapy of topical treatment in psoriatic patients. However, the interest of emollients has never been clearly demonstrated; i.e. are they able to improve topical treatment efficacy and/or maintain continuous remission of the disease? The aim of this study was to evaluate the effect of an emollient on patients with mild plaque psoriasis during and after standard local corticosteroid therapy. Results showed that the use of an emollient can limit relapses after the end of corticotherapy, and maintain the improvement obtained after 1 month corticotherapy at clinical level (physician global assessment) and skin dryness.
Conti, Andrea; Esposito, Ilaria; Lasagni, Claudia; Miglietta, Roberta; Padalino, Claudia; Fabiano, Antonella; Pellacani, Giovanni
Moderate-to-severe psoriasis is treated using biological drugs targeting cytokines involved in the pathogenesis of the disease, such as tumor necrosis factor alpha (TNF-α) (adalimumab, infliximab, etanercept) and interleukin 12/23 (IL 12/23) (ustekinumab). There is a slight risk of developing hematological malignancies, such as monoclonal gammopathy of undetermined significance (MGUS) with anti TNF-α agents. There are no data available on anti-IL12/23 drugs. This retrospective study of data from 191 patients describes the appearance and follow-up of MGUS in three patients with psoriasis receiving long-term biological therapy. Since the appearance of MGUS occurred after about 6 years of anti-TNFα treatment in only three subjects, it was deemed unlikely to be due to the biological treatment. The decision not to suspend biological therapy after the appearance of MGUS was taken after careful assessment of the possible risks and benefits.
Gond, Pushpa; Rani, Rekha; Shringi, M. K.
Purpose: Modern medical science treats psoriasis with PUVA, corticosteroid, anti-mitotic drugs which gives serious side effects like liver and kindney failure etc. There is a need to discover safe and effective medicine without any side effects for Psoriasis and the role of Leech Therapy (Shodhan) and Panchatikta Ghrita (Shaman Karma) is evaluated in this study. Method: 30 patients were included who matched the clinical signs and symptoms of psoriasis. These patients were randomised into three groups. Group A Only on leech therapy, Group B-Only on panchatikta ghrita and Group C On both leech therapy and panchatikta ghrita Result: Group A showed 45% improvement and group B showed 47% improvement, while group C reported 65% improvement. Conclusion: It can be concluded that shodan(leech application) along with shaman (panchatikta ghrita) is effective in the management of psoriasis as it is safe, cost effective and free from any side effects.
de Vasconcellos, Jaqueline Barbeito; Pereira, Daniele do Nascimento; Vargas, Thiago Jeunon de Sousa; Levy, Roger Abramino; Pinheiro, Geraldo da Rocha Castelar; Cursi, Ígor Brum
The use of tumor necrosis factor antagonists (anti-TNF) has become a usual practice to treat various inflammatory diseases. Although indicated for the treatment of psoriasis, anti-TNF may paradoxically trigger a psoriasiform condition. We present a case of a female patient who, during the use of infliximab for rheumatoid arthritis, developed psoriasis. In an attempt to switch anti-TNF class, we observed a cumulative worsening of the lesions requiring suspension of the immunobiological agent and the introduction of other drugs for clinical control. The therapeutic challenge of this paradoxical form of psoriasis is the focus of our discussion. The use of another anti-TNF in these patients is a matter of debate among experts. PMID:28300922
van de Kerkhof, Peter C M
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.
Matsumoto, Ai; Komine, Mayumi; Karakawa, Masaru; Kishimoto, Megumi; Ohtsuki, Mamitaro
We report a case of a 70-year-old woman with generalized pustular psoriasis (GPP) who responded well to infliximab therapy and adalimumab therapy after secondary failure of infliximab therapy, but did not respond to ustekinumab therapy. We speculate that the pathogenic factor in this case favored anti-tumor necrosis factor (TNF)-α therapy to anti-interleukin-12/23 therapy. Herein, we also briefly present three additional cases of treatment with adalimumab after secondary failure of infliximab. GPP is often difficult to treat, and no placebo-controlled trials have been conducted to guide the use of biologics against it because of a paucity of cases. Infliximab and adalimumab are anti-TNF-α antibodies that specifically block the interaction of TNF-α with its receptors. Infliximab has been reported to be effective, with a rapid clearance of symptoms, even in cases of severe GPP. Adalimumab could be a good biologic candidate that can be administrated after secondary failure of infliximab therapy. © 2016 Japanese Dermatological Association.
Agnusdei, Concetto P; Mastronardi, Cristina
This report covers a case of severe psoriasis that appeared to respond well to treatment with subcutaneous etanercept, with good recovery of the arthropathic component. However, there were distinct areas at the patient's hands and wrists that failed to respond to such treatment. A standard series of patch tests yielded strong positive responses to the vaseline ointment and mercaptobenzothiazole mix, substances that the patient had constantly applied, twice daily, before and during the anti-tumour necrosis factor alpha therapy course, as an emollient, rubber-gloved topical treatment. This case is reported to provide further evidence of the efficacy of etanercept treatment, and to confirm that the immunopathological pathway leading to psoriasis and allergic contact dermatitis (ACD) sometimes goes into 'overdrive' in ACD, giving a mixed pattern, involving each of the branches of the immune system.
Elyoussfi, Sarah; Thomas, Benjamin J; Ciurtin, Coziana
The diverse clinical picture of PsA suggests the need to identify suitable therapies to address the different combinations of clinical manifestations. This review aimed to classify the available biologic agents and new small molecule inhibitors (licensed and nonlicensed) based on their proven efficacy in treating different clinical manifestations associated with psoriasis and PsA. This review presents the level of evidence of efficacy of different biologic treatments and small molecule inhibitors for certain clinical features of treatment of PsA and psoriasis, which was graded in categories I-IV. The literature searches were performed on the following classes of biologic agents and small molecules: TNF inhibitors (adalimumab, etanercept, infliximab, golimumab, certolizumab), anti-IL12/IL23 (ustekinumab), anti-IL17 (secukinumab, brodalumab, ixekizumab), anti-IL6 (tocilizumab), T cell modulators (alefacept, efalizumab, abatacept, itolizumab), B cell depletion therapy (rituximab), phosphodiesterase 4 inhibitor (apremilast) and Janus kinase inhibitor (tofacitinib). A comprehensive table including 17 different biologic agents and small molecule inhibitors previously tested in psoriasis and PsA was generated, including the level of evidence of their efficacy for each of the clinical features included in our review (axial and peripheral arthritis, enthesitis, dactylitis, and nail and skin disease). We also proposed a limited set of recommendations for a sequential biologic treatment algorithm for patients with PsA who failed the first anti-TNF therapy, based on the available literature data. There is good evidence that many of the biologic treatments initially tested in psoriasis are also effective in PsA. Further research into both prognostic biomarkers and patient stratification is required to allow clinicians the possibility to make better use of the various biologic treatment options available. This review showed that there are many potentially new treatments that are
Kim, Byung-Soo; Jwa, Seung-Wook; Jang, Bong-Seok; Kim, Moon-Bum; Oh, Chang-Keun; Kwon, Yoo-Wook; Kwon, Kyung-Sool
We report a case of 61-yr-old man with stable psoriasis who progressively developed generalized pustular eruption, erythroderma, fever, and hepatic dysfunction following oral terbinafine. Skin biopsy was compatible with pustular psoriasis. After discontinuation of terbinafine and initiating topical corticosteroid and calcipotriol combination with narrow band ultraviolet B therapy, patient'S condition slowly improved until complete remission was reached 2 weeks later. The diagnosis of generalized pustular psoriasis (GPP) induced by oral terbinafine was made. To our knowledge, this is the first report of GPP accompanied by hepatic dysfunction associated with oral terbinafine therapy. PMID:17297275
Wald, Jenna M; Klufas, Daniel M; Strober, Bruce E
Palmoplantar psoriasis is a chronic debilitating type of psoriasis. Treatment options for this disease are poorly studied. This chart review evaluated the use of methotrexate alone and in combination with 7 other systemic therapies in 48 patients with palmoplantar psoriasis. The findings demonstrate that methotrexate is a relatively well-tolerated and effective treatment for palmoplantar psoriasis, amenable as either monotherapy or in combination with other systemic agents.
Jacobi, Arnd; Rustenbach, Stephan J; Augustin, Matthias
Psoriasis often requires lifelong therapy, and adherence to treatment is considered a marker for treatment success. Data on the drug survival of biologics in psoriasis patients with comorbidities are lacking. This study was designed to estimate the long-term drug survival rates of different biologic agents in a cohort of psoriasis patients and to evaluate reasons and predictors for treatment adherence. Drug survival rates and outcome parameters in psoriasis patients treated with biologic agents were analyzed. A total of 125 treatment periods with adalimumab (n = 37), efalizumab (n = 9), etanercept (n = 55), infliximab (n = 13), and ustekinumab (n = 11) were administered to 67 psoriasis patients. Patients with psoriatic arthritis (P = 0.010) and without comorbidity (P = 0.033) demonstrated significantly greater rates of drug survival. The overall efficacy of biologic agents is reduced with time. Patients with the comorbidity of metabolic syndrome demonstrate a loss of adherence to biologic treatment. © 2015 The International Society of Dermatology.
Jakobsen, Maria; Stenderup, Karin; Rosada, Cecilia; Moldt, Brian; Kamp, Søren; Dam, Tomas N; Jensen, Thomas G; Mikkelsen, Jacob Giehm
Tumor necrosis factor-alpha (TNF-alpha) is upregulated in psoriatic skin and represents a prominent target in psoriasis treatment. The level of TNF-alpha-encoding mRNA, however, is not increased in psoriatic skin, and it remains unclear whether intervention strategies based on RNA interference (RNAi) are therapeutically relevant. To test this hypothesis the present study describes first the in vitro functional screening of a panel of short hairpin RNAs (shRNAs) targeting human TNF-alpha mRNA and, next, the transfer of the most potent TNF-alpha shRNA variant, as assessed in vitro, to human skin in the psoriasis xenograft transplantation model by the use of lentiviral vectors. TNF-alpha shRNA treatment leads to amelioration of the psoriasis phentotype in the model, as documented by reduced epidermal thickness, normalization of the skin morphology, and reduced levels of TNF-alpha mRNA as detected in skin biopsies 3 weeks after a single vector injection of lentiviral vectors encoding TNF-alpha shRNA. Our data show efficient lentiviral gene delivery to psoriatic skin and therapeutic applicability of anti-TNF-alpha shRNAs in human skin. These findings validate TNF-alpha mRNA as a target molecule for a potential persistent RNA-based treatment of psoriasis and establish the use of small RNA effectors as a novel platform for target validation in psoriasis and other skin disorders.
Fan, Xiao-Dong; Xia, Xiang; Zhang, Chun-Yan; Kong, Wen-Qiang; Zhou, Chun-Yang; DU, Biao
To evaluate the efficacy and safety of anti-interleukin-17 antibody in the treatment of plaque psoriasis. Randomized controlled trials (RCT) of anti-interleukin-17 antibody (Secukinumab, Brodalumab, and Ixekizumab) in the treatment of plaque psoriasis published between January, 2000 and March, 2017 were searched from PubMed, Cochrane Library, EBSCO, EMbase, CBM, CNKI, VIPdetabase, and Wangfang database. The quality of the retrieved trials was evaluated and the results of studies were analyzed using RevMan 5.0 software. Thirteen RCTs were included involving a total of 11 203 patients. Meta-analysis showed a significant differences between anti-interleukin-17 antibody and placebo (or positive drug) in terms of PASI75 and sPGA (P<0.05). The total incidence of adverse events differed significantly between anti- interleukin-17 antibody and placebo, but no significant differences were found between them in the incidence of serious adverse events and discontinuation rate due to adverse events (P>0.05). Anti-interleukin-17 antibody is safe and effective for treatment of plaque psoriasis.
Luan, Li; Han, Shixin; Wang, Hua; Liu, Xiaoming
Psoriasis is a T-cell-mediated chronic inflammatory dermatosis. Th1, Th17 and Th22 cells are suggested to contribute to the pathogenesis of psoriasis. To determine whether treatment with the anti-tumor-necrosis-factor antagonist, adalimumab, induces significant modulation of the Th1, Th17 and Th22 pathways, and correlates cellular activity with clinical response. This study included 21 patients with moderate-to-severe psoriasis who were treated with adalimumab, and 10 healthy control subjects. Blood samples were collected at baseline and at week 12. Flow cytometry was used to analyze the frequency of circulating Th1, Th17 and Th22 cells. Real-time polymerase chain reaction was used to analyze the expression of T-bet (Th1-related), retinoid-acid receptor-related orphan receptor gamma t (RORγt, Th17-related) and aryl hydrocarbon receptor (AHR, Th22-related). An enzyme-linked immunosorbent assay was used to analyze the serum levels of IFN-γ, IL-17, IL-22, IL-6 and tumor necrosis factor-α (TNF-α). At baseline, the frequencies of Th1, Th17 and Th22 cells were higher in psoriasis patients compared to the healthy controls. The expression of transcription factors T-bet, RORγt and AHR, and the serum levels of IFN-γ, IL-17, IL-22, IL-6 and TNF-α were higher in psoriasis patients compared to the healthy controls. After adalimumab therapy, there was a significant decline in the frequencies of Th1, Th17 and Th22 cells, and a concomitant decrease in the levels of their associated transcription factors and cytokines. The results suggest that the anti-tumor-necrosis-factor antagonist, adalimumab, disrupts the Th1, Th17 and Th22 pathways, resulting in clinical improvement of psoriasis. Copyright © 2015 Elsevier B.V. All rights reserved.
Aldredge, Lakshi M.; Young, Melodie S.
ABSTRACT Psoriasis is a chronic, immune-mediated disease characterized by itchy, scaly, and often painful plaques in the skin. Psoriasis can have significant psychosocial burdens and increased risks for numerous comorbidities, including diabetes, hypertension, and cardiovascular disease, particularly in patients with moderate-to-severe disease. Dermatology nurse practitioners and physician assistants are an important part of the healthcare team, contributing to all aspects of psoriasis management. This review reinforces the unique aspects of care that nurse practitioners and physician assistants provide to patients with psoriasis, such as facilitating conversations about managing disease, setting appropriate expectations, and considering treatment options, including when treatment response or tolerability is suboptimal. The importance of relationship building is stressed. Patient management topics discussed include helpful tips about assessing treatment options, initiating biologic therapy, optimizing patient adherence, and managing comorbidities. Also reviewed are how to deal with common barriers including lack of knowledge about psoriasis or making healthy lifestyle changes, fear of injections or side effect risks, lack of health insurance, and concerns about treatment costs. Overall, by forming meaningful relationships and engaging patients in their psoriasis care, nurse practitioners and physician assistants can help to optimize clinical efficacy outcomes and consistently manage moderate-to-severe psoriasis and its comorbidities over the patient’s life course. PMID:27004085
Rafael, Adilia; Torres, Tiago
Psoriasis is a common, chronic and disabling skin disorder affecting approximately 2% of the population, associated with significant negative impact on the patient's quality of life. Approximately 80% of those affected with psoriasis have mild-to-moderate forms and are usually treated with topical therapy, whereas phototherapy and systemic therapies are used for those with severe disease. In the past three decades, the major advances in psoriasis therapy have been in systemic agents for the treatment of moderate-to-severe psoriasis, particularly new immunomodulatory and biological molecules, while topical therapies have remained relatively unchanged over the past decades. Indeed, topical corticosteroids and vitamin D3 analogs are still the gold standard of therapy for mild-to-moderate psoriasis. Thus, there is a need to develop new and more effective topical agents in the short and long term, with a better efficacy and safety profile than corticosteroids and vitamin D3 analogs. Over the past five years, investigation into topical therapy has expanded, with exciting new drugs being developed. Preliminary results of these emerging agents that selectively target disease-defining pathogenic pathways seem to be promising, although long-term and large-scale studies assessing safety and efficacy are still lacking. The aim of this article was to review the clinical and research data of some emerging topical agents, focusing on Janus kinase-signal transducer and activator of transcription and phosphodiesterase type 4 inhibitors, which are currently being investigated.
Barth, J; Pinzer, B
22 patients suffering from exanthematic psoriasis were irradiated with the UV-lamps UVS 65-2 (Narva, Brand-Erbisdorf) or TL-01 (Philips Company, Eindhoven, Niederlande) respectively. The latter one emits a narrow-band UV-spectrum at 311 nm which seems to be most suitable for the treatment of psoriasis. On our condition the clearing rate was higher and the cumulative irradiation dose was significantly lower with the TL-01 lamp.
Wu, Meng-Chi; Lee, J Yu-Yun
New onset or exacerbation of psoriasis vulgaris has been reported in a small number of patients after interferon (IFN)-α therapy. Herein, we report a case of generalized flare of pustular psoriasis induced by PEGylated IFN-α2b (PEG-IFN-α2b) in a 59-year-old woman with a 15-year history of pustular psoriasis and chronic hepatitis C. Interferon-α therapy was discontinued and the rash resolved after treatment with cyclosporin and systemic methylprednisolone. The potential side effect of PEG-IFN-α2b in inducing or exacerbating psoriasis should be kept in mind when treating patients with a history of psoriasis or pustular psoriasis. © 2011 The Authors. Australasian Journal of Dermatology © 2011 The Australasian College of Dermatologists.
Weisenseel, P; Wilsmann-Theis, D; Kahl, C; Reich, K; Mössner, R
A number of pustular skin diseases share clinical, pathogenetic, and epidemiological aspects with plaque-type psoriasis, and their classification as a separate clinical entity or as a subtype of psoriasis remains controversial, which is also reflected in the multitude of their names. They include generalized pustular psoriasis with its subtypes, acrodermatitis continua suppurativa (Hallopeau), acute pustulosis palmopantaris, palmoplantar pustular psoriasis, and pustular variants of a mostly TNF-blocker triggered paradoxical psoriasiform dermatitis. In this article, the epidemiology, clinical picture, pathogenesis, genetics, and therapy of these pustular skin diseases are described.
Hawkes, Jason E; Chan, Tom C; Krueger, James G
Psoriasis is caused by a complex interplay between the immune system, psoriasis-associated susceptibility loci, autoantigens, and multiple environmental factors. Over the last 2 decades, research has unequivocally shown that psoriasis represents a bona fide T cell-mediated disease primarily driven by pathogenic T cells that produce high levels of IL-17 in response to IL-23. The discovery of the central role for the IL-23/type 17 T-cell axis in the development of psoriasis has led to a major paradigm shift in the pathogenic model for this condition. The activation and upregulation of IL-17 in prepsoriatic skin produces a "feed forward" inflammatory response in keratinocytes that is self-amplifying and drives the development of mature psoriatic plaques by inducing epidermal hyperplasia, epidermal cell proliferation, and recruitment of leukocyte subsets into the skin. Clinical trial data for mAbs against IL-17 signaling (secukinumab, ixekizumab, and brodalumab) and newer IL-23p19 antagonists (tildrakizumab, guselkumab, and risankizumab) underscore the central role of these cytokines as predominant drivers of psoriatic disease. Currently, we are witnessing a translational revolution in the treatment and management of psoriasis. Emerging bispecific antibodies offer the potential for even better disease control, whereas small-molecule drugs offer future alternatives to the use of biologics and less costly long-term disease management. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
Jensen, J Daniel; Delcambre, Macey Renault; Nguyen, Gloria; Sami, Naveed
Biologic therapy represents a relatively new class of drugs which have revolutionized the treatment of psoriasis and are used with increasing frequency in order to control this chronic, systemic inflammatory disease. However, it is unclear what role there is for combination therapy of biologics with traditional topical agents. The purpose of this article is to assess the literature on the role of topical agents as adjuvants to biological treatments in the treatment of psoriasis and identify areas for further research. A MEDLINE search was performed in order to identify English-language publications from 1996 to 2014 examining combination biologic therapy with topical medications in the treatment of psoriasis. Data from these clinical studies are summarized and the outcomes are discussed. In general, the addition of adjuvant topical therapy to systemic biologic therapy allowed for a reduction in dosage and side effects of both agents, maintenance of initial response to biologics, treatment of recalcitrant lesions in partial responders, and potential acceleration of response to biologic therapies. The current data, though limited, suggest that using topical therapies as adjunct treatment to biologics is a well tolerated and effective means of controlling psoriasis and improving quality of life for patients. However, the treating physician should remain attentive to signs of adverse events and seek opportunities to reduce the dose or treatment frequency during chronic use.
Teixeira, Marcus Zulian
Employing the secondary action or adaptative reaction of the organism as therapeutic response, homeopathy uses the treatment by similitude (similia similibus curentur) administering to sick individuals the medicines that caused similar symptoms in healthy individuals. Such homeostatic or paradoxical reaction of the organism is scientifically explained through the rebound effect of drugs, which cause worsening of symptoms after withdrawal of several palliative treatments. Despite promoting an improvement in psoriasis at the beginning of the treatment, modern biological therapies provoke worsening of the psoriasis (rebound psoriasis) after discontinuation of drugs. Exploratory qualitative review of the literature on the occurrence of the rebound effect with the use of immunomodulatory drugs [T-cell modulating agents and tumor necrosis factor (TNF) inhibitors drugs] in the treatment of psoriasis. Several researches indicate the rebound effect as the mechanism of worsening of psoriasis with the use of efalizumab causing the suspension of its marketing authorization in 2009, in view of some severe cases. Other studies also have demonstrated the occurrence of rebound psoriasis with the use of alefacept, etanercept and infliximab. As well as studied in other classes of drugs, the rebound effect of biologic agents supports the principle of similitude (primary action of the drugs followed by secondary action and opposite of the organism). Copyright Â© 2016 The Faculty of Homeopathy. Published by Elsevier Ltd. All rights reserved.
Lin, Yin-Ku; Yang, Sien-Hung; Chen, Chin-Chuan; Kao, Hsiao-Ching; Fang, Jia-You
Objective Psoriasis is a chronic inflammatory skin disease and topical therapy remains a key role for treatment. The aim of this study is to evaluate the influence of psoriasis-like lesions on the cutaneous permeation of anti-psoriatic drugs. Methods We first set up imiquimod-induced dermatitis in mice that closely resembles human psoriasis lesions. The development of the lesions is based on the IL-23/IL17A axis for phenotypical and histological characteristics. Four drugs, 5-aminolevulinic acid (ALA), tacrolimus, calcipotriol, and retinoic acid, were used to evaluate percutaneous absorption. Results The most hydrophilic molecule, ALA, revealed the greatest enhancement on skin absorption after imiquimod treatment. Imiquimod increased the skin deposition and flux of ALA by 5.6 to 14.4-fold, respectively, compared to normal skin. The follicular accumulation of ALA was also increased 3.8-fold. The extremely lipophilic drug retinoic acid showed a 1.7- and 3.8-fold increase in skin deposition and flux, respectively. Tacrolimus flux was enhanced from 2 to 21 μg/cm2/h by imiquimod intervention. However, imiquimod did not promote skin deposition of this macrolide. The lipophilicity, but not the molecular size, dominated drug permeation enhancement by psoriatic lesions. The in vivo percutaneous absorption of ALA and rhodamine B examined by confocal microscopy confirmed the deficient resistance of epidermal barrier for facilitating cutaneous delivery of drugs via psoriasis-like skin. Conclusion We established the topical delivery profiles of anti-psoriatic drugs via imiquimod-treated psoriasis-like skin. PMID:26355594
Cabaleiro, T; Prieto-Pérez, R; Navarro, R; Solano, G; Román, M; Ochoa, D; Abad-Santos, F; Daudén, E
Paradoxical psoriasiform reactions to anti-tumor necrosis factor α (TNFα) agents have been described. We aimed to study the association between these reactions and polymorphisms in genes previously associated with psoriasis or other autoimmune diseases. A total of 161 patients with plaque-type psoriasis treated with anti-TNFα drugs were genotyped for 173 single-nucleotide polymorphisms (SNPs) using the Illumina Veracode genotyping platform. Among the 161 patients, 25 patients developed a paradoxical psoriasiform reaction consisting of a change in morphology, mostly to guttate psoriasis (88%). These lesions developed 9.20±13.52 months after initiating treatment, mainly with etanercept (72%). Psoriasis type and a Psoriasis Area and Severity Index (PASI) 75 response to treatment were not associated with lesions. Multivariate logistic regression revealed that five SNPs (rs11209026 in IL23R, rs10782001 in FBXL19, rs3087243 in CTLA4, rs651630 in SLC12A8 and rs1800453 in TAP1) were associated with paradoxical reactions. This is the first study to show an association between genetic polymorphisms and paradoxical reactions in patients with psoriasis treated with anti-TNFα drugs.The Pharmacogenomics Journal advance online publication, 21 July 2015; doi:10.1038/tpj.2015.53.
Cather, Jennifer C; Crowley, Jeffrey J
Psoriasis is a chronic inflammatory skin disorder, which is associated with a significant negative impact on a patient's quality of life. Traditional therapies for psoriasis are often not able to meet desired treatment goals, and high-dose and/or long-term use is associated with toxicities that can result in end-organ damage. An improved understanding of the involvement of cytokines in the etiology of psoriasis has led to the development of biologic agents targeting tumor necrosis factor (TNF)-α and interleukins (ILs)-12/23. While biologic agents have improved treatment outcomes, they are not effective in all individuals with psoriasis. The combination of biologic agents with traditional therapies may provide improved therapeutic options for patients who inadequately respond to a single drug or when efficacy may be increased with supplementation of another treatment. In addition, combination therapy may reduce safety concerns and cumulative toxicity, as lower doses of individual agents may be efficacious when used together. This article reviews the current evidence available on the efficacy and safety of combining biologic agents with systemic therapies (methotrexate, cyclosporine, or retinoids) or with phototherapy, and the combination of biologic agents themselves. Guidance is provided to help physicians identify situations and the characteristics of patients who would benefit from combination therapy with a biologic agent. Finally, the potential clinical impact of biologic therapies in development (e.g., those targeting IL-17A, IL-17RA, or IL-23 alone) is analyzed.
Yamanaka, Keiichi; Umezawa, Yoshinori; Yamagiwa, Akisa; Saeki, Hidehisa; Kondo, Makoto; Gabazza, Esteban C; Nakagawa, Hidemi; Mizutani, Hitoshi
Therapy with monoclonal antibodies to tumor necrosis factor (TNF)-α and the interleukin (IL)-12/23 p40 subunit has significantly improved the clinical outcome of patients with psoriasis. These antibodies inhibit the effects of the target cytokines and thus the major concern during their use is the induction of excessive immunosuppression. Recent studies evaluating the long-term efficacy and safety of biologic therapy in psoriasis have shown no significant appearance of serious adverse effects including infections and malignancies. However, the immunological consequence and the mechanism by which the blockade of a single cytokine by biologics can successfully control the activity of psoriasis remain unclear. In the current study, we investigated the effect of biologic therapy on cytokine production of various lymphocytes and on the activity of monocytes and neutrophils in psoriatic patients. Neutrophils, monocytes and T cells were purified from heparinized peripheral venous blood by Ficoll density gradient centrifugation, and γ-interferon, TNF-α and IL-17 production from lymphocytes was measured by flow cytometer. The activation maker of neutrophils and the activated subsets of monocytes were also analyzed. Biologic therapy induced no significant changes in the cytokine production by lymphocytes from the skin and gut-homing T cells. However, neutrophil activity and the ratio of activated monocyte population increased in severely psoriatic patients were normalized in psoriatic patients receiving biologic therapy. The present study showed that biologic therapy ameliorates clinical symptoms and controls the immune response in patients with psoriasis.
Kerdel, Francisco; Zaiac, Martin
Switching psoriasis treatment is a common, accepted practice that is used to improve disease management and improve patient outcomes (e.g., when patients are experiencing suboptimal efficacy and/or tolerability with a given therapy). Historically, switching treatment was often performed to limit patients' cumulative exposure to conventional systemic agents (e.g., methotrexate, cyclosporine) with the goal of reducing end-organ toxicity. However, the practice of switching treatments has evolved in recent years with the availability of highly effective and tolerable biologic agents. In current practice, near-complete skin clearance with minimal side effects should be a realistic treatment goal for most patients with moderate-to-severe psoriasis, and consideration for switching therapies has shifted to become more focused on achieving maximum possible skin clearance, enhanced quality of life, and improved patient satisfaction. This review provides a discussion of recent guidance on switching psoriasis therapies, including initial considerations for when switching therapy may be advisable and challenges associated with switching therapy, along with an overview of published clinical studies evaluating outcomes associated with switching therapy. The goal of this review is to empower dermatologists to optimally manage their patients' psoriasis by providing the tools needed to develop rational strategies for switching treatments based on the pharmacologic characteristics of available treatments and each patient's clinical needs and treatment preferences.
Samarasekera, E J; Sawyer, L; Wonderling, D; Tucker, R; Smith, C H
The majority of people with psoriasis have localized disease, where topical therapy forms the cornerstone of treatment. We set out to summarize evidence on the relative efficacy, safety and tolerability of different topical treatments used in plaque psoriasis. We undertook a systematic review and meta-analyses of randomized trial data of U.K.-licensed topical therapies. The primary outcome was clear or nearly clear status stratified for (i) trunk and limbs; and (ii) scalp. Network meta-analyses allowed ranking of treatment efficacy. In total, 48 studies were available for trunk and limb psoriasis, and 17 for scalp psoriasis (22,028 patients in total); the majority included people with at least moderate severity psoriasis. Strategies containing potent corticosteroids (alone or in combination with a vitamin D analogue) or very potent corticosteroids dominated the treatment hierarchy at both sites (trunk and limbs, scalp); coal tar and retinoids were no better than placebo. No significant differences in achievement of clear or nearly clear status were observed between twice- and once-daily application of the same intervention or between any of the following: combined vitamin D analogue and potent corticosteroid (applied separately or in a single product), very potent corticosteroids, or potent corticosteroids (applied twice daily). Investigator and patient assessment of response differed significantly for some interventions (response rates to very potent corticosteroids: 78% and 39%, respectively). No significant differences were noted for tolerability or steroid atrophy, but data were limited. In conclusion, corticosteroids are highly effective in psoriasis when used continuously for up to 8 weeks and intermittently for up to 52 weeks. Coal tar and retinoids are of limited benefit. There is a lack of long-term efficacy and safety data available on topical interventions used for psoriasis.
Kubo, Ryoji; Muramatsu, Shinnosuke; Sagawa, Yoko; Saito, Chiyo; Kasuya, Saori; Nishioka, Akiko; Nishida, Emi; Yamazaki, Sayuri; Morita, Akimichi
Bath-psoralen plus ultraviolet light A (PUVA) therapy is an effective, safe, and inexpensive treatment for psoriasis. Psoriasis might be due to an unbalanced ratio of Th17 cells and regulatory T cells (Treg). The Treg functional ratio is significantly lower in patients with psoriasis compared with controls and is inversely correlated with the Psoriasis Area and Severity Index score. We previously reported that bath-PUVA therapy significantly increases the number of Treg and restores Treg function to almost normal in most patients with psoriasis. We examined the effects of bath-PUVA therapy on three distinct Foxp3(+) subsets: activated Treg (aTreg), resting Treg (rTreg), and cytokine-secreting non-suppressive T cells. We enrolled 15 patients with psoriasis and 11 healthy controls. We examined aTreg, rTreg, and cytokine-secreting non-suppressive T cells in peripheral blood obtained from the psoriasis patients before and after every fifth bath-PUVA therapy session. Levels of aTreg, which are considered to have the strongest suppressive activity in patients with psoriasis, were significantly increased in the early bath-PUVA therapy sessions, and then diminished. Levels of rTreg were lower in psoriasis patients than in healthy controls, and increased during bath-PUVA therapy. Bath-PUVA therapy induced aTreg and rTreg concomitantly with an improvement in the psoriatic lesions, suggesting a mechanism for the effectiveness of bath-PUVA therapy for psoriasis patients. Copyright © 2017 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.
Yacoby, Iftach; Benhar, Itai
The increasing development of bacterial resistance to traditional antibiotics has reached alarming levels, thus necessitating a strong need to develop new antimicrobial agents. These new antimicrobials should possess novel modes of action and/or different cellular targets compared with the existing antibiotics. As a result, new classes of compounds designed to avoid defined resistance mechanisms are undergoing pre clinical and clinical evaluation. Microbial and phage genomic sequencing are now being used to find previously unidentified genes and their corresponding proteins. In both traditional and newly developed antibiotics, the target selectivity lies in the drug itself, in its ability to affect a mechanism that is unique to prokaryotes. As a result, a vast number of potent agents that, due to low selectivity, in addition to the pathogen also affect the eukaryote host have been excluded from use as therapeutics. Such compounds could be re-considered for clinical use if applied as part of a targeted delivery platform where the drug selectivity is replaced by target-selectivity borne by the targeting moiety. With a large number of antibodies and antibody-drug conjugates already approved or near approval as cancer therapeutics, targeted therapy is becoming increasingly attractive and additional potential targeting moieties that are non-antibody based, such as peptides, non-antibody ligand-binding proteins and even carbohydrates are receiving increasing attention. Still, targeted therapy is mostly focused on cancer, with targeted anti bacterial therapies being suggested only very recently. This review will focus in the various methods of antimicrobial targeting, by systemic and local application of targeted antimicrobial substances.
Engin, Burhan; Aşkın, Özge; Tüzün, Yalçın
Palmoplantar psoriasis refers to a localized psoriasis variant. The disease can be associated with many clinical forms, including predominantly pustular lesions to thick scaly, hyperkeratotic plaques, or an overlapping of both of them. Palmoplantar psoriasis accounts for 3-4% of all psoriasis cases in most studies. Although it is localized only on the palms and the soles, the fissures, the hardening of the tissue, and hyperkeratosis affect daily routine activities. Taking the body surface area as a measure of severity can sometimes be misleading. In clinical practice, the level of functional impairment should be taken into account rather than relying on traditional instruments to evaluate the severity. Palmoplantar psoriasis is usually managed with topical therapy as a first step. Systemic therapy is needed when the topicals fail or when the disease becomes more severe. Sometimes, biologic agents are required for adequate maintenance of clinical response.
Menon, Roshni; David, Brinda G
Management of psoriasis is a challenge to the treating physician. The chronic inflammatory state of psoriasis with exacerbations and remissions necessitate "on-and-off" treatment schedules. The safety profiles of drugs and tolerability issues for patients are important factors to be considered during treatment. Various biological agents targeting T-cells and the inflammatory cytokines are available for systemic treatment of psoriasis. However, major causes of concern while using these drugs are risk of susceptibility to infection and development of anti-drug antibodies, which will affect the pharmacokinetic properties, efficacy, and safety profile of the drug. Itolizumab, a humanized anti-CD6 monoclonal antibody, is a new molecule that acts by immunomodulating the CD6 molecule. CD6 is a co-stimulatory molecule required for optimal T-cell stimulation by the antigen-presenting cells. This step is crucial in T-cell proliferation to form Th1 and Th17 cells, which play a major role in the pathogenesis of psoriasis. This article deals with the properties of Itolizumab and its role in the treatment of psoriasis. Based on the available published data, Itolizumab seems to have a better adverse effects profile and at the same time comparatively less efficacy when compared to other biological agents available for treating psoriasis. Larger studies with longer duration are required to clearly depict the long-term side effects profile.
Psoriasis is a common chronic inflammatory skin disease. Recently, few data have been published on epidemiology, comorbidity, or therapy in children with psoriasis. Psoriasis affects up to 2% of children in Europe, even during the first months of life. The link between psoriasis and metabolic comorbidities has been highlighted, notably in relation to excessive weight and obesity. The clinical picture of psoriasis in childhood resembles adult disease, however, some clinical features are noteworthy: neonatal diaper rash is relatively specific, face involvement and guttate psoriasis are more common, plaques are often smaller, and scales are finer and softer than in adults. Napkin, guttate and palmoplantar psoriasis appear to have specific features in childhood and prevalence depends on the age of the child. Although benign, the effect of psoriasis on social interaction can be major, especially in children. Topical therapies are the first line of treatment for skin-limited disease. For chronic cases and more severe cases, phototherapy or traditional biologic systemic treatments must be discussed. The great challenge will be to propose international guidelines to manage these children.
Randeberg, Lise L.; Hernandez-Palacios, Julio; Lilleeng, Mila; Nilsen, Lill Tove; Krogstad, Anne-Lene
Psoriasis is a common autoimmune disease with inflammatory symptoms affecting skin and joints. One way of dealing with psoriasis is by controlled solar UV exposure treatment. However, this treatment should be optimized to get the best possible treatment effect and to limit negative side effects such as erythema and an increased risk of skin cancer. In this study 24 patients at Valle Marina Treatment Center in Gran Canaria were monitored throughout a treatment period of three weeks starting at the beginning of November. The total UV dose to the location was monitored by UV-meters placed on the roof of the treatment centere, and the patients wore individual film dosimeters throughout the treatment period. Skin parameters were accessed by reflection spectroscopy (400-850nm). This paper presents preliminary findings from the skin measurements in the visible part of the spectrum, such as blood oxygenation, erythema and melanin indexes. Reflection spectroscopy was found to be a good tool for such treatment monitoring.
Menter, A.; Korman, N.J.; Elmets, C.A.; Feldman, S.R.; Gelfand, J.M.; Gordon, K.B.; Gottlieb, A.; Koo, J.Y.M.; Lebwohl, M.; Lim, H.W.; Van Voorhees, A.S.; Beutner, K.R.; Bhushan, R.
Psoriasis is a common, chronic, inflammatory, multi-system disease with predominantly skin and joint manifestations affecting approximately 2% of the Population. In this third of 6 sections of the guidelines of care for psoriasis, we discuss the use of topical medications for the treatment of psoriasis. The majority of patients with psoriasis have limited disease (<5% body surface area involvement) and can be treated with topical agents, which generally provide a high efficacy-to-safety ratio. Topical agents may also be used adjunctively for patients with more extensive psoriasis undergoing therapy with either ultraviolet light, systemic or biologic medications. However, the use of topical agents as monotherapy in the setting of extensive disease or in the setting of limited, but recalcitrant, disease is not routinely recommended. Treatment should be tailored to meet individual patients' needs. We will discuss the efficacy and safety of as well as offer recommendations for the use of topical corticosteroids, vitamin D analogues, tazarotene, tacrolimus, pimecrolimus, emollients, salicylic acid, anthralin, coal tar, as well as combination therapy.
Langkilde, Ane; Olsen, Lene C.; Sætrom, Pål; Drabløs, Finn; Besenbacher, Søren; Raaby, Line; Johansen, Claus; Iversen, Lars
Psoriasis is a chronic cutaneous inflammatory disease. The immunopathogenesis is a complex interplay between T cells, dendritic cells and the epidermis in which T cells and dendritic cells maintain skin inflammation. Anti-tumour necrosis factor (anti-TNF)-α agents have been approved for therapeutic use across a range of inflammatory disorders including psoriasis, but the anti-inflammatory mechanisms of anti-TNF-α in lesional psoriatic skin are not fully understood. We investigated early events in skin from psoriasis patients after treatment with anti-TNF-α antibodies by use of bioinformatics tools. We used the Human Gene 1.0 ST Array to analyse gene expression in punch biopsies taken from psoriatic patients before and also 4 and 14 days after initiation of treatment with the anti-TNF-α agent adalimumab. The gene expression was analysed by gene set enrichment analysis using the Functional Annotation Tool from DAVID Bioinformatics Resources. The most enriched pathway was visualised by the Pathview Package on Kyoto Encyclopedia of Genes and Genomes (KEGG) graphs. The analysis revealed new very early events in psoriasis after adalimumab treatment. Some of these events have been described after longer periods of anti-TNF-α treatment when clinical and histological changes appear, suggesting that effects of anti-TNF-α treatment on gene expression appear very early before clinical and histological changes. Combining microarray data on biopsies from psoriasis patients with pathway analysis allowed us to integrate in vitro findings into the identification of mechanisms that may be important in vivo. Furthermore, these results may reflect primary effect of anti-TNF-α treatment in contrast to studies of gene expression changes following clinical and histological changes, which may reflect secondary changes correlated to the healing of the skin. PMID:28005985
Langkilde, Ane; Olsen, Lene C; Sætrom, Pål; Drabløs, Finn; Besenbacher, Søren; Raaby, Line; Johansen, Claus; Iversen, Lars
Psoriasis is a chronic cutaneous inflammatory disease. The immunopathogenesis is a complex interplay between T cells, dendritic cells and the epidermis in which T cells and dendritic cells maintain skin inflammation. Anti-tumour necrosis factor (anti-TNF)-α agents have been approved for therapeutic use across a range of inflammatory disorders including psoriasis, but the anti-inflammatory mechanisms of anti-TNF-α in lesional psoriatic skin are not fully understood. We investigated early events in skin from psoriasis patients after treatment with anti-TNF-α antibodies by use of bioinformatics tools. We used the Human Gene 1.0 ST Array to analyse gene expression in punch biopsies taken from psoriatic patients before and also 4 and 14 days after initiation of treatment with the anti-TNF-α agent adalimumab. The gene expression was analysed by gene set enrichment analysis using the Functional Annotation Tool from DAVID Bioinformatics Resources. The most enriched pathway was visualised by the Pathview Package on Kyoto Encyclopedia of Genes and Genomes (KEGG) graphs. The analysis revealed new very early events in psoriasis after adalimumab treatment. Some of these events have been described after longer periods of anti-TNF-α treatment when clinical and histological changes appear, suggesting that effects of anti-TNF-α treatment on gene expression appear very early before clinical and histological changes. Combining microarray data on biopsies from psoriasis patients with pathway analysis allowed us to integrate in vitro findings into the identification of mechanisms that may be important in vivo. Furthermore, these results may reflect primary effect of anti-TNF-α treatment in contrast to studies of gene expression changes following clinical and histological changes, which may reflect secondary changes correlated to the healing of the skin.
From the Medical Board of the National Psoriasis Foundation: Recommendations for screening for hepatitis B infection prior to initiating anti-tumor necrosis factor-alfa inhibitors or other immunosuppressive agents in patients with psoriasis.
Motaparthi, Kiran; Stanisic, Vladimir; Van Voorhees, Abby S; Lebwohl, Mark G; Hsu, Sylvia
No consensus exists regarding the optimal laboratory screening for hepatitis B infection that should be performed before initiating therapy with tumor necrosis factor-alfa inhibitors or other immunosuppressive agents. We sought to give guidelines on which tests to order for hepatitis B screening. We review the pathophysiology and serology of hepatitis B infection and provide recommendations for screening for hepatitis B infection in patients with psoriasis before beginning anti-tumor necrosis factor-alfa therapy or other immunosuppressive agents. We propose the standardized use of triple serology testing: hepatitis B surface antigen, hepatitis B surface antibody, and hepatitis B core antibody in combination with liver function tests as screening. Conclusions based on review of available literature is a limitation. All patients with psoriasis who are candidates for tumor necrosis factor-alfa inhibitor should undergo screening for hepatitis B virus infection using the triple serology: hepatitis B surface antigen, hepatitis B surface antibody, and hepatitis B core antibody. It is advisable that patients, who are candidates for ustekinumab, cyclosporine, or methotrexate undergo the same screening. Copyright © 2013 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.
Jacobi, Arnd; Mayer, Anke; Augustin, Matthias
Psoriasis is a common chronic disease with significant impairment in quality of life. As there is no cure, it often requires lifelong disease control to minimize the development of skin lesions and to relieve symptoms. The aim of this publication is to systematically review the role of currently used emollients and keratolytics in the treatment of psoriasis. A systematic literature search was conducted in Medline via PubMed regarding reviews, meta-analyses, and trials published from January 1983 to December 2013 dealing with topical administration of emollients and keratolytics in patients with psoriasis. A subsequent search in EMBASE regarding clinical trials published from 1983 to 2013 was performed to complement the findings. A total of 60 publications met the inclusion criteria for full-text evaluation. While current reviews, meta-analyses, and guidelines state that adjuvant therapy with emollients and keratolytics should be an obligatory part in the therapy of psoriasis to facilitate descaling and/or penetration enhancement, comprehensive trials on these agents are missing, with the exception of combination products containing salicylic acid and corticosteroids. In the mentioned trials, addition of salicylic acid was beneficial in inducing a more rapid onset of action as well as a reduction of severity parameters and the area affected. However, its use has substantial limitations in young children, in patients with renal/hepatic impairment, with widespread psoriasis, those undergoing phototherapy, or those concomitantly treated with calcipotriene/systemic salicylates. In view of these shortcomings, there is a need for well-designed studies on suitable keratolytic alternatives to salicylic acid offering an indisputable positive benefit-risk ratio.
Raychaudhuri, Siba P; Kundu-Raychaudhuri, Smriti; Tamura, Kouichi; Masunaga, Taro; Kubo, Kaori; Hanaoka, Kaori; Jiang, Wen-Yue; Herzenberg, Leonore A; Herzenberg, Leonard A
In psoriasis, CD28/B7 costimulatory molecules are well characterized. Here, using the severe combined immunodeficient (SCID) mouse-psoriasis xenograft model, we report therapeutic efficacy of a humanized anti-CD28 monoclonal antibody (FR255734; Astellas Pharmaceuticals Inc., Tokyo, Japan). Transplanted psoriasis plaques on the SCID mouse were treated weekly for 4 weeks with intraperitoneal injections of FR255734 at 10, 3, and 1-mg kg(-1) doses. Groups treated with doses of 10 and 3 mg kg(-1) had significant thinning of the epidermis and reduced HLA-DR-positive lymphocytic infiltrates. The length of the rete pegs changed from 415.2+/-59.6 to 231.4+/-40.4 microm (P<0.005) in the 10-mg kg(-1) group, and from 323.4+/-69.6 to 237.5+/-73.6 microm in the 3-mg kg(-1) group (P=0.002). Positive controls treated with CTLA4-Ig and cyclosporine had significant histological improvement, whereas plaques treated with saline and isotype controls (human and mouse IgG2) remained unchanged. In vitro studies have shown that FR255734 effectively blocked T-cell proliferation and proinflammatory cytokine production. These observations warrant studies to evaluate the efficacy of FR255734 in human autoimmune diseases.
Johnson-Huang, Leanne M.; Lowes, Michelle A.; Krueger, James G.
Psoriasis vulgaris is a chronic, debilitating skin disease that affects millions of people worldwide. There is no mouse model that accurately reproduces all facets of the disease, but the accessibility of skin tissue from patients has facilitated the elucidation of many pathways involved in the pathogenesis of psoriasis and highlighted the importance of the immune system in the disease. The pathophysiological relevance of these findings has been supported by genetic studies that identified polymorphisms in genes associated with NFκB activation, IL-23 signaling and T helper 17 (Th17)-cell adaptive immune responses, and in genes associated with the epidermal barrier. Recently developed biologic agents that selectively target specific components of the immune system are highly effective for treating psoriasis. In particular, emerging therapeutics are focused on targeting the IL-23–Th17-cell axis, and several agents that block IL-17 signaling have shown promising results in early-phase clinical trials. This review discusses lessons learned about the pathogenesis of psoriasis from mouse-and patient-based studies, emphasizing how the outcomes of clinical trials with T-cell-targeted and cytokine-blocking therapies have clarified our understanding of the disease. PMID:22730473
Farber, E.M.; Abel, E.A.; Cox, A.J.
It has been more than eight years since photochemotherapy with methoxsalen and UV-A (psoralen and UV-A (PUVA)) was introduced for the treatment of psoriasis. This treatment remained under investigation until May 1982 because of concerns about possible chronic toxic effects. With recent Food and Drug Administration approval of PUVA therapy for severe psoriasis, strict drug labeling for administration and patient use and continued monitoring of side effects have become essential. The full effects of PUVA in regard to carcinogenicity, prematurelly induced aging of the skin, pigmentary changes, immunologic alterations, and ocular side effects are still unknown. A review of the risks of PUVA therapy is presented, with the aim of maintaining a proper perspective for its limited use in treating selected patients.
Dalhoff, K; Faerber, P; Arnholdt, H; Sack, K; Strubelt, O
24 days after starting treatment of psoriasis with fumaric acid derivatives (0.8-1.0 g orally, plus unknown quantities locally) a 21-year-old woman developed acute oliguric renal failure with a rise of serum creatinine levels to 1094 mumol/l (12.4 mg/dl). Deterioration of renal function had been preceded by severe abdominal symptoms with nausea, vomiting and colicky pain. On admission to hospital she was dehydrated with hyponatraemia and hypokalaemia. There was glomerular microhaematuria, increased excretion of renal epithelia, and tubular proteinuria. Renal biopsy demonstrated acute tubular damage with vacuolization of proximal epithelia, dilated tubules and scattered necroses. After intermittent haemodialysis (13 courses over two weeks) renal function gradually recovered, as demonstrated at a follow-up examination four months after discharge.
Ansaripour, Amir; Thio, Hok Bing; Maessen, Rob; Redekop, William Ken
To investigate the cost-effectiveness of blue-light therapy versus a two-compound formulation (TCF) (Dovobet(®) gel [calcipotriol and betamethasone]) in mild-to-moderate psoriasis. A Markov model was applied to describe the course of disease among Dutch patients with a Psoriasis Area and Severity Index (PASI) score ≤ 10 over a 52-week time horizon. Patients received either 12-week blue-light therapy or two 4-week treatments with TCF. Patients, experiencing no PASI reduction after either therapy, were assumed to receive 12-week ultraviolet B phototherapy. There was no significant difference in PASI reduction between two interventions (71 vs 72%). However, blue-light therapy was associated with a cost savings of EU€248. Treatment of mild-to-moderate chronic plaque psoriasis using blue-light therapy may be more cost-effective than TCF.
Dogra, Sunil; Kaur, Inderjeet
Psoriasis is a common dermatosis in children with about one third of all patients having onset of disease in the first or second decade of life. A chronic disfiguring skin disease, such as psoriasis, in childhood is likely to have profound emotional and psychological effects, and hence requires special attention. Psoriasis in children has been reported to differ from that among adults being more frequently pruritic; plaque lesions are relatively thinner, softer, and less scaly; face and flexural involvement is common and guttate type is the characteristic presentation. Whether onset in childhood predicts a more severe form of psoriasis is a matter of controversy, it may cause significant morbidity particularly if it keeps relapsing. Most children have mild form of psoriasis which can be generally treated effectively with topical agents such as emollients, coal tar, corticosteroids, dithranol, calcipotriol etc. according to age and the sites affected. Narrow band UVB is the preferred form of phototherapy in children for moderate to severe disease or in patients not responding to topical therapy alone. Systemic therapies are reserved for more severe and extensive cases that cannot be controlled with topical treatment and/or phototherapy such as severe plaque type, unstable forms like erythrodermic and generalized pustular psoriasis and psoriatic arthritis. There are no controlled trials of systemic therapies in this age group, most experience being with retinoids and methotrexate with favorable results. Cyclosporine can be used as a short-term intermittent crisis management drug. There is an early promising experience with the use of biologics (etanercept and infliximab) in childhood psoriasis. Systemic treatments as well as phototherapy have limited use in children due to cumulative dose effects of drugs, low acceptance, and risk of gonadal toxicity. More evidence-based data is needed about the effectiveness and long-term safety of topical, phototherapy and systemic
Nilsen, L. T. N.; Søyland, E.; Krogstad, A. L.
Psoriasis is a chronic inflammatory disease involving about 2-3% of the Norwegian population. Sun exposure has a positive effect on most psoriasis lesions, but ultraviolet (UV) radiation also causes a direct DNA damage in the skin cells and comprises a carcinogenic potential. UV exposure on the skin causes a local as well as a systemic immune suppressive effect, but the relation between sun exposure and these biological effects is not well known. In March 2006 a study was carried out to investigate possible therapeutic outcome mechanisms in 20 psoriasis patients receiving climate therapy at Gran Canaria. This paper presents estimates of their individual skin UV-doses based on UV measurements and the patients' diaries with information on time spent in the sun. On the first day of exposure the patients received on average 5.1 Standard Erythema Doses (SED: median=4.0 SED, range 2.6-10.3 SED) estimated to the skin. During the 15 days study they received 165.8 SED (range 104.3-210.1 SED). The reduction in PASI score was 72.8% on average, but there was no obvious relation between the improvement and the UV dose. The UV doses were higher than those found from climate therapy studies at other locations. It seems beneficial to use more strict exposure schedules that consider the available UV irradiance, depending on time of the day, time of the year and weather conditions.
Lazaroff, I; Shimshoni, R
Stress medicine has shown that emotional disharmony can be a substantial factor for skin diseases. The harmonisation of the emotional status and a corresponding reduction of stress hormones by the Medical Resonance Therapy Music (MRT-Music) as shown in other studies (1,2,3,4) inspired us to investigate its benefits for patients with psoriasis vulgaris and neurodermatitis (neurodermatitis constitutionalis atopica). Over a period of 14 days we measured the parameters of blood pressure, heart rate, stimulus to scratch and the degree of sickness in two, respectively four groups of 68 patients in total: two experimental groups (psoriasis/neurodermatitis) and two control groups. All patients received the normal treatment of our hospital, the experimental groups were additionally treated with 3 x 30 minutes of MRT-Music per day, while the controls were asked to somehow relax during this time. In the experimental groups the measurements showed a reduction of blood pressure and heart rate and revealed an enhanced reduction of the stimulus to scratch and an enhanced reduction in the degree of sickness. Interestingly the effects of MRT-Music were stronger with the psoriasis patients than with the neurodermatitis patients. The results of this pilot study convinced us to offer the treatment with the Medical Resonance Therapy Music to all our patients.
Bakkour, W; Purssell, H; Chinoy, H; Griffiths, C E M; Warren, R B
There is limited evidence as to whether biologic therapy should be stopped or continued in patients with psoriasis and/or psoriatic arthritis (PsA) who are undergoing surgical procedures. Current guidelines of care recommend a planned break from biologic therapy in those undergoing major surgical procedures. To audit current practice of managing biologic therapy peri-operatively in a tertiary referral psoriasis clinic against guidelines of care and to investigate the effects of continuing/stopping biologic therapy in psoriasis and PsA patients. A retrospective audit of psoriasis and PsA patients who had a surgical procedure whilst on biologic therapy. A proforma was used to collect information on the biologics used, whether they were stopped peri-operatively and whether patients developed post-operative complications and/or disease flare. A total of 42 patients who had 77 procedures were identified. Procedures ranged from skin surgery to orthopaedic and cardiothoracic surgery. Biologic therapy was continued in the majority of procedures (76%). There was no significant difference in post-operative risk of infection and delayed wound healing between those patients who continued and those who stopped biologic therapy, including those undergoing major surgery. Interrupting biologic therapy peri-operatively was associated with a significant (P = 0.003) risk of flare of psoriasis or PsA. Continuing biologic therapy in psoriasis and PsA patients peri-operatively did not increase the risk of post-operative complications. Interrupting biologic therapy peri-operatively significantly increased the risk of disease flare. This study is limited by cohort size and requires replication, ideally in a prospective randomized controlled manner. © 2015 European Academy of Dermatology and Venereology.
Ito, Taisuke; Furukawa, Fukumi; Iwatsuki, Keiji; Matsue, Hiroyuki; Shimada, Shinji; Takigawa, Masahiro; Tokura, Yoshiki
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. © 2014 Japanese Dermatological Association.
Au, Shiu-Chung; Madani, Abdulaziz; Alhaddad, Marwan; Alkofide, Maha; Gottlieb, Alice B
The efficacy of biologic treatment for psoriasis has not been compared to that of conventional systemic therapies and phototherapy outside of clinical trial settings. Retrospective, cross-sectional. All patient visits with a code for psoriasis (ICD-9 696.1) in the clinical practice of two dermatologists with a high percentage (over 70% of chief complaints) of psoriasis patients from Jan 1, 2008 to Jan 4, 2012 inclusive were included in this retrospective data analysis. Patients were excluded if the baseline Physician's Global Assessment (PGA) at start of treatment was unknown, or less than 3 (moderate). The practice is a comprehensive psoriasis care center in the Northeastern United States serving a metropolitan population of over 4 million people. Patients were divided by treatment type (biologic, conventional systemic or both) and history of previous treatments. Patients were evaluated by Body Surface Area (BSA), PGA, Simple-Measure for Assessing Psoriasis Activity (S-MAPA, calculated by BSA multiplied by PGA). Patients were evaluated at baseline, 8, 12, 16, and 24 weeks after start of treatment. Patients must have completed at least 8 weeks on a single treatment in order to be included. 46 courses of biologics, 12 courses of conventional systemic therapies, and 18 courses of both together were identified with PGA 3 or greater at baseline. Baseline S-MAPA for biologics was 74, for non-biologic systemics was 62.25. At week 24, S-MAPA improved 70.2% over baseline in patients treated with biologics, patients treated with non-biologic systemics improved by only 40.4% (P<0.05). The average number of prior treatments for patients on biologics was 1.87 versus 1.25 for patients on conventional systemic therapies (P=0.169). Biologics show superior results to conventional systemic therapies (70% improvement versus 40% improvement) for the treatment of patients with moderate to severe psoriasis, as measured by decrease in S-MAPA (PGA multiplied by BSA) at week 24. These
Pelletier, Fabien; Garnache-Ottou, Francine; Biichlé, Sabeha; Vivot, Aurore; Humbert, Philippe; Saas, Philippe; Seillès, Estelle; Aubin, François
Psoriasis involves TNF-α secretion leading to release of microparticles into the bloodstream. We investigated the effect of TNF blockers on microparticles levels before and after treatment in patients (twenty treated by anti-TNF-α agents and 6 by methotrexate) with severe psoriasis. Plasmatic microparticles were labelled using fluorescent monoclonal antibodies and were analysed using cytometry. Three months later, 70% of patients treated with anti-TNF-α agents achieved a reduction in PASI score of at least 75%. The clinical improvement in patients treated with anti-TNF-α agents was associated with a significant reduction of the mean number of platelet microparticles (2837/μl vs 1849/μl, P = 0.02) and of endothelial microparticles (64/μl vs 22/μl, P = 0.001). Microparticles are significantly decreased in psoriatic patients successfully treated by anti-TNF-α. Microparticles levels as circulating endothelial cells represent signs of endothelial dysfunction and are elevated in psoriasis. Then, TNF blockade may be effective to reduce cardiovascular risk through the reduction of circulating microparticles. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Dawn, Aerlyn; Yosipovitch, Gil
Itch is an important, but underestimated symptom in psoriasis. Many therapies are available for pruritus; however, few are effective for psoriatic itch. Antipruritic therapies that are potentially effective in psoriasis include coal tar products, topical corticosteroids, topical salicylates, menthol and pramoxine, capsaicin, phototherapy, vitamin D analogs, topical immunomodulators, methotrexate, oral mirtazapine, and biologics. Using these therapies can benefit psoriasis patients in the outpatient clinical setting.
Yiu, Z Z N; Griffiths, C E M; Warren, R B
The effects of biological therapies for psoriasis on pregnancy outcomes and lactation, and male fertility and mutagenicity are common concerns in the clinical setting. There is relatively little evidence to guide the clinician and patient. Here, we review the safety profile of the commonly used biological therapies for psoriasis in individuals of reproductive potential. Safety data were derived from large-scale registries, adverse event reporting databases, clinical trials and case reports. We assessed the effect of each therapy on adverse pregnancy outcomes including congenital malformations, and lactation with maternal administration, and male fertility and potential mutagenicity with paternal administration. We provide applicable guidance to inform clinician and patient before and after conception.
Osmancevic, Amra; Landin-Wilhelmsen, Kerstin; Larkö, Olle; Mellström, Dan; Wennberg, Ann-Marie; Hulthén, Lena; Krogstad, Anne-Lene
The aims of this study were to examine whether postmenopausal women with psoriasis who were exposed to regular ultraviolet light B (UVB) therapy had greater bone mineral density than women of similar age from the same region, and to estimate the influence of risk factors on bone status. A total of 35 randomly selected women, age (mean +/- SD) 69.3 +/- 6.29 years (age range 60-82 years), with active psoriasis, mean onset at 37.0 years (+/- 23.5 SD) were studied. The patients had been previously exposed to broadband or narrowband UVB. Age-matched, women (n = 2448) from Göteborg, examined at the Geriatric out-patient clinic during the years 2001 and 2002, were used as controls. Bone mineral density was examined by Dual-Energy X-ray Absorptiometry (Hologic Delphi A) at the hip and the lumbar spine. Medical history and lifestyle factors were assessed with a questionnaire. Postmenopausal women with psoriasis were found to have higher bone mineral density than age-matched controls. Higher body weight, physical activity and UVB exposure could explain this finding.
Bardazzi, F; Balestri, R; Baldi, E; Antonucci, A; De Tommaso, S; Patrizi, A
Obesity is common in psoriatic patients, and it has been shown to be important for many aspects of the condition. In particular, low-calorie diets can improve the symptoms and response to treatment in pustular psoriasis. The present study investigates the influence of body-weight alteration on the disease's clinical manifestations in moderate to severe psoriasis patients treated with biological drugs. Finally, the influence of a caloric restriction was assessed. This observational transversal study enrolled 33 patients attending our Severe Psoriasis Outpatient Clinic, who were treated with biological drugs. Body Mass Index (BMI) was used as a diagnostic indicator of being overweight and of obesity. Waist circumference was also measured. Body weight and Psoriasis Area Severity Index (PASI) index were measured at follow-up visits at 4 and 8 months. Nonparametric test of Mann-Whitney was used to detect the differences between patient groups. Fisher's exact test was performed to evaluate the different results depending on the therapeutic changes of BMI. There was a strong prevalence of overweight-obese individuals in the group with a mean BMI of 30.59 +/- 6.94. Waist circumference was also above normal in the majority of the patients. Obese patients had a PASI index higher than the average of the whole group (25.03 +/- 12.43), with grade III obese patients having an average PASI of 44 +/- 3.37. At the first and second follow-ups, patients who put on weight did not achieve PASI 50; patients who had a stable weight presented variable response to treatment, while patients who decreased their weight achieved PASI 90 or PASI 75 even when not responding at the first. Further studies are needed to understand if the poor response observed in heavier patients is due to biological drugs pharmacokinetics or because therapy should be BMI based rather than administered in fixed doses, posing then an ethical consideration.
Aira, Lazaro E; López-Requena, Alejandro; Fuentes, Dasha; Sánchez, Liset; Pérez, Teresita; Urquiza, Aleida; Bautista, Heber; Falcón, Leopoldina; Hernández, Patricia; Mazorra, Zaima
Psoriasis is a chronic inflammatory disease with a prevalence of approximately 2–3% in the general population. The majority of diagnosed patients have plaque psoriasis, and about 20% have moderate-to-severe disease. Itolizumab, a new monoclonal antibody specific for the CD6 molecule mainly expressed on T lymphocytes, has demonstrated to inhibit in vitro ligand-induced proliferation and pro-inflammatory cytokine production. We assessed the immunological and histopathological effect of the antibody using clinical samples taken from 26 patients with moderate-to-severe psoriasis included in a clinical trial. The precursor frequency of lymphocytes activated with anti-CD2/CD3/CD28 beads, as well as the number of interferon (IFN)-γ-secreting T cells after stimulation, were measured at different time points of the study. Serum cytokine levels and anti-idiotypic antibody response to itolizumab were also evaluated. Additionally, lymphocyte infiltration and epidermis hyperplasia were studied in five patients. A significant reduction in T cell proliferation capacity and number of IFN-γ-producing T cells was found in treated patients. Serum levels of interleukin-6, tumor necrosis factor and IFN-γ showed an overall trend toward reduction. No anti-idiotypic antibody response was detected. A significant reduction in the epidermis hyperplasia was observed in analyzed patients. These results support the relevance of the CD6 molecule as a therapeutic target for the treatment of this disease. PMID:24594862
Aira, Lazaro E; López-Requena, Alejandro; Fuentes, Dasha; Sánchez, Liset; Pérez, Teresita; Urquiza, Aleida; Bautista, Heber; Falcón, Leopoldina; Hernández, Patricia; Mazorra, Zaima
Psoriasis is a chronic inflammatory disease with a prevalence of approximately 2-3% in the general population. The majority of diagnosed patients have plaque psoriasis, and about 20% have moderate-to-severe disease. Itolizumab, a new monoclonal antibody specific for the CD6 molecule mainly expressed on T lymphocytes, has demonstrated to inhibit in vitro ligand-induced proliferation and pro-inflammatory cytokine production. We assessed the immunological and histopathological effect of the antibody using clinical samples taken from 26 patients with moderate-to-severe psoriasis included in a clinical trial. The precursor frequency of lymphocytes activated with anti-CD2/CD3/CD28 beads, as well as the number of interferon (IFN)-γ-secreting T cells after stimulation, were measured at different time points of the study. Serum cytokine levels and anti-idiotypic antibody response to itolizumab were also evaluated. Additionally, lymphocyte infiltration and epidermis hyperplasia were studied in five patients. A significant reduction in T cell proliferation capacity and number of IFN-γ-producing T cells was found in treated patients. Serum levels of interleukin-6, tumor necrosis factor and IFN-γ showed an overall trend toward reduction. No anti-idiotypic antibody response was detected. A significant reduction in the epidermis hyperplasia was observed in analyzed patients. These results support the relevance of the CD6 molecule as a therapeutic target for the treatment of this disease.
Psoriasis is an immune-mediated highly heterogeneous skin disease in which genetic as well as environmental factors play important roles. In spite of the local manifestations of the disease, psoriasis may progress to affect organs deeper than the skin. These effects are documented by epidemiological studies, but they are not yet mechanistically understood. In order to provide insight into the systemic effects of psoriasis, we performed a nontargeted high-resolution LC–MS metabolomics analysis to measure plasma metabolites from individuals with mild or severe psoriasis as well as healthy controls. Additionally, the effects of the anti-TNFα drug Etanercept on metabolic profiles were investigated in patients with severe psoriasis. Our analyses identified significant psoriasis-associated perturbations in three metabolic pathways: (1) arginine and proline, (2) glycine, serine and threonine, and (3) alanine, aspartate, and glutamate. Etanercept treatment reversed the majority of psoriasis-associated trends in circulating metabolites, shifting the metabolic phenotypes of severe psoriasis toward that of healthy controls. Circulating metabolite levels pre- and post-Etanercept treatment correlated with psoriasis area and severity index (PASI) clinical scoring (R2 = 0.80; p < 0.0001). Although the responsible mechanism(s) are unclear, these results suggest that psoriasis severity-associated metabolic perturbations may stem from increased demand for collagen synthesis and keratinocyte hyperproliferation or potentially the incidence of cachexia. Data suggest that levels of circulating amino acids are useful for monitoring both the severity of disease as well as therapeutic response to anti-TNFα treatment. PMID:25361234
Piérard-Franchimont, C; Henry, F; Szepetiuk, G; Piérard, G E
Psoriasis is primarily a chronic inflammatory skin disease burdened by some comorbidities including psoriatic alopecia, arthropathies, Crohn's disease, the metabolic syndrome and some cardiovascular involvement. During the past years, several biologicals corresponding to monoclonal antibodies were offered to treat psoriasis refractory to other potent conventional treatments. We review the effects of biologicals, in particular adalimumab (Humira), on psoriatic comorbidities.
Gojani, Parvin Jamali; Masjedi, Mohsen; Khaleghipour, Shahnaz; Behzadi, Ehsan
Background: This study aimed to compare the effects of the schema along with mindfulness-based therapies in the psoriasis patients. Materials and Methods: This semi-experimental study with post- and pre-tests was conducted on the psoriasis patients in the Dermatology Clinic of the Isfahan Alzahra Hospital, Iran using the convenience sampling in 2014. The patients had a low general health score. The experimental groups included two treatment groups of schema-based (n = 8) and mindfulness (n = 8). Both groups received eight 90-min sessions therapy once a week; they were compared with 8 patients in the control group. To evaluate the psoriasis patients’ maladaptive schema, Young schema questionnaire was used. Data were analyzed through the covariance analysis test. Results: There was a significant difference between the schema-based therapy and mindfulness groups with the control group. There was also a significant difference between the schema-based therapy groups consisting of the defeated schema, dependence/incompetence schema, devotion schema, stubbornly criteria schema, merit schema, restraint/inadequate self-discipline schema, and the control group. Moreover, a significant difference existed between the maladaptive schema of mindfulness therapy group and the controls. There was a significant difference concerning the improvement of the psychopathologic symptoms between the mindfulness therapy group and the control group. Conclusions: This study showed similar effects of both the schema and mindfulness-based therapies on the maladaptive schemas in improving the psoriasis patients with the psychopathologic symptoms. PMID:28217649
Afshar, M.; Martinez, A.D.; Gallo, R.L.; Hata, T.R.
Background Interferon-alpha (IFN-α) therapy is used to treat hepatitis C infection. The exacerbation and occurrence of psoriasis in hepatitis C patients treated with IFN-α is increasingly recognized, but the distinct associated features, etiology, and management have not been reviewed. Objective To review all published cases of hepatitis C patients who developed psoriasis while receiving IFN-α therapy. Methods The review was conducted by searching the PubMed database using the keywords “hepatitis C” AND “psoriasis.” In addition, references to additional publications not indexed for PubMed were followed to obtain a complete record of published data. Results We identified 32 publications describing 36 subjects who developed a psoriatic eruption while receiving IFN-α therapy for hepatitis C. Topical therapies were a commonly employed treatment modality but led to resolution in only 30% of cases in which they were employed solely. Cessation of IFN-α therapy led to resolution in 93% of cases. 100% of those who developed psoriasis while on IFN-α therapy responded to systemic therapy and were able to continue the drug. Conclusion Further studies and analysis of IFN-α-induced lesions are necessary to clarify the role of IFN-α and the hepatitis C virus in the development of psoriatic lesions. PMID:22671985
Gojani, Parvin Jamali; Masjedi, Mohsen; Khaleghipour, Shahnaz; Behzadi, Ehsan
This study aimed to compare the effects of the schema along with mindfulness-based therapies in the psoriasis patients. This semi-experimental study with post- and pre-tests was conducted on the psoriasis patients in the Dermatology Clinic of the Isfahan Alzahra Hospital, Iran using the convenience sampling in 2014. The patients had a low general health score. The experimental groups included two treatment groups of schema-based (n = 8) and mindfulness (n = 8). Both groups received eight 90-min sessions therapy once a week; they were compared with 8 patients in the control group. To evaluate the psoriasis patients' maladaptive schema, Young schema questionnaire was used. Data were analyzed through the covariance analysis test. There was a significant difference between the schema-based therapy and mindfulness groups with the control group. There was also a significant difference between the schema-based therapy groups consisting of the defeated schema, dependence/incompetence schema, devotion schema, stubbornly criteria schema, merit schema, restraint/inadequate self-discipline schema, and the control group. Moreover, a significant difference existed between the maladaptive schema of mindfulness therapy group and the controls. There was a significant difference concerning the improvement of the psychopathologic symptoms between the mindfulness therapy group and the control group. This study showed similar effects of both the schema and mindfulness-based therapies on the maladaptive schemas in improving the psoriasis patients with the psychopathologic symptoms.
Tacastacas, Joselin D; Oyetakin-White, Patricia; Soler, David C; Young, Andrew; Groft, Sarah; Honda, Kord; Cooper, Kevin D; McCormick, Thomas S
Psoriasis continues to be a debilitating skin disease affecting 1-3% of the United States population. Although the effectiveness of several current biologic therapies have described this pathology as a IL-23, TNF-a and Th17-mediated disease, less invasive approaches are still in use and in need of refinement. One of these is the usage of narrow band-UVB (NB-UVB) therapy to deplete specifically intra-epidermal CD3+, CD4+ and CD8+ cells to clear psoriatic plaques. In order to improve NB-UVB therapy, we sought to determine whether skin pre-treatment with the TLR7 agonist imiquimod (IMQ) would help increase the efficiency of the former at resolving psoriatic plaques. Eucerin(®) Original Moisturizing Lotion (topical vehicle) or Aldara(®) (imiquimod 5% topical cream) were applied for 5 days once daily to a maximum contiguous area of 25 cm(2) (5 cm × 5 cm area). Patients were provided with sachets containing 12.5 mg of imiquimod each and were instructed to apply imiquimod (I) to two psoriasis plaques (5 sachets of imiquimod allotted to each plaque). A PHAROS excimer Laser EX-308 (Ra Medical Systems, Inc. Carlsbad, CA, USA) with an output of monochromatic 308-nm light and pulse width of 20-50 ns was used for all patients. Punch biopsies of psoriatic lesions (6 mm) were taken at 4 and 48 h after final application of topical treatment with or without excimer laser treatment. Real-time quantitative RT-PCR was performed according to manufacturer's instructions and Inmunohistochemistry was used as described before. Our results suggests that although IMQ seemed to activate the type I interferon pathway as previously described, its concomitant usage with NB-UVB for clearing psoriatic skin was ineffective. Although upregulation of genes MxA, GRAMD1A and DMXL2 suggested that IMQ treatment did induce skin changes in psoriasis patients, more optimal dosing of IMQ and NB-UVB might be necessary to achieve desired treatment responses. The observation that psoriasis involvement was
Steinke, Sabine I. B.; Peitsch, Wiebke K.; Ludwig, Alexander; Goebeler, Matthias
Treatment modalities of chronic plaque psoriasis have dramatically changed over the past ten years with a still continuing shift from inpatient to outpatient treatment. This development is mainly caused by outpatient availability of highly efficient and relatively well-tolerated systemic treatments, in particular BioLogicals. In addition, inpatient treatment is time- and cost-intense, conflicting with the actual burst of health expenses and with patient preferences. Nevertheless, inpatient treatment with dithranol and UV light still is a major mainstay of psoriasis treatment in Germany. The current study aims at comparing the total costs of inpatient treatment and outpatient follow-up to mere outpatient therapy with different modalities (topical treatment, phototherapy, classic systemic therapy or BioLogicals) over a period of 12 months. To this end, a retrospective cost-of-illness study was conducted on 120 patients treated at the University Medical Centre Mannheim between 2005 and 2006. Inpatient therapy caused significantly higher direct medical, indirect and total annual costs than outpatient treatment (13,042 € versus 2,984 €). Its strong influence on cost levels was confirmed by regression analysis, with total costs rising by 104.3% in case of inpatient treatment. Patients receiving BioLogicals produced the overall highest costs, whereas outpatient treatment with classic systemic antipsoriatic medications was less cost-intense than other alternatives. PMID:24194911
Costantino, M; Filippelli, A
The plaque psoriasis, one of the most common form of psoriasis, is a chronic inflammatory disease. This pathology can cause devastating effects on quality of life and social relations with significant physical and psychological distress. Currently among the therapeutic agents available for the treatment of psoriasis is including SPA therapy, whose mechanism of action is only partially known, as well as very few studies examined the impact of this therapy on the quality of life. On the basis of these considerations, the research analyzed the effectiveness of SPA bath therapy (BLT) and its impact on quality of life and psychological distress in patients suffering from chronic plaque psoriasis. The study was conducted on 35 patients with chronic plaque psoriasis: 23% male and 77% female; mean age:56 ± 19 years; age range:17-85 years. The subjects were treated, for 2 weeks, with sulphureous SPA bath therapy from Terme of Telese SpA (Benevento-Italy). At the beginning and at the end of the SPA treatment considered was evaluated: the itching symptom (using NRS scale); the PASI Index; the impact on quality of life (using SF-36 and DLQI questionnaires) and on psychological distress (using ZUNG -tests). At the end of the SPA treatment, the mean values ± SD, compared to baseline, have showed a significant (p <0.01) reduction in itching symptom (1.8 ± 1.1-->1.0 ± 1.0) and PASI score (4 ± 4-->1.7 ± 2) with an improvement in quality of life and psichological distress as demonstrated by SF-36, DLQI and ZUNG tests. The data of this research show that the sulphureous SPA bath therapy can be considered very useful in patients with mild-to-moderate psoriasis for the improving of the quality of life and social relationship.
Maki, Nobuki; Demitsu, Toshio; Umemoto, Naoka; Nagashima, Kazutaka; Nakamura, Toshinobu; Kakurai, Maki; Nakamura, Satoshi; Yamada, Tomoko; Ishii, Norito; Hashimoto, Takashi
A 61-year-old Japanese man developed bullous skin lesions during topical therapy for psoriasis vulgaris. Physical examination demonstrated numerous tense bullae and scaly erythemas on the trunk and extremities. Histopathology of the skin biopsy demonstrated subepidermal bullae and lymphocytic infiltration with eosinophils in the dermis. Direct immunofluorescence revealed linear deposits of immunoglobulin (Ig)G, IgA and C3 along the basement membrane zone. Indirect immunofluorescence of 1 mol/L NaCl-split skin showed IgG reactivity with both epidermal and the dermal sides. IgM reactivity with both the epidermal and dermal sides was also detected. Enzyme-linked immunosorbent assays showed negative results for both BP180 and BP230. Immunoelectrophoresis of serum and bone marrow aspiration revealed underlying primary macroglobulinemia with M-proteinemia of IgM-κ type. Immunoblot analysis revealed IgG, but not IgM, antibodies to recombinant protein of BP180 C-terminal domain. We diagnosed the present case as bullous pemphigoid with IgG anti-BP180 C-terminal domain autoantibodies associated with primary macroglobulinemia and psoriasis vulgaris. Systemic administration of prednisolone 30 mg/day resulted in dramatic improvement of both bullous and psoriatic skin lesions. When the bullous and psoriatic lesions relapsed, DRC chemotherapy (dexamethasone, rituximab and cyclophosphamide) for macroglobulinemia was performed. Then, the psoriatic lesions improved and the bullous lesions disappeared. We suggested that the present case may be paraneoplastic syndrome of bullous pemphigoid associated with primary macroglobulinemia and psoriasis vulgaris.
Wang, Xiuxiu; Wang, Guanghua; Gong, Yu; Liu, Yeqiang; Gu, Junying; Chen, Wenjuan; Shi, Yuling
Narrow-band UVB (NB-UVB) therapy is widely used in the treatment of psoriasis; however, its precise mechanism is still unclear. To investigate the circulating CD4(+) T-lymphocyte subpopulations in psoriasis patients before and after NB-UVB, thus providing new insights into the mechanism of NB-UVB in the treatment of psoriasis. We performed NB-UVB treatments for psoriasis patients (n = 30) and used flow cytometry, real-time PCR, and ELISA for the detection of circulating CD4(+) T-lymphocyte subpopulations. The results were compared with healthy controls (n = 20) as well. We found increased circulating T helper 1 (Th1) and Th17 cell levels as well as decreased circulating regulatory T cells (Treg) levels compared to healthy controls. Additionally, there was a positive correlation between the percentage of circulating Th17 cells and Psoriasis Area and Severity Index (PASI) score. Furthermore, the percentage of circulating Th17 cells was negatively correlated with the Treg cells which led to an imbalance of Th17/Treg. NB-UVB therapy significantly reduced circulating Th1and Th17 cell levels while increasing Treg cell levels. These findings indicate that the overexpression of Th1 and Th17 cells together with the imbalance of Th17/Treg cells may play an important role in the pathogenesis of psoriasis. The mechanism of NB-UVB in the treatment of psoriasis may be through the inhibition of Th1 and Th17 cell immune response as well as the promotion of Treg cell immune response, thus ameliorating the disorder of circulating CD4(+) T-lymphocyte subsets.
Adelzadeh, L; Jourabchi, N; Wu, J J
Recent advances in biological therapies have proved highly effective in treating psoriasis and other inflammatory conditions, including psoriatic arthritis, rheumatoid arthritis, inflammatory bowel disease and ankylosing spondylitis. However, adverse effects related to their immunosuppression have been observed, including an increased propensity to viral infections. This review evaluates the evidence of herpes zoster (HZ) risk from biologics based on clinical reports, cohort studies and randomized controlled studies. The risk of HZ associated with these agents remains controversial, especially when comparing their risk with non-biological therapy used to treat the same inflammatory conditions. This review specifically assesses the risk of the TNF inhibitors etanercept, adalimumab and infliximab, as well as interleukin-12/23 inhibitor ustekinumab. We found multiple cohort studies, randomized controlled trials and case reports that suggest infliximab increases risk of HZ, whereas adalimumab, etanercept and ustekinumab HZ risk remain controversial. Nevertheless, HZ vaccination should be considered prior to initiation of biological therapy, particularly infliximab.
de la Brassinne, M; Nikkels, Af
The treatment of psoriasis is mainly based on anti-inflammatory and/or anti-hyperproliferative agents. The topical steroids appeared in the fifties and were the first therapeutic breakthrough for psoriasis, followed by methotrexate and phototherapy in the sixties, photochemotherapy (PUVA) in the seventies and acitretin and cyclosporine in the eighties. The targeted biologic therapies represent a whole new era of therapeutic possibilities with a highly beneficial safety record. The choice of treatment depends on a large series of factors, including the type and extend of the psoriasis, the patient's preferences, co-medications, comorbidities and drug tolerance. This overview presents the currently available topical and systemic agents for treating psoriasis, including topical corticosteroids, vitamin D derivatives, UV-light based therapies, methotrexate, cyclosporine, acitretin, and the biologic agents such as the TNF antagonists etanercept, adalimumab and infliximab, as well as the anti-p40 IL12/23 agent ustekinumab. Newer, very promising, agents aiming the Th17 pathway are under development for psoriasis.
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van Bezooijen, Ji Sun; Balak, Deepak M.W.; van Doorn, Martijn B.A.; Looman, Caspar W.N.; Schreurs, Marco W.J.; Koch, Birgit C.P.; van Gelder, Teun; Prens, Errol P.
Background Biologics are a safe and efficacious therapy for psoriasis. The drug survival of biologics may be disappointing, primarily due to loss of efficacy. Therefore, safe combination treatments are sought to improve their clinical response. Objective To assess the efficacy, safety and tolerability of the combination therapy of etanercept with fumarates versus etanercept monotherapy. Methods Thirty-three patients with psoriasis were randomized 1:1 to receive etanercept combined with fumarates or etanercept monotherapy. The primary outcome measure was the difference in PASI-75 response after 24 weeks; additionally, a longitudinal analysis was performed. An important secondary outcome measure was the proportion of patients with a Physician Global Assessment (PGA) of clear or almost clear. Adverse events were collected throughout the study. Results In the combination therapy group, 78% (14 out of 18 patients) reached PASI-75 at week 24 versus 57% (8 out of 14 patients) in the monotherapy group (p = 0.27). The longitudinal analysis showed a PASI reduction of 5.97% per week for the combination therapy group and of 4.76% for the monotherapy group (p = 0.11). In the combination therapy group, 94% (17 out of 18 patients) of patients had a PGA of clear/almost clear versus 64% (9 out of 14 patients) in the monotherapy group (p = 0.064). The incidence of mild gastrointestinal complaints was higher in the combination group than in the monotherapy group. Conclusion Using the PGA, combination therapy showed a trend towards faster improvement in the first 24 weeks. The difference in the PASI score between the two groups was not statistically significant. Addition of fumarates to etanercept for 48 weeks appeared safe with an acceptable tolerability. PMID:27576483
Shmidt, Eugenia; Wetter, David A; Ferguson, Sara B; Pittelkow, Mark R
Tumor necrosis factor (TNF)-α antagonists have been associated with the induction of de novo or worsening psoriasis. We sought to retrospectively examine the clinical characteristics and outcomes of patients with psoriasis associated with anti-TNF-α therapy. We performed a retrospective review of patients with new-onset or worsening psoriasis during TNF-α inhibitor therapy between 1998 and 2010. Of the 56 patients (mean age at psoriasis onset, 48.1 years), 41 (73%) were female. In all, 22 patients (39%) had Crohn's disease and 14 (25%) had rheumatoid arthritis. Thirty patients (54%) were treated with infliximab, 19 (34%) with adalimumab, and 7 (12%) with etanercept. New-onset or worsening psoriasis occurred after a mean treatment duration of 17.1 months. Plaque psoriasis (n = 27), palmoplantar pustulosis (n = 25), scalp psoriasis (n = 12), generalized pustular psoriasis (n = 7), erythrodermic psoriasis (n = 2), and inverse psoriasis (n = 2) were the cutaneous presentations. Among the 39 patients for whom full treatment response data were available, 33 (85%) had a complete or partial response; combined response rates (complete and partial) were slightly higher among those who discontinued anti-TNF-α therapy (16 of 17 patients [94%]) than among those who continued anti-TNF-α therapy (17 of 22 patients [77%]). Retrospective nature, possible referral bias, and lack of complete follow-up for some patients are limitations. Although some patients sufficiently controlled their psoriasis while continuing anti-TNF-α therapy, those who discontinued therapy achieved higher rates of complete response. Further studies should explore the efficacy and safety of switching to an alternative anti-TNF-α agent. Copyright © 2011 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.
Castaldo, Giuseppe; Galdo, Giovanna; Rotondi Aufiero, Felice; Cereda, Emanuele
Psoriasis is a chronic disease associated with overweight/obesity and related cardiometabolic complications. The link between these diseases is likely the inflammatory background associated with adipose tissue, particularly the visceral one. Accordingly, previous studies have demonstrated that in the long-term weight loss may improve the response to systemic therapies. We report a case report of a woman in her 40s suffering from relapsing moderate-to-severe plaque psoriasis and obesity-related metabolic syndrome, in whom adequate response to ongoing treatment with biological therapy (adalimumab) was restored after only 4 weeks of very low-calorie, carbohydrate-free (ketogenic), protein-based diet. Accordingly, through rapid and consistent weight loss, very low calorie ketogenic diet may allow restoring a quick response to systemic therapy in a patient suffering from relapsing psoriasis. This intervention should be considered in overweight/obese patients before the rearrangement of systemic therapy. Nonetheless, studies are required to evaluate whether very low calorie ketogenic diets should be preferred to common low-calorie diets to improve the response to systemic therapy at least in patients with moderate-to-severe psoriasis. Copyright © 2015 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.
Tan, Wang Sin Gina; Kelly, Stephen; Pitzalis, Costantino
Biologic therapy has revolutionized treatment pathways in psoriatic joint and skin disease. It has also provided a useful tool with which pathological pathways of this condition may be explored. Areas covered: This review presents data on the clinical and biological effects of targeted therapy in psoriatic arthritis and psoriasis. Therapeutic agents covered include inhibitors of TNFα, inhibitors of the IL-23/IL-17 axis and inhibitors of intracellular small molecules involved in the transduction of the inflammatory signal. Trial data on clinical and imaging efficacy is reviewed in parallel with studies on biological effects at tissue level. Pathological insights gained from the use of these treatments are explored. Expert commentary: A close relationship exists between specific pathological types and clinical manifestations of psoriatic disease, including responses to treatment. Studying these relationships is likely to improve understanding of disease and enable rational selection of specific treatments for patients with specific pathotypes.
Menon, Roshni; David, Brinda G
Management of psoriasis is a challenge to the treating physician. The chronic inflammatory state of psoriasis with exacerbations and remissions necessitate “on-and-off” treatment schedules. The safety profiles of drugs and tolerability issues for patients are important factors to be considered during treatment. Various biological agents targeting T-cells and the inflammatory cytokines are available for systemic treatment of psoriasis. However, major causes of concern while using these drugs are risk of susceptibility to infection and development of anti-drug antibodies, which will affect the pharmacokinetic properties, efficacy, and safety profile of the drug. Itolizumab, a humanized anti-CD6 monoclonal antibody, is a new molecule that acts by immunomodulating the CD6 molecule. CD6 is a co-stimulatory molecule required for optimal T-cell stimulation by the antigen-presenting cells. This step is crucial in T-cell proliferation to form Th1 and Th17 cells, which play a major role in the pathogenesis of psoriasis. This article deals with the properties of Itolizumab and its role in the treatment of psoriasis. Based on the available published data, Itolizumab seems to have a better adverse effects profile and at the same time comparatively less efficacy when compared to other biological agents available for treating psoriasis. Larger studies with longer duration are required to clearly depict the long-term side effects profile. PMID:25945063
Ayroldi, Emira; Bastianelli, Alessandra; Cannarile, Lorenza; Petrillo, Maria Grazia; Delfino, Domenico V; Fierabracci, Alessandra
Psoriasis is a chronic inflammatory disease with a complex pathophysiology and a multigenic background. Autoimmunity and genetic hallmarks couple to confer the disease, which is characterized by chronic plaques (85-90% of all cases) and/or psoriasis arthritis (PsA), and involve the peripheral and sacro-iliac joints, nails, and skeleton. Dissecting the ethiopathogenetic mechanisms of psoriasis and PsA is a major basic research challenge. One important question is whether a single inflammatory mediator can be responsible for the interactive network that forms between immune cells and cytokines in this disease. Despite much progress, no research has yet been able to define a single model to explain the multifaceted pathogenesis of psoriasis and PsA. It is known that both the innate and adaptive immune systems are involved, antigen presenting cells and T lymphocytes play a prominent role, and that the deregulation of the T helper (Th)- 1/Th-2/Th-17/Th-23 axis is directly implicated in disease pathogenesis. Pharmacological therapy for psoriasis has evolved with the development of human knowledge of the disease pathophysiology. Thus, the first "ethiopathogenetic" drugs (e.g., methotrexate, cyclosporin, and alefacept) inhibited T-cell activation directly or targeted co-accessory molecules implicated in T-cell activation. When the mechanism underlying psoriatic inflammation was accepted as a cytokine network disorder, more specific biologics were studied in murine models and were later used clinically. Tumor necrosis factor was the first successful target of cytokine inhibition therapy for psoriasis and PsA (e.g., infliximab, adalimumab, and etanercept). With the recently discovered role for Th-17 in autoimmunity, drugs targeting interleukin-23 (ustekinumab) have become accepted for the pharmacological treatment of psoriasis. The expansion of pharmacological treatment options for psoriasis is not complete. As the knowledge of pathogenetic mechanisms increases, it may be
Rosenberg, Alexander; Fan, Hongtao; Chiu, Yahui G; Bolce, Rebecca; Tabechian, Darren; Barrett, Rick; Moorehead, Sharon; Baribaud, Frédéric; Liu, Hao; Peffer, Nancy; Shealy, David; Schwarz, Edward M; Ritchlin, Christopher T
The immune inflammatory disorders rheumatoid arthritis (RA), psoriatic arthritis (PsA) and psoriasis (Ps) share common pathologic features and show responsiveness to anti-tumor necrosis factor (TNF) agents yet they are phenotypically distinct. The aim of this study was to examine if anti-TNF therapy is associated with divergent gene expression profiles in circulating cells and target tissues of patients with these diseases. Peripheral blood CD14+ and CD14- cells were isolated from 9 RA, 12 PsA and 10 Ps patients before and after infliximab (IFX) treatment. Paired synovial (n=3, RA, PsA) and skin biopsies (n=5, Ps) were also collected. Gene expression was analyzed by microarrays. 26 out of 31 subjects responded to IFX. The transcriptional response of CD14+ cells to IFX was unique for the three diseases, with little overlap (<25%) in significantly changed gene lists (with PsA having the largest number of changed genes). In Ps, altered gene expression was more pronounced in lesional skin (relative to paired, healthy skin) compared to blood (relative to healthy controls). Marked suppression of up-regulated genes in affected skin was noted 2 weeks after therapy but the expression patterns differed from uninvolved skin. Divergent patterns of expression were noted between the blood cells and skin or synovial tissues in individual patients. Functions that promote cell differentiation, proliferation and apoptosis in all three diseases were enriched. RA was enriched in functions in CD14- cells, PsA in CD14+ cells and Ps in both CD14+ and CD14- cells, however, the specific functions showed little overlap in the 3 disorders. Divergent patterns of altered gene expression are observed in RA, PsA and Ps patients in blood cells and target organs in IFX responders. Differential gene expression profiles in the blood do not correlate with those in target organs.
Lee, Young-Sun; Jun, Hee-Sook
Glucagon-like peptide-1 (GLP-1) is an incretin hormone mainly secreted from intestinal L cells in response to nutrient ingestion. GLP-1 has beneficial effects for glucose homeostasis by stimulating insulin secretion from pancreatic beta-cells, delaying gastric emptying, decreasing plasma glucagon, reducing food intake, and stimulating glucose disposal. Therefore, GLP-1-based therapies such as GLP-1 receptor agonists and inhibitors of dipeptidyl peptidase-4, which is a GLP-1 inactivating enzyme, have been developed for treatment of type 2 diabetes. In addition to glucose-lowering effects, emerging data suggests that GLP-1-based therapies also show anti-inflammatory effects in chronic inflammatory diseases including type 1 and 2 diabetes, atherosclerosis, neurodegenerative disorders, nonalcoholic steatohepatitis, diabetic nephropathy, asthma, and psoriasis. This review outlines the anti-inflammatory actions of GLP-1-based therapies on diseases associated with chronic inflammation in vivo and in vitro, and their molecular mechanisms of anti-inflammatory action. PMID:27110066
Gupta, Ruchi; Gupta, Madhu; Mangal, Sharad; Agrawal, Udita; Vyas, Suresh Prasad
The aim of the current investigation is to evaluate the potential of capsaicin (CAP)-containing liposomes, niosomes and emulsomes in providing localized and controlled delivery, to improve the topical delivery of drug. CAP-bearing systems were prepared by the film hydration method and compared through various in vitro and in vivo parameters. The TEM photographs suggested that the carrier systems were spherical in shape and nanometric in size range. Skin retention studies of CAP from in vitro and in vivo experiments revealed significantly higher accumulation of drug in the case of the emul-gel formulation. Based on the results, we concluded that the emul-gel may be a potential approach for the topical delivery of CAP, for an effective therapy for psoriasis.
Chandran, Vinod; Maharaj, Ajesh B
The management of psoriatic arthritis (PsA) and psoriasis has undergone major advancements over the last decade. This has been made possible, in part, due to the introduction of new therapies for their management, as well as global collaboration in the development of outcome measures and "treat- to- target" paradigms. In this review article, we discuss how disease activity is measured and the outcome measures that have been recently developed for the management of PsA. The importance of assessing the individual domains as well as global assessments both from the physician and patient perspective, and the development of composite measures are discussed. The newer PsA specific measures are expected to be more commonly used in clinical trials as well as clinical practice.
Gönül, Müzeyyen; Gönül, Engin
A 45-year-old man who had psoriasis had applied topical clobetasol 17 propionate ointment on his whole body 2-3 times a week after the bath for 20 years. Physical examination showed abdominal distension, atrophy all over the skin, psoriatic plaques on the trunk, and extremities and multiple striae on the shoulders and legs. Morning plasma cortisol level and ACTH stimulation test confirmed the diagnosis of hypothalamic insufficiency. Bone mineral densitometry showed severe osteoporosis. Multiple bone fractures in the vertebrae and costa were detected on lumbar magnetic resonance imaging, the (99)Tc MDP whole-body bone scan, and thoracoabdominal computerized tomography imaging. Topical corticosteroid therapies have possible local and/or systemic side effects such as atrophy, telangiectasia, hypertricosis, and suppression of pituitary-adrenal axis. We present an interesting case with multiple bone fractures caused by long-time topical corticosteroid use.
Furue, Masutaka; Kadono, Takafumi
Psoriasis is a chronic inflammatory skin disease characterized by a significant deterioration in the quality of life of affected individuals. Notably, psoriasis is significantly associated with cardiovascular and metabolic syndrome and other autoimmune disorders. Recent progress in biologic therapies has revealed the fundamental role of tumor necrosis factor-α, interleukin (IL)-23 and the IL-17A axis together with aberrant overproduction of epidermal IL-36γ in the pathogenesis of psoriasis. This review provides an update on the clinical, pathological and therapeutic advancements involving psoriasis.
Weidemann, Anja K; Crawshaw, Ania A; Byrne, Emily; Young, Helen S
Psoriasis is a common inflammatory autoimmune condition in which environmental factors and genetic predisposition contribute to the development of disease in susceptible individuals. Angiogenesis is known to be a key pathogenic feature of psoriasis. Local and systemic elevation of vascular endothelial growth factor (VEGF)-A has been demonstrated in the skin and plasma of patients with psoriasis and is known to correlate with improvement following some traditional psoriasis treatments. A number of VEGF inhibitors are licensed for the treatment of malignancies and eye disease and isolated case reports suggest that some individuals with psoriasis may improve when exposed to these agents. The small number of cases and lack of unified reporting measures makes it difficult to draw generalizations and underline the heterogeneity of psoriasis as a disease entity. Though not yet licensed for the treatment of psoriasis in humans, experimental data supports the potential of VEGF inhibitors to influence relevant aspects of human cell biology (such as endothelial cell differentiation) and to improve animal models of skin disease. Given the multi-factorial nature of psoriasis it is unlikely that VEGF inhibitors will be effective in all patients, however they have the potential to be a valuable addition to the therapeutic arsenal in selected cases. Current VEGF inhibitors in clinical use are associated with a number of potentially serious side effects including hypertension, left ventricular dysfunction, and gastrointestinal perforation. Such risks require careful consideration in psoriasis populations particularly in light of growing concerns linking psoriasis to increased cardiovascular risk. PMID:24101875
Langeland, E; Robinson, H S; Moum, T; Larsen, M H; Wahl, A K
This study investigated the mental health of people with psoriasis undergoing patient education in climate therapy. A prospective design included a baseline assessment and two follow-ups after a 3-week patient education program. Participants were 254 adults. Positive mental health was measured by the mental health continuum short form (0-70), and negative mental health by the emotional distress subscale (1-4) of the health education impact questionnaire. Paired-samples t-tests were used to evaluate changes in mental health from baseline to follow-up. Multiple linear regression was used to analyse the ability of socio-demographic and clinical variables and emotional distress to predict changes in positive mental health. To predict change in negative mental health we repeated the same analysis but with a change in negative mental health as a dependent variable and positive mental health as an independent variable. The results show that positive mental health and health-related emotional distress improved significantly from before to after the intervention by 7.1 points, p < 0.001 and 0.21 points, p < 0.001) respectively. At the second follow-up, health-related emotional distress remained significantly improved compared with baseline levels by 0.11 points, p = 0.004. The longer participants had lived with psoriasis ( β = 146, p = 0.027), and the presence of co-morbid health problems (β = 111, p = 0.051) the greater the improvement in the positive mental health immediately after the intervention. No predictors were identified for negative mental health. This study indicates that the promotion of positive mental health needs to be integrated into the climate therapy program, and sustained in their home context.
Hollywood, Katherine A; Winder, Catherine L; Dunn, Warwick B; Xu, Yun; Broadhurst, David; Griffiths, Christopher E M; Goodacre, Royston
Psoriasis is a common, immune-mediated inflammatory skin disease characterized by red, heavily scaled plaques. The disease affects over one million people in the UK and causes significant physical, psychological and societal impact. There is limited understanding regarding the exact pathogenesis of the disease although it is believed to be a consequence of genetic predisposition and environmental triggers. Treatments vary from topical therapies, such as dithranol, for disease of limited extent (<5% body surface area) to the new immune-targeted biologic therapies for severe psoriasis. Dithranol (also known as anthralin) is a topical therapy for psoriasis believed to work by inhibiting keratinocyte proliferation. To date there have been no metabolomic-based investigations into psoriasis. The HaCaT cell line is a model system for the epidermal keratinocyte proliferation characteristic of psoriasis and was thus chosen for study. Dithranol was applied at therapeutically relevant doses to HaCaT cells. Following the optimisation of enzyme inactivation and metabolite extraction, gas chromatography-mass spectrometry was employed for metabolomics as this addresses central metabolism. Cells were challenged with 0-0.5 μg mL(-1) in 0.1 μg mL(-1) steps and this quantitative perturbation generated data that were highly amenable to correlation analysis. Thus, we used a combination of traditional principal components analysis, hierarchical cluster analysis, along with correlation networks. All methods highlighted distinct metabolite groups, which had different metabolite trajectories with respect to drug concentration and the interpretation of these data established that cellular metabolism had been altered significantly and provided further clarification of the proposed mechanism of action of the drug.
Cataño, Juan; Morales, Milena
Background The use of biological therapy has been linked with an increased risk of tuberculosis (TB) reactivation. Objective The aim of this study was to present the follow-up results for Isoniazid (INH) chemoprophylaxis in patients with psoriasis receiving different biological therapies. Methods In this prospective observational study, patients with latent tuberculosis infection (LTBI) were given INH chemoprophylaxis between two and nine months prior to the beginning of biological therapy. All patients were followed up monthly for any signs or symptoms of active TB or INH toxicity. Results A total of 101 patients, 44.5% females, with a mean age of 46.9 ± 11.5 years (20-73) were enrolled. LTBI was identified in 100 patients (99%), of whom 81.2% completed nine months of chemoprophylaxis. Three patients (2.9%) developed active TB and 17 patients (16.8%) developed intolerance or toxicity related to INH. Conclusions Chemoprophylaxis with INH seems to be effective and safe for the prevention of most TB reactivations in individuals with LTBI receiving biological therapy, but toxicity must be monitored during follow-up.
Rayburn, Elizabeth R.; Ezell, Scharri J.; Zhang, Ruiwen
Inflammation is closely linked to cancer, and many anti-cancer agents are also used to treat inflammatory diseases, such as rheumatoid arthritis. Moreover, chronic inflammation increases the risk for various cancers, indicating that eliminating inflammation may represent a valid strategy for cancer prevention and therapy. This article explores the relationship between inflammation and cancer with an emphasis on epidemiological evidence, summarizes the current use of anti-inflammatory agents for cancer prevention and therapy, and describes the mechanisms underlying the anti-cancer effects of anti-inflammatory agents. Since monotherapy is generally insufficient for treating cancer, the combined use of anti-inflammatory agents and conventional cancer therapy is also a focal point in discussion. In addition, we also briefly describe future directions that should be explored for anti-cancer anti-inflammatory agents. PMID:20333321
Hernández, José L.; López-Mejías, Raquel; Blanco, Ricardo; Pina, Trinitario; Ruiz, Sheila; Sierra, Isabel; Ubilla, Begoña; Mijares, Verónica; González-López, Marcos A.; Armesto, Susana; Corrales, Alfonso; Pons, Enar; Fuentevilla, Patricia; González-Vela, Carmen; González-Gay, Miguel Á.
Studies on trabecular bone score (TBS) in psoriasis are lacking. We aim to assess the association between TBS and inflammation, metabolic syndrome features, and serum adipokines in 29 nondiabetic patients with psoriasis without arthritis, before and after 6-month adalimumab therapy. For that purpose, adjusted partial correlations and stepwise multivariable linear regression analysis were performed. No correlation was found between TBS and disease severity. TBS was negatively associated with weight, BMI, waist perimeter, fat percentage, and systolic and diastolic blood pressure before and after adalimumab. After 6 months of therapy, a negative correlation between TBS and insulin resistance (p = 0.02) and leptin (p = 0.01) and a positive correlation with adiponectin were found (p = 0.01). The best set of predictors for TBS values at baseline were female sex (p = 0.015), age (p = 0.05), and BMI (p = 0.001). The best set of predictors for TBS following 6 months of biologic therapy were age (p = 0.001), BMI (p < 0.0001), and serum adiponectin levels (p = 0.027). In conclusion, in nondiabetic patients with moderate-to-severe psoriasis, TBS correlates with metabolic syndrome features and inflammation. This association is still present after 6 months of adalimumab therapy. Moreover, serum adiponectin levels seem to be an independent variable related to TBS values, after adalimumab therapy. PMID:27293954
Hernández, José L; López-Mejías, Raquel; Blanco, Ricardo; Pina, Trinitario; Ruiz, Sheila; Sierra, Isabel; Ubilla, Begoña; Mijares, Verónica; González-López, Marcos A; Armesto, Susana; Corrales, Alfonso; Pons, Enar; Fuentevilla, Patricia; González-Vela, Carmen; González-Gay, Miguel Á
Studies on trabecular bone score (TBS) in psoriasis are lacking. We aim to assess the association between TBS and inflammation, metabolic syndrome features, and serum adipokines in 29 nondiabetic patients with psoriasis without arthritis, before and after 6-month adalimumab therapy. For that purpose, adjusted partial correlations and stepwise multivariable linear regression analysis were performed. No correlation was found between TBS and disease severity. TBS was negatively associated with weight, BMI, waist perimeter, fat percentage, and systolic and diastolic blood pressure before and after adalimumab. After 6 months of therapy, a negative correlation between TBS and insulin resistance (p = 0.02) and leptin (p = 0.01) and a positive correlation with adiponectin were found (p = 0.01). The best set of predictors for TBS values at baseline were female sex (p = 0.015), age (p = 0.05), and BMI (p = 0.001). The best set of predictors for TBS following 6 months of biologic therapy were age (p = 0.001), BMI (p < 0.0001), and serum adiponectin levels (p = 0.027). In conclusion, in nondiabetic patients with moderate-to-severe psoriasis, TBS correlates with metabolic syndrome features and inflammation. This association is still present after 6 months of adalimumab therapy. Moreover, serum adiponectin levels seem to be an independent variable related to TBS values, after adalimumab therapy.
Resources - psoriasis ... The following organizations are good resources for information about psoriasis : American Academy of Dermatology -- www.aad.org/skin-conditions/dermatology-a-to-z/psoriasis National Institute of ...
Głażewska, Edyta Katarzyna; Niczyporuk, Marek; Ławicki, Sławomir; Szmitkowski, Maciej; Zajkowska, Monika; Będkowska, Grażyna Ewa; Przylipiak, Andrzej
Background Matrix metalloproteinases (MMPs), which show a significant ability to cleave the components of extracellular matrix, and tissue inhibitors of metalloproteinases (TIMPs), which slow down the activity of those enzymes, may be implicated in the pathogenesis and spread of psoriatic disease. This study aims to analyze plasma levels of MMP-2 and TIMP-2 in plaque psoriasis patients before and after the course of narrowband ultraviolet-B (NBUVB) therapy with respect to disease advancement. Patients and methods A total of 49 patients suffering from plaque psoriasis and 40 healthy volunteers were enrolled into the study. Plasma levels of MMP-2 and TIMP-2 were determined using enzyme-linked immunosorbent assay, while Psoriasis Area and Severity Index (PASI) was used to define the disease advancement. Results The results showed increased plasma levels of MMP-2 and TIMP-2, but this change was significant only in case of MMP-2 in total psoriatic group compared to healthy subjects. Moreover, there was an increase in the concentrations of chosen factors with an increase in the severity of the disease. The NBUVB therapy causes a decline in the concentration of the analyzed enzyme and its inhibitor, although this change was statistically significant in the total psoriatic group only in case of MMP-2. There was also a positive correlation between MMP-2, TIMP-2, and PASI score value. Conclusion Our study highlights a possible important role of MMP-2 in the activity of psoriasis and clearance of disease symptoms. Moreover, plasma MMP-2 seems to be a valuable psoriasis biomarker. PMID:27799779
Fisch, Adam S.; Perry, Christina G.; Stephens, Sarah H.; Horenstein, Richard B.; Shuldiner, Alan R.
Arterial thrombosis is a major component of vascular disease, especially myocardial infarction (MI) and stroke. Current anti-thrombotic therapies such as warfarin and clopidogrel are effective in inhibiting cardiovascular events; however, there is great inter-individual variability in response to these medications. In recent years, it has been recognized that genetic factors play a significant role in drug response, and, subsequently, common variants in genes responsible for metabolism and drug action have been identified. These discoveries along with the new diagnostic targets and therapeutic strategies on the horizon hold promise for more effective individualized anti-coagulation and anti-platelet therapy. PMID:23797323
Liu, Juan; Zhou, Bing-Rong; Yi, Fei; Wu, Hong-Jin; Zhang, Jia-An; Luo, Dan
Pyogenic granuloma (PG) is an acquired benign vascular tumor of unknown etiology. In the present case report, PG was detected in a 49-year-old Chinese male patient with chronic plaque psoriasis. The psoriasis lesions on the finger where the granuloma had developed had been scratched excessively, as declared by the patient. No retinoid therapeutic agents were used during treatment. The patient responded poorly to cryotherapy and surgical curettage. However, following one session of 5-aminolevulinic acid photodynamic therapy (ALA-PDT), signs of improvement were demonstrated 1 week after the treatment, and 1 month following treatment, there were no signs of reoccurrence. Although a report demonstrating treatment success in one patient may be inadequate to estimate the true efficiency of ALA-PDT, dermatologists may consider ALA-PDT as an alternative therapy for stubborn PG.
LIU, JUAN; ZHOU, BING-RONG; YI, FEI; WU, HONG-JIN; ZHANG, JIA-AN; LUO, DAN
Pyogenic granuloma (PG) is an acquired benign vascular tumor of unknown etiology. In the present case report, PG was detected in a 49-year-old Chinese male patient with chronic plaque psoriasis. The psoriasis lesions on the finger where the granuloma had developed had been scratched excessively, as declared by the patient. No retinoid therapeutic agents were used during treatment. The patient responded poorly to cryotherapy and surgical curettage. However, following one session of 5-aminolevulinic acid photodynamic therapy (ALA-PDT), signs of improvement were demonstrated 1 week after the treatment, and 1 month following treatment, there were no signs of reoccurrence. Although a report demonstrating treatment success in one patient may be inadequate to estimate the true efficiency of ALA-PDT, dermatologists may consider ALA-PDT as an alternative therapy for stubborn PG. PMID:26889266
Rosenberg, E. W.; Noah, P. W.; Skinner, R. B.
It has been suggested previously that psoriasis is best explained as a distinctive inflammatory response to a variety of microbial stimuli, all acting primarily through activation of the alternative complement pathway. For the past several years we have conducted a "Problem Psoriasis Clinic" based on that premise. Patients are questioned, examined, and subjected to microbiologic laboratory investigations in an attempt to identify possibly relevant microorganisms, and then are treated with antibiotics. This article lists the most commonly found microorganisms in psoriasis patients and describes the usual treatment for each. Results obtained with this approach compare favorably with those achieved with more usual anti-psoriasis treatments. We recommend that a microbiologic investigation and a trial of antimicrobial treatment should precede any plan to treat psoriasis patients with anything more than the simplest topical agents. PMID:8040907
Segaert, Siegfried; Shear, Neil H; Chiricozzi, Andrea; Thaçi, Diamant; Carrascosa, Jose-Manuel; Young, Helen; Descamps, Vincent
Fixed-dose combination topical therapy with corticosteroid and vitamin D analog provides effective treatment and possible long-term management of psoriasis. The anti-inflammatory and immunomodulatory effects of corticosteroids and vitamin D analogs in treating psoriasis are well investigated; their complementary effects lead to the disruption of the inflammatory feedback loop underlying psoriasis pathogenesis. Recent preclinical data showed that combination therapy is more effective than monotherapies of the active ingredients in preventing activation of resting pro-inflammatory cells, inducing immunomodulation, reducing inflammatory responses by regulating T cell production, and normalizing keratinocytes. The increased understanding of the mechanism of action of fixed-dose combination therapy from preclinical studies is supported by several clinical studies. As the efficacy of topical therapy is correlated with the skin penetration of the active ingredients, new drug delivery systems have been developed. The fixed-dose combination Cal/BD aerosol foam creates a modified supersaturated formulation when applied to the skin, which is maintained for at least 26 h in the laboratory setting. Clinical studies have demonstrated superior efficacy of fixed-dose combination calcipotriol (Cal) 50 µg/g and betamethasone dipropionate (BD) 0.5 mg/g aerosol foam compared with monotherapies of the active ingredients. Furthermore, Cal/BD aerosol foam has shown significantly improved efficacy compared with more traditional formulations, such as Cal/BD ointment and gel, in other studies. Calcipotriol also mitigates risks associated with betamethasone dipropionate and vice versa, resulting in the favorable safety profile observed with fixed-dose combination treatment. Recent data also suggest that fixed-dose combination treatment could provide long-term management of psoriasis, although further clinical investigations are needed. Overall, these data support the value of fixed
Schöpf, E; Mueller, J M; Ostermann, T
Atopic dermatitis and psoriasis vulgaris belong to the most common diseases in dermatology. Since these chronical diseases progress over years and decades, they may lead to restrictions in private and professional life as well as to psychological stress of concerned patients. Therefore, a lasting, stabilising, stage-adjusted topical treatment is necessary. Main component of this treatment in a complete therapeutical concept consists in an adjuvant basic therapy with oil baths and with emollients containing urea or no drug additives at all. Thus the vehicle itself is therapeutically effective. Altered structure and function of the skin measured by increased transepidermal water loss, dysfunction of skin lipid barrier, augmented skin permeability and skin roughness can be improved. Due to this treatment clinical symptoms can be diminished and relapses can be avoided. Corticosteroids and other specific medications can be reduced by using basic therapeutics with little side effects. This means economical benefit as well. So far adjuvant basic treatment is an essential part in the therapy of chronic inflammatory skin diseases.
Chandran, Nisha Suyien; Chong, Wei-Sheng
Generalized pustular psoriasis of von Zumbusch is an unstable, inflammatory form of psoriasis, with the hallmark of neutrophil infiltration in cutaneous as well as extracutaneous lesions. It is often recalcitrant, making treatment difficult. Tumour necrosis factor-alpha antagonists including infliximab have been used with success in treating recalcitrant cases. We report a case of a 48-year-old Chinese female patient with a long-standing history of poorly controlled generalized pustular psoriasis which was resistant to multiple therapies. During a severe flare, a single dose of infliximab resulted in rapid clearing of cutaneous lesions, together with resolution of liver function abnormalities that are likely secondary to neutrophilic cholangitis. Subsequent maintenance therapy with acitretin allowed remission of pustular disease for 7 months. This demonstrates the efficacy of single-dose infliximab for both cutaneous lesions and systemic hepatic involvement in generalized pustular psoriasis.
Wu, Shaowei; Han, Jiali; Qureshi, Abrar A
Non-steroidal anti-inflammatory drugs (NSAIDs) have been reported to induce or exacerbate psoriasis. We aimed to evaluate the association between several widely used analgesics, including aspirin, non-aspirin NSAIDs, and acetaminophen (paracetamol), and risk of psoriasis and psoriatic arthritis (PsA) in a large cohort of US women, the Nurses' Health Study II (1991-2005). Information on regular use of aspirin, NSAIDs, and acetaminophen was collected for 95,540 participants during the follow-up. During 1,321,280 person-years of follow-up, we documented 646 incident psoriasis cases and 165 concomitant PsA cases. Compared to women who reported no use, regular acetaminophen and NSAIDs users with more than 10 years of use had multivariate hazard ratios of 3.60 [95% confidence interval (CI): 2.02-6.41] and 2.10 (95% CI: 1.11-3.96) for PsA, respectively. There was no clear association between aspirin and risk of psoriasis or PsA. In conclusion, long-term acetaminophen and NSAIDs use may be associated with an increased risk of PsA. Special attention on psoriasis and PsA screening may be needed for those who are prescribed for acetaminophen and NSAIDs for long-term periods.
Wu, Shaowei; Han, Jiali; Qureshi, Abrar A.
Non-steroidal anti-inflammatory drugs (NSAIDs) have been reported to induce or exacerbate psoriasis. We aimed to evaluate the association between several widely used analgesics, including aspirin, nonaspirin NSAIDs, and acetaminophen (paracetamol), and risk of psoriasis and psoriatic arthritis (PsA) in a large cohort of US women (1991–2005). Information on regular use of aspirin, NSAIDs, and acetaminophen was collected for 95 540 participants during the follow-up. During 1 321 280 person-years of follow-up, we documented 646 incident psoriasis cases and 165 concomitant PsA cases. Compared to women who reported no use, regular acetaminophen and NSAIDs users with more than 10 years of use had multivariate hazard ratios (HRs) of 3.60 [95% confidence interval (CI): 2.02–6.41] and 2.10 (95% CI: 1.11–3.96) respectively for PsA. There was no clear association between aspirin and risk of psoriasis or PsA. In conclusion, long-term acetaminophen and NSAIDs use may be associated with an increased risk of PsA. Special attention on psoriasis and PsA screening may be needed for those who are prescribed for acetaminophen and NSAIDs. PMID:24691893
Kurizky, Patricia Shu; Ferreira, Clarissa de Castro; Nogueira, Lucas Souza Carmo; Mota, Licia Maria Henrique da
Psoriasis is a chronic inflammatory disease that affects primarily the skin and joints, with a worldwide incidence of 2-3%. Fifty percent of patients are women, most still diagnosed during childbearing years. Currently,the estimate is that up to 107 thousand deliveries are performed annually in women with psoriasis, a percentage of them in women with moderate to severe disease. Fetal risks in pregnant women with psoriasis derive both from maternal disease and the medications used to control the illness. The purpose of this review is to study the effect of the main drugs used in the treatment of psoriasis and psoriatic arthritis during pregnancy and lactation, with particular focus on disease-modifying anti-rheumatic biological drugs, biological therapies, immunobiologics or biologics.
Raposo, Inês; Torres, Tiago
Palmoplantar psoriasis and palmoplantar pustulosis are chronic skin diseases with a large impact on patient quality of life. They are frequently refractory to treatment, being generally described as a therapeutic challenge. This article aims to review the definitions of palmoplantar psoriasis and palmoplantar pustulosis, highlighting the similarities and differences in terms of epidemiology, clinical presentation, genetics, histopathology, and pathogenesis, as well as treatment options for both entities. Classical management of mild to moderate palmoplantar pustulosis and palmoplantar psoriasis relies on use of potent topical corticosteroids, phototherapy, and/or acitretin. Nevertheless, these drugs have proven to be insufficient in long-term control of extensive disease. Biologic therapy-namely, anti-interleukin-17 agents and phosphodiesterase type 4 inhibitors-has recently shown promising results in the treatment of palmoplantar psoriasis. Knowledge of the pathophysiologic pathways of both entities is of utmost importance and may, in the future, allow development of molecularly targeted therapeutics.
Kurizky, Patricia Shu; Ferreira, Clarissa de Castro; Nogueira, Lucas Souza Carmo; da Mota, Licia Maria Henrique
Psoriasis is a chronic inflammatory disease that affects primarily the skin and joints, with a worldwide incidence of 2-3%. Fifty percent of patients are women, most still diagnosed during childbearing years. Currently,the estimate is that up to 107 thousand deliveries are performed annually in women with psoriasis, a percentage of them in women with moderate to severe disease. Fetal risks in pregnant women with psoriasis derive both from maternal disease and the medications used to control the illness. The purpose of this review is to study the effect of the main drugs used in the treatment of psoriasis and psoriatic arthritis during pregnancy and lactation, with particular focus on disease-modifying anti-rheumatic biological drugs, biological therapies, immunobiologics or biologics. PMID:26131868
Chen, Wenjuan; Gong, Yu; Zhang, Xilin; Tong, Yunlei; Wang, Xiuxiu; Fei, Chengwen; Xu, Hui; Yu, Qian; Wang, Yao; Shi, Yuling
Psoriasis is a high-incident T-cell-mediated autoimmune disease mainly affecting the skin. Interleukin (IL)-27 is a novel member of the IL-6/IL-12 cytokine family, which plays a versatile role in the differentiation and function of distinct T cell subsets. Previous studies uncovered that IL-27 promoted the onset of psoriasis through enhancing the differentiation of T helper (Th) 1 cells. However, the role of IL-27 in other psoriasis-related Th lineages, especially Th17 cells, remains elusive. The study aimed to investigate the role of IL-27 in the progression of psoriasis and its underlying mechanisms, particularly its influence on Th1 and Th17. IL-27 and IL-27 receptor α (IL-27Rα) expressions in normal and lesional skin were determined by immunohistochemistry and western blot analysis. Serum levels of IL-27 and IL-10 were measured by ELISA. Expression levels of IL-27 and IL-27 receptor (IL-27R) mRNA in the skin tissue and peripheral blood mononuclear cells (PBMC) were assessed by quantitative polymerase chain reaction (PCR) analysis. To explore the function of IL-27 in vivo, we used imiquimod (IMQ)-induced psoriasis mouse model. We treated mice with IL-27 or its antagonist, evaluated disease severity and detected the cytokine secretion from splenic CD4+ T cells by flow cytometric analysis and the expression levels of IL-17 and IFN-γ in serum and skin lesion. The expression levels of IL-27 and IL-27Rα were significantly reduced in the moderate-to-severe psoriatic lesions, along with a consistent decrease in serum IL-27 levels, compared with those of healthy control subjects. Moreover, subcutaneous administration of IL-27 recombinant protein lessened severity of IMQ-induced psoriasis-like cutaneous lesions, whereas IL-27p28 antagonist exaggerated the disease severity. Further analysis revealed that IL-27 significantly repressed IL-17 secretion from CD4+ T lymphocytes. Also administration of IL-27 decreased IL-17A level while IL-27p28 antagonist increased IL-17A
Golden, Jackelyn B.; McCormick, Thomas S.; Ward, Nicole L.
Psoriasis is a prevalent, chronic inflammatory disease of the skin mediated by cross-talk occurring between epidermal keratinocytes, dermal vascular cells and immunocytes, including activated antigen presenting cells (APCs), monocytes/macrophages, and Th1 and Th17 cells. Increased proliferation of keratinocytes and endothelial cells in conjunction with immune cell infiltration leads to the distinct epidermal and vascular hyperplasia that is characteristic of lesional psoriatic skin. Interaction of activated T cells with monocytes/macrophages occurs via the Th17/IL-23 axis and is crucial for maintaining the chronic inflammation. Recent epidemiological evidence has demonstrated that psoriasis patients have an increased risk of developing and dying of cardiovascular disease. Similar pathology between psoriasis and cardiovascular disease, including involvement of key immunologic cell populations together with release of common inflammatory mediators such as IL-17A suggest a mechanistic link between the two diseases. This review will focus on concepts critical to psoriasis pathogenesis, systemic manifestations of psoriasis, the role of IL-17 in psoriasis and cardiovascular disease and the potential role for IL-17 in mediating cardiovascular co-morbidities in psoriasis patients. PMID:23562549
Jókai, Hajnalka; Szakonyi, József; Kontár, Orsolya; Barna, Gábor; Inotai, Dóra; Kárpáti, Sarolta; Holló, Péter
A considerable number of patients with psoriasis show secondary resistance during long-term TNF-alpha inhibitor therapy, necessitating the identification of reliable predictive markers. Predictive role of cutaneous lymphocyte-associated antigen (CLA) was investigated. Thirty-eight severe patients with psoriasis were treated for a 24-week-long study period. Clinical responsiveness (PASI) and changes in flow cytometry-measured peripheral lymphocyte CLA expression (week 0-2-6) were statistically analysed. Regarding 24-week-long treatment outcome patients were divided into two groups: During the first 6 weeks, mean CLA expression showed significant (P = 0.034604) increase among responders (32/38), while after a preliminary increase, it was significantly (P = 0.012539) decreasing in the relapsing group (6/38). Pearson's correlation analysis showed significant negative correlation between PASI and CLA changes. Responders showed (not significantly) lower initial CLA expression than relapsing patients. Our observations suggest change in CLA expression during the first 6 weeks of induction period to serve as a potential predictive marker of TNF-alpha inhibitor therapy in psoriasis.
Ayer, Jean; Young, Helen S
Pimecrolimus is a calcineurin inhibitor which has a role in the treatment of psoriasis. However, it remains an off-license treatment, despite its potential use in patients with treatment-resistant psoriasis or in those who have had multiple adverse effects to other therapies. This review covers the efficacy and role of both topical and oral Pimecrolimus in the management of psoriasis and compares them to other available treatments. The paper provides a comprehensive review of the literature on topical and oral Pimecrolimus and its utility in the treatment of patients with psoriasis following literature searches via PubMed and Embase. Topical Pimecrolimus is an effective, off-license treatment option particularly for facial and intertriginous psoriasis. Oral Pimecrolimus shows great promise as an alternative systemic treatment option, but Phase III trials are required before further recommendations can be made.
Investigation of dietary supplements prevalence as complementary therapy: Comparison between hospitalized psoriasis patients and non-psoriasis patients, correlation with disease severity and quality of life.
Yousefzadeh, Hadis; Mahmoudi, Mahmoud; Banihashemi, Mahnaz; Rastin, Maryam; Azad, Farahzad Jabbari
Psoriasis patients are often displeased with traditional medical treatments and they may self-prescribe dietary supplements as an alternative or complementary treatments. We aimed to investigate the prevalence of self-medication of dietary supplements among psoriasis and non-psoriasis cases and its impact on disease severity and quality of life. This case-control study evaluated 252 records of psoriasis patients and 245 non-psoriasis cases. Dietary supplementation over last 30days and characteristics, including age, age at onset of disease, co-morbidities, smoking and education were recorded. Psoriasis area and severity index (PASI) and dermatology quality of life index (DLQI) were calculated. P value less than 0.05 was considered as significant level. This study consisted 138 psoriasis (females; 54) and 138 non-psoriasis cases (females; 50), aged between 21 and 91 years. Among psoriasis patients, 72% reported using at least one of dietary supplements, which was different from non-psoriasis cases (25.36%, P=0.01). Multivitamin/mineral supplements (MVM) were the most frequent used dietary supplements (26.81%) and the most common reasons for the consumption of these supplements were to maintain and improve health. The consumption of folic acid (21.73%), omega-3 fatty acids or fish oil (10.14%), herbs (12.31%) and vitamin E (1.44%) had the most frequencies after MVM. No significant differences in PASI and DLQI were found among patients with consumption of different supplements (P>0.05). There was non-significant and negative correlation between education and use of supplements (P=0.21, r=-0.02). Self-medicating of MVM over last 30days was prevalent among studied psoriasis patients. They took dietary supplements in order to improve and maintain their health. Copyright © 2017 Elsevier Ltd. All rights reserved.
Barrett, N E; Holbrook, L; Jones, S; Kaiser, W J; Moraes, L A; Rana, R; Sage, T; Stanley, R G; Tucker, K L; Wright, B; Gibbins, J M
Platelets have long been recognized to be of central importance in haemostasis, but their participation in pathological conditions such as thrombosis, atherosclerosis and inflammation is now also well established. The platelet has therefore become a key target in therapies to combat cardiovascular disease. Anti-platelet therapies are used widely, but current approaches lack efficacy in a proportion of patients, and are associated with side effects including problem bleeding. In the last decade, substantial progress has been made in understanding the regulation of platelet function, including the characterization of new ligands, platelet-specific receptors and cell signalling pathways. It is anticipated this progress will impact positively on the future innovations towards more effective and safer anti-platelet agents. In this review, the mechanisms of platelet regulation and current anti-platelet therapies are introduced, and strong, and some more speculative, potential candidate target molecules for future anti-platelet drug development are discussed. PMID:18587441
Gisondi, Paolo; Girolomoni, Giampiero
Chronic plaque psoriasis presents clinically as an inflammatory disease of the skin, which is often associated with comorbidities and responsible for a poor quality of life. It can widely vary among patients because of different age of onset, type of symptoms, areas of involvement, and disease severity. The choice of the treatment of psoriasis should be personalized according to the specific needs of the patients. Apremilast is a well-tolerated and effective phosphodiesterase type 4 inhibitor that is indicated for the treatment of moderate-to-severe plaque psoriasis and psoriatic arthritis. In this article, the pharmacological, clinical, and safety aspects of apremilast are reviewed. Based on these data, apremilast could be indicated for patients with a Psoriasis Area and Severity Index score <10 but with a significant impact on quality of life and seems to be an appropriate treatment for elderly patients also. PMID:27307707
anticancer therapy and focal light illumination is expected to be an effective treatment with reduced phototoxicity given the quenched state of the...to months following photodynamic therapy (PDT). Herein, we report a novel design of protease-mediated photosensitization by which phototoxicity can...W81XWH-05-1-0515 TITLE: Protease Mediated Anti-Cancer Therapy PRINCIPAL INVESTIGATOR: Ching-Hsuan Tung CONTRACTING ORGANIZATION
Naldi, Luigi; Gambini, Daniele
The clinical picture of psoriasis is not uniform. Being one of the most common chronic inflammatory skin disorders, psoriasis may present in many different forms and may include extracutaneous manifestations. Classifications have been proposed based on disease onset or the clinical course of psoriasis. Chronic plaque psoriasis occurs in a variety of clinical forms primarily distinguished by size, distribution, and dynamics of psoriatic plaques. In addition, psoriasis inversa, localized and generalized pustular forms, erythrodermic psoriasis, as well as a number of more uncommon forms have been recognized, a distinction on clinical grounds that is relevant for the overall prognosis and impact on the patients' quality of life as well as for the choice of therapy. The broad and rather colorful clinical spectrum of psoriasis as well as implications for clinical practice will be comprehensively reviewed in this article.
Kaffenberger, Benjamin H; Lee, Grace L; Tyler, Kelly; Chan, Derek V; Jarjour, Wael; Ariza, Maria E; Williams, Marshall V; Wong, Henry K
Psoriasis is a chronic, immune skin disease associated with significant morbidity. Development of psoriasis is influenced by numerous genes, one allele is HLA-CW*0602. Other genes and single nucleotide polymorphisms affect immunologic pathways and antimicrobial peptide synthesis. Dendritic cells initiate psoriasis by activating T-cells toward a Th1 and Th17 response, with increased cytokines including TNF-α, IL-6, -12, -17, -22, and -23. IL-22 appears to promote keratinocyte dedifferentiation and increased antimicrobial peptide synthesis while TNF-α and IL-17 induce leukocyte localization within the psoriatic plaque. These recent insights identifying key cytokine pathways have led to the development of inhibitors with significant efficacy in the treatment of psoriasis. While a strategy for vaccine modulation of the immune response in psoriasis is in progress, with new technology they may provide a cost-effective long-term treatment that may induce tolerance or targeted self-inhibition for patients with autoimmune disorders, such as psoriasis. PMID:24492530
Egeberg, Alexander; Skov, Lone
Patients with psoriasis have an increased incidence and prevalence of cardiovascular (CV) risk factors, and CV undertreatment in these patients is a well-established problem. The link between psoriasis and CV disease is present on a pathogenic level, as well as due to modifiable lifestyle factors such as smoking and alcohol abuse. In this manuscript we describe the evidence associating psoriasis with CV disease, as well as the pharmacological and non-pharmacological treatment of CV risk factors including the CV effects of anti-psoriatic therapy and vice versa. Current guidelines recommend that patients with psoriasis are screened for CV risk factors, and recommend smoking cessation, reduced alcohol consumption, altering of lifestyle to move to a normal-weight body-mass index, exercising 3 times a week for 30 minutes, and monitoring and modifying cholesterol levels, respectively. While the current sum of evidence is not sufficient to recommend specific therapies for psoriasis solely based on their potential CV impact, some guidelines have suggested a 1.5 multiplication factor, in patients with severe psoriasis, to the Framingham risk score. Indeed, the importance of screening for CV risk factors and strict adherence to established primary and secondary preventive measures in these patients should be emphasized.
Chong, Benjamin F.; Wong, Henry K.
The pathogenesis of various inflammatory cutaneous diseases such as psoriasis, atopic dermatitis and mycosis fungoides relies greatly on the abnormal function of T cells. Fundamental knowledge of the role of T cells in the cutaneous immune response has led to the development and production of biologic molecules designed to block T cell function at various steps, specifically activation (i.e. alefacept, efalizumab), trafficking into inflamed skin (i.e. efalizumab) and effector function under cytokine control (i.e. etanercept, infliximab, adalimumab, and anti-IL-12 antibody). We review the immune abnormalities and the role of T cells in psoriasis, and the recent biologic therapies, which share the common mission to hinder T cell activity in inflammatory diseases. An advantage from the preciseness of these biologic therapies is the potential limit of non-specific and potentially devastating organ toxicity, which commonly plagues other systemic therapies. PMID:17317321
Galiano Mejías, S; Carretero, G; Ferrandiz, C; Vanaclocha, F; Daudén, E; Gómez-García, F J; Herrera-Ceballos, E; Belinchón-Romero, I; Sánchez-Carazo, J L; López-Estebaranz, J L; Alsina, M; Ferrán, M; Torrado, R; Carrascosa, J M; Rivera, R; Llamas-Velasco, M; Jiménez-Puya, R; Mendiola, Mª V; Ruiz-Genao, D; Descalzo, M A; de la Cueva Dobao, P
We now have considerable experience in the use of biologic agents to treat psoriasis, but doubts about management arise in certain clinical settings. Surgery is one of them. Although treatment guidelines advise that biologics be suspended before major surgery, data about actual clinical practices and associated complications are lacking. We aimed to analyze current practice in the clinical management of these cases. Retrospective study of cases in the Biobadaderm database. We analyzed the management of biologic therapy in patients with psoriasis who underwent surgical procedures. Forty-eight of the 2113 patients registered in Biobadaderm underwent surgery. The largest percentage of procedures (31%) involved skin lesions. Biologic treatment was interrupted in 42% of the cases. No postsurgical complications were significantly related to treatment interruption. Likewise we detected no associations between treatment interruption and other variables, such as sex, age, or duration or severity of psoriasis. Continuity of biologic treatment and the risk of postsurgical complications were not associated in this study, although conclusions are limited by the small sample size. Copyright © 2016 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.
Wcisło-Dziadecka, Dominika; Zbiciak-Nylec, Martyna; Brzezińska-Wcisło, Ligia; Mazurek, Urszula
Psoriasis is a chronic immunological skin disease and patients with this disorder typically experience a significant decrease in their quality of life. The disease is traditionally managed with topical and systemic agents (retinoids, ciclosporin A, methotrexate), but these treatment options are often long-term and their effects can be inconsistent and not ideal. The use of biological drugs in dermatological treatment is relatively new and began in the early 2000s. It should be noted that, in most countries, in order for biological treatment to be administered, specific criteria must be met. The current treatment options for psoriasis and psoriatic arthritis include tumour necrosis factor alpha (TNF-α) blockers, interleukin (IL)-12 and IL-23 inhibitors, T cell inhibitors and B cell inhibitors. These classes of biological drugs are characterised by protein structure as well as high molecular weight and their effectiveness is evaluated based on the Psoriasis Area and Severity Index (PASI), Body Surface Area (BSA) and the Dermatology Life Quality Index (DLQI). TNF-α antagonists are one such class of biological drugs which includes infliximad, etanercept and adalimumab. Infliximab is a chimeric protein that is administered via intravenous infusions as a monotherapy in psoriasis vulgaris. Etanercept is indicated for use in both psoriasis vulgaris and psoriatic arthritis and it is the only drug that can be used as a treatment for children under the age of 8 with psoriasis. The drug is administered subcutaneously. Finally, adalimumab is a fully human monoclonal antibody that neutralises both free and membrane-bound TNF-α and is used in the treatment of psoriasis vulgaris and psoriatic arthritis. This article reviews the latest research in the use of TNF-α for the treatment of moderate to severe psoriasis and psoriatic arthritis. The results of research in this field are promising and confirm the effectiveness and safety of biological drugs as dermatological treatments
Young, Melodie; Bergman, Martin Jan
Psoriasis is a dynamic systemic disease that can have a profound affect on a patient’s self-esteem. Fortunately, numerous therapeutic advances have been made over the last 10 years. In order to help patients manage their disease, healthcare providers should be aware of the modifiable risk factors that may exacerbate psoriasis. Additionally, exploring the impact the disease has on a patient and how it may change over their lifespan will help ensure appropriate therapies are used. Patients are unique so one medication will not fit all of our patients’ needs. In this paper, the authors look at available treatment options for psoriasis and psoriatic arthritis. Educating psoriasis patients, in addition to collaborating with patients and other healthcare providers, may help initiate therapies that will result in patients living their lives to the fullest. PMID:28360971
Desmet, Eline; Ramadhas, Anesh; Lambert, Jo; Van Gele, Mireille
Psoriasis is a complex chronic immune-mediated inflammatory cutaneous disease associated with the development of inflammatory plaques on the skin. Studies proved that the disease results from a deregulated interplay between skin keratinocytes, immune cells and the environment leading to a persisting inflammatory process modulated by pro-inflammatory cytokines and activation of T cells. However, a major hindrance to study the pathogenesis of psoriasis more in depth and subsequent development of novel therapies is the lack of suitable pre-clinical models mimicking the complex phenotype of this skin disorder. Recent advances in and optimization of three-dimensional skin equivalent models have made them attractive and promising alternatives to the simplistic monolayer cultures, immunological different in vivo models and scarce ex vivo skin explants. Moreover, human skin equivalents are increasing in complexity level to match human biology as closely as possible. Here, we critically review the different types of three-dimensional skin models of psoriasis with relevance to their application potential and advantages over other models. This will guide researchers in choosing the most suitable psoriasis skin model for therapeutic drug testing (including gene therapy via siRNA molecules), or to examine biological features contributing to the pathology of psoriasis. However, the addition of T cells (as recently applied to a de-epidermized dermis-based psoriatic skin model) or other immune cells would make them even more attractive models and broaden their application potential. Eventually, the ultimate goal would be to substitute animal models by three-dimensional psoriatic skin models in the pre-clinical phases of anti-psoriasis candidate drugs. Impact statement The continuous development of novel in vitro models mimicking the psoriasis phenotype is important in the field of psoriasis research, as currently no model exists that completely matches the in vivo psoriasis
Sánchez-Regaña, M; Aldunce Soto, M J; Belinchón Romero, I; Ribera Pibernat, M; Lafuente-Urrez, R F; Carrascosa Carrillo, J M; Ferrándiz Foraster, C; Puig Sanz, L; Daudén Tello, E; Vidal Sarró, D; Ruiz-Villaverde, R; Fonseca Capdevila, E; Rodríguez Cerdeira, M C; Alsina Gibert, M M; Herrera Acosta, E; Marrón Moya, S E
Psoriatic lesions affecting the scalp, nails, palms, and the soles of the feet are described as difficult-to-treat psoriasis and require specific management. Involvement of these sites often has a significant physical and emotional impact on the patient and the lesions are difficult to control with topical treatments owing to inadequate penetration of active ingredients and the poor cosmetic characteristics of the vehicles used. Consequently, when difficult-to-treat sites are involved, psoriasis can be considered severe even though the lesions are not extensive. Scant information is available about the use of biologic therapy in this setting, and published data generally comes from clinical trials of patients who also had moderate to severe extensive lesions or from small case series and isolated case reports. In this article we review the quality of the scientific evidence for the 4 biologic agents currently available in Spain (infliximab, etanercept, adalimumab, and ustekinumab) and report level i evidence for the use of biologics to treat nail psoriasis (level of recommendation A) and a somewhat lower level of evidence in the case of scalp involvement and palmoplantar psoriasis. Copyright © 2013 Elsevier España, S.L.U. y AEDV. All rights reserved.
Kawamoto, Eiji; Nakahashi, Susumu; Okamoto, Takayuki; Imai, Hiroshi; Shimaoka, Motomu
Integrins are the foremost family of cell adhesion molecules that regulate immune cell trafficking in health and diseases. Integrin alpha4 mediates organ-specific migration of immune cells to the inflamed brain, thereby playing the critical role in the pathogenesis of multiple sclerosis. Anti-alpha4 integrin therapy aiming to block infiltration of autoreactive lymphocytes to the inflamed brain has been validated in several clinical trials for the treatment of multiple sclerosis. This paper provides readers with an overview of the molecular and structural bases of integrin activation as well as rationale for using anti-alpha4 integrin therapy for multiple sclerosis and then chronicles the rise and fall of this treatment strategy using natalizumab, a humanized anti-alpha4 integrin.
Winthrop, Kevin L.; Baddley, John W.; Chen, Lang; Liu, Liyan; Grijalva, Carlos G.; Delzell, Elizabeth; Beukelman, Timothy; Patkar, Nivedita M.; Xie, Fenglong; Saag, Kenneth G.; Herrinton, Lisa J.; Solomon, Daniel H.; Lewis, James D.; Curtis, Jeffrey R.
Importance Herpes zoster (HZ) reactivation disproportionately affects patients with rheumatoid arthritis (RA). It is unclear whether anti-tumor necrosis factor (anti-TNF) therapy elevates HZ risk, and whether monoclonal antibodies carry greater risk than etanercept. Objectives To ascertain whether initiation of anti-TNF therapy compared with non-biologic comparators is associated with increased HZ risk Design, Setting, and Patients We identified new users of anti-TNF therapy among cohorts of rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and psoriasis-psoriatic arthritis-ankylosing spondylitis (PsO-PsA-AS) patients during 1998–2007 within a large US multi-institutional collaboration combining data from Kaiser Permanente Northern California, Pharmaceutical Assistance Contract for the Elderly, Tennessee Medicaid, and national Medicaid/Medicare programs. We compared HZ incidence between new anti-TNF users and patients initiating non-biologic disease modifying drugs (DMARDs) within each inflammatory disease cohort (last participant follow-up Dec 31, 2007). Within these cohorts, we used Cox regression models to compare propensity-score adjusted HZ incidence between new anti-TNF and non-biologic DMARD users while controlling for baseline corticosteroid use. Main Outcome Measure Incidence of herpes zoster cases occurring after initiation of new anti- TNF or non-biologic DMARD therapy Results Among 32,208 new users of anti-TNF therapy, we identified 310 HZ cases. Crude incidence rates among anti-TNF users for RA, IBD, and PsO-PsA-AS were 12.1/1000 pt-yrs, (95% CI 10.7–13.6), 11.3/1000 (95% CI 7.7–16.7), and 4.4/1000 (95% CI 2.8–7.0) respectively. Baseline use of corticosteroids of > 10mg/day was associated with elevated risk [adjusted HR 2.13 (1.64, 2.75) compared with no baseline use. For RA patients, adjusted incidence rates were similar between anti-TNF and nonbiologic DMARD initiators [adjusted HR 1.00 (95% CI 0.77–1.29) and comparable between
Ovejero-Benito, María C; Muñoz-Aceituno, Ester; Reolid, Alejandra; Saiz-Rodríguez, Miriam; Abad-Santos, Francisco; Daudén, Esteban
Pharmacogenetics is the study of variations in DNA sequence related to drug response. Moreover, the evolution of biotechnology and the sequencing of human DNA have allowed the creation of pharmacogenomics, a branch of genetics that analyzes human genes, the RNAs and proteins encoded by them, and the inter-and intra-individual variations in expression and function in relation to drug response. Pharmacogenetics and pharmacogenomics are being used to search for biomarkers that can predict response to systemic treatments, including those for moderate-to-severe psoriasis. Psoriasis is a chronic inflammatory disease with an autoimmune contribution. Although its etiology remains unknown, genetic, epigenetic, and environmental factors play a role in its development. Diverse systemic and biologic therapies are used to treat moderate-to-severe psoriasis. However, these treatments are not curative, and patients exhibit a wide range of responses to them. Moderate-to-severe psoriasis is usually treated with systemic immunomodulators such as acitretin, ciclosporin, and methotrexate. Anti-tumor necrosis factor (TNF) drugs (adalimumab, etanercept, or infliximab) are the first-line treatment for patients resistant to conventional systemic therapies. Although these therapies are very efficient, around 30-50% of patients have inadequate response. Ustekinumab is a monoclonal antibody that targets interleukin (IL)-12 and IL-23 and is used for moderate-to-severe psoriasis. New drugs (apremilast, brodalumab, guselkumab, ixekizumab, and secukinumab) have recently been approved for psoriasis. However, response rates to systemic treatments for moderate-to-severe psoriasis range from 35 to 80%, so it is necessary to identify non-invasive biomarkers that could help predict treatment outcomes of these therapies and individualize care for patients with psoriasis. These biomarkers could improve patient quality of life and reduce health costs and potential side effects. Pharmacogenetic studies
Rajagopalan, Murlidhar; Mital, Asit
The biologics currently in use for psoriasis in India are etanercept, infliximab and recently introduced itolizumab and secukinumab. Biosimilars, expected to play a significant role in psoriasis management in future, have also been available for the last few years. Patients with psoriasis may be considered eligible to receive treatment with any of the licensed biologic interventions when they fulfill the eligibility criteria. The decision to proceed with treatment must be made in collaboration with the patient and include a careful assessment of the associated risks and benefits. Etanercept is indicated in moderate to severe psoriasis and moderate to severe psoriatic arthritis with a dose of 25 mg or 50 mg twice weekly. Methotrexate may be recommended as co-medication in certain clinical circumstances, e.g., where it is required for associated arthropathy, or to improve efficacy. Infliximab is indicated in severe psoriasis and moderate to severe psoriatic arthritis. Infliximab therapy should be initiated at a dose of 5 mg/kg at weeks 0, 2 and 6 and disease response assessed at 3 months. In patients who respond, subsequent infusions (5 mg/kg) should be given at 8-week intervals to maintain disease control although long-term data are available only up to 1 year. Interrupted therapy should be avoided given the associated increased risk of infusion reactions and poorer disease control. Itolizumab is indicated in moderate to severe plaque psoriasis. It is given in a dose of 1.6mg/kg iv infusions every 2 weeks for 12 weeks initially and then 1.6mg/kg every 4 weeks up to 24 weeks. Long term data are unavailable. Secukinumab is indicated in moderate to severe plaque psoriasis and psoriatic arthritis. An initial loading dosing regimen of 300 mg secukinumab should be given by subcutaneous injection at weeks 0, 1, 2 and 3 followed by maintenance dose of 300 mg every 4 weeks starting at week 4. To exclude tuberculosis (TB) before anti TNF alfa therapy and therapy with
Rajagopalan, Murlidhar; Mital, Asit
The biologics currently in use for psoriasis in India are etanercept, infliximab and recently introduced itolizumab and secukinumab. Biosimilars, expected to play a significant role in psoriasis management in future, have also been available for the last few years. Patients with psoriasis may be considered eligible to receive treatment with any of the licensed biologic interventions when they fulfill the eligibility criteria. The decision to proceed with treatment must be made in collaboration with the patient and include a careful assessment of the associated risks and benefits. Etanercept is indicated in moderate to severe psoriasis and moderate to severe psoriatic arthritis with a dose of 25 mg or 50 mg twice weekly. Methotrexate may be recommended as co-medication in certain clinical circumstances, e.g., where it is required for associated arthropathy, or to improve efficacy. Infliximab is indicated in severe psoriasis and moderate to severe psoriatic arthritis. Infliximab therapy should be initiated at a dose of 5 mg/kg at weeks 0, 2 and 6 and disease response assessed at 3 months. In patients who respond, subsequent infusions (5 mg/kg) should be given at 8-week intervals to maintain disease control although long-term data are available only up to 1 year. Interrupted therapy should be avoided given the associated increased risk of infusion reactions and poorer disease control. Itolizumab is indicated in moderate to severe plaque psoriasis. It is given in a dose of 1.6mg/kg iv infusions every 2 weeks for 12 weeks initially and then 1.6mg/kg every 4 weeks up to 24 weeks. Long term data are unavailable. Secukinumab is indicated in moderate to severe plaque psoriasis and psoriatic arthritis. An initial loading dosing regimen of 300 mg secukinumab should be given by subcutaneous injection at weeks 0, 1, 2 and 3 followed by maintenance dose of 300 mg every 4 weeks starting at week 4. To exclude tuberculosis (TB) before anti TNF alfa therapy and therapy with
Since the introduction in the 1970s of treatment with oral psoralens with longwave ultraviolet radiation in the A range (PUVA), there has been an increasing concern about the long term carcinogenic effect of the therapy. The main indication for PUVA is psoriasis, a common, chronic and intractable skin disease that affects 1 to 3% of the world's population. The effectiveness of PUVA in inducing and maintaining the remission of severe psoriasis has been amply documented. Although psoriasis is not a life-threatening disorder, it may be associated with restriction of activities and days lost to hospitalisation. Therefore, a number of systemic treatments such as methotrexate and cyclosporin have been used. None of these treatments has been as carefully studied for long term adverse effects as PUVA. The short-term adverse effects of PUVA are generally well known and tolerated. The major mid-term adverse effect, squamous cell carcinoma of the skin, has been well documented in a number of large-scale epidemiological studies that have led to recommendations such as to restrict the lifetime number of treatments. Although squamous cell carcinoma is potentially life-threatening, it is usually slow growing and can be adequately managed by proper surveillance, treatment and follow-up. The situation is quite different for malignant melanoma, which is often fast growing and fatal. Except for anecdotal reports, malignant melanoma has not been observed in PUVA patients until recently. However, a report of a cohort of 1380 patients with psoriasis has concluded that about 15 years after the first treatment the risk of melanoma is increased approximately 5-fold in patients treated with high doses. Although this report needs to be confirmed by other multicentre trials, it is alarming since the association between exposure to ultraviolet light and development of melanoma is well established both in humans and in experimental animals. Until this study is validated, it is recommended that
Armstrong, April W.; Lin, Steven W.; Chambers, Cynthia J.; Sockolov, Mary E.; Chin, David L.
Background Epidemiologic studies have provided new insights into the association between psoriasis and cardiovascular diseases. Previous population studies have examined hypertension frequency in psoriasis patients. However, the relationship between severity of hypertension and psoriasis has not been characterized. Objective We sought to investigate whether patients with psoriasis have more difficult-to-manage hypertension compared to non-psoriatic hypertensive patients. Approach We performed a case-control study using the University of California Davis electronic medical records. The cases were defined as patients diagnosed with both psoriasis and hypertension, and controls were defined as patients with hypertension and without psoriasis. In this identified population, 835 cases were matched on age, sex, and body mass index (BMI) to 2418 control patients. Key Results Treatment with multiple anti-hypertensives was significantly associated with the presence of psoriasis using univariate (p<0.0001) and multivariable analysis, after adjusting for diabetes, hyperlipidemia, and race (p<0.0001). Compared to hypertensive patients without psoriasis, psoriasis patients with hypertension were 5 times more likely to be on a monotherapy antihypertensive regimen (95% CI 3.607.05), 9.5 times more likely to be on dual antihypertensive therapy (95% CI 6.68–13.65), 16.5 times more likely to be on triple antihypertensive regimen (95% CI 11.01–24.84), and 19.9 times more likely to be on quadruple therapy or centrally-acting agent (95% CI 10.58–37.33) in multivariable analysis after adjusting for traditional cardiac risk factors. Conclusions Psoriasis patients appear to have more difficult-to-control hypertension compared to non-psoriatic, hypertensive patients. PMID:21479272
Maytin, Edward V; Honari, Golara; Khachemoune, Amor; Taylor, Charles R; Ortel, Bernhard; Pogue, Brian W; Sznycer-Taub, Nathaniel; Hasan, Tayyaba
We previously showed that select agents (methotrexate or Vitamin D), when administered as a preconditioning regimen, are capable of promoting cellular differentiation of epithelial cancer cells while simultaneously enhancing the efficacy of 5-aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT). In solid tumors, pretreatment with Vitamin D simultaneously promotes cellular differentiation and leads to selective accumulation of target porphyrins (mainly protoporphyrin IX, PpIX) within diseased tissue. However, questions of whether or not the effects upon cellular differentiation are inexorably linked to PpIX accumulation, and whether these effects might occur in hyperproliferative noncancerous tissues, have remained unanswered. In this paper, we reasoned that psoriasis, a human skin disease in which abnormal cellular proliferation and differentiation plays a major role, could serve as a useful model to test the effects of pro-differentiating agents upon PpIX levels in a non-neoplastic setting. In particular, Vitamin D, a treatment for psoriasis that restores (increases) differentiation, might increase PpIX levels in psoriatic lesions and facilitate their responsiveness to ALA-PDT. This concept was tested in a pilot study of 7 patients with bilaterally-matched psoriatic plaques. A regimen in which calcipotriol 0.005% ointment was applied for 3 days prior to ALA-PDT with blue light, led to preferential increases in PpIX (~130%), and reductions in thickness, redness, scaling, and itching in the pretreated plaques. The results suggest that a larger clinical trial is warranted to confirm a role for combination treatments with Vitamin D and ALA-PDT for psoriasis.
Maytin, Edward V.; Honari, Golara; Khachemoune, Amor; Taylor, Charles R.; Ortel, Bernhard; Pogue, Brian W.; Sznycer-Taub, Nathaniel; Hasan, Tayyaba
We previously showed that select agents (methotrexate or Vitamin D), when administered as a preconditioning regimen, are capable of promoting cellular differentiation of epithelial cancer cells while simultaneously enhancing the efficacy of 5-aminolevulinic acid (ALA)-mediated photodynamic therapy (PDT). In solid tumors, pretreatment with Vitamin D simultaneously promotes cellular differentiation and leads to selective accumulation of target porphyrins (mainly protoporphyrin IX, PpIX) within diseased tissue. However, questions of whether or not the effects upon cellular differentiation are inexorably linked to PpIX accumulation, and whether these effects might occur in hyperproliferative noncancerous tissues, have remained unanswered. In this paper, we reasoned that psoriasis, a human skin disease in which abnormal cellular proliferation and differentiation plays a major role, could serve as a useful model to test the effects of pro-differentiating agents upon PpIX levels in a non-neoplastic setting. In particular, Vitamin D, a treatment for psoriasis that restores (increases) differentiation, might increase PpIX levels in psoriatic lesions and facilitate their responsiveness to ALA-PDT. This concept was tested in a pilot study of 7 patients with bilaterally-matched psoriatic plaques. A regimen in which calcipotriol 0.005% ointment was applied for 3 days prior to ALA-PDT with blue light, led to preferential increases in PpIX (~130%), and reductions in thickness, redness, scaling, and itching in the pretreated plaques. The results suggest that a larger clinical trial is warranted to confirm a role for combination treatments with Vitamin D and ALA-PDT for psoriasis. PMID:23264699
Garber, Caren; Plotnikova, Natalia; Au, Shiu-chung; Sorensen, Eric P; Gottlieb, Alice
Despite the aging population, few studies have documented the treatment of geriatric psoriasis. The purpose of this study is to compare the efficacy, safety, and prescribing patterns of biologics and conventional systemic medications in elderly versus adult psoriasis. All patient visits coded for psoriasis or psoriatic arthritis (ICD-9 696.1 or 696.0) at the Tufts Medical Center General Dermatology Clinic from January 1, 2008, to March 1, 2015 were included in this retrospective cohort study. The outcome measure used was the validated simple-measure for assessing psoriasis activity (S-MAPA), the product of the physician's global assessment and the body surface area. 194 patients who underwent 278 treatment courses were included in the study. 48 patients were included in the elderly cohort (≥ 65 years old) and 146 in the adult cohort (18-64 years old). There was no significant difference in S-MAPA improvement at 12 weeks between the two cohorts when treated with biologics (42.92% improvement in adults, 48.77% in elderly; P=0.498) or conventional systemics (43.96% and 51.82%, respectively; P=0.448). Within the elderly cohort, there was no significant difference in efficacy of biologics versus conventional systemics at any time point. Topical prescription rates were significantly higher in the elderly cohort ( P=0.004) while biologic prescription rates were significantly lower ( P=0.014) despite the same baseline S-MAPA in both age groups. For both biologics and conventional systemics, there was no statistically significant intergroup difference in the rate of adverse events ( P=0.322 for biologics; P=0.581 for conventional systemics) or infection ( P=0.753 for biologics; P=0.828 for conventional systemics). Within the elderly cohort, there was a higher rate of adverse events with conventional systemic treatment than with biologic treatment ( P=0.033). This study provides preliminary evidence to suggest that biologic and conventional systemic therapies are similarly
Sala, M; Elaissari, A; Fessi, H
Psoriasis is a chronic inflammatory disease affecting mainly the skin but which can be complicated by psoriatic arthritis (PsA).This autoimmune skin disorder concerns 2-5% of the world population. To date, the physiopathology of psoriasis is not still completely elucidated but many researches are ongoing which have led for example to the discovery of the Th17/Th22 pathway. The conventional therapeutic approaches (local or systemic route) appeal to various classes of drugs with complex mechanisms of action and non-negligible side effects. Although there is no therapy capable to cure psoriasis, the current goal is to relieve symptoms as longer as possible with a good benefit/risk ratio. That is one of the principal limits of conventional antipsoriatic drugs. New formulations based on nanoencapsulation are a promising opportunity to answer to this limit by offering an optimization of the conventional antipsoriatic drug use (higher activity, lower side effects and frequency of application, etc.). Herein, we tried to put in perspective the mechanistic insights (histological and immunological views) proposed into scientific literature these last years in order to have a better comprehension of psoriasis physiopathology resulting in skin lesions and PsA. The therapeutic armamentarium and the different strategies in the management of psoriasis are discussed in greater details. To finish, the field of encapsulation in nanoparticles is broached in order to put forward recent advances in innovative skin drug delivery systems (ISDDSs) of antipsoriatic active agents for a better efficacy, safety and compliance.
Lehman, Julia S; Rahil, Anudeep K
While childhood psoriasis is fairly common, congenital psoriasis appears to be rare and has not been well characterized. We present a patient with histologically confirmed congenital psoriasis. By reviewing the literature, we aim to both define this disease and compare it to infantile and childhood psoriasis. Electronic searches found articles reporting patients with biopsy-proven congenital psoriasis. We recorded clinical features, such as family history, anatomic involvement, and disease severity. We compared these data with previous descriptions of infantile and childhood psoriasis. We included nine patients with congenital psoriasis in our analysis. No patient had a first-degree family history of psoriasis. While the face, scalp, chest, and trunk were frequently involved, the buttocks generally were spared. Several patients had persistent disease despite therapy. In this series, congenital psoriasis differed from infantile and childhood psoriasis in several respects. Specifically, congenital psoriasis was associated with a lower prevalence of relevant family history, which could increase over time, and a different pattern of anatomic involvement, which may reflect exposure to age-associated environmental factors. Although several patients with congenital psoriasis had severe disease, this likely represents publication bias. Additional reports of congenital psoriasis with extended follow-up are needed to better characterize this condition.
Gibellini, Lara; De Biasi, Sara; Bianchini, Elena; Bartolomeo, Regina; Fabiano, Antonella; Manfredini, Marco; Ferrari, Federica; Albertini, Giuseppe; Trenti, Tommaso; Nasi, Milena; Pinti, Marcello; Iannone, Anna; Salvarani, Carlo; Cossarizza, Andrea; Pellacani, Giovanni
TNF-α has a central role in the development and maintenance of psoriatic plaques, and its serum levels correlate with disease activity. Anti-TNF-α drugs are, however, ineffective in a relevant percentage of patients for reasons that are currently unknown. To understand whether the response to anti-TNF-α drugs is influenced by the production of anti-drug antibodies or by the modulation of the TNFα-TNFα receptor system, and to identify changes in monocyte phenotype and activity, we analysed 119 psoriatic patients who either responded or did not respond to different anti-TNF-α therapies (adalimumab, etanercept or infliximab), and measured plasma levels of TNF-α, TNF-α soluble receptors, drug and anti-drug antibodies. Moreover, we analyzed the production of TNF-α and TNF-α soluble receptors by peripheral blood mononuclear cells (PBMCs), and characterized different monocyte populations. We found that: i) the drug levels varied between responders and non-responders; ii) anti-infliximab antibodies were present in 15% of infliximab-treated patients, while anti-etanercept or anti-adalimumab antibodies were never detected; iii) plasma TNF-α levels were higher in patients treated with etanercept compared to patients treated with adalimumab or infliximab; iv) PBMCs from patients responding to adalimumab and etanercept produced more TNF-α and sTNFRII in vitro than patients responding to infliximab; v) PBMCs from patients not responding to infliximab produce higher levels of TNF-α and sTNFRII than patients responding to infliximab; vi) anti- TNF-α drugs significantly altered monocyte subsets. A complex remodelling of the TNFα-TNFα receptor system thus takes place in patients treated with anti-TNF-α drugs, that involves either the production of anti-drug antibodies or the modulation of monocyte phenotype or inflammatory activity.
Bianchini, Elena; Bartolomeo, Regina; Fabiano, Antonella; Manfredini, Marco; Ferrari, Federica; Albertini, Giuseppe; Trenti, Tommaso; Nasi, Milena; Pinti, Marcello; Iannone, Anna; Salvarani, Carlo; Pellacani, Giovanni
TNF-α has a central role in the development and maintenance of psoriatic plaques, and its serum levels correlate with disease activity. Anti-TNF-α drugs are, however, ineffective in a relevant percentage of patients for reasons that are currently unknown. To understand whether the response to anti-TNF-α drugs is influenced by the production of anti-drug antibodies or by the modulation of the TNFα-TNFα receptor system, and to identify changes in monocyte phenotype and activity, we analysed 119 psoriatic patients who either responded or did not respond to different anti-TNF-α therapies (adalimumab, etanercept or infliximab), and measured plasma levels of TNF-α, TNF-α soluble receptors, drug and anti-drug antibodies. Moreover, we analyzed the production of TNF-α and TNF-α soluble receptors by peripheral blood mononuclear cells (PBMCs), and characterized different monocyte populations. We found that: i) the drug levels varied between responders and non-responders; ii) anti-infliximab antibodies were present in 15% of infliximab-treated patients, while anti-etanercept or anti-adalimumab antibodies were never detected; iii) plasma TNF-α levels were higher in patients treated with etanercept compared to patients treated with adalimumab or infliximab; iv) PBMCs from patients responding to adalimumab and etanercept produced more TNF-α and sTNFRII in vitro than patients responding to infliximab; v) PBMCs from patients not responding to infliximab produce higher levels of TNF-α and sTNFRII than patients responding to infliximab; vi) anti- TNF-α drugs significantly altered monocyte subsets. A complex remodelling of the TNFα-TNFα receptor system thus takes place in patients treated with anti-TNF-α drugs, that involves either the production of anti-drug antibodies or the modulation of monocyte phenotype or inflammatory activity. PMID:27936119
Dogra, Sunil; Uprety, Shraddha; Suresh, Swaroop Hassan
Psoriasis, a chronic immune-mediated skin disorder is associated with significant physical, psychological, and quality of life impairments. Along with well-documented genetic and environmental factors, immunological factors also contribute to the pathogenesis of psoriasis. Among the immunological factors, CD6 - dependent T-cell proliferation to form Th1 and Th17 cells play a major role in the pathogenesis of psoriasis. Itolizumab is the first humanized IgG1 monoclonal antibody, which selectively targets CD6. Areas covered: The current article presents the pharmacology of itolizumab and provides a review of the currently available data on the efficacy and safety of itolizumab for management of moderate to severe plaque psoriasis. Expert opinion: The use of biologics to attenuate the immune-mediated pathological events in psoriasis is a relatively well-established clinical practice. However, the safety and efficacy of biologics continues to be an unsettled topic of ongoing research. While available data seems to suggest that itolizumab may be a safer option, additional studies with higher sample sizes and active comparators are needed before definitive conclusions can be drawn on the place of itolizumab in the management of psoriasis.
Pijls, Philippe A R R; Gilissen, Lennard P L
The treatment of patients with inflammatory bowel diseases has been revolutionized by the introduction of biological therapy with TNF-alpha blockers. However, TNF-alpha blockers are also associated with a wide variety of dermatological side effects, such as local skin infections, psoriasis and eczema. A new biological therapy, targeting the gut-specific adhesion molecule alpha4beta7 integrin, is the humanized monoclonal IgG1 antibody vedolizumab. Vedolizumab prevents leukocyte migration to the gastrointestinal tract, thereby reducing inflammation. This gut-specific therapy has the potential to reduce systemic side effects, including dermatological ones. We describe 3 inflammatory bowel disease patients who experience anti-TNF-alpha therapy-induced dermatological side effects, consisting of hidradenitis suppurativa, a folliculitis, scalp psoriasis and a dissecting folliculitis. In all patients, anti-TNF-alpha therapy-induced dermatological side effects diminished after switching to vedolizumab. Vedolizumab may be a viable alternative biological therapy in inflammatory bowel disease patients who experience anti-TNF-alpha therapy-induced dermatological side effects. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
Secrest, Aaron M.; Matinrazm, Ali
Objective: To determine which factors (i.e., cost, efficacy, safety, and method of delivery) influence choice of psoriasis treatment by patients and how patients obtain information regarding treatment options. Design: Anonymous survey. Setting: Specialty Psoriasis Clinic at an academic dermatology department over a six-month period. Participants: Convenience sample of 40 psoriasis patients. Measurements: Participant demographics, psoriasis treatment history, sources of information about treatment options, factors influencing treatment choices, and knowledge of treatment costs. Results: The mean (±SD) patient age and duration of psoriasis was 50 (±17) and 19 (±17) years, respectively. Factors influencing patient’s choice of psoriasis treatment were, in order of importance: efficacy (90% very important), safety/side effects (65%), patient’s own cost (53%), then total treatment cost (46%), frequency of use (37%), and method of medication delivery (i.e., topical, oral, or injection; 17%). Eighty percent of patients reported not knowing the total cost of any psoriasis treatments. The patient’s dermatologist was identified as both the most important (90%) and the most influential (75%) source of information for selecting psoriasis treatments, with the internet being the second most important source. Conclusion: Patients, in large measure, are unaware of the costs for different psoriasis treatments. Efficacy, safety, and out-of-pocket costs are the most important factors to patients in deciding on a psoriasis treatment. PMID:25584135
Takeshita, Junko; Wang, Shuwei; Shin, Daniel B.; Duffin, Kristina Callis; Krueger, Gerald G.; Kalb, Robert E.; Weisman, Jamie D.; Sperber, Brian R.; Stierstorfer, Michael B.; Brod, Bruce A.; Schleicher, Stephen M.; Robertson, Andrew D.; Linn, Kristin A.; Shinohara, Russell T.; Troxel, Andrea B.; Van Voorhees, Abby S.; Gelfand, Joel M.
Background The effectiveness of psoriasis therapies in real-world settings remains relatively unknown. Objective To compare the effectiveness of less commonly used systemic monotherapies and commonly used combination therapies for psoriasis. Methods Multi-center cross-sectional study of 203 patients with plaque psoriasis receiving less common systemic monotherapy (acitretin, cyclosporine, or infliximab) or common combination therapies (adalimumab, etanercept, or infliximab and methotrexate) compared to 168 patients receiving methotrexate evaluated at one of ten US outpatient dermatology sites participating in the Dermatology Clinical Effectiveness Research Network. Results In adjusted analyses, patients on acitretin (relative response rate 2.01; 95% confidence interval, 1.18–3.41), infliximab (1.93; 1.26–2.98), adalimumab and methotrexate (3.04; 2.12–4.36), etanercept and methotrexate (2.22; 1.25–3.94), and infliximab and methotrexate (1.72; 1.10–2.70) were more likely to have clear or almost clear skin compared to patients on methotrexate. There were no differences among treatments when response rate was defined by health-related quality of life. Limitations Single time point assessment may result in overestimation of effectiveness. Conclusions The efficacy of therapies in clinical trials may overestimate their effectiveness as utilized in clinical practice. While physician-reported relative response rates were different among therapies, absolute differences were small and did not correspond to differences in patient-reported outcomes. PMID:25260564
Di Domizio, Jeremy; Conrad, Curdin; Gilliet, Michel
Psoriasis is a chronic autoimmune skin disease affecting approximately 2 % of the population with a major psychosocial and socioeconomic impact. A causal therapy leading to permanent cure is not available, and current treatments only lead to limited amelioration, and therefore new therapeutic targets need to be identified. Recent works demonstrated a predominant role of TH17 cells in the pathogenesis of psoriasis; yet the underlying molecular mechanisms driving the development of the disease are still largely elusive. Several mouse models of psoriasis including drug-induced models (topical application of imiquimod to the skin) and genetically engineered mice (constitutive activation of epidermal STAT3, epidermal deletion of JunB/c-Jun, and epidermal overexpression of Tie2) have been used to study the pathophysiology of the disease; however such models cannot fully recapitulate all molecular and cellular pathways occurring in human psoriasis. Xenotransplantation of human pre-psoriatic skin onto immunodeficient mice and triggering its conversion into a psoriatic plaque is the best model to dissect the mechanisms occurring during the development of human psoriasis. One model is based on the transplantation of human pre-psoriatic skin onto SCID mice followed by the transfer of activated autologous T cells. The ex vivo activation of T cells required to induce the psoriatic conversion of the graft limits the study of early events in the pathogenesis of psoriasis. Another model is based on transplantation of human pre-psoriatic skin onto AGR129 mice. In this model, the skin grafting is sufficient to activate human cells contained in the graft and trigger the conversion of the graft into a psoriatic skin, without the need of transferring activated T cells. Here we review the methodological aspects of this model and illustrate how this model can be used to dissect early events of psoriasis pathogenesis.
Dantow, James E.
Psoriasis is a common skin disease with a variety of clinical presentations. Fortunately, many treatment options are available to the patient and to the physician. Topical, systemic, and physical therapies can be tailored to the patient's needs. Patient compliance and a knowledgeable, caring physician are vital to successful control of the disease. Continuing research offers hope for the chronically disabled. PMID:21221381
Zhang, Yong-Tai; Shen, Li-Na; Wu, Zhong-Hua; Zhao, Ji-Hui; Feng, Nian-Ping
Recent reports have indicated that psoriasis may be caused by malfunctioning dermal immune cells, and psoralen ultraviolet A (PUVA) is an effective treatment for this chronic disease. However, conventional topical formulations achieve poor drug delivery across patches of psoriasis to their target sites. The present study describes the development of a novel psoralen transdermal delivery system employing ethosomes, flexible vesicles that can penetrate the stratum corneum and target deep skin layers. An in vitro skin permeation study showed that the permeability of psoralen-loaded ethosomes was superior to that of liposomes. Using ethosomes, psoralen transdermal flux and skin deposition were 38.89±0.32 μg/cm(2)/h and 3.87±1.74 μg/cm(2), respectively, 3.50 and 2.15 times those achieved using liposomes, respectively. The ethosomes and liposomes were found to be safe following daily application to rat skin in vivo, for 7 days. The ethosomes showed better biocompatibility with human embryonic skin fibroblasts than did an equivalent ethanol solution, indicating that the phosphatidylcholine present in ethosome vesicles improved their biocompatibility. These findings indicated that ethosomes could potentially improve the dermal and transdermal delivery of psoralen and possibly of other drugs requiring deep skin delivery.
The development of targeted biologic agents has revolutionized the treatment of psoriasis. In this review, the authors focus on the published long-term (≥ one year) safety data for the use of tumor necrosis factor-α antagonists etanercept, infliximab, and adalimumab, as well as the IL-12/IL-23 antagonist ustekinumab, in adult patients with moderate-to-severe psoriasis. The efficacy of these currently available biologic therapies has been demonstrated in several studies, and their safety profiles are also reassuring. PMID:25741401
Should tumour necrosis factor antagonist safety information be applied from patients with rheumatoid arthritis to psoriasis? Rates of serious adverse events in the prospective rheumatoid arthritis BIOBADASER and psoriasis BIOBADADERM cohorts.
García-Doval, I; Hernández, M V; Vanaclocha, F; Sellas, A; de la Cueva, P; Montero, D
Information on the safety of tumour necrosis factor (TNF) antagonists frequently arises from their use in rheumatic diseases, their first approved indications, and is later applied to psoriasis. Whether the risk of biological therapy is similar in psoriasis and rheumatoid arthritis has been considered a priority research question. To compare the safety profile of anti-TNF drugs in patients with rheumatoid arthritis and psoriasis. We compared two prospective safety cohorts of patients with rheumatoid arthritis and psoriasis that share methods (BIOBADASER and BIOBADADERM). There were 1248 serious or mortal adverse events in 16 230 person-years of follow-up in the rheumatoid arthritis cohort (3171 patients), and 124 in the 2760 person-years of follow-up of the psoriasis cohort (946 patients). Serious and mortal adverse events were less common in patients with psoriasis than in rheumatoid arthritis (incidence rate ratio of serious adverse events in psoriasis/rheumatoid arthritis: 0·6, 95% confidence interval 0·5-0·7). This risk remained after adjustment for sex, age, treatment, disease, hypertension, diabetes, hypercholesterolaemia and simultaneous therapy with methotrexate (hazard ratio 0·54, 95% confidence interval 0·47-0·61), and after excluding patients receiving corticosteroids. Patients with rheumatoid arthritis showed a higher rate of infections, cardiac disorders, respiratory disorders and infusion-related reactions, whereas patients with psoriasis had more skin and subcutaneous tissue disorders and hepatobiliary disorders. Patients with rheumatoid arthritis clinical practice have almost double the risk of serious adverse events compared with patients with psoriasis, with a different pattern of adverse events. Safety data from rheumatoid arthritis should not be fully extrapolated to psoriasis. These differences are likely to apply to other immune-mediated inflammatory diseases. © 2016 British Association of Dermatologists.
Fotiadou, Christina; Lazaridou, Elizabeth; Ioannides, Demetrios
Psoriasis is a chronic inflammatory cutaneous disorder affecting 2%–4% of the world’s population. The prevalence of the disease in childhood and adolescence ranges between 0.5% and 2%. The management of psoriasis in adolescence is an intriguing and complicated task. Given the paucity of officially approved therapies, the very limited evidence-based data from randomized controlled trials, and the absence of standardized guidelines, physicians must rely on published experience from case reports both from the field of dermatology as well as from the application of these drugs for other pediatric conditions coming from the disciplines of rheumatology, gastroenterology, and oncology. Psoriatic adolescents deal with a potentially disfiguring and lifelong disease that could permanently impair their psychological development. It must be clarified to them that psoriasis does not have a permanent cure, and therefore the main goal of treatments is to establish disease control and prolonged periods between flares. The majority of adolescents suffer from mild psoriasis, and thus they are treated basically with topical treatment modalities. Phototherapy is reserved for adolescents with mild-to-moderate plaque disease and/or guttate psoriasis when routine visits to specialized centers do not create practical problems. Systemic agents and biologics are administered to patients with moderate-to-severe plaque psoriasis, pustular psoriasis, or erythrodermic psoriasis. PMID:24729738
Dey, Nandini; De, Pradip; Brian, Leyland-Jones
Vascular endothelial growth factor (VEGF) dependent tumor angiogenesis is an essential step for the initiation and promotion of tumor progression. The hypothesis that VEGF-driven tumor angiogenesis is necessary and sufficient for metastatic progression of the tumor, has been the major premise of the use of anti-VEGF therapy for decades. While the success of anti-VEGF therapy in solid tumors has led to the success of knowledge-based-therapies over the past several years, failures of this therapeutic approach due to the development of inherent/acquired resistance has led to the increased understanding of VEGF-independent angiogenesis. Today, tumor-angiogenesis is not a synonymous term to VEGF-dependent function. The extensive study of VEGF-independent angiogenesis has revealed several key factors responsible for this phenomenon including the role of myeloid cells, and the contribution of entirely new phenomenon like vascular mimicry. In this review, we will present the cellular and molecular factors related to the development of anti-angiogenic resistance following anti-VEGF therapy in different solid tumors. PMID:26692917
... Old Feeding Your 1- to 2-Year-Old Psoriasis KidsHealth > For Parents > Psoriasis Print A A A ... treatment doesn't work, another probably will. About Psoriasis Psoriasis (suh-RYE-uh-sus) is a non- ...
Glaudemans, A W J M; Dierckx, R A J O; Kallenberg, C G M; Fuentes, K L Anzola
Radiolabelled cytokines and monoclonal antibodies are an emerging class of radiopharmaceuticals for imaging inflammation. These radiopharmaceuticals bind to their targets with high affinity and specificity and therefore have excellent diagnostic potential for imaging of patients with chronic inflammatory diseases. One of the key cytokines involved in the process of inflammation is tumor necrosis factor alpha (TNFα). With the introduction of anti-TNFα monoclonal antibodies over the past decade, treatment of inflammatory diseases has evolved, which allowed remarkable advances in controlling signs and symptoms of inflammation and in slowing destruction. However, drugs may lose efficacy over time in patients or induce adverse events. Using immediately the right medication tailored to the patient's molecular status avoids unnecessary costs and side effects. Significant differences in mechanisms of action and in therapy outcome, depending on the disease to be treated, exist among the different TNFα antagonists. Labelling these agents may help to find out if TNFα is present in the inflammatory process and will therefore help in therapy prediction and stratification in the individual patient. This review describes the role of cytokines and in particular of TNFα in the process of inflammation as well as the influence of TNFα in some well-known and common inflammatory diseases, such as rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel diseases, psoriasis and sarcoidosis. The main focus of this article is to review the role of molecular imaging with radiolabelled anti-TNFα monoclonal antibodies for diagnostic purposes, and in therapy precision, decision-making and evaluation.
Zimmermann, J; Utermann, S
The effectiveness of salt water baths and subsequent selective ultraviolet phototherapy (SUP) was investigated in a prospective study on 40 patients with psoriasis vulgaris and atopic dermatitis. There were two groups with 20 patients each. The first group was treated with salt water (15%) that contained synthetic Dead Seas salt called "Psorisal"; the patients in the second group had a bath in a 3% NaCl solution. After 4 weeks of daily treatment, we found that 80% of the patients in the group treated with "Psorisal" had significantly better results than the second group. The subjective feeling of being ill had decreased significantly in both groups by the end of the study. The only side effect we found was the occurrence of sunburn in few cases, but this occurred significantly less in the "Psorisal" group. Both groups generally accepted the balneophototherapy, so it can easily be employed on an outpatient basis.
Joshi, Aditya A; Lerman, Joseph B; Aberra, Tsion M; Afshar, Mehdi; Teague, Heather L; Rodante, Justin A; Krishnamoorthy, Parasuram; Ng, Qimin; Aridi, Tarek Z; Salahuddin, Taufiq; Natarajan, Balaji; Lockshin, Benjamin N; Ahlman, Mark A; Chen, Marcus Y; Rader, Daniel J; Reilly, Muredach P; Remaley, Alan T; Bluemke, David A; Playford, Martin P; Gelfand, Joel M; Mehta, Nehal N
GlycA, an emerging inflammatory biomarker, predicted cardiovascular events in population-based studies. Psoriasis, an inflammatory disease associated with increased cardiovascular risk, provides a model to study inflammatory biomarkers in cardiovascular disease (CVD). Whether GlycA associates with psoriasis and how it predicts subclinical CVD beyond high-sensitivity C-reactive protein in psoriasis is unknown. To investigate the relationships between GlycA and psoriasis and between GlycA and subclinical CVD. Patients with psoriasis and controls (n=412) participated in a 2-stage study. We measured GlycA by nuclear magnetic resonance spectroscopy. National Institutes of Health (NIH) participants underwent 18-F Fluorodeoxyglucose Positron Emission Tomography Computed Tomography (18-FDG PET/CT) scans to assess vascular inflammation (VI) and coronary computed tomographic angiography to quantify coronary artery disease burden. Psoriasis cohorts were young (mean age=47.9), with low cardiovascular risk and moderate skin disease. high-sensitivity C-reactive protein and GlycA were increased in psoriasis compared with controls (GlycA: [PENN: 408.8±75.4 versus 289.4±60.2, P<0.0001; NIH: 415.8±63.2 versus 346.2±46, P<0.0001]) and demonstrated a dose-response with psoriasis severity. In stage 2, VI (β=0.36, P<0.001) and coronary artery disease (β=0.29, P=0.004) associated with GlycA beyond CV risk factors in psoriasis. In receiver operating characteristic analysis, GlycA added value in predicting VI (P=0.01) and coronary artery disease (P<0.01). Finally, initiating anti-tumor necrosis factor therapy (n=16) reduced psoriasis severity (P<0.001), GlycA (463.7±92.5 versus 370.1±78.5, P<0.001) and VI (1.93±0.36 versus 1.76±0.19, P<0.001), whereas GlycA remained associated with VI (β=0.56, P<0.001) post treatment. GlycA associated with psoriasis severity and subclinical CVD beyond traditional CV risk and high-sensitivity C-reactive protein. Moreover, psoriasis treatment
Syed Nong Chek, Sharifah Rosniza; Robinson, Suganthy; Mohd Affandi, Azura; Baharum, Nurakmal
Psoriasis involving the face is visible and can cause considerable emotional distress to patients. Its presence may also confer a poorer prognosis for the patient. This study sought to evaluate the characteristics of facial psoriasis in Malaysia. A cross-sectional study conducted using data from the Malaysian Psoriasis Registry from 2007 to 2011. Specific risk factors, i.e., age, age of onset, gender, duration of disease, obesity group, body surface area, Dermatology Life Quality Index (DLQI), family history of psoriasis, nail involvement, psoriatic arthritis, phototherapy, systemic therapy, clinic visit, days of work/school, and hospital admission due to psoriasis in the last 6 months were analyzed. A total of 48.4% of patients had facial psoriasis. Variables significantly associated with facial psoriasis are younger age, younger age of onset of psoriasis of ≤ 40 years, male, severity of psoriasis involving >10% of the body surface area, higher DLQI of >10, nail involvement, and history of hospitalization due to psoriasis. This study found that facial psoriasis is not as rare as previously thought. Ambient ultraviolet light, sebum, and contact with chemicals from facial products may reduce the severity of facial psoriasis, but these factors do not reduce the prevalence of facial psoriasis. The association with younger age, younger age of onset, higher percentage of body surface area involvement, higher DLQI of > 10, nail involvement, and hospitalization due to psoriasis support the notion that facial psoriasis is a marker of severe disease. © 2016 The International Society of Dermatology.
The scalp is involved in up to 80% of individuals with psoriasis. Eighty percent of those with scalp psoriasis experience a negative impact on quality of life. Topical treatment with corticosteroids with or without vitamin D3 analogues is the mainstay of treatment. Topical therapy most suitable for the scalp is formulated as a solution, lotion, gel, foam, spray, oil, or shampoo. Twice weekly maintenance in frequent relapsers may decrease the time to first relapse. Intralesional steroids, phototherapy and the excimer laser are occasionally used for resistant cases. In patients with moderate-to-severe psoriasis, apremilast, adalimumab and etanercept have been shown to significantly improve scalp psoriasis. They should be considered in patients who have failed topical therapy.
... It usually appears after an infection, most notably strep throat caused by group A strep. Guttate psoriasis is ... healthy cells for harmful substances. In addition to strep throat, the following may trigger an attack of guttate ...
Boehncke, Wolf-Henning; Menter, Alan
Psoriatic arthritis (PsA) increases the disease burden associated with psoriasis by further diminishing quality of life, increasing health care costs and cardiovascular risk, and potentially causing progressive joint damage. The presence of PsA influences psoriasis treatment by increasing overall disease complexity and, within the framework of current guidelines and recommendations, requiring the use of conventional disease-modifying anti-rheumatic drugs or tumor necrosis factor-α inhibitors in order to prevent progressive joint damage. Despite its important impact, PsA is still under-diagnosed in dermatology practice. Dermatologists are well positioned to recognize and treat PsA, given that it characteristically presents, on average, 10 years subsequent to the appearance of skin symptoms. Regular screening of psoriasis patients for early evident joint symptoms should be incorporated into daily dermatologic practice. Although drugs effective in PsA are available, not all patients may respond to treatment, and others may lose their initial response over time. New investigational therapies, such as inhibitors of interleukin-17A, interleukin-12/23, Janus kinase 3, or phosphodiesterase-4, may address unmet needs in psoriatic disease, with further research needed to determine the role of these agents in reducing joint damage and other comorbidities.
Dulak, Józef; Józkowicz, Alicja
Angiogenesis is indispensable for the growth of solid tumors and angiogenic factors are also involved in the progression of hematological malignancies. Targeting the formation of blood vessels is therefore regarded as a promising strategy in cancer therapy. Interestingly, besides demonstration of some beneficial effects of novel anti-angiogenic compounds, recent data on the activity of already available drugs point to their potential application in anti-angiogenic therapy. Among these are the statins, the inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase. Statins are very efficient in the treatment of hypercholesterolemia in cardiovascular disorders; however, their effects are pleiotropic and some are not directly related to the inhibition of cholesterol synthesis. Some reports particularly highlight the pro-angiogenic effects of statins, which are caused by low, nanomolar concentrations and are regarded as beneficial for the treatment of cardiovascular diseases. On the other hand, the anti-angiogenic activities, observed at micromolar concentrations of statins, may be of special significance for cancer therapy. Those effects are caused by the inhibition of both proliferation and migration and induction of apoptosis in endothelial cells. Moreover, the statin-mediated inhibition of vascular endothelial growth factor synthesis, the major angiogenic mediator, may contribute to the attenuation of angiogenesis. It has been suggested that the anti-cancer effect of statins can be potentially exploited for the cancer therapy. However, several clinical trials aimed at the inhibition of tumor growth by treatment with very high doses of statins did not provide conclusive data. Herein, the reasons for those outcomes are discussed and the rationale for further studies is presented. PMID:16375664
Nascimento, Bianca Angelina Macêdo do; Carvalho, Alessandra Haber; Dias, Carolina Moraes; Lage, Thaiane Lima; Carneiro, Clívia Maria Oliveira; Bittencourt, Maraya de Jesus Semblano
Lithium has been implicated in the exacerbation of pre-existing psoriasis, in the induction of psoriasis on previously uninvolved skin of psoriasis patients, and in the triggering of psoriasis for the first time in patients without a personal or family history. Lithium-induced psoriasis (and its resistance to treatment) is one of the major reasons for noncompliance in patients treated with lithium. We describe a male patient who developed generalized ostraceous psoriasis whose clinical appearance mimicked dermatitis neglecta, 10 months after starting therapy with lithium.
do Nascimento, Bianca Angelina Macêdo; Carvalho, Alessandra Haber; Dias, Carolina Moraes; Lage, Thaiane Lima; Carneiro, Clívia Maria Oliveira; Bittencourt, Maraya de Jesus Semblano
Lithium has been implicated in the exacerbation of pre-existing psoriasis, in the induction of psoriasis on previously uninvolved skin of psoriasis patients, and in the triggering of psoriasis for the first time in patients without a personal or family history. Lithium-induced psoriasis (and its resistance to treatment) is one of the major reasons for noncompliance in patients treated with lithium. We describe a male patient who developed generalized ostraceous psoriasis whose clinical appearance mimicked dermatitis neglecta, 10 months after starting therapy with lithium. PMID:26312715
Giunta, Alessandro; Ventura, Alessandra; Chimenti, Maria Sole; Bianchi, Luca; Esposito, Maria
Psoriasis is a chronic inflammatory disease affecting up to 3% of the general population, associated with discomfort and impaired quality of life. In recent years, the pathogenic cytokine network of psoriasis has been extensively studied leading to the development of new treatments that provide greater efficacy. Interleukin 17A (IL-17A) has been recognized as a crucial cytokine that mediates immunopathogenesis of psoriasis. Ixekizumab – indicated for the treatment of adults with moderate-to-severe plaque psoriasis – is a subcutaneously administered humanized monoclonal antibody that targets IL-17A. A large percentage of patients affected by psoriasis achieved consistent benefits in terms of disease control and rapid onset of action during clinical trials. Overall, ixekizumab brought clinical improvement and a favorable safety profile in phase III trials. Ixekizumab is characterized by consistent efficacy and rapid onset of response; it is not influenced by previous exposure to biologics and has shown good results in areas that are difficult to treat and in severe clinical variants of psoriasis. Ixekizumab has shown significant improvements in the activity of the disease and in those physical functions that inhibit radiographic progression in patients with concomitant involvement of joints. Our data support ixekizumab as a successful therapeutic option for patients affected by moderate-to-severe plaque-type psoriasis. PMID:28652702
Gkalpakiotis, Spyridon; Arenbergerova, Monika; Gkalpakioti, Petra; Potockova, Jana; Arenberger, Petr; Kraml, Pavel
Psoriasis is a chronic systemic immune-mediated inflammatory dermatosis associated with several comorbidities. Psoriasis patients are at increased risk of developing cardiovascular diseases (CVD), namely, coronary heart disease, stroke or peripheral vascular disease, and psoriasis seems to be an independent cardiovascular risk factor. Antipsoriatic systemic therapy, especially anti-tumor necrosis factor (TNF)-α, seems to exert a beneficial effect on these comorbidities. The purpose of this study was: (i) to measure the level of cardiovascular serum markers in psoriasis patients in comparison with healthy volunteers; and (ii) to compare the serum level of the same markers in patients before and 3 months after adalimumab therapy. We investigated six biomarkers connected to CVD: C-reactive protein (measured high sensitively, hsCRP), oxidized low-density lipoproteins (oxLDL), oxLDL/β-glycoprotein I complex (oxLDL/β2GPI), vascular endothelial adhesion molecule 1 (VCAM-1), E-selectin and interleukin (IL)-22. These biomarkers were measured in 21 patients with moderate/severe psoriasis before and after treatment with adalimumab and in healthy volunteers. hsCRP (P < 0.05), oxLDL-β2GPI complex (P < 0.05), E-selectin (P < 0.001) and IL-22 (P < 0.001) were significantly increased in comparison with healthy controls, whereas oxLDL and VCAM-1 were also higher in psoriasis patients but the difference did not reach statistical significance. A decrease of E-selectin (P < 0.001) and IL-22 (P < 0.001) was observed after 3 months of adalimumab therapy. Inhibition of TNF-α seems to not only improve psoriasis but also decreases serum cardiovascular biomarkers. E-selectin and IL-22 could serve for monitoring of the efficacy of antipsoriatic systemic therapy on cardiovascular risk. © 2016 Japanese Dermatological Association.
Choi, Jung Ran; Yun, Gak Won; Park, Yoo Mi; Kim, Jie Hyun; Youn, Young Hoon; Park, Hyo Jin; Park, Jae Jun
Thanks to the introduction of immumomodulators and biologics, therapeutic approaches in Crohn's disease have changed significantly during the past decade. Although new biologic therapy has dramatically improved the treatment of Crohn's disease, a substantial number of patients are refractory to these therapies or lose their initial response. Methotrexate (MTX) is a structural analogue of folic acid that can competitively inhibit the binding of dihydrofolic acid to the enzyme dihydrofolate reductase and has been widely used as immunomodulator in rheumatology area for patients with rheumatoid arthritis and psoriasis. Although MTX has also been shown to be an effective agent for remission induction and maintenance of remission in Crohn's disease, the use of MTX in Crohn's disease has not yet been reported in Korea. Herein, we report a case of Crohn's disease patient who was successfully treated with MTX after treatment failure with thiopurine and anti-tumor necrosis factor.
Feldman, Steven R; Koo, John Y M; Johnson, Lori A; Preston, Norman J
Moderate to severe psoriasis often requires systemic treatment, but even biologic medications do not always induce complete clearing in patients. In many instances, physicians supplement biologic treatment with topical agents as adjunctive therapy to obtain additional clearing of plaques. To evaluate the effectiveness of the addition of a superpotent corticosteroid--clobetasol propionate spray 0.05%--to various psoriasis treatments, a phase 4, multicenter, open-label, community-based trial was conducted. In this study, clobetasol propionate spray 0.05% applied twice daily was added on to a variety of existing stable treatments including systemic biologic agents in participants with moderate, severe, or very severe plaque psoriasis. The decision to add clobetasol propionate spray 0.05% to stable psoriasis therapy was determined by each investigator based on his/her evaluation of a participant's needs. A total of 159 participants from the trial adhered to stable (> or = 3 months' duration) therapeutic regimens that included a biologic treatment. In this population, at the end of the study period, 81.0% of participants with moderate disease at baseline, 79.5% of participants with severe disease at baseline, and 58.8% of participants with very severe disease at baseline were rated as clear or almost clear (target plaque severity [TPS]). Worst skin tolerability response was assessed postbaseline and included erythema (20.3% mild, 8.9% moderate, 1.9% severe), peeling (26.6% mild, 7.0% moderate, 1.3% severe), dryness (34.8% mild, 8.9% moderate, 1.3% severe), and stinging (25.3% mild, 3.8% moderate, 0.6% severe). Telangiectasia and skin atrophy were reported in 1.3% of participants each at some point during the study (postbaseline). Pruritus was reported in 7.6% of participants and folliculitis was reported in 1.9% of participants. Eight participants experienced adverse events (AEs) that were regarded as probably related to the study medication (clobetasol propionate spray
Sharma, Manju; Levenson, Corey; Clements, Ian; Castella, Paul; Gebauer, Kurt; Cox, Michael E.
Psoriasis, a chronic inflammatory skin disease marked by hyper proliferation and aberrant differentiation of keratinocytes, affects 2–3% of the world’s population. Research into the pathogenesis of psoriasis has been hampered by the lack of models that accurately reflect the biology of the psoriatic phenotype. We have previously reported that East Indian Sandalwood oil (EISO) has significant anti-inflammatory properties in skin models and hypothesized that EISO might provide therapeutic benefit to psoriasis patients due to its anti-inflammatory and anti-proliferative properties. Here we present interim results from an on-going proof-of-concept Phase 2 clinical trial in which topically applied EISO is demonstrating to be well tolerated and helpful in alleviating mild to moderate psoriasis symptoms. This led us to evaluate the ability of EISO to affect the psoriatic phenotype using MatTek Corporation reconstituted organotypic psoriatic and normal human skin models. EISO had no impact on the phenotype of the normal skin tissue model, however, EISO treatment of the psoriasis tissue model reverted psoriatic pathology as demonstrated by histologic characterization and expression of keratinocyte proliferation markers, Ki67 and psoriasin. These phenotypic affects correlated with suppressed production of ENA-78, IL-6, IL-8, MCP-1, GM-CSF, and IL-1β. Demonstration of the ability of EISO to abrogate these psoriasis symptoms in well-characterized in vitro psoriatic tissue models, supports the hypothesis that the clinically observed symptom alleviation is due to suppression of intrinsic tissue inflammation reactions in afflicted lesions. This study presents a systematic approach to further study the underlying mechanisms that cause psoriasis, and presents data supporting the potential of EISO as a new ethnobotanical therapeutic concept to help direct and accelerate the development of more effective therapies. PMID:28360856
Matsushita, Y; Shimada, Y; Kawara, S; Takehara, K; Sato, S
Psoriasis is believed to be a T cell-mediated autoimmune disease, but also exhibits autoantibody production. Calpastatin is an endogenous inhibitor of calpain, a ubiquitous protease that regulates inflammatory processes. Anti-calpastatin autoantibody was first identified as an autoantibody specific to rheumatoid arthritis, but has been also detected in other autoimmune diseases. In this study, we examined the presence and levels of anti-calpastatin antibody in 77 psoriasis patients by enzyme-linked immunosorbent assay. Compared with normal controls, psoriasis patients exhibited significantly elevated IgG anti-calpastatin antibody levels that were similar to those found in rheumatoid arthritis patients. Remarkably, IgG anti-calpastatin autoantibody in sera from psoriasis patients inhibited calpastatin activity. Calpain II expression was up-regulated in psoriasis skin lesions compared with normal skin while calpastatin expression was normal. The results of this study reveal the presence of anti-calpastatin autoantibody in psoriasis. PMID:15654835
Sarac, Gulbahar; Koca, Tuba Tulay; Baglan, Tolga
Psoriasis is a chronic inflammatory dermatosis that is thought to onset as a result of T lymphocyte-mediated immunological response. Disease may manifest itself in different modalities with regard to clinical features and severity. Clinical type of psoriasis is an important element in determining the therapy regimen. This article reviews clinical types of psoriasis. PMID:28058392
Beyer, Vivianne; Wolverton, Stephen E
To analyze the current total cost of systemic therapy for psoriasis and to compare annual trends in the cost of both generic and brand-name therapies with trends in the Consumer Price Index-Urban since 2000. A cost model was developed that includes costs for prescription drugs, office visits, and suggested laboratory tests and monitoring procedures. Annual trends in psoriasis drug costs from 2000 through 2008 were analyzed by calculating the percentage change in the average wholesale price from the previous year; these values were compared with changes in the yearly Consumer Price Index-Urban values. The United States. Total annual costs for systemic psoriasis therapies and trends in cost compared with the trends in Consumer Price Index-Urban values (equivalent to inflation). Current total annual costs for systemic psoriasis therapies ranged from $1197 (methotrexate) to $27,577 (alefacept, two 12-week courses). Trends in the average wholesale price of brand-name psoriasis therapies from 2000 through 2008 demonstrate an average increase of 66% (range, -24% to +316%); thus, costs of several brand-name psoriasis drugs greatly outpaced the rates of inflation for all items and all prescription drugs. Despite the higher monitoring costs associated with traditional systemic therapies, annual costs of biologics exceed those of other available therapies. Current trends demonstrate that systemic psoriasis therapy costs are increasing at a much higher rate compared with general inflation.
Roth, P E; Grosshans, E; Bergoend, H
In a retrospective study we tried to evaluate the number of severe psoriasis with a lethal outcome observed in France in a 20-year period from 1965 to 1985. Among 992 psoriatic in-patients on care during this period in the Dermatology Clinic of Strasbourg, 7 died of different complications directly related to the skin disease or its therapy; 39 further cases could be gathered through different departments of dermatology of France. Patients who died had generalized psoriasis (13 cases), psoriatic erythroderma (15 cases) and generalized pustular psoriasis (18 cases); 18 (39 p. 100) also had psoriatic polyarthritis. Circumstances leading to death (table I) were metabolic disorders, related to erythroderma in most cases, non-specific complications (infections, amyloidosis) or complications of specific treatments (methotrexate, etretinate, corticosteroids, mechlorethamine). A comprehensive review of the literature over a century showed that only 72 lethal psoriasis cases have been reported: this rather low number may be due to the fact that some rare pathologies, such as visceral amyloidosis (12 cases) (table III) and fatal complications of methotrexate therapy (38 cases) (table V), paradoxically are more often published than non-specific complications occurring in severe psoriasis, such as cardiovascular failure or cachexy in erythrodermic patients. However, the review of the literature shows, as our own inquiry, the poor prognosis of generalized pustular forms and of psoriasis-associated polyarthropathies: among 42 lethal cases where enough data were available, 23 (55 p. 100) had psoriatic polyarthritis.(ABSTRACT TRUNCATED AT 250 WORDS)
Schons, Karen Regina Rosso; Knob, Cristiane Faccin; Murussi, Nádia; Beber, André Avelino Costa; Neumaier, Walter; Monticielo, Odirlei André
Nails are considered epidermal appendages, and as such, are commonly affected in patients with psoriasis, 80% of whom are likely to develop nail psoriasis as a result of their condition. Two patterns of nail disorders have been shown to be caused by psoriasis. Nail matrix involvement can result in features such as leukonychia, pitting (punctures or cupuliform depressions), red spots in the lunula and crumbling. Nail bed involvement, on the other hand, can cause onycholysis, salmon or oil-drop patches, subungual hyperkeratosis and splinter hemorrhages. Nail disease causes aesthetic and functional impairment, and is indicative of more severe forms of psoriasis as well as of joint involvement. The treatment for nail psoriasis involves behavioral interventions, topical medications, or systemic therapy in case of extensive skin or joint involvement. This article presents a review of the main features of nail psoriasis, its clinical presentation, diagnostic and assessment methods, clinical repercussions, and of its available treatment options. PMID:24770509
Schons, Karen Regina Rosso; Knob, Cristiane Faccin; Murussi, Nádia; Beber, André Avelino Costa; Neumaier, Walter; Monticielo, Odirlei André
Nails are considered epidermal appendages, and as such, are commonly affected in patients with psoriasis, 80% of whom are likely to develop nail psoriasis as a result of their condition. Two patterns of nail disorders have been shown to be caused by psoriasis. Nail matrix involvement can result in features such as leukonychia, pitting (punctures or cupuliform depressions), red spots in the lunula and crumbling. Nail bed involvement, on the other hand, can cause onycholysis, salmon or oil-drop patches, subungual hyperkeratosis and splinter hemorrhages. Nail disease causes aesthetic and functional impairment, and is indicative of more severe forms of psoriasis as well as of joint involvement. The treatment for nail psoriasis involves behavioral interventions, topical medications, or systemic therapy in case of extensive skin or joint involvement. This article presents a review of the main features of nail psoriasis, its clinical presentation, diagnostic and assessment methods, clinical repercussions, and of its available treatment options.
Saad, F; Haider, A; Gooren, L
Psoriasis is increasingly recognised as a skin disease with far-reaching systemic effects, associated with a high prevalence of comorbid disease such as cardiometabolic dysfunction, shifting the focus from a single organ disease confined to the skin to a systemic inflammatory condition. Chronic and systemic inflammation plays a major role in the development of these diseases, and there are striking similarities between the molecular and inflammatory pathways in psoriasis and atherosclerosis. In a single-centre, cumulative, prospective registry study of 347 hypogonadal men (total testosterone ≤12.1 nmol l(-1) ), fifteen men with psoriasis could be studied. Upon testosterone administration, the skin disease improved considerably. Scores on the Psoriasis Area and Severity Index and Physician Global Assessment for Psoriasis showed significant improvement for the first 24 months. Thereafter, these improvements were sustained. Upon testosterone treatment, C-reactive protein declined significantly. There were significant improvements of obesity and of lipid profiles. Adipose tissue is now regarded as a source of inflammatory factors. These preliminary results deserve to be studied in a specifically designed study to investigate the effects of testosterone on psoriasis and its associated immunopathology.
Kristensen, Tina Bøgelund; Knutsson, Malin L. T.; Wehland, Markus; Laursen, Britt Elmedal; Grimm, Daniela; Warnke, Elisabeth; Magnusson, Nils E.
Neo-angiogenesis is a critical process for tumor growth and invasion and has become a promising target in cancer therapy. This manuscript reviews three currently relevant anti-angiogenic agents targeting the vascular endothelial growth factor system: bevacizumab, ramucirumab and sorafenib. The efficacy of anti-angiogenic drugs in adjuvant therapy or as neo-adjuvant treatment has been estimated in clinical trials of advanced breast cancer. To date, the overall observed clinical improvements are unconvincing, and further research is required to demonstrate the efficacy of anti-angiogenic drugs in breast cancer treatments. The outcomes of anti-angiogenic therapy have been highly variable in terms of tumor response. New methods are needed to identify patients who will benefit from this regimen. The development of biomarkers and molecular profiling are relevant research areas that may strengthen the ability to focus anti-angiogenic therapy towards suitable patients, thereby increase the cost-effectiveness, currently estimated to be inadequate. PMID:25514409
Sminkels, O Q J; Prins, M; Veeniiuis, R T; De Boo, T; Gerritsen, M J P; Van Der Wilt, G J; Van De Kerkhof, P C M; Van Der Valk, P G M
The efficacy of UVB-phototherapy (UVB) and dithranol treatment for psoriasis is well established. However, well-conducted clinical trials on the efficacy of dithranol are not available, making comparison between these time-honoured treatments with currently available therapies impossible. We studied the effectiveness of dithranol in a care instruction programme using short time exposures (short contact treatment), UVB-phototherapy and dithranol treatment in an inpatient setting. In an open randomised study we included 250 patients with moderate to severe psoriasis. The intention to treat group existed of 238 patients. 100 patients were treated with short contact dithranol, 78 Patients were treated with UVB and 60 patients underwent inpatient dithranol treatment. We found UVB and dithranol treatment to be effective and safe in moderate to severe psoriasis. The efficacy of short contact dithranol treatment equals the efficacy of UVB-phototherapy. Dithranol treatment at the inpatient department showed superior efficacy in clinical response rate and treatment duration as compared to UVB and short contact treatment. The median number of days in remission was significantly longer after short contact treatment as compared to inpatient treatment. Although the use of dithranol is hampered by skin irritation and staining, the present study shows that dithranol treatment has an outstanding efficacy and safety profile. Comparison between different antipsoriatic treatments should, besides clearing capacity, reconcile duration of remission, safety, patient acceptability and costs.
... Kids’ zone Video library Find a dermatologist Scalp psoriasis Overview Scalp psoriasis: When psoriasis forms on the scalp, it can creep beyond the scalp. Scalp psoriasis: Overview Psoriasis (sore-EYE-ah-sis) can appear ...
... Kids’ zone Video library Find a dermatologist Scalp psoriasis Overview Scalp psoriasis: When psoriasis forms on the scalp, it can creep beyond the scalp. Scalp psoriasis: Overview Psoriasis (sore-EYE-ah-sis) can appear ...
Choi, Chong Won; Kim, Bo Ri; Ohn, Jungyoon
Background Psoriasis is a chronic inflammatory disease. In the treatment of psoriasis, cyclosporine is commonly prescribed systemic agents. However, long-term use of cyclosporine is not recommended because of side effects such as nephrotoxicity or hypertension. Objective To ascertain the improved safety of rotational therapy using cyclosporine and methotrexate, we investigated the frequency of abnormal results in laboratory test after long term rotational therapy using cyclosporine and methotrexate. Methods From January 2009 to June 2014, patients who were treated with cyclosporine or methotrexate were enrolled. The clinical data and usage of medications were reviewed. Laboratory tests were conducted before starting the treatment and regularly follow-up. The occurrences of any laboratory abnormalities during the treatments were investigated. Results A total of 21 psoriatic patients were enrolled. The mean of medication period and cumulative dose of cyclosporine and methotrexate were 497.81±512.06 days and 115.68±184.34 g in cyclosporine and 264.19±264.71 days and 448.71±448.63 mg in methotrexate. Laboratory abnormalities were found in total two patients after rotational therapy: two patients (9.5%) in aspartate aminotransferase/alanine aminotransferase and one patient (4.8%) in uric acid. No laboratory abnormalities were found in renal function test. Conclusion We found that the rotational approaches using cyclosporine and methotrexate reduced the possibility of the development of nephrotoxicity. In addition to other advantage such as quick switching from one agent to another, the rotational therapy using cyclosporine and methotrexate can minimize the adverse events during the systemic treatment of chronic plaque psoriasis. PMID:28223747
Ayala, Fabio; Lambert, Julien
Biologic anti-tumor necrosis factor-α (anti-TNF-α) therapies have revolutionized the management of psoriasis. However, despite similar mechanisms of action, inter-patient variability in the clinical responses to therapy remain unexplained. Possible differences between agents include stability or bioavailability and anti-drug antibody development, and patient factors such as compliance may play a role. As a result, it is not uncommon for physicians to switch a patient from one anti-TNF-α agent to another when initial response is inadequate. This multicenter, single-arm, observational, Phase IV study assessed the efficacy and safety of infliximab therapy in patients with moderate-to-severe psoriasis who had not responded to 24 weeks' etanercept treatment. Drug efficacy was assessed using specific psoriasis indexes; health-related quality of life (HRQoL) was measured using the Dermatology Life Quality Index and the Skindex-29. A total of 48 patients were screened, 38 were treated with infliximab and 31 completed the study. Of these, 71% achieved Psoriasis Area and Severity Index 75 after 10 weeks, and improvement in HRQoL was documented. The results of this study showed that patients with moderate-to-severe psoriasis could be successfully switched from etanercept to infliximab, with improvements in both clinical parameter and HRQoL.
Ekman, Anna-Karin; Sigurdardottir, Gunnthorunn; Carlström, Maria; Kartul, Natalja; Jenmalm, Maria C; Enerbäck, Charlotta
Chemokines may contribute to the systemic inflammation that is linked to the increased risk of co-morbidities in patients with psoriasis. The aim of this study was to investigate circulating chemokines in patients with psoriasis and their relationship to disease severity. Analysis of plasma levels of chemokines in patients with psoriasis before narrowband ultraviolet B (UVB) therapy revealed increased expression of Th1-associated CXCL9 and -10, Th2-associated CCL17 and CCL22, and Th17-associated CCL20. CCL20 correlated with disease severity. UVB therapy reduced skin symptoms, but did not affect the chemokine levels in plasma. Anti-CD3 and anti-CD28-mediated activation of peripheral blood mononuclear cells (PBMCs) caused a higher secretion of Th2 cytokine interleukin (IL)-13 by PBMCs from patients with psoriasis than from healthy controls. The sustained high expression of inflammatory chemokines is a potential link to systemic inflammation in psoriasis. UVB therapy may be a more effective treatment of local rather than systemic inflammation.
Detrez, Iris; Van Steen, Kristel; Segaert, Siegfried; Gils, Ann
The association between etanercept serum concentration and psoriasis disease severity is poorly investigated, and currently etanercept serum concentration monitoring that is aiming to optimize the psoriasis treatment lacks evidence. In this prospective study, we investigated the relation between etanercept exposure and disease severity via measuring etanercept concentrations at five consecutive time points in 56 psoriasis patients. Disease severity assessments included the Psoriasis Area and Severity Index (PASI), body surface area (BSA) and Physician Global Assessment (PGA), and etanercept and anti-etanercept antibody concentrations were determined every 3 months for a period of 1 year. The present study demonstrated that the association between etanercept concentration and psoriasis severity is age-dependent: when patients were stratified into three groups, patients in the youngest age group (-50 years) showed a lower PASI at a higher etanercept concentration (β = -0.26), whereas patients in the oldest age group (+59 years) showed the opposite trend (β =0.22). Similar age effects were observed in the relation of etanercept concentration with BSA (P=0.02) and PGA (P=0.02). The influence of age and length of time in therapy on the etanercept concentration-disease severity relation was unaffected by body mass index (BMI) or any other possible confounder. Incidence of anti-etanercept antibodies was low (2%). The age-dependent relation between etanercept serum concentrations is both unexpected and intriguing and needs further investigation. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.
McCoy, John; Goren, Andy; Lotti, Torello
Ultraviolet-B (UVB) phototherapy is a well-established mode of treatment for several types of dermatological disease. For psoriasis and vitiligo, narrow band UVB (NB-UVB) phototherapy is an effective therapy, demonstrating greater efficacy and safety compared to broadband UVB or psoralen plus UVA treatments. While the treatment efficacy of NB-UVB artificial light sources is well documented, the long term time and cost commitment of the therapy remains a barrier to treatment adherence. Natural sunlight is an ideal source of accessible UVB radiation; however, exposure to natural sunlight generally results in erythema prior to the accumulation of sufficient dosage of therapeutic wavelengths of UVB. This communication describes a novel topical cream designed to selectively deliver NB-UVB therapy when exposed to sunlight. The topical cream when combined with natural sunlight could offer patients a more convenient phototherapy option for psoriasis and vitiligo, potentially increasing patient compliance. © 2013 Applied Biology Inc. Dermatologic Therapy © 2013 Wiley Periodicals, Inc.
... Information Psoriasis Find a Clinical Trial Journal Articles Psoriasis PDF Version Size: 54 KB Audio Version Time: ... Size: 6.4 MB November 2014 What Is Psoriasis? Fast Facts: An Easy-to-Read Series of ...
Napolitano, Maddalena; Megna, Matteo; Balato, Anna; Ayala, Fabio; Lembo, Serena; Villani, Alessia; Balato, Nicola
Psoriasis is a chronic, immune-mediated, inflammatory skin disease, affecting 1-3% of the white population. Although the existence of two psoriasis incidence peaks has been suggested (one in adolescence before 20 years of age and another in adulthood), its onset may occur at any age, including childhood and adolescence, in which the incidence is now estimated at 40.8 per 100,000. As for adult psoriasis, pediatric psoriasis has recently been associated with obesity, metabolic syndrome, increased waist circumference percentiles and metabolic laboratory abnormalities, warranting early monitoring and lifestyle modifications. In addition, due to psoriasis' chronic nature and frequently occurring relapses, psoriatic patients tend to have an impaired quality of life, often requiring long-term treatment. Therefore, education of both pediatric patients and their parents is essential to successful and safe disease management. Given the lack of officially approved therapies, the very limited evidence-based data from randomized controlled trials, and the absence of standardized guidelines, to date, pediatric psoriasis treatment is primarily based on published case reports, case series, guidelines for adult psoriasis, expert opinions and experience with these drugs in other pediatric disorders coming from the disciplines of rheumatology, gastroenterology and oncology. This review focuses on the use of systemic treatments in pediatric psoriasis and their specific features, analyzing the few literature evidences available, expanding the treatment repertoire and guiding dermatologists in better managing of recalcitrant pediatric psoriasis.
Epstein, J. David
Psoriasis is a relatively common chronic dermatosis that is genetically determined and environmentally influenced. Because it is ideopathic, therapy is presently supportive, directed at optimal control, patient understanding, and prevention of recurrence. Because this multifactorial condition may involve skin and nails, musculoskeletal system, and psyche in various combinations and degrees, an organized co-operative team approach involving the patient, the family, and appropriately experienced health-care providers is most beneficial. Many topical and systemic medications, as well as physical therapeutic modalities, both established and innovative, are available for use sequentially or in various combinations to suite the individual and his/her particular psoriasis. This brief review will outline the better established dermatologic therapeutic principles and options currently available for this patient group. PMID:21263959
Shahwan, Kathryn T; Kimball, Alexa B
Psoriasis is a systemic inflammatory disease that confers significant risk of metabolic derangements and adverse cardiovascular outcomes. Early detection and treatment of modifiable risk factors and modulation of the systemic inflammatory response are important treatment goals. Studies have shown that there is a significant lack of awareness of the relationship between psoriasis and cardiovascular disease, so future considerations should focus on education of and collaboration with health care providers, especially those in primary care, and development of updated, rigorous screening guidelines. In addition, targeted biologic therapies such as TNF-a inhibitors have shown immense promise in targeting the systemic inflammation associated with psoriatic disease, but whether they will impact long-term cardiovascular outcomes remains to be seen. Copyright © 2015 Elsevier Inc. All rights reserved.
Kurgan, D M; Kokoruz, M V; Kurgan, M G; Novak, V L
The therapy T-cell skin lymphoma and psoriasis by the application of activation mechanisms sanogenesis methods, such as: original--a treatment plasmapheresis, a standard heparin infusion; used for the first time--wobenzym; solutions of acid acetic food and sodium bicarbonate; known--the basic sanitations of concomitant diseases, photopheresis caused remissions in 79.6% patients with different stages T-cell skin lymphoma (observed over an 8-year span), and in 67% of patients with psoriasis (observed over an 6-year span). Depuration reactions (phagocytosis, pinocytosis, toxin neutralization) has been activated by detoxication of treatment plasmapheresis and heparin infusions. The topical therapy with wobenzym, solutions of acid acetic food and sodium bicarbonate renewed natural immune barrier of skin. Basic therapy of concomitant diseases enhanced of patient state of health and mobilized compensatory resources. Photopheresis initiated autoimmunization processes by malignant CD4+ lymphocytes. When remission was achieved, the parameters of cellular and humoral immunity returned to normal levels, or the parameters made worse in the absence of remission.
In the event of failure of maintenance therapy with biologic agents for moderate to severe plaque psoriasis, the possible approaches are to switch to another agent or escalate the dose (generally by increased dosing frequency). Knowledge of the economic impact of the 2 alternatives would be extremely useful for therapeutic decision making. The present analysis aimed to determine the moment in which the annualized additional cost of escalation exceeds a specified cost overrun. Based on the purchase cost (average wholesale price) of approved biologics for the treatment of moderate to severe psoriasis, the number of weeks of escalation of the initial biologic until the annualized cost of dose escalation ran €1000 over the cost of switching to another biologic was calculated for a typical patient weighing 80 kg. According to this model, switching to another biologic is always cost effective, with adalimumab followed by ustekinumab the best choices in this respect. Ustekinumab allows for a longer trial escalation period (2 to 4 injections) before the cost overrun threshold is reached, whereas the threshold is reached in a single infusion if a patient is on infliximab. The study does not take into account the differential efficacy of the various biologic therapies as rescue treatment for failure of maintenance therapy given the lack of scientific evidence. The results nevertheless show substantial differences in the period during which treatment can be intensified before reaching the preset cost overrun. Copyright © 2013 Elsevier España, S.L. and AEDV. All rights reserved.
Psoriasis vulgaris (PV) is a cutaneous inflammatory disorder stemming from abnormal, persistent activation of the interleukin- (IL-)23/Th17 axis. Pustular psoriasis (PP) is a clinicopathological variant of psoriasis, histopathologically defined by the predominance of intraepidermal collections of neutrophils. Although PP pathogenesis is thought to largely follow that of (PV), recent evidences point to a more central role for IL-1, IL-36, and IL-6 in the development of PP. We review the role of IL-6 in the pathogenesis of PV and PP, focusing on its cross-talk with cytokines of the IL-23/Th17 axis. Clinical inhibitors of IL-6 signaling, including tocilizumab, have shown significant effectiveness in the treatment of several inflammatory rheumatic diseases, including rheumatoid arthritis and juvenile idiopathic arthritis; accordingly, anti-IL-6 agents may potentially represent future promising therapies for the treatment of PP. PMID:25126586
Nalla, Arun K.; Trobridge, Grant D.
Stem cell gene therapy approaches for Human Immunodeficiency Virus (HIV) infection have been explored in clinical trials and several anti-HIV genes delivered by retroviral vectors were shown to block HIV replication. However, gammaretroviral and lentiviral based retroviral vectors have limitations for delivery of anti-HIV genes into hematopoietic stem cells (HSC). Foamy virus vectors have several advantages including efficient delivery of transgenes into HSC in large animal models, and a potentially safer integration profile. This review focuses on novel anti-HIV transgenes and the potential of foamy virus vectors for HSC gene therapy of HIV. PMID:28536375
Kupetsky, Erine; Houston, Neil A.M.
Background: Calcipotriene/betamethasone topical suspension is a topical therapy that is often used as monotherapy as a first-line treatment for plaque psoriasis. The objective of this preliminary, open label, single arm study was to determine the efficacy of adding a topical suspension to a traditional systemic therapy for psoriasis, either methotrexate or acitretin. Methods: In this exploratory study, eight patients with chronic plaque psoriasis who were on stable methotrexate or acitretin treatment without clearance were treated with once-daily calcipotriene/betamethasone topical suspension. Subjects completed five study visits over 12 weeks. Primary outcome measure was improvement of two or more points in Investigator Global Assessment. Secondary endpoints included change in Body Surface Area, Dermatology Life Quality Index, and Patient’s Global Assessment from baseline to Week 12. Results: Overall, the median decrease in Investigator Global Assessment over 12 weeks was 1.5 points, with 50 percent of subjects experiencing a drop of two or more points in Investigator Global Assessment. All eight subjects had a reduction in Body Surface Area and Patient’s Global Assessment. There was a mean decrease in Dermatology Life Quality Index score of 78.9 percent, showing improved patient quality of life. In addition, all patients tolerated the treatment well and 6 of 8 patients had improved satisfaction level with their treatment by the end of the study. Conclusion: The topical suspension was effective and well-tolerated in conjunction with stable methotrexate or acitretin treatment in all eight patients in this study. These results support the feasibility of a larger scale study to further investigate the efficacy of these treatment combinations. The trial is registered at ClinicalTrials.gov, number NCT01761019. PMID:27462386
Differential Drug Survival of Biologic Therapies for the Treatment of Psoriasis: A Prospective Observational Cohort Study from the British Association of Dermatologists Biologic Interventions Register (BADBIR).
Warren, Richard B; Smith, Catherine H; Yiu, Zenas Z N; Ashcroft, Darren M; Barker, Jonathan N W N; Burden, A David; Lunt, Mark; McElhone, Kathleen; Ormerod, Anthony D; Owen, Caroline M; Reynolds, Nick J; Griffiths, Christopher E M
Drug survival reflects a drug's effectiveness, safety, and tolerability. We assessed the drug survival of biologics used to treat psoriasis in a prospective national pharmacovigilance cohort (British Association of Dermatologists Biologic Interventions Register (BADBIR)). The survival rates of the first course of biologics for 3,523 biologic-naive patients with chronic plaque psoriasis were compared using survival analysis techniques and predictors of discontinuation analyzed using a multivariate Cox proportional hazards model. Data for patients on adalimumab (n=1,879), etanercept (n=1,098), infliximab (n=96), and ustekinumab (n=450) were available. The overall survival rate in the first year was 77%, falling to 53% in the third year. Multivariate analysis showed that female gender (hazard ratio (HR) 1.22; 95% confidence interval (CI): 1.09-1.37), being a current smoker (HR 1.19; 95% CI: 1.03-1.38), and a higher baseline dermatology life quality index (HR 1.01; 95% CI: 1.00-1.02) were predictors of discontinuation. Presence of psoriatic arthritis (HR 0.82; 95% CI: 0.71-0.96) was a predictor for drug survival. As compared with adalimumab, patients on etanercept (HR 1.63; 95% CI: 1.45-1.84) or infliximab (HR 1.56; 95% CI: 1.16-2.09) were more likely to discontinue therapy, whereas patients on ustekinumab were more likely to persist (HR 0.48; 95% CI: 0.37-0.62). After accounting for relevant covariates, ustekinumab had the highest first-course drug survival. The results of this study will aid clinical decision making when choosing biologic therapy for psoriasis patients.
Vasku, Vladimir; Bienertova Vasku, Julie; Slonková, Veronika; Kanková, Katerina; Vasku, Anna
the psoriasis susceptibility region on 16q (psoriasis susceptibility 8, PSORS8) should be considered as a gene modulator of psoriasis in specific subgroups of patients. In the future, similar genetic characteristics could contribute to the data assembly of genetic predisposition to psoriasis and could lead to therapy improvement based on time-proved individual pharmacogenetic aspects detected in psoriasis patients.
Robinson, Amanda; Van Voorhees, Abby S; Hsu, Sylvia; Korman, Neil J; Lebwohl, Mark G; Bebo, Bruce F; Kalb, Robert E
A task force of the National Psoriasis Foundation Medical Board was convened to evaluate treatment options for pustular psoriasis. Meetings were held by teleconference. Consensus on treatment of pustular psoriasis was achieved. Pustular psoriasis has been classified into localized and generalized forms. There are a number of treatment modalities, but there is little evidence-based information to guide the management of this type of psoriasis. The purpose of this article was to present treatment recommendations to aid in the treatment of patients with pustular psoriasis. A literature review was conducted to examine treatment options for pustular psoriasis and assess the strength of the literature for each option. Overall the quality of the literature about the treatment of pustular psoriasis is weak. Treatment should be governed by the extent of involvement and severity of disease. Acitretin, cyclosporine, methotrexate, and infliximab are considered to be first-line therapies for those with generalized pustular psoriasis. Adalimumab, etanercept, and psoralen plus ultraviolet A are second-line modalities in this setting. Pustular psoriasis in children, in pregnant women, and in localized forms alter which agents are first-line modalities as concerns such as teratogenicity need to be factored into the decisionmaking for the individual patient. There are few high-quality studies examining treatment options for pustular psoriasis. Treatment of patients with pustular psoriasis depends on the severity of presentation and patient's underlying risk factors. The data are extremely limited for this type of psoriasis and we encourage further exploration. Copyright © 2011 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.
Stüttgen, G; Brinkmann-Raestrupp, I; Haller, L; Kentsch, V; Schalla, W
Melanin-containing basal cells of the epidermis, melanin-containing macrophages, mast cells, eosinophilic granulocytes and plasma cells were quantitatively investigated with the purpose of gaining an understanding of the quantitative changes in these cell systems under PUVA therapy. This patients have been exposed to solar radiation some weeks or months before the begin of the PUVA-treatment. Different dying-processes were used to investigate biopsy samples of psoriatically healthy and psoriatically affected skin, from 28 patients before, and 39 patients after PUVA therapy, using a 2 d micrometer with a field of view of 0.1 mm2. Altogether more than 9,000 fields of view have been analysed. The average radiation amount was 12 irradiations with an average total energy of 21.5 J/cm2. It was found that the count of granula-containing basal layer cells decreases in the psoriatic "healthy" region due to pigment incontinence and increase in the psoriatically affected region. The subepidermal melanin-containing phagocytes increase in both regions to a similar extent. In the case of the mast cells there was no trend to degranulation. The count of eosinophilic granulocytes and plasma cells was unchanged.
Fornara, L; Fornara, C; Cananzi, R; Lilleri, D; Furione, M; Brazzelli, V
psoriasis is a chronic inflammatory skin disease that affects approximately 2-3% of the world population.(1) Among the cytokines produced by T cells, TNF-α has a crucial role in psoriasis.(2) Thus, TNF-α blocking therapy is efficient in the treatment of psoriasis. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
Kawamura, Ai; Ochiai, Toyoko
Pustular eruptions caused by anti-hypertension drugs are relatively rare. They have been reported with beta-adrenergic blocking agents, calcium channel blocker and angiotensin converting enzyme (ACE) inhibitors. Angiotensin II type 1 (AT 1) receptor antagonists, as a new class of drug for hypertension, has become an established and popular treatment. We describe a patient with generalized pustular psoriasis induced by candesartan cilexetil (AT1 receptor antagonist), who was previously diagnosed as flexural psoriasis. It is known that AT1 receptor antagonists do not increase the bradykinin level, inhibiting the renin-angiotensin system more potently than ACE inhibitor. But our results suggest that AT 1 receptor antagonists could have some ACE inhibitor potency as an up-regulator for bradykinin in our patient, with pustular eruptions developing on the psoriatic background. To the best of our knowledge, there have been no reported cases of pustular psoriasis associated with AT1 receptor antagonists.
Aragona, Emanuela; Rania, Laura; Postorino, Elisa Imelde; Interdonato, Alberto; Giuffrida, Roberta; Cannavò, Serafinella Patrizia; Puzzolo, Domenico; Aragona, Pasquale
Psoriasis is a skin disease with also systemic involvement: its impact on the eye is not well established and often clinically underestimated. Aim of this study was to investigate the presence of ocular discomfort symptoms and of ocular surface changes in a population of patients with psoriasis. For this cross-sectional, comparative study, 66 patients with psoriasis were subdivided according to the presence of arthritis and to the use of biological therapy. All patients underwent clinical evaluation with the following tests: Ocular Surface Disease Index Questionnaire, Tearscope examination, meibometry, tear film breakup time, corneal and conjunctival fluorescein staining, Schirmer I test, corneal aesthesiometry, meibomian gland dysfunction (MGD) assessment and conjunctival impression cytology. 28 healthy subjects were also enrolled and treated with the same clinical tests. A statistical analysis of the results was performed. Patients with psoriasis showed a significant deterioration of the ocular surface tests, if compared with healthy subjects, demonstrated by tear film lipid layer alteration, tear film instability, corneal and conjunctival epithelial suffering and mild squamous metaplasia at impression cytology. No differences were found in ocular surface test results of the psoriatic group when patients were divided according to the presence of arthritis, whereas the anti-inflammatory treatment with biological drugs demonstrated a significant improvement of corneal stain and MGD. Our findings suggest that the ocular surface involvement in patients with psoriasis indicates the need of periodic ophthalmological examinations to diagnose the condition and allow a proper treatment, so contributing to the amelioration of patients' quality of life. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
The effects of tumour necrosis factor inhibitors, methotrexate, non-steroidal anti-inflammatory drugs and corticosteroids on cardiovascular events in rheumatoid arthritis, psoriasis and psoriatic arthritis: a systematic review and meta-analysis
Roubille, Camille; Richer, Vincent; Starnino, Tara; McCourt, Collette; McFarlane, Alexandra; Fleming, Patrick; Siu, Stephanie; Kraft, John; Lynde, Charles; Pope, Janet; Gulliver, Wayne; Keeling, Stephanie; Dutz, Jan; Bessette, Louis; Bissonnette, Robert; Haraoui, Boulos
The objective of this systematic literature review was to determine the association between cardiovascular events (CVEs) and antirheumatic drugs in rheumatoid arthritis (RA) and psoriatic arthritis (PsA)/psoriasis (Pso). Systematic searches were performed of MEDLINE, EMBASE and Cochrane databases (1960 to December 2012) and proceedings from major relevant congresses (2010–2012) for controlled studies and randomised trials reporting confirmed CVEs in patients with RA or PsA/Pso treated with antirheumatic drugs. Random-effects meta-analyses were performed on extracted data. Out of 2630 references screened, 34 studies were included: 28 in RA and 6 in PsA/Pso. In RA, a reduced risk of all CVEs was reported with tumour necrosis factor inhibitors (relative risk (RR), 0.70; 95% CI 0.54 to 0.90; p=0.005) and methotrexate (RR, 0.72; 95% CI 0.57 to 0.91; p=0.007). Non-steroidal anti-inflammatory drugs (NSAIDs) increased the risk of all CVEs (RR, 1.18; 95% CI 1.01 to 1.38; p=0.04), which may have been specifically related to the effects of rofecoxib. Corticosteroids increased the risk of all CVEs (RR, 1.47; 95% CI 1.34 to 1.60; p<0.001). In PsA/Pso, systemic therapy decreased the risk of all CVEs (RR, 0.75; 95% CI 0.63 to 0.91; p=0.003). In RA, tumour necrosis factor inhibitors and methotrexate are associated with a decreased risk of all CVEs while corticosteroids and NSAIDs are associated with an increased risk. Targeting inflammation with tumour necrosis factor inhibitors or methotrexate may have positive cardiovascular effects in RA. In PsA/Pso, limited evidence suggests that systemic therapies are associated with a decrease in all CVE risk. PMID:25561362
Carceller, Elena; Ballegeer, Marlies; Deckers, Julie; Riccardi, Carlo; Bruscoli, Stefano; Hochepied, Tino; Libert, Claude; Pérez, Paloma
Psoriasis vulgaris is a chronic inflammatory skin disease affecting millions of people. Its pathophysiology is complex and involves a skin compartment with epidermal and immune cells which produce cytokines, e.g. belonging to the IL-23–Th17-cell axis. Glucocorticoids (GCs) are the most common therapeutics used in cutaneous inflammatory disorders and GC-induced leucine zipper (GILZ) has emerged as a mediator of GCs due to its anti-inflammatory actions, theoretically lacking GC side-effects. We evaluated whether GILZ may provide a better therapeutic index in comparison to GCs during the onset and progression of psoriasis by generating and characterizing a mouse model with generalized overexpression of this protein (GILZ-Tg mice) and the imiquimod (IMQ) psoriasis model. Unexpectedly, in GILZ-Tg mice, the severity of IMQ-induced psoriasis-like skin lesions as well as induction of cytokines commonly up-regulated in human psoriasis (Il-17, Il-22, Il-23, Il-6, S100a8/a9, and Stat3) was significantly more pronounced relative to GILZ-Wt mice. The increased susceptibility to IMQ-induced psoriasis of GILZ-Tg mice was significantly associated with skin-specific over-activation of TGF-β1-mediated signaling via SMAD2/3. Our findings demonstrate that GILZ may behave as pro-inflammatory protein in certain tissues and that, similar to prolonged GC therapy, GILZ as an alternative treatment for psoriasis may also have adverse effects. PMID:27934944
Bangsgaard, Nannie; Rørbye, Christina; Skov, Lone
Psoriasis is a chronic inflammatory disease with a well-documented negative effect on the quality of life of affected patients. Psoriasis often occurs in the reproductive years, during which the issue of pregnancy needs to be addressed. The course of psoriasis during pregnancy is unpredictable, and many patients face the challenge of needing treatment during pregnancy. In this review we provide an overview of the key considerations for managing psoriasis in pregnant women, covering the potential effects of active psoriasis and co-morbid conditions on the health of the mother and fetus, as well as the effects of psoriasis treatment options on the developing fetus. Although there are no robust data on the safety of systemic treatment of pregnant women, increasing evidence regarding the safety of cyclosporine (ciclosporin) treatment as well as anti-tumor necrosis factor-α is available and should be considered in pregnant women with moderate to severe psoriasis unresponsive to local corticosteroids and UVB light treatment.
Gan, Emily Yiping; Chong, Wei-Sheng; Tey, Hong Liang
Psoriatic arthritis affects approximately 6-42 % of patients with psoriasis. It is useful for physicians or dermatologists managing psoriasis patients to be aware of how to concurrently manage the joint manifestations, as it is preferable and convenient to use a single agent in such patients. However, only certain therapies are effective for both. Systemic agents, which can be used for both skin and joint manifestations, include methotrexate and ciclosporin. For the group of biologic agents, the tumor necrosis factor inhibitors such as adalimumab, etanercept, infliximab, golimumab and certolizumab are effective. Ustekinumab is a more recently developed agent belonging to the group of anti-IL-12p40 antibodies and has been shown to be efficacious. Newer drugs in the treatment armamentarium that have shown efficacy for both psoriasis and psoriatic arthritis consist of the anti-IL-17 agent, secukinumab, and a phosphodiesterase-4 inhibitor, apremilast. The other anti-IL-17 agents, ixekizumab and brodalumab, as well as the oral Jak inhibitor, tofacitinib, have very limited but promising data. This review paper provides a good overview of the agents that can be used for the concurrent management of skin and joint psoriasis.
Safety profiles and efficacy of infliximab therapy in Japanese patients with plaque psoriasis with or without psoriatic arthritis, pustular psoriasis or psoriatic erythroderma: Results from the prospective post-marketing surveillance.
Torii, Hideshi; Terui, Tadashi; Matsukawa, Miyuki; Takesaki, Kazumi; Ohtsuki, Mamitaro; Nakagawa, Hidemi
A large-scale prospective post-marketing surveillance was conducted to evaluate the safety and efficacy of infliximab in Japanese patients with plaque psoriasis, psoriatic arthritis, pustular psoriasis and psoriatic erythroderma. This study was conducted in all psoriasis patients treated with infliximab after its Japanese regulatory approval. Infliximab was administrated at 5 mg/kg at weeks 0, 2 and 6, and every 8 weeks thereafter. Patients were serially enrolled and observed for 6 months to evaluate the safety and efficacy. The safety and efficacy were evaluated in 764 and 746 patients, respectively. Incidences of any and serious adverse drug reactions were 22.51% and 6.94%, respectively, and those of any and serious infusion reactions were 6.15% and 1.31%, respectively, which were comparable with the results in the post-marketing surveillance with 5000 rheumatoid arthritis patients in Japan. Major adverse drug reactions during the follow-up period were infections (5.10%) including pneumonia, cellulitis and herpes zoster, however, no tuberculosis was observed. The safety profiles were equivalent, regardless of the psoriasis types. No new safety problems were identified. The response rates on global improvement and median improvement rate of Psoriasis Area and Severity Index in all patients were 88.0% and 85.0%, respectively. Of note, the efficacy was equivalent for each psoriasis type as well as for each body region. Infliximab was also effective in pustular psoriasis symptoms, joint symptoms and nail psoriasis, as well as improvement of quality of life. Infliximab was confirmed to be highly effective and well tolerated in treating refractory psoriasis, including pustular psoriasis and psoriatic erythroderma. © 2015 Japanese Dermatological Association.
Alic, Nazif; Partridge, Linda
Reduction in the expression and activity of a well-known proto-oncogene, Myc, has a beneficial effect on mouse health and survival to old age, in part independently of cancer impact, a recent study reveals. Is this new anti-ageing intervention pointing a way towards new treatments for age-related diseases?
Nakamura, Mio; Farahnik, Benjamin; Bhutani, Tina
Phototherapy involves repeated exposure of the skin to ultraviolet light to treat various inflammatory skin conditions such as psoriasis. Recent studies have identified specific immunologic effects of phototherapy that may underlie phototherapy efficacy. Furthermore, recent advancements have been made in developing safe and effective targeted phototherapy modalities for difficult-to-treat areas such as scalp psoriasis. Targeted phototherapy in the form of the excimer laser holds potential for more aggressive, effective treatment and long-lasting remission of psoriasis. Phototherapy is now also used successfully with biologic agents as combination therapy to treat recalcitrant psoriasis. Therefore, though one of the oldest therapeutic modalities for psoriasis, phototherapy remains a mainstay treatment with promise for further advancement. PMID:27499849
Shelling, Michael L; Federman, Daniel G; Prodanovich, Srdjan; Kirsner, Robert S
Psoriasis is an immune disease most commonly recognized for its skin and joint manifestations. These produce significant physical, social, and psychological distress in affected patients and resultant reductions in their quality of life. As expected, these concerns are vital in providing symptomatic improvement and in selecting an individualized therapy. Yet, the approach in management of these patients is likely to change given the growing body of evidence linking psoriasis and vascular disease. Stemming from an anecdotally described relationship, the association between psoriasis and vascular disease has become a focus of current research to further elucidate the pathophysiology underlying and connecting these two diseases. This article includes a review of the classical cardiovascular risk factors, the atherothrombotic markers, and the environmental stressors associated with psoriasis, as well as a critical review of the observed vascular diseases, the proposed mechanism of atherosclerosis, and the benefits of treatment of psoriasis.
Kemeny, L; Amaya, M; Cetkovska, P; Rajatanavin, N; Lee, W-R; Szumski, A; Marshall, L; Mahgoub, E Y; Aldinç, E
Psoriasis prevalence and characteristics in Asia, Central Europe, and Latin America have not been thoroughly investigated and there are no large trials for biologic treatments for patients from these regions. The goal of this analysis was to report clinical response to anti-tumor necrosis factor-alpha treatment in these patients. Patients from Argentina, Czech Republic, Hungary, Mexico, Taiwan, and Thailand (N=171) were included in this subset analysis of the PRISTINE trial. Patients with stable moderate-to-severe plaque psoriasis were blinded and randomized to receive etanercept 50 mg once weekly (QW) or biweekly (BIW) for 12 weeks, followed by 12 weeks of open-label QW treatment with etanercept 50 mg through week 24 (QW/QW vs. BIW/QW). Concomitant methotrexate (≤20 mg/week) and mild topical corticosteroids or other agents were permitted at the physician's discretion, in accordance with therapeutic practice. As early as week 8, 26.7 % in the etanercept QW group and 44.0 % in the BIW group achieved Psoriasis Area and Severity Index (PASI) 75. At weeks 12 and 24, respectively, PASI 75 increased to 39.5 % and 62.8 % in the QW/QW group and 66.7 % and 83.3 % in the BIW/QW group. PASI 75 was significantly different between treatment groups from week 8 through the end of study (p<0.05). The Kaplan-Meier estimate of the proportions achieving PASI 75 in QW/QW and BIW/QW groups, respectively, was 27.4 % and 45.8 % through week 8; 41.9 % and 68.7 % through week 12; and 72.5 % and 95.2 % through week 24. Treatment with etanercept 50 mg provided rapid relief of psoriasis symptoms in patients from Asia, Central Europe, and Latin America. A more rapid response was observed in patients who received BIW treatment for the first 12 weeks which was sustained after reducing to QW dosing for the subsequent 12 weeks. Response rates were similar to those observed in the overall PRISTINE population. ClinicalTrials.gov identifier NCT00663052 .
Gordon, Kenneth B
Knowledge about the pathophysiology of psoriasis has evolved substantially in recent years, since the identification of the T helper 17 (Th17) cells. Cytokines produced by these cells appear to play major roles in psoriatic inflammation. The cytokine interleukin (IL)-23 appears to promote regulatory T cells to differentiate into Th17 cells. Available and investigational therapies act on targets within these pathways.
Mizutani, Hitoshi; Yamanaka, Keiichi; Konishi, Hiroshi; Murakami, Takaaki
Investigation of psoriasis and pustular psoriasis is presently hampered by the lack of appropriate animal models. So far, more than ten models have been developed in mice by spontaneous gene mutations and by gene manipulation. However, none of them has satisfactorily reproduced the clinicopathological and immunopathological phenotypes of these diseases. Xenotransplantation techniques have been used for designing models of psoriasis vulgaris, in which CD4(+) T cells have been shown to play an important role. An ideal model for pustular psoriasis should have an immunological background and fulfill the diagnostic criteria of psoriasis.
Alonso Abreu, Gara S; Brito Armas, José M; Castro Fuentes, Rafael
Alzheimer's disease is the most common cause of dementia in the elderly population. Currently, there are no effective treatments to prevent or delay the natural course of the disease. Numerous studies have provided information about the molecular processes underlying biological ageing and, perhaps more importantly, potential interventions to slow ageing and promote healthy longevity in laboratory model systems. The main issue addressed in this review is whether an intervention that has anti-ageing properties can alter the appearance and/or progression of Alzheimer's disease, a disease in which age is the biggest risk factor. Different anti-ageing interventions have been shown to prevent (and in some cases possibly restore) several parameters recognised as central symptoms to the development of Alzheimer's disease. In addition, they are taking the first steps towards translating these laboratory discoveries into clinical applications. Copyright © 2017 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.
Chen, Wenjuan; Xu, Hui; Wang, Xiuxiu; Gu, Junying; Xiong, Huizi; Shi, Yuling
Numerous published data on the tumor necrosis factor receptor superfamily member 1B (TNFRSF1B) gene polymorphisms are shown to be associated with response or non-response to anti-TNF therapy in autoimmune diseases such as rheumatoid arthritis (RA), psoriasis and Crohn's Disease (CD). The aim of this study is to investigate whether the TNFRSF1B rs1061622 T/G or TNFRSF1A A/G rs767455 polymorphisms can predict the response to anti-TNF-based therapy in patients with autoimmune diseases. We conducted a meta-analysis of studies on the association between TNFRSF1B rs1061622 T/G polymorphism or TNFRSF1A A/G rs767455 polymorphism and non-responsiveness to anti-TNF therapy in autoimmune diseases. A total of 8 studies involving 929 subjects for TNFRSF1B rs1061622 and 564 subjects for TNFRSF1A rs767455 were finally considered. These studies consisted of seven studies on the TNFRSF1B polymorphism and four studies on the TNFRSF1A polymorphism. Meta-analysis showed significant association between the TNFRSF1B rs1061622 allele and non-responders to anti-TNF therapy [T/G odds ratio (OR) 0.72, 95% confidence interval (CI) 0.57-0.93, p=0.01]. Stratification by disease type indicated an association between the TNFRSF1B rs1061622 allele and non-responders to TNF antagonist in RA (T/G OR 0.69, 95% CI 0.48-0.99, p<0.05) and psoriasis (T/G OR 0.39, 95% CI 0.23-0.67, p<0.001), but not in CD (T/G OR 1.14, 95% CI 0.57-0.93, p=0.57). And there was no association between TNFRSF1A rs767455 genotype and non-responders to the anti-TNF therapy (A/G OR 0.93, 95% CI 0.70-1.23, p=0.59). This meta-analysis demonstrates that TNFRSF1B T allele carriers show a better response to anti-TNF therapy, and individuals carrying TNFRSF1A A allele have no relationship with the response to anti-TNF therapy for autoimmune diseases. The genotyping of this polymorphism could help to optimize the treatment by identifying patients with a likely poor response to biological drugs.
Lila, Mohd Azmi Mohd; Siew, John Shia Kwong; Zakaria, Hayati; Saad, Suria Mohd; Ni, Lim Shen; Abdullah, Jafri Malin
Gene therapy is a promising approach towards cancer treatment. The main aim of the therapy is to destroy cancer cells, usually by apoptotic mechanisms, and preserving others. However, its application has been hindered by many factors including poor cellular uptake, non-specific cell targeting and undesirable interferences with other genes or gene products. A variety of strategies exist to improve cellular uptake efficiency of gene-based therapies. This paper highlights advancements in gene therapy research and its application in relation to anti-cancer treatment. PMID:22977356
Dreyfus, David H
Many chronic human diseases may have an underlying autoimmune mechanism. In this review, the author presents a case of autoimmune CIU (chronic idiopathic urticaria) in stable remission after therapy with a retroviral integrase inhibitor, raltegravir (Isentress). Previous reports located using the search terms "autoimmunity" and "anti-viral" and related topics in the pubmed data-base are reviewed suggesting that novel anti-viral agents such as retroviral integrase inhibitors, gene silencing therapies and eventually vaccines may provide new options for anti-viral therapy of autoimmune diseases. Cited epidemiologic and experimental evidence suggests that increased replication of epigenomic viral pathogens such as Epstein-Barr Virus (EBV) in chronic human autoimmune diseases such as rheumatoid arthritis (RA), systemic lupus Erythematosus (SLE), and multiple sclerosis (MS) may activate endogenous human retroviruses (HERV) as a pathologic mechanism. Memory B cells are the reservoir of infection of EBV and also express endogenous retroviruses, thus depletion of memory b-lymphocytes by monoclonal antibodies (Rituximab) may have therapeutic anti-viral effects in addition to effects on B-lymphocyte presentation of both EBV and HERV superantigens. Other novel anti-viral therapies of chronic autoimmune diseases, such as retroviral integrase inhibitors, could be effective, although not without risk.
Marsella, Alessandra; Valentini, Paola; Tarantino, Paolo; Congedo, Maurizio; Pompa, Pier Paolo
We report a simple, rapid and low-cost test, based on gold nanoparticles, for the naked-eye colorimetric detection of a signature of single nucleotide polymorphisms (SNPs) relevant for the personalized medicine of psoriasis patients. We validated the colorimetric assay on real-world DNA samples from a cohort of 30 psoriasis patients and we compared the results, in double-blind, with those obtained with two state-of-the-art instrumental techniques, namely reverse dot blotting and direct sequencing, finding 100% agreement. We demonstrated high accuracy, sensitivity and specificity of the colorimetric test that can be easily adapted for the genotypization of different SNPs, important for the pharmacogenomics of various diseases, and in other fields, such as food traceability and population structure analysis.
IL-17-driven pathways are active in the skin of patients with psoriasis. Kim et al. examined lesions from mild and moderate to severe psoriasis and found that differences in cutaneous disease severity may be the outcome of lapses in immunoregulatory mechanisms; because as much, if not more, T helper type 17-induced inflammation was seen in mild psoriasis, these patients may also benefit from anti-IL-17-targeted biologics.
Mehta, Nehal N.; Yu, YiDing; Pinnelas, Rebecca; Krishnamoorthy, Parasuram; Shin, Daniel B.; Troxel, Andrea B.; Gelfand, Joel M.
Background Recent studies suggest that psoriasis, particularly if severe, may be a risk factor for major adverse cardiac events such as myocardial infarction, stroke, and mortality from cardiovascular disease. We compared the risk of major adverse cardiac events between patients with psoriasis and the general population and estimated the attributable risk of severe psoriasis. Methods We performed a cohort study in the General Practice Research Database. Severe psoriasis was defined as receiving a psoriasis diagnosis and systemic therapy (N=3,603). Up to 4 patients without psoriasis were selected from the same practices and start dates for each patient with psoriasis (N=14,330). Results Severe psoriasis was a risk factor for major adverse cardiac events (hazard ratio 1.53; 95% confidence interval 1.26, 1.85) after adjusting for age, gender, diabetes, hypertension, tobacco use and hyperlipidemia. After fully adjusted analysis, severe psoriasis conferred an additional 6.2% absolute risk of 10-year major adverse cardiac events. Conclusions Severe psoriasis confers an additional 6.2% absolute risk of 10-year rate of major adverse cardiac events compared to the general population. This potentially has important therapeutic implications for cardiovascular risk stratification and prevention in patients with severe psoriasis. Future prospective studies are needed to validate these findings. PMID:21787906
Orfanos, C E
Oral retinoids such as etretinate/acitretin are well established for the treatment of severe generalized psoriasis. They are particularly useful for the management of pustular and erythrodermic variants and plaque-type psoriasis because they act synergistically with many other topical antipsoriatic agents (corticosteroids, anthralin, tar, and phototherapies). Oral regimens are dose-dependent, and, if carefully administered, are manageable and tolerable. Long-term toxicity is rare; however, teratogenicity restricts the use of oral retinoids and requires close monitoring in females. In recent years, a topical agent, tazarotene, has been developed and added to the armamentarium of psoriasis therapy.
Leman, JA; Burden, AD
Psoriasis is a chronic, immune mediated inflammatory disease characterized by increased cell signalling via cytokines and chemokines on a background of up-regulated gene expression. There is substantial evidence that psoriasis should be regarded as more than a cutaneous disease; major psychological morbidity and increased mortality from cardiovascular disease and cancer are increasingly recognized. Improved understanding of the genetic and immunological mechanisms underpinning psoriasis has occurred concurrently with the development of targeted biological therapies including infliximab. These newer therapeutic approaches can be very effective but their long term safety profile is not yet fully determined. PMID:19337424
Leman, Ja; Burden, Ad
Psoriasis is a chronic, immune mediated inflammatory disease characterized by increased cell signalling via cytokines and chemokines on a background of up-regulated gene expression. There is substantial evidence that psoriasis should be regarded as more than a cutaneous disease; major psychological morbidity and increased mortality from cardiovascular disease and cancer are increasingly recognized. Improved understanding of the genetic and immunological mechanisms underpinning psoriasis has occurred concurrently with the development of targeted biological therapies including infliximab. These newer therapeutic approaches can be very effective but their long term safety profile is not yet fully determined.
Rongioletti, F; Burlando, M; Parodi, A
In recent years, the use of biologic drugs has greatly changed the therapy of psoriasis and psoriatic arthritis, but they have some adverse effects. In particular, skin lesions induced by anti-tumor necrosis factor (TNF) and anti-interleukin (IL) 12/23 drug (ustekinumab) have been reported with an increased incidence, highlighting the importance of the skin as a major target of the side effects of these drugs. There is a wide spectrum of skin lesions of different morphology and etiology that includes skin lesions directly related to drug administration, the development of cutaneous immune-mediated conditions and cutaneous infections. The aim of this review is to revisit the literature data on inflammatory/infectious skin adverse effects of biologics both anti-TNF-α inhibitors and anti-IL 12/23 antagonists and to report and update our personal data on inflammatory/infectious side effects in patients with psoriasis/psoriatic arthritis treated with biologics.
Esposito, M; Gisondi, P; Cassano, N; Ferrucci, G; Del Giglio, M; Loconsole, F; Giunta, A; Vena, G A; Chimenti, S; Girolomoni, G
Adherence is an overall marker of treatment success, and it depends on multiple factors including efficacy and safety. Despite the wide use of tumour necrosis factor (TNF)-α blockers in the treatment of plaque-type psoriasis, few data regarding treatment adherence in routine clinical practice are available. To estimate the long-term survival rate of anti-TNF-α therapy in a cohort of patients with psoriasis in routine clinical practice; to evaluate the reasons for and predictors of treatment discontinuation. The Outcome and Survival rate Concerning Anti-TNF Routine treatment (OSCAR) study was based on a retrospective analysis to estimate the long-term survival rate of the first anti-TNF-α treatment in patients with psoriasis, from three Italian academic referral centres. Adult patients (n = 650) with plaque psoriasis treated with a first course of adalimumab, etanercept or infliximab for ≥ 3 months were included. Global adherence to anti-TNF-α treatments after 28·9 ± 15·4 months (867 ± 462 days) of observation was 72·6%. Etanercept showed a longer survival (mean 51·4 months, 1565 days; P < 0·001) compared with infliximab (36·8 months, 1120 days) and adalimumab (34·7 months, 1056 days). Treatment discontinuation due to primary and secondary inefficacy was observed in 5·2% and 14·5% of patients, respectively, whereas discontinuation due to adverse events was reported in 29 subjects (4·5%). Independent predictors of treatment withdrawal were female gender [hazards ratio (HR) 1·3], treatment with adalimumab or infliximab compared with etanercept (HR 2·7 and 1·7, respectively), and the concomitant use of traditional systemic treatment, as a rescue therapy, compared with monotherapy (HR 1·9). Overall survival of anti-TNF-α agents in psoriasis is elevated, with drug discontinuation mostly due to inefficacy. Etanercept showed a longer adherence compared with adalimumab and infliximab. © 2013 British Association of Dermatologists.
Miyanaga, Akihiko; Gemma, Akihiko
Tumor angiogenesis contributes to the development of tumor progression. Several vascular endothelial growth factor(VEGF)-targeted agents, administered either as single agents or in combination with chemotherapy, have been shown to benefit patients with advanced-stage malignancies. In particular, bevacizumab is a humanized monoclonal antibody that specifically targets VEGF, inhibiting angiogenesis, thereby impeding tumor growth and survival. It is also possible that combined VEGF and the epidermal growth factor (EGFR) pathway blockade could further enhance antitumor efficacy and help prevent resistance to therapy. Preclinical and clinical studies have shown new various molecular targets and the functional characteristics of tumor angiogenesis, which may provide strategies for improving the therapeutic benefit.
Castano, Ana P.; Mroz, Pawel; Hamblin, Michael R.
Photodynamic therapy (PDT) uses non-toxic photosensitizers and harmless visible light in combination with oxygen to produce cytotoxic reactive oxygen species that kill malignant cells by apoptosis and/or necrosis, shut down the tumour microvasculature and stimulate the host immune system. In contrast to surgery, radiotherapy and chemotherapy that are mostly immunosuppressive, PDT causes acute inflammation, expression of heat-shock proteins, invasion and infiltration of the tumour by leukocytes, and might increase the presentation of tumour-derived antigens to T cells. PMID:16794636
Akbulut, Sabiye; Gür, Günes; Topal, Firdevs; Topal, Fatih Esad; Alli, Nuran; Saritas, Ülkü
Background The possible relationship between psoriasis and coeliac disease (CD) has been attributed to the common pathogenic mechanisms of the two diseases and the presence of antigliadin antibodies in patients has been reported to increase the incidence of CD. Objective The aim of this report was to study CD-associated antibodies serum antigliadin antibody immunoglobulin (Ig)A, IgG, anti-endomysial antibody IgA and anti-transglutaminase antibody IgA and to demonstrate whether there is an increase in the frequency of those markers of CD in patients with psoriasis. Methods Serum antigliadin antibody IgG and IgA, antiendomysial antibody IgA and anti-transglutaminase antibody IgA were studied in 37 (19 males) patients with psoriasis and 50 (23 males) healthy controls. Upper gastrointestinal endoscopy and duodenal biopsies were performed in patients with at least one positive marker. Results Antigliadin IgA was statistically higher in the psoriasis group than in the controls (p<0.05). Serological markers were found positive in 6 patients with psoriasis and 1 person from the control group. Upper gastrointestinal endoscopy was performed in all these persons, with biopsies collected from the duodenum. The diagnosis of CD was reported in only one patient with psoriasis following the pathological examination of the biopsies. Whereas one person of the control group was found to be positive for antigliadin antibody IgA, pathological examination of the duodenal biopsies obtain from this patient were found to be normal. Conclusion Antigliadin IgA prominently increases in patients diagnosed with psoriasis. Patients with psoriasis should be investigated for latent CD and should be followed up. PMID:24003271
Sudakin, Valery; Yen, Timothy J
Basic research that has focused on achieving a mechanistic understanding of mitosis has provided unprecedented molecular and biochemical insights into this highly complex phase of the cell cycle. The discovery process has uncovered an ever-expanding list of novel proteins that orchestrate and coordinate spindle formation and chromosome dynamics during mitosis. That many of these proteins appear to function solely in mitosis makes them ideal targets for the development of mitosis-specific cancer drugs. The clinical successes seen with anti-microtubule drugs such as taxanes and the vinca alkaloids have also encouraged the development of drugs that specifically target mitosis. Drugs that selectively inhibit mitotic kinesins involved in spindle and kinetochore functions, as well as kinases that regulate these activities, are currently in various stages of clinical trials. Our increased understanding of mitosis has also revealed that this process is targeted by inhibitors of farnesyl transferase, histone deacetylase, and Hsp90. Although these drugs were originally designed to block cell proliferation by inhibiting signaling pathways and altering gene expression, it is clear now that these drugs can also directly interfere with the mitotic process. The increased attention to mitosis as a chemotherapeutic target has also raised an important issue regarding the cellular determinants that specify drug sensitivity. One likely contribution is the mitotic checkpoint, a failsafe mechanism that delays mitotic exit so that cells whose chromosomes are not properly attached to the spindle have extra time to correct their errors. As the biochemical activity of the mitotic checkpoint is finite, cells cannot indefinitely sustain the delay, as in cases where cells are treated with anti-mitotic drugs. When the mitotic checkpoint activity is eventually lost, cells will exit mitosis and become aneuploid. While many of the aneuploid cells may die because of massive chromosome imbalance
Schwartz, Julia; Evers, Andrea W. M.; Bundy, Christine; Kimball, Alexandra B.
Psoriasis is a chronic inflammatory skin condition with significant physical and psychosocial comorbidity. A workshop of leading experts in dermatology and psychology with the purpose of better understanding the current role of psychological comorbidities in psoriasis was held by the International Psoriasis Council in November 2013. The role of stress reactivity with a focus on the hypothalamic-pituitary-adrenal axis was emphasized. While cognitive behavioral therapy remains the most extensively studied and successful treatment strategy in patients with psoriasis and various psychological comorbidities, new and innovative interventions such as online-based therapies have recently emerged. Strategies and recommendations toward approaching psychological comorbidities are discussed. PMID:26869982
Schwartz, Julia; Evers, Andrea W M; Bundy, Christine; Kimball, Alexandra B
Psoriasis is a chronic inflammatory skin condition with significant physical and psychosocial comorbidity. A workshop of leading experts in dermatology and psychology with the purpose of better understanding the current role of psychological comorbidities in psoriasis was held by the International Psoriasis Council in November 2013. The role of stress reactivity with a focus on the hypothalamic-pituitary-adrenal axis was emphasized. While cognitive behavioral therapy remains the most extensively studied and successful treatment strategy in patients with psoriasis and various psychological comorbidities, new and innovative interventions such as online-based therapies have recently emerged. Strategies and recommendations toward approaching psychological comorbidities are discussed.
Yonezawa, Atsushi; Dutt, Suparna; Chester, Cariad; Kim, Jeewon; Kohrt, Holbrook E.
In the past 5 years, immunomodulatory antibodies have revolutionized cancer immunotherapy. CD137, a member of the tumor necrosis factor receptor superfamily, represents a promising target for enhancing antitumor immune responses. CD137 helps regulate the activation of many immune cells, including CD4+ T cells, CD8+ T cells, dendritic cells, and natural killer cells. Recent studies indicate that the antitumor efficacy of therapeutic tumor-targeting antibodies can be augmented by the addition of agonistic antibodies targeting CD137. As ligation of CD137 provides a costimulatory signal in multiple immune cell subsets, combination therapy of CD137 antibody with therapeutic antibodies and/or vaccination has the potential to improve cancer treatment. Recently, clinical trials of combination therapies with agonistic anti-CD137 mAbs have been launched. In this review, we discuss the recent advances and clinical promise of agonistic anti-CD137 monoclonal antibody therapy. PMID:25908780
Chmiel, James F.; Konstan, Michael W.; Elborn, J. Stuart
Cystic fibrosis (CF) lung disease is characterized by chronic bacterial infection and an unremitting inflammatory response, which are responsible for most of CF morbidity and mortality. The median expected survival has increased from <6 mo in 1940 to >38 yr now. This dramatic improvement, although not great enough, is due to the development of therapies directed at secondary disease pathologies, especially antibiotics. The importance of developing treatments directed against the vigorous inflammatory response was realized in the 1990s. New therapies directed toward the basic defect are now visible on the horizon. However, the impact of these drugs on downstream pathological consequences is unknown. It is likely that antibiotics and anti-inflammatory drugs will remain an important part of the maintenance regimen for CF in the foreseeable future. Current and future antibiotic and anti-inflammatory therapies for CF are reviewed. PMID:23880054
Sarıcaoglu, Hayriye; Oz, Arife; Turan, Hakan
Psoriasis is a common, chronic disease which affects nearly 3% of the population. The lifetime incidence of nail involvement increases up to 80-90% for psoriatic patients. Nail psoriasis is considered a significant social problem. Many topical agents have been used for psoriatic nails with various side effects and some benefits; management is currently inconclusive. Methotrexate (MTX) is a folic acid analog, which irreversibly binds to dehydrofolate reductase and blocks deoxyribonucleic acid synthesis. It is considered a potential treatment option for rapidly growing cells and has an anti-inflammatory effect through inhibition of the polyamine pathway in autoimmune diseases. Intralesional MTX has been used successfully for various indications. We present a case successfully treated with low-dose intralesional MTX with no observed side effects in a 26-year-old female psoriatic patient suffering from nail dystrophy. In contrast, conventional topical and systemic therapies have various side effects, which limit their use. We conclude that intralesional MTX injection seems to be a safe and effective treatment option for nail psoriasis; however, large controlled studies are needed.
Goiriz, R; Daudén, E; Pérez-Gala, S; Guhl, G; García-Díez, A
Tumour necrosis factor (TNF) blockers represent an exciting advance in the management of psoriasis. However, the safety profile of these drugs is not completely established. We present a review of the literature, and report on eight patients: two with the unexpected appearance of psoriasis, and the remaining six with exacerbation and change in morphology of their existing psoriasis, all of which occurred during treatment with the TNF blockers adalimumab, etanercept and infliximab. The two new cases, neither of whom had any personal or family history of psoriasis, developed pustular psoriasis on the palms and/or soles. The other six patients, previously diagnosed with severe chronic plaque psoriasis (four patients), generalized pustular psoriasis (one) and erythrodermic psoriasis (one), developed eruptive guttate psoriasis between 15 days and 18 months after the beginning of therapy. These patients had never before presented guttate-type psoriatic lesions, and the lesions appeared in areas of the body that were free of psoriatic plaques at baseline.
Yalcin, Arzu Didem
Omalizumab depletes free IgE in the blood and interstitial space and inhibits IgE binding to FcεRI on basophils, mast cells, and dendritic cells. We stopped omalizumab treatment after four years. Recurrences of urticaria symptoms were found to be higher in patients with chronic urticaria than recurrences of asthmatic symptoms in severe persistent asthma patients. For the very first time, we used omalizumab in symptomatic therapy of recurrent laryngeal oedema and urticaria attacks in a patient with postoperative pulmonary carcinoid tumor for eight months. During the four years of follow-up, no recurrence was noted in pulmonary carcinoid tumor. Control PET CT results revealed normal findings. After omalizumab treatment, laryngeal oedema and urticaria symptoms were decreased. The most common adverse reaction from omalizumab is injection site induration, injection site itching, injection site pain, and bruising but the package insert contains warnings regarding parasitic infections. While there are no reports of fatal anaphylaxis as a result of omalizumab, some cases have been serious and potentially life-threatening. Therefore, the FDA requires that people receiving omalizumab be monitored in the physician's office for a period of time after their injections. PMID:26075226
... 723-9166 | Submit a Question | Learn More National Psoriasis Foundation provides you with the help you need to best manage your psoriasis or psoriatic arthritis, while promoting research to find ...
... accompanied by fever, chills, severe itching, and fatigue. Inverse psoriasis. This causes smooth, raw-looking patches of ... a healthy weight. This decreases the risk of inverse psoriasis. Remind your child to keep skin clean ...
Reddy, Swathi B; Possick, Jennifer D; Kluger, Harriet M; Galan, Anjela; Han, Dale
Immune checkpoint inhibitors represent the newest treatment for stage IV melanoma. These agents are generally well tolerated, however severe immune-related adverse effects have been noted in a small, but clinically significant percentage of patients. Specifically, sarcoidosis is a known potential complication following anti-CTLA-4 therapy. We present 2 cases of pulmonary and cutaneous sarcoidosis developing in patients with stage IV melanoma. Both patients were treated with ipilimumab and anti-PD-1 therapy, and both experienced good oncologic responses to treatment; neither had evidence of preexisting sarcoidosis. Of note, both patients developed sarcoidosis only after undergoing immune checkpoint inhibitor therapy. In 1 patient, sarcoidosis developed after initiation of anti-PD-1 therapy, 3 months after the last dose of anti-CTLA-4 monotherapy, suggesting a synergistic immune dysmodulating effect of both checkpoint inhibitors. Ultimately, both patients' symptoms and radiologic findings resolved with corticosteroid treatment, and both patients have tolerated retreatment with PD-1 inhibitors. Sarcoidosis is a rare complication of immune checkpoint inhibitors and can manifest with severe pulmonary manifestations. However, sarcoidosis in this setting is responsive to corticosteroids and does not necessarily recur with retreatment. It is yet unclear whether the development of sarcoidosis in these patients represents unmasking of preexisting autoimmune tendencies or is a marker of oncologic response.
Stacker, Steven A; Achen, Marc G
The theory that angiogenesis could support tumor growth and therefore be a target for cancer therapy was explored in publications by Judah Folkman in the 1970s. This theory was then fostered by Folkman for over 2 decades until, via modern molecular and cell biology techniques, it was vindicated in animal tumor models, and subsequently with the successful clinical trials of a humanized monoclonal antibody which neutralizes vascular endothelial growth factor (VEGF). In the process of proving the "anti-angiogenesis" theory, researchers in vascular, cancer, and developmental biology have gained insight into how the vascular network operates at the molecular level. Following on from the wave of activity that accompanied the study of angiogenesis, some of the molecular mechanisms controlling the related process of lymphangiogenesis have now been identified. The growth of lymphatic vessels was found to be controlled by proteins related to VEGF, namely VEGF-C and VEGF-D, which are associated with a number of human tumor types. The experimental inhibition of this process in animal models has suggested that lymphangiogenic growth factors facilitate the metastatic spread of tumor cells via lymphatics. Unlike the anti-angiogenesis strategy, anti-lymphangiogenesis is yet to be tested clinically; however, the notion that anti-lymphangiogenesis may be beneficial for cancer therapy is supported by extensive data from animal models and clinicopatholgical data. History may show that anti-angiogenesis provided the vantage point from which anti-lymphangiogenesis was seen as a viable concept for targeting tumors and other pathological conditions.
Musgrave, K M; Powell, J
There is limited guidance available to clinicians regarding the management of antithrombotic therapy during epistaxis, whilst there has been an increase in the use of anticoagulation and antiplatelet therapy. In addition, the introduction of direct oral anticoagulants (DOACs), such as dabigatran and rivaroxaban, over the last decade has significantly increased the complexity of managing the anticoagulated epistaxis patient. We undertook a systemic literature review investigating potential management strategies for each class of anti-thrombotic therapy during epistaxis. A PubMED and Cochrane Library search was performed on 10/03/16 using, but not limited to, the search terms epistaxis, nosebleed, nose bleeding, nasal haemorrhage, nasal bleeding AND each of the following search terms: antithrombotic, anticoagulant, antiplatelet, aspirin, clopidogrel, warfarin, dabigatran, rivaroxaban, apixaban and tranexamic acid. This yielded 3815 results, of which 29 were considered relevant. Other sources such as national and international guidelines related to the management of anti-thrombotics were also utilised. We present the findings related to the management of each class of anti-thrombotic therapy during epistaxis. Overall we found a lack of evidence regarding this topic and further high quality research is needed. This is an area growing in complexity and the support of colleagues in Haematology and Cardiology is increasingly important.
Patil, Vishakha; Mali, Rohini; Mali, Amita
Periodontitis is an infectious disease with marked inflammatory response, leading to destruction of underlying tissues. The aim of periodontal therapy is to eradicate the pathogens associated with the disease and attain periodontal health. This is achieved by non-surgical and surgical therapy; however, mechanical debridement and topical application of antiseptics may not be helpful in all cases. In such cases, adjunctive systemic antibiotic therapy remains the treatment of choice. It can reach micro-organisms at the base of the deep periodontal pockets and furcation areas via serum, and also affect organisms residing within gingival epithelium and connective tissue. Before advising any anti-microbial agent, it is necessary to have knowledge of that agent. The aim of this review article is to provide basic details of each systemic anti-microbial agent used in periodontal therapy. The points discussed are its mode of action, susceptible periodontal pathogens, dosage, its use in treatment of periodontal disease, and mechanism of bacterial resistance to each anti-microbial agent. It might be of some help while prescribing these drugs. PMID:23869120
Zweegers, J; de Jong, E M G J; Nijsten, T E C; de Bes, J; te Booij, M; Borgonjen, R J; van Cranenburgh, O D; van Deutekom, H; van Everdingen, J J E; de Groot, M; Van Hees, C L M; Hulshuizen, H; Koek, M B G; de Korte, W J A; de Korte, J; Lecluse, L L A; Pasch, M C; Poblete-Gutiérrez, P A; Prens, E P; Seyger, M M B; Thio, H B; Torcque, L A; de Vries, A C Q; van de Kerkhof, P C M; Spuls, Ph I
This document provides a summary of the Dutch S3-guidelines on the treatment of psoriasis. These guidelines were finalized in December 2011 and contain unique chapters on the treatment of psoriasis of the face and flexures, childhood psoriasis as well as the patient's perspective on treatment. They also cover the topical treatment of psoriasis, photo(chemo)therapy, conventional systemic therapy and biological therapy.
Schukur, Lina; Geering, Barbara; Charpin-El Hamri, Ghislaine; Fussenegger, Martin
Psoriasis is a chronic inflammatory skin disease characterized by a relapsing-remitting disease course and correlated with increased expression of proinflammatory cytokines, such as tumor necrosis factor (TNF) and interleukin 22 (IL22). Psoriasis is hard to treat because of the unpredictable and asymptomatic flare-up, which limits handling of skin lesions to symptomatic treatment. Synthetic biology-based gene circuits are uniquely suited for the treatment of diseases with complex dynamics, such as psoriasis, because they can autonomously couple the detection of disease biomarkers with the production of therapeutic proteins. We designed a mammalian cell synthetic cytokine converter that quantifies psoriasis-associated TNF and IL22 levels using serially linked receptor-based synthetic signaling cascades, processes the levels of these proinflammatory cytokines with AND-gate logic, and triggers the corresponding expression of therapeutic levels of the anti-inflammatory/psoriatic cytokines IL4 and IL10, which have been shown to be immunomodulatory in patients. Implants of microencapsulated cytokine converter transgenic designer cells were insensitive to simulated bacterial and viral infections as well as psoriatic-unrelated inflammation. The designer cells specifically prevented the onset of psoriatic flares, stopped acute psoriasis, improved psoriatic skin lesions and restored normal skin-tissue morphology in mice. The antipsoriatic designer cells were equally responsive to blood samples from psoriasis patients, suggesting that the synthetic cytokine converter captures the clinically relevant cytokine range. Implanted designer cells that dynamically interface with the patient's metabolism by detecting specific disease metabolites or biomarkers, processing their blood levels with synthetic circuits in real time, and coordinating immediate production and systemic delivery of protein therapeutics may advance personalized gene- and cell-based therapies. Copyright © 2015
González-Parra, E; Daudén, E; Carrascosa, J M; Olveira, A; Botella, R; Bonanad, C; Rivera, R
Psoriasis is a chronic inflammatory disease that has been associated with cardiovascular and metabolic comorbidities, particularly in young patients and patients with more severe forms of the disease. Recent studies have also linked psoriasis to kidney disease, and this would seem only logical, as the kidney is both a target of classic cardiovascular risk factors and susceptible to the toxic effects of some of the traditional drugs used to control psoriasis. In this article, we would like to draw readers' attention to this recently described comorbidity and stress the importance of early detection, as once chronic kidney disease develops, it cannot be reversed. When evaluating patients with psoriasis, particularly when they are candidates for systemic therapy, we believe it is important to order laboratory tests including glomerular filtration rate and a simple urine test to screen for albuminuria (albumin/creatinine ratio).
Fialová, Jorga; Vojáčková, Nadežda; Vaňousová, Daniela; Hercogová, Jana
An 8-year-old boy with general pustular psoriasis (GPP) and iatrogenic secondary Cushing syndrome was treated successfully with etanercept after he had failed on acitretin, methotrexate, and methylprednisolone therapy. GPP is a severe and very rare variant of psoriasis in children often accompanied by life-threatening complications. Retinoids, cyclosporine, methotrexate, or dapsone used in a small number of case series and case reports were effective. Etanercept is a recombinant human tumor necrosis factor-alpha (TNF-alpha) receptor protein fused with Fc portion of IgG1 that binds to TNF-alpha, approved by Food and Drug Administration for the treatment of moderate-to-severe plaque psoriasis in children and teens who have not responded to other psoriasis treatments. In our patient, etanercept demonstrated significant clinical response associated with long-term efficacy without acute exacerbation, excellent tolerability, and good safety profile. © 2013 Wiley Periodicals, Inc.
Piruzian, A.; Korsunskaya, I.; Goldenkova, I.; Hertsen, A.; Sarkisova, M.; Egorenkova, L.
Psoriasis is a chronic, genetically-determined disease, characterized by an immuno-mediated pathogenesis. Treatment of psoriasis is often complicated and remains a challenge. Along with the many new immunomodulatory approaches, various laser systems have been employed for chronic plaque psoriasis treatment. Recently, it has been demonstrated that the light produced by xenon-chloride excimers (generated by sophisticated devices with peak emission of 308 nm) is effective in the treatment of several psoriasis forms. We treated patients, ranging in age from 35 to 55 years, affected by plaque-type psoriasis vulgaris with monochromatic excimer light (MEL). We used MEL in a complex with basic treatment. Therapy was administered three times a week. At the end of the 3th week of treatment all patients showed an improvement, as evidenced by flattening of plaques, decreased scaling and erythema, and decreased vesicle and pustule formation. Unwanted side effects such as pain, blistering was not observed. Minimal erythema and a hyperpigmentation were noted in some patients. It was concluded that the MEL therapy may be a valuable option for treatment of plaque-type psoriasis vulgaris in shorter time compare with traditional NB UVB, with exposure to lower cumulative doses
Mahajan, Rahul; Handa, Sanjeev
Psoriasis is a chronic inflammatory papulosquamous disease characterized by multiple remissions and relapses. For long, it was believed to be primarily a disorder of keratinization. However, the successful use of traditional immunosupressants and newer immunomodulatory agents in the treatment of psoriasis led to the belief that psoriasis is primarily a disease of Th1 cell immune dysregulation. Recent developments have brought up several new findings such as the role of Th17 cells and evidence of skin barrier dysfunction in psoriasis, akin to atopic dermatitis. The present review aims to focus on these new developments and explain the pathogenesis of psoriasis on the basis of currently available information.
Carrascosa, J M; Bonanad, C; Dauden, E; Botella, R; Olveira-Martín, A
Nonalcoholic fatty liver disease (NAFLD) is the most prevalent liver condition in the West. The prevalence and severity of NAFLD is higher and the prognosis worse in patients with psoriasis. The pathogenic link between psoriasis and NAFLD is chronic inflammation and peripheral insulin resistance, a common finding in diseases associated with psoriasis. NAFLD should therefore be ruled out during the initial evaluation of patients with psoriasis, in particular if they show signs of metabolic syndrome and require systemic treatment. Concomitant psoriasis and NAFLD and the likelihood of synergy between them place limitations on general recommendations and treatment for these patients given the potential for liver toxicity. As hepatotoxic risk is associated with some of the conventional drugs used in this setting (e.g., acitretin, methotrexate, and ciclosporin), patients prescribed these treatments should be monitored as appropriate. Anti-tumor necrosis factor agents hold the promise of potential benefits based on their effects on the inflammatory process and improving peripheral insulin resistance. However, cases of liver toxicity have also been reported in relation to these biologics. No evidence has emerged to suggest that anti-p40 or anti-interleukin 17 agents provide benefits or have adverse effects.
Ariyasu, Ryo; Horiike, Atsushi; Yoshizawa, Takahiro; Dotsu, Yosuke; Koyama, Junji; Saiki, Masafumi; Sonoda, Tomoaki; Nishikawa, Shingo; Kitazono, Satoru; Yanagitani, Noriko; Nishio, Makoto
Adrenal insufficiency is one of the adverse events (AEs) associated with anti-programmed death-1 (PD1) therapy. Delaying diagnoses can lead to serious conditions. It is necessary to elucidate detailed clinical features of these AEs. Patients treated with anti-PD-1 monotherapy or in combination with anti-cytotoxic T cell lymphocyte-4 therapy at our hospital from January 2013 to December 2016 were identified. The patients' clinical characteristics and laboratory and radiologic findings were collected. Adrenal insufficiency occurred in 3% of the patients. All patients were male. At the onset of symptoms, eosinophilia (>500/μl) was observed in four cases. Eosinophilia was observed more than a month before onset of symptoms in three cases. Other pituitary hormones remained relatively stable. Radiological evidence of pituitary inflammation was detected only in one case. Most anti-PD1-related adrenal insufficiency cases involved an isolated ACTH deficiency. Eosinophilia may be an early indicator before the onset of symptoms. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
Vangipuram, Ramya; Alikhan, Ali
Psoriasis is a chronic inflammatory skin disease characterized by erythematous plaques on extensor surfaces, scalp, and back. Current therapies for psoriasis are limited by route of administration, side effects, and cost. Apremilast is the first oral phosphodiesterase inhibitor approved for moderate-to-severe plaque psoriasis. It is a small molecule inhibitor of phosphodiesterase-4, and decreases the inflammatory activity associated with psoriasis. Areas covered: This review will discuss the pharmacology of apremilast, mechanism of action, results from key clinical trials, and its use in managing psoriasis. Currently approved treatments are also discussed. Expert commentary: The advantages of apremilast include convenient oral administration and dosing, a favorable safety and tolerability profile, and significant efficacy in moderate-to-severe plaque psoriasis.
Abbas, Mariam; Holfeld, Karen; Desjardins, Danielle; Zimmer, June
Pustular psoriasis of the digits (acrodermatitis continua of Hallopeau) may be localized to one or more digits for over an extended period of time. Characteristic presentation is that of tender, diffusely eroded, and fissured pustular plaques on one or more digits. Transition to other forms of psoriasis and to generalized pustular psoriasis is known to occur. These patients have an increased risk of acute generalized exanthematous pustulosis (AGEP) compared to the general population. Pustular psoriasis is often therapy resistant. We report the case of a 54-year-old Caucasian woman who presented with a pustular psoriasis flare complicated by AGEP. Treatment course included hospital admission, cyclosporine, acitretin, and discontinuation of cephalexin. The precipitating factor in the course of treatment is thought to be cephalexin. When treating patients with pustular psoriasis the occurrence of druginduced complications should be carefully examined. Our case suggests that avoidance of β-lactam antibiotics in these patients is warranted unless absolutely indicated.
Yiu, Zenas Z N; Warren, Richard B
The quality of life for a patient has been transformed in the last 15 years due to innovations that have resulted in better treatments for severe psoriasis, a chronic inflammatory cutaneous disease. Now, novel therapies for psoriasis need to reach a high standard in order to offer patients with psoriasis a genuine alternative. Here we outline a suggested critical checklist that will help industry sponsors, researchers, and clinicians evaluate novel therapeutics for psoriasis. © 2017 American Society for Clinical Pharmacology and Therapeutics.
Bovolenta, Chiara; Porcellini, Simona; Alberici, Luca
The multiple therapeutic approaches developed so far to cope HIV-1 infection, such as anti-retroviral drugs, germicides and several attempts of therapeutic vaccination have provided significant amelioration in terms of life-quality and survival rate of AIDS patients. Nevertheless, no approach has demonstrated efficacy in eradicating this lethal, if untreated, infection. The curative power of gene therapy has been proven for the treatment of monogenic immunodeficiensies, where permanent gene modification of host cells is sufficient to correct the defect for life-time. No doubt, a similar concept is not applicable for gene therapy of infectious immunodeficiensies as AIDS, where there is not a single gene to be corrected; rather engineered cells must gain immunotherapeutic or antiviral features to grant either short- or long-term efficacy mostly by acquisition of antiviral genes or payloads. Anti-HIV/AIDS gene therapy is one of the most promising strategy, although challenging, to eradicate HIV-1 infection. In fact, genetic modification of hematopoietic stem cells with one or multiple therapeutic genes is expected to originate blood cell progenies resistant to viral infection and thereby able to prevail on infected unprotected cells. Ultimately, protected cells will re-establish a functional immune system able to control HIV-1 replication. More than hundred gene therapy clinical trials against AIDS employing different viral vectors and transgenes have been approved or are currently ongoing worldwide. This review will overview anti-HIV-1 infection gene therapy field evaluating strength and weakness of the transgenes and payloads used in the past and of those potentially exploitable in the future.
Curtis, Ashley R; Yosipovitch, Gil
Verrucous psoriasis is characterized clinically by symmetric hypertrophic verrucous plaques on an erythematous base and histologically by overlapping features of both verrucae and psoriasis with negative human papilloma virus (HPV) studies. A 46-year-old African-American male presented with an 8-year history of extensive malodorous, symmetric, verrucous plaques manifesting as erythroderma. Biopsies showed epidermal hyperplasia and papillomatosis, parakeratosis with neutrophils, and dilated vessels in the dermal papillae. The polymerase chain reaction of lesional skin was negative for HPV DNA, and T-cell gene rearrangement was negative. The patient was diagnosed with erythrodermic verrucous psoriasis. Verrucous psoriasis is a rare presentation of psoriasis and has only been reported as a localized variant. To the authors' knowledge, erythrodermic verrucous psoriasis has not been reported. This presentation was a diagnostic and therapeutic challenge and serves to heighten the awareness of a unique variant of psoriasis.
Amoaku, W M; Chakravarthy, U; Gale, R; Gavin, M; Ghanchi, F; Gibson, J; Harding, S; Johnston, R L; Kelly, S P; Kelly, S; Lotery, A; Mahmood, S; Menon, G; Sivaprasad, S; Talks, J; Tufail, A; Yang, Y
The introduction of anti-vascular endothelial growth factor (anti-VEGF) has made significant impact on the reduction of the visual loss due to neovascular age-related macular degeneration (n-AMD). There are significant inter-individual differences in response to an anti-VEGF agent, made more complex by the availability of multiple anti-VEGF agents with different molecular configurations. The response to anti-VEGF therapy have been found to be dependent on a variety of factors including patient's age, lesion characteristics, lesion duration, baseline visual acuity (VA) and the presence of particular genotype risk alleles. Furthermore, a proportion of eyes with n-AMD show a decline in acuity or morphology, despite therapy or require very frequent re-treatment. There is currently no consensus as to how to classify optimal response, or lack of it, with these therapies. There is, in particular, confusion over terms such as 'responder status' after treatment for n-AMD, 'tachyphylaxis' and 'recalcitrant' n-AMD. This document aims to provide a consensus on definition/categorisation of the response of n-AMD to anti-VEGF therapies and on the time points at which response to treatment should be determined. Primary response is best determined at 1 month following the last initiation dose, while maintained treatment (secondary) response is determined any time after the 4th visit. In a particular eye, secondary responses do not mirror and cannot be predicted from that in the primary phase. Morphological and functional responses to anti-VEGF treatments, do not necessarily correlate, and may be dissociated in an individual eye. Furthermore, there is a ceiling effect that can negate the currently used functional metrics such as >5 letters improvement when the baseline VA is good (ETDRS>70 letters). It is therefore important to use a combination of both the parameters in determining the response.The following are proposed definitions: optimal (good) response is defined as when there
Psoriasis is a chronic, inflammatory disease affecting 1-3% of the world's population. Joints can be affected in up to 30% of patients. About one third of patients have either severe or moderate (involving more than 10% of body surface area) disease. Patients affected with extensive psoriasis have an impaired quality of life. Psoriasis has a large spectrum of clinical features and evolution, so no complete agreement on the classification of the clinical variants exists. Plaque psoriasis is the commonest form (more than 80% of affected patients). The course of plaque psoriasis varies. Spontaneous resolution is possible, but rarely occurs. Plaques tend to remain static or slowly enlarge. Flexural (inverse, intertriginous) psoriasis manifests with lesions thinner than those of plaque form with no or minimal scaling, and is localized in the skin folds. Guttate (eruptive) psoriasis has frequently a sudden onset and frequently appears abruptly after a bacterial or viral febrile episode of inflammation of the upper ways. Pustular and erythrodermic psoriasis are the most severe clinical variants. In the diffuse pustular form recurrent episodes of fever occur, followed by new outbreaks of pustules. Erythrodermic psoriasis corresponds to the generalized form of the disease. The entire skin is bright red and is covered by superficial scales. Fatigue, myalgia, shortness of breath, fever and chills may also occur. In sebopsoriasis (seborrheic dermatitis + psoriasis) the lesions tend to occur at the same sites as seborrheic dermatitis; greasy scales predominate, but silvery scales can be found in some areas. Nail psoriasis shows various features: nail pits; oil spots; subungual hyperkeratosis; onycholysis. Rare forms include psoriasis circinata, lip psoriasis and oral psoriasis. Differential diagnosis includes many other dermatological conditions.
Clifford, Vanessa; Zufferey, Christel; Street, Alan; Denholm, Justin; Tebruegge, Marc; Curtis, Nigel
The ability to monitor response to therapy for tuberculosis (TB) and confirm adequate treatment would be a major advance. The low reversion rate of interferon-gamma based assays means that they are unlikely to be useful for monitoring therapy. Several exploratory studies have evaluated the diagnostic potential of cytokine biomarkers other than interferon-gamma for monitoring anti-tuberculous therapy. A systematic review of these studies was performed to identify the most promising candidate biomarkers. TNF-α, IL-2, IL-6, IL-10 and IL-12 were the most extensively investigated cytokines. There was significant heterogeneity between studies in relation to study design and laboratory methodology, complicating direct comparisons. There was marked variation between studies in the observed changes during treatment for many of the biomarkers. Further longitudinal studies in sufficiently large patient cohorts with rigorous methodology are needed to determine the true potential of individual cytokine biomarkers, or combinations, for monitoring TB treatment.
Budamakuntla, L; Madaiah, M; Sarvajnamurthy, S; Kapanigowda, S
There is an unmet need for psoriasis therapies that provide long-term remission. Itolizumab is a humanized recombinant anti-CD6 monoclonal antibody shown to be effective in psoriasis. We report a patient who received itolizumab in a phase 2 clinical trial, and experienced long-term remission. At baseline, the patient's Psoriasis Area and Severity Index (PASI) was 12.2, and Physician's Global Assessment (PGA) score was 3. After 8 weeks of treatment, the patient achieved 97% improvement in PASI. She continued to have ≥ 90% improvement, initially for 4 weeks (follow-up phase), and later for 20 weeks (follow-up extension phase). She continued to visit the hospital after the final study visit; her most recent visit was on 10 May 2013. PGA results during the visits revealed sustained response for 4 years and 5 months after stopping itolizumab. Itolizumab could be therefore an important treatment option for moderate to severe psoriasis, with potential to provide long-lasting remission.
Fabri, Gisele Maria C; Pereira, Rosa Maria R; Savioli, Cynthia; Saad, Carla G S; de Moraes, Júlio Cesar B; Siqueira, José Tadeu T; Bonfa, Eloisa
Recently, it has been demonstrated that patients with ankylosing spondylitis (AS) and rheumatoid arthritis (RA) have a higher risk of periodontitis; however, the effect of anti-TNF therapy in periodontal status of patients with AS and particularly in dental attachment is not known. To evaluate longitudinally the local periodontal effect of TNF-antagonist in AS and compare to patients with RA. Fifteen patients with AS and 15 RA control patients were prospectively evaluated at baseline and after 6 months (6 M) of anti-TNF therapy. Periodontal assessment included: probing pocket depth (PPD), clinical attachment level (CAL), gingival bleeding index, and plaque index. Rheumatologic clinical and laboratory evaluations were the following: Bath AS Disease Activity Index, Bath AS Metrology Index, Bath AS Functional Index, C-reactive protein and erythrocyte sedimentation rate for AS and Disease Activity Score 28 joints, and C-reactive protein and erythrocyte sedimentation rate for patients with RA. At baseline, periodontal parameters were alike in AS and RA (P > 0.05). After 6 M of anti-TNF therapy, clinical and laboratory parameters of rheumatic diseases decreased significantly in the patients with AS and RA (P < 0.05). A significant improvement in periodontal attachment measurements were observed in the patients with AS (PPD, 2.18 vs 1.94 mm; P = 0.02; CAL, 2.29 vs.2.02 mm; P = 0.03), but not in RA (PPD, 1.92 vs 2.06 mm; P = 0.06; CAL, 2.14 vs 2.28 mm; P = 0.27). Oral hygiene and gingival inflammation remained unchanged from baseline to 6-M evaluation in AS and RA (P > 0.05). Patients with AS under anti-TNF improved periodontal attachment. The mechanism for this effect needs further studies.
Game theory suggests an anti-cancer treatment based on the use of modified cancer cells that disrupt cooperation within the tumor. Cancer cells are harvested from the patient, the genes for the production of essential growth factors are knocked out in vitro and the cells are then reinserted in the tumor, where they lead to its collapse. Current anti-cancer drugs and treatments based on gene therapy are prone to the evolution of resistance, because cancer is a process of clonal selection: resistant cell lines have a selective advantage and therefore increase in frequency, eventually conferring resistance to the whole tumor and leading to relapse. An effective treatment must be evolutionarily stable, that is, immune to the invasion of resistant mutant cells. This study shows how such a treatment can be achieved by autologous cell therapy using modified cancer cells, knocked out for genes coding for diffusible factors like growth factors. The evolutionary dynamics of a population of cells producing diffusible factors are analyzed using a nonlinear public goods game in a structured population in which the interaction neighborhood and the update neighborhood are decoupled. The analysis of the dynamics of the system reveals what interventions can drive the population to a stable equilibrium in which no diffusible factors are produced. A treatment based on autologous knockout cell therapy can be designed to lead to the spontaneous collapse of a tumor, without targeting directly the cancer cells, their growth factors or their receptors. Critical parameters that can make the therapy effective are identified. Concepts from evolutionary game theory and mechanism design, some of which are counterintuitive, can be adopted to optimize the treatment. Although it shares similarities with other approaches based on gene therapy and RNA interference, the method suggested here is evolutionarily stable under certain conditions. This method, named autologous cell defection, can be
Game theory suggests an anti-cancer treatment based on the use of modified cancer cells that disrupt cooperation within the tumor. Cancer cells are harvested from the patient, the genes for the production of essential growth factors are knocked out in vitro and the cells are then reinserted in the tumor, where they lead to its collapse. Background and objectives: Current anti-cancer drugs and treatments based on gene therapy are prone to the evolution of resistance, because cancer is a process of clonal selection: resistant cell lines have a selective advantage and therefore increase in frequency, eventually conferring resistance to the whole tumor and leading to relapse. An effective treatment must be evolutionarily stable, that is, immune to the invasion of resistant mutant cells. This study shows how such a treatment can be achieved by autologous cell therapy using modified cancer cells, knocked out for genes coding for diffusible factors like growth factors. Methodology: The evolutionary dynamics of a population of cells producing diffusible factors are analyzed using a nonlinear public goods game in a structured population in which the interaction neighborhood and the update neighborhood are decoupled. The analysis of the dynamics of the system reveals what interventions can drive the population to a stable equilibrium in which no diffusible factors are produced. Results: A treatment based on autologous knockout cell therapy can be designed to lead to the spontaneous collapse of a tumor, without targeting directly the cancer cells, their growth factors or their receptors. Critical parameters that can make the therapy effective are identified. Concepts from evolutionary game theory and mechanism design, some of which are counterintuitive, can be adopted to optimize the treatment. Conclusions and implications: Although it shares similarities with other approaches based on gene therapy and RNA interference, the method suggested here is evolutionarily stable under
Yu, Hai-jing; Wang, Qi; Yang, Jian-min; Lian, Zhen-qiang; Zhang, An-qin; Li, Wen-ping; Xu, Juan; Zhu, Cai-xia; Gao, Hong-yi; Lai, You-xng
To study the etiology, clinical and pathologic characteristics of periductal mastitis with fistula and estimate the effect of anti-mycobacterial agents for periductal mastitis with fistula. Totally 27 patients of periductal mastitis with fistula received anti-mycobacteria drugs therapy from December 2008 to September 2011 were analyzed retrospectively. All of the patients were female. The mean age at onset was 28 years (range 15 to 40 years old). The main clinical manifestation of the 27 patients was breast fistula, including 21 patients with single fistula and 6 patients with multiple fistula. Three patients manifested with pure fistula, 14 patients with both fistula and lump, 10 patients with fistula, lump and abscess. The samples including pus or tissues of all patients were underwent bacteria culture and all patients core needle biopsy. All patients were given primary anti-mycobacteria drugs therapy, parts of patients received surgery based on the evaluation of medical treatment. The common bacteria culture of all patients failed to demonstrate any causative microorganism. Four cases were selected randomly to undergo PCR of mycobacteria, only one case was identified as Massiliense in bacteria culture of mycobacteria. Twenty-seven patients with periductal mastitis with fistula were treated with anti-mycobacterial agents (isoniazid, rifampicin and ethambutol or pyrazinamide of triple oral drugs) for 1 to 3 months, the fistula of all 27 patients were closed well. Sixteen patients were treated with the agents only and cured. Eleven patients received surgical treatment after treated with the medical agents. None of the patients were given mastectomy. All patients had no reccurence until now. The periductal mastitis with fistula has a closely relationship with the infection of nontuberculosis mycobacteria. Those patients could be treated with triple anti-mycobacterial agents and could also avoided mastectomy.
Leenders, William P. J.
Since the recognition of the importance of the vascular bed for growth and metastasis of solid tumours, many researchers have investigated the approach of attacking the tumour vascular bed instead of the tumour cells themselves in anti-cancer therapy. Such approaches have become possible with the increasing knowledge of the angiogenic process and the factors that regulate it. Especially the potent angiogenic factor VEGF has been the subject of extensive study in this regard. A number of studies showed that inactivation of this factor or its receptors led to a profound negative effect on the development of experimental tumours. However, despite the encouraging results obtained in animal studies, it remains to be established whether human tumours, which might be in a state of relative quiescence, are as sensitive to anti-VEGF treatment as the fast-growing tumours that are generally used in animal studies. If so, anti-VEGF treatment might certainly represent a powerful tool in anti-cancer therapy, either or not in combination with other blockers of angiogenesis. PMID:10319015
Psoriatic skin disease is common; it occurs at all ages and co-exists with joint disease in approximately 10% of cases. All areas of skin, scalp and nails may be involved. In the typical case, the skin lesions are easy to recognize. Atypical forms of skin involvement and lesions at unusual sites are less easily diagnosed by non-specialists. The cause is unknown, but there is a clear genetic element, with external factors being important in precipitation and exacerbations of the condition. Topical treatment is successful in most patients, but in resistant cases combinations of systemic therapy and ultraviolet radiation usually give good control. Although there is no cure, the majority of sufferers live normal lives and, with the exception of severe erythrodermic or generalized pustular psoriasis, there is no mortality. Morbidity, particularly social and occupational, is more of a problem than is often acknowledged.
Melnik, Bodo C
This review based on translational research predicts that the transcription factor p53 is the key effector of all anti-acne therapies. All-trans retinoic acid (ATRA) and isotretinoin (13-cis retinoic acid) enhance p53 expression. Tetracyclines and macrolides via inhibiting p450 enzymes attenuate ATRA degradation, thereby increase p53. Benzoyl peroxide and hydrogen peroxide elicit oxidative stress, which upregulates p53. Azelaic acid leads to mitochondrial damage associated with increased release of reactive oxygen species inducing p53. p53 inhibits the expression of androgen receptor and IGF-1 receptor, and induces the expression of IGF binding protein 3. p53 induces FoxO1, FoxO3, p21 and sestrin 1, sestrin 2, and tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), the key inducer of isotretinoin-mediated sebocyte apoptosis explaining isotretinoin's sebum-suppressive effect. Anti-androgens attenuate the expression of miRNA-125b, a key negative regulator of p53. It can thus be concluded that all anti-acne therapies have a common mode of action, i.e., upregulation of the guardian of the genome p53. Immortalized p53-inactivated sebocyte cultures are unfortunate models for studying acne pathogenesis and treatment.
Fabiano, Antonella; De Simone, Clara; Gisondi, Paolo; Piaserico, Stefano; Lasagni, Claudia; Pellacani, Giovanni; Conti, Andrea
Tumor necrosis factor alpha (TNF-α) is a cytokine that plays a critical role in inflammatory and immune processes and in the control of infections and sepsis. Data on the perioperative management of patients treated with biologic drugs are limited and mainly in patients with rheumatoid arthritis (RA) and inflammatory bowel disease (IBD). This retrospective study assesses variations in the incidence of side effects between psoriatic patients who temporarily discontinue or continue biological therapy before surgical treatment. Despite the immunosuppressive risk, our results suggest that postoperative complications are not influenced by the suspension of biologic therapies. As TNF-α plays a role in promoting collagen synthesis and wound healing, we suggest that anti-TNFs should be discontinued before major surgery, whereas for minor surgery, the lower rates of infections favor anti-TNF-α continuation, particularly since suspending anti-TNF therapy is known to induce psoriasis relapse.
Bitler, Benjamin G; Schroeder, Joyce A
Cell penetrating peptides (CPPs) are 9-35mer cationic and/or amphipathic peptides that are rapidly internalized across cell membranes. Importantly, they can be linked to a variety of cargo, including anti-cancer therapeutics, making CPPs an efficient, effective and non-toxic mechanism for drug delivery. In this review, we discuss a number of CPP conjugated therapies (CTTs) that are either patented are in the progress of patenting, and show strong promise for clinical efficacy. The CTTs discussed here target a number of different processes specific to cancer progression, including proliferation, survival and migration. In addition, many of these CTTs also increase sensitivity to current anti-cancer therapy modalities, including radiation and other DNA damaging chemotherapies, thereby decreasing the toxic dosage required for effective treatment. Mechanistically, these CTTs function in a dominant-negative manner by blocking tumor-specific protein-protein interactions with the CPP-conjugated peptide or protein. The treatment of both cell lines and mouse models demonstrates that this method of molecular targeting results in equal if not greater efficacy than current standards of care, including DNA damaging agents and topoisomerase inhibitors. For the treatment of invasive carcinoma, these CTTs have significant clinical potential to deliver highly targeted therapies without sacrificing the patient's quality of life.
Antúnez-Lay, Andrea; Cabrolier, Jorge; Andino-Navarrete, Romina
Apart from involving skin, psoriasis can compromise the nails and adjacent structures. Even though there are multiple therapeutic alternatives, there is great interest in biological therapy, but no consensus on its role exists. Searching in Epistemonikos database, which is maintained by screening 30 databases, we identified two systematic reviews including three randomized trials. We combined the evidence using meta-analysis and generated a summary of findings table following the GRADE approach. We concluded it is not clear whether biological therapy is superior to placebo in the treatment of nail psoriasis because the certainty of the evidence is very low.
Feng, Qing-Yang; Wei, Ye; Chen, Jing-Wen; Chang, Wen-Ju; Ye, Le-Chi; Zhu, De-Xiang; Xu, Jian-Min
Colorectal liver metastasis (CLM) is common worldwide. Targeted therapies with monoclonal antibodies have been proven effective in numerous clinical trials, and are now becoming standards for patients with CLM. The development and application of anti-epidermal growth factor receptor (anti-EGFR) and anti-vascular endothelial growth factor (anti-VEGF) antibodies represents significant advances in the treatment of this disease. However, new findings continue to emerge casting doubt on the efficacy of this approach. The Kirsten rat sarcoma viral oncogene (KRAS) has been proven to be a crucial predictor of the success of anti-EGFR treatment in CLM. Whereas a recent study summarized several randomized controlled trials, and showed that patients with the KRAS G13D mutation significantly benefited from the addition of cetuximab in terms of progress-free survival (PFS, 4.0 mo vs 1.9 mo, HR = 0.51, P = 0.004) and overall survival (OS, 7.6 mo vs 5.7 mo, HR = 0.50, P = 0.005). Some other studies also reported that the KRAS G13D mutation might not be absolutely predictive of non-responsiveness to anti-EGFR therapy. At the same time, "new" RAS mutations, including mutations in neuroblastoma RAS viral (v-ras) oncogene homolog (NRAS) and exons 3 and 4 of KRAS, have been suggested to be predictors of a poor treatment response. This finding was first reported by the update of the PRIME trial. The update showed that for patients with non-mutated KRAS exon 2 but other RAS mutations, panitumumab-fluorouracil, leucovorin, and oxaliplatin (FOLFOX)4 treatment led to inferior PFS (HR = 1.28, 95%CI: 0.79-2.07) and OS (HR = 1.29, 95%CI: 0.79-2.10), which was consistent with the findings in patients with KRAS mutations in exon 2. Then, the update of the PEAK trial and the FIRE-III trial also supported this finding, which would reduce candidates for anti-EGFR therapy but enhance the efficacy. In first-line targeted combination therapy, the regimens of cetuximab plus FOLFOX was called into
Gong, Rui; Yu, Fa-Xing
The Hippo signaling pathway is critical in regulating tissue homeostasis, organ size, and tumorigenesis. YAP and TAZ, two major effectors of the Hippo pathway, function as transcriptional co-activators and promote target gene expression mainly through interaction with TEAD family transcription factors. As oncoproteins, YAP and TAZ are frequently activated or highly expressed in various cancer specimens. Moreover, their activity has been linked to resistance to a few widely used anti-cancer drugs, and YAP activation contributes to cancer relapse. Thus, the Hippo pathway, especially YAP/TAZ-TEAD interaction, represents an attractive target for anti-cancer therapies. Here, we will discuss potential approaches to inhibit YAP/TAZ activity, and also review currently available small molecules targeting the Hippo pathway.
Parker, Shefton; Zhang, Anthony Lin; Zhang, Claire Shuiqing; Goodman, Greg; Wen, Zehuai; Lu, Chuanjian; Xue, Charlie Changlie
Probably related to immune dysfunction, psoriasis vulgaris is a chronic, painful, disfiguring and disabling dermatological disease, carrying an increased risk of serious comorbidities. Current conventional therapies can be costly, show risks of side effects and have limited efficacy, with relapse common on treatment cessation. Chinese herbal medicine is effective in treating psoriasis vulgaris. However, any benefit of adding Chinese herbal medicine to conventional treatments when treating psoriasis vulgaris is yet to be determined. This is a pilot randomized, placebo controlled, double-blinded trial. The pilot is primarily to determine the feasibility of undertaking a full size randomized trial. Thirty participants with psoriasis vulgaris and Psoriasis Area Severity Index (PASI) scores ≥ 7 and ≤ 12 will be included. Participants will be randomized (in a 1:1 ratio) to receive oral granulated Chinese herbal medicine YXBCM01 plus topical calcipotriol 0.005% or oral YXBCM01 placebo plus topical calcipotriol 0.005% treatment for 12 weeks, with a 12-week follow-up phase. The Chinese herbal medicine or placebo will be administered orally as dissolvable granules. The primary outcome measure will be PASI change (%) from baseline to the end of treatment phase. Secondary outcomes will include safety, key psoriasis-related cytokine changes (for example, IL12, IL17 and IL 23) during the entire trial and symptom relapse rates at the end of the follow-up phase. The study will evaluate the feasibility of a randomized controlled trial investigating combined conventional and Chinese herbal medicine therapy for psoriasis vulgaris. The ingredients of YXBCM01 were selected based on literature, the expert opinion on herbal medicine and pre-clinical evidence, for instance Chinese herbal medicine possesses anti-inflammatory or antiproliferative properties. Australian New Zealand Clinical Trials Registry ACTRN12614000493640.
Balta, F; Merticariu, M; Taban, C; Neculau, G; Merticariu, A; Muresanu, D; Badescu, D; Jinga, V
Objective: To study the effects of intravitreal anti-Vascular Endothelial Growth Factor (VEGF) therapy with Avastin for wet Age-Related Macular Degeneration (AMD) on Benign Prostatic Hyperplasia (BPH)-related symptoms. Methods: An exploratory trial was conducted from August 1, 2013 to February 1, 2014, that included 14 male patients previously diagnosed with BPH, who were aged between 59 and 69 years. The trial was performed in Bucharest and involved two medical institutions: the Clinical Hospital of Eye Emergencies and the “Prof. Dr. Theodor Burghele” Hospital. This prospective study utilized both objective and subjective indicators to analyze the link between intravitreal anti-VEGF therapy for wet AMD and BPH. The evaluations consisted of uroflowmetry and International Prostate Symptom Score (I-PSS) assessments. Results: The maximum flow rate (Qmax) improved by an average of 5.05 ml/ sec in 9 patients, whereas the remaining 5 patients showed a slight decrease in Qmax (mean 1.6 ml/ sec). The I-PSS score improved, with an overall decrease of 1.18 points at follow-up compared to the initial score (mean initial score = 2.42; mean follow-up score = 1.24). Conclusion: The analysis revealed that anti-VEGF therapy for wet AMD had a significant positive effect on all BPH-related symptoms; patients reported improved urinary streams and decreased nocturia. Abbreviations: BPH = benign prostatic hyperplasia, AMD = age-related macular degeneration, VEGF = vascular endothelial growth factor, I-PSS = international prostate symptom score, Qmax = maximum flow rate, TSP-1 = thrombospondin-1, FGF-2 = fibroblast growth factor, mRNA = precursor messenger ribonucleic acid, PSA = prostate-specific antigen, DRE = digital rectal examination, AUR = acute urinary retention, COX2 = cyclooxygenase 2, QoL = quality of life PMID:27928444
Balta, F; Merticariu, M; Taban, C; Neculau, G; Merticariu, A; Muresanu, D; Badescu, D; Jinga, V
Objective: To study the effects of intravitreal anti-Vascular Endothelial Growth Factor (VEGF) therapy with Avastin for wet Age-Related Macular Degeneration (AMD) on Benign Prostatic Hyperplasia (BPH)-related symptoms. Methods: An exploratory trial was conducted from August 1, 2013 to February 1, 2014, that included 14 male patients previously diagnosed with BPH, who were aged between 59 and 69 years. The trial was performed in Bucharest and involved two medical institutions: the Clinical Hospital of Eye Emergencies and the "Prof. Dr. Theodor Burghele" Hospital. This prospective study utilized both objective and subjective indicators to analyze the link between intravitreal anti-VEGF therapy for wet AMD and BPH. The evaluations consisted of uroflowmetry and International Prostate Symptom Score (I-PSS) assessments. Results: The maximum flow rate (Qmax) improved by an average of 5.05 ml/ sec in 9 patients, whereas the remaining 5 patients showed a slight decrease in Qmax (mean 1.6 ml/ sec). The I-PSS score improved, with an overall decrease of 1.18 points at follow-up compared to the initial score (mean initial score = 2.42; mean follow-up score = 1.24). Conclusion: The analysis revealed that anti-VEGF therapy for wet AMD had a significant positive effect on all BPH-related symptoms; patients reported improved urinary streams and decreased nocturia. Abbreviations: BPH = benign prostatic hyperplasia, AMD = age-related macular degeneration, VEGF = vascular endothelial growth factor, I-PSS = international prostate symptom score, Qmax = maximum flow rate, TSP-1 = thrombospondin-1, FGF-2 = fibroblast growth factor, mRNA = precursor messenger ribonucleic acid, PSA = prostate-specific antigen, DRE = digital rectal examination, AUR = acute urinary retention, COX2 = cyclooxygenase 2, QoL = quality of life.
El-Gharabawy, Rehab M; Ahmed, Amira S; Al-Najjar, Amal H
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. Copyright © 2016 Elsevier Masson SAS
Efficacy and safety of guselkumab, an anti-interleukin-23 monoclonal antibody, compared with adalimumab for the treatment of patients with moderate to severe psoriasis with randomized withdrawal and retreatment: Results from the phase III, double-blind, placebo- and active comparator-controlled VOYAGE 2 trial.
Reich, Kristian; Armstrong, April W; Foley, Peter; Song, Michael; Wasfi, Yasmine; Randazzo, Bruce; Li, Shu; Shen, Y-K; Gordon, Kenneth B
Phase II data suggested that guselkumab, an anti-interleukin-23 monoclonal antibody, was efficacious in psoriasis. We sought to assess efficacy and safety of guselkumab in moderate to severe psoriasis versus placebo and adalimumab, including interrupted treatment and switching adalimumab nonresponders to guselkumab. Patients were randomized to guselkumab 100 mg (weeks 0 and 4, then every 8 weeks; n = 496); placebo→guselkumab (weeks 0, 4, and 12 then guselkumab at weeks 16 and 20; n = 248); or adalimumab (80 mg week 0, then 40 mg week 1, and every 2 weeks through week 23; n = 248). At week 28, guselkumab 90% or greater improvement in Psoriasis Area and Severity Index (PASI) score from baseline (PASI 90) responders were rerandomized to guselkumab or placebo with guselkumab after loss of response. Placebo→guselkumab responders and adalimumab responders received placebo, then guselkumab after loss of response. Nonresponders received guselkumab. At week 16, more patients receiving guselkumab achieved an Investigator Global Assessment (IGA) score 0/1 (cleared/minimal) (84.1% vs 8.5%) and PASI 90 (70.0% vs 2.4%) versus placebo (coprimary end points). Guselkumab was superior to adalimumab at week 16 (IGA score 0/1, 75% or greater improvement in PASI score from baseline, and PASI 90) and week 24 (IGA score 0/1 and 0, PASI 90, 100% improvement in PASI score from baseline) (P < .001). From weeks 28 to 48, better persistence of response was observed in guselkumab maintenance versus withdrawal groups (P < .001). Of adalimumab nonresponders who switched to guselkumab, 66.1% achieved PASI 90 at week 48. Guselkumab improved patient-reported outcomes. Adverse events were comparable among groups. One-year follow-up limits retreatment data. Guselkumab is a highly effective, well-tolerated, maintenance therapy, including in adalimumab nonresponders. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.
Keerthi, Subramaniam; Rangaraj, Murugaiyan; Karthikeyan, Kaliaperumal
Pustular psoriasis is characterized by abrupt onset of macroscopic pustules associated with erythema and symptoms of burning pain and constitutional symptoms. There are several precipitating factors, both physiological such as pregnancy and routinely prescribed drugs like antihypertensives, antifungals, corticosteroids and progesterone. We present a case of a 50-year-old male patient with pustular psoriasis, well controlled on oral methotrexate, who presented with sudden exacerbation of pustular psoriasis following the use of telmisartan. This case is presented due to the absence of prior reports of telmisartan aggravating pustular psoriasis. PMID:25969662
Effectiveness and safety of traditional Chinese medical bath therapy combined with ultraviolet irradiation in the treatment of psoriasis: A systematic review and meta-analysis of randomized controlled trials
Wu, Hanqimuge; Na, Risu; Wu, Xueqin; Wang, Xin
Background and objective To systematically evaluate the clinical effects and safety of traditional Chinese medical bath therapy (TCMBT) combined with ultraviolet irradiation in the treatment of psoriasis. Methods Electronic database retrieval was utilized. The foreign retrieval databases consulted included those of the Cochrane Library, PubMed and EMBASE; the domestic retrieval databases included the Chinese Biomedical Literature Database (Sino-Med), the China National Knowledge Infrastructure (CNKI), VIP and the WangFang Database. Clinical randomized controlled trials were conducted to evaluate the effects of TCMBT combined with ultraviolet irradiation in the treatment of psoriasis; the language of the retrieved articles was Chinese or English. Each database was searched from its inception to August 1, 2015. Two researchers independently collected the data and analyzed the methodology of the documented literature. The researchers conducted a meta-analysis with RevMan 5.2.3 software. Results According to the available literature, 25 RCTs (randomized controlled trials) of low research quality were conducted. According to the meta-analysis, the total effective rate of TCMBT combined with ultraviolet irradiation was relatively higher than that of ultraviolet irradiation alone. The recurrence rate, incidence of adverse reactions and Psoriasis Area and Severity Index (PASI) for the combined therapy was lower than that of ultraviolet irradiation (P<0.05). Conclusion For the treatment of psoriasis, the clinical effects and safety of TCMBT combined with ultraviolet irradiation are generally better than those of ultraviolet irradiation alone. However, the original literature was written in Chinese, and the quality of the studies was not high. Thus, it is difficult to confirm the clinical effects and safety of TCMBT combined with ultraviolet irradiation. It is necessary to conduct a scientific, normalized and high-quality RCT with multiple large samples and centers. PMID
Effectiveness and safety of traditional Chinese medical bath therapy combined with ultraviolet irradiation in the treatment of psoriasis: A systematic review and meta-analysis of randomized controlled trials.
Guan, Jingzhi; Yuan, Shaofei; Wu, Hanqimuge; Na, Risu; Wu, Xueqin; Wang, Xin; Bao, Shan
To systematically evaluate the clinical effects and safety of traditional Chinese medical bath therapy (TCMBT) combined with ultraviolet irradiation in the treatment of psoriasis. Electronic database retrieval was utilized. The foreign retrieval databases consulted included those of the Cochrane Library, PubMed and EMBASE; the domestic retrieval databases included the Chinese Biomedical Literature Database (Sino-Med), the China National Knowledge Infrastructure (CNKI), VIP and the WangFang Database. Clinical randomized controlled trials were conducted to evaluate the effects of TCMBT combined with ultraviolet irradiation in the treatment of psoriasis; the language of the retrieved articles was Chinese or English. Each database was searched from its inception to August 1, 2015. Two researchers independently collected the data and analyzed the methodology of the documented literature. The researchers conducted a meta-analysis with RevMan 5.2.3 software. According to the available literature, 25 RCTs (randomized controlled trials) of low research quality were conducted. According to the meta-analysis, the total effective rate of TCMBT combined with ultraviolet irradiation was relatively higher than that of ultraviolet irradiation alone. The recurrence rate, incidence of adverse reactions and Psoriasis Area and Severity Index (PASI) for the combined therapy was lower than that of ultraviolet irradiation (P<0.05). For the treatment of psoriasis, the clinical effects and safety of TCMBT combined with ultraviolet irradiation are generally better than those of ultraviolet irradiation alone. However, the original literature was written in Chinese, and the quality of the studies was not high. Thus, it is difficult to confirm the clinical effects and safety of TCMBT combined with ultraviolet irradiation. It is necessary to conduct a scientific, normalized and high-quality RCT with multiple large samples and centers.
Ruiz, V; Manubens, E; Puig, L
Scarce scientific evidence is available to define the precise effects that certain drugs might have on embryonic and fetal development if taken by pregnant women with psoriasis, given the ethical concerns that preclude enrolling such women in clinical trials. The little information on the use of biologics during gestation that has been published is based on retrospective and observational studies, and experience with these drugs in this context in psoriasis is still very limited. The literature seems to suggest that biologic therapy is safe during pregnancy, but there is no certainty. This detailed review of accumulated experience with biologic therapy during pregnancy relies mainly on descriptions of the management of other types of rheumatic disease, although the use of these agents in psoriasis is growing steadily.
Kim, Dae Hun; Jeong, Nam Ji; Im, Myung; Lee, Young; Seo, Young Joon; Lee, Jeung Hoon
Trastuzumab (Herceptin), a humanized monoclonal antibody, is a cancer drug developed to target the human epidermal receptor (HER) 2, which is overexpressed in some cancer cells. Cutaneous side effects, such as folliculitis, xerosis, and alopecia have not been reported with therapies targeting HER2, in spite of the frequent observances of such with the therapies targeting the epidermal growth factor receptor. We experienced a patient in whom psoriasis was triggered by the trastuzumab treatment for breast cancer. She was a 57-year-old woman with erythematous and scaly plaques occurring a few months after starting trastuzumab, with repeated aggravation after the re-administration of trastuzumab for the breast cancer. Histologic examination showed the typical features of psoriasis with parakeratosis, epidermal hyperplasia, elongation of the rete ridges, and a lymphocytic and polymorphonuclear cell infiltrate in the dermis. To the best of our knowledge, this is the first report of psoriasis triggered by trastuzumab treatment for breast cancer.
Babar, Tania; Blomberg, Christopher; Hoffner, Eileen; Yan, Xinhua
A significant milestone in the treatment of breast cancer is the identification of the HER2 receptor as a drug target for cancer therapies. Trastuzumab (Herceptin), a monoclonal antibody that blocks the HER2 receptor, is among the first of such drugs approved by the US Food and Drug Administration for targeted cancer therapy. Clinical studies have shown that Trastuzumab significantly improves the overall survival of breast cancer patients. However, an unforeseen significant side-effect of cardiotoxicity manifested as left ventricular dysfunction and heart failure. Concurrent studies have demonstrated the essential role of the HER2 receptor in cardiac development and maintaining the physiological function of an adult heart. The HER2 receptor, therefore, has become a critical link between the oncology and cardiology fields. In addition to Trastuzumab, new drugs targeting the HER2 receptor, such as Lapatinib, Pertuzumab and Afatinib, are either approved or being evaluated in clinical trials for cancer therapy. With the concern of cardiotoxicity caused by HER2 inhibition, it becomes clear that new therapeutic strategies for preventing such cardiac side effects need to be developed. It is the intent of this paper to review the potential cardiac impact of anti-HER2 cancer therapy.
Ladoyanni, E; Nambi, R
Interferon-alpha can exacerbate existing psoriasis and induce de novo psoriasis and psoriatic arthritits. The exact underlying mechanism is not very well understood. It is not a contraindication to treat patients with pre-existing psoriasis with interferon-alpha. In these patients interferon-alpha should be used with care and only if the potential benefits justify the potential risk. Control of psoriasis prior to initiation of interferon-alpha and simultaneous antipsoriatic therapy while on interferon-alpha are essential. We would like to report a 61-year-old male patient with stable psoriasis for over 20 years, who experienced exacerbation of his psoriasis after receiving interferon-alpha for chronic myeloid leukemia. The association between the interferon-alpha therapy and the exacerbation of his psoriasis was only recognized on rechallenge at the stage he was referred to our department.
Sapse, A T
Elevated cortisol is found in many diseases, including infectious, aging-related, depression and depression-associated conditions; even in some with no known origin, and no known therapy. While it was initially thought that 'high cortisol' is the result of these diseases, there is mounting evidence to the contrary, namely, that high cortisol actually plays a major role in inducing them, opening the possibility that anti-cortisol drugs might represent a new beneficial therapy. Evidence is here presented, showing that the use of anti-cortisol drugs has already induced beneficial results in conditions ranging from AIDS to depression. A main reason for not realizing the major role played by cortisol is due to a defective interpretation of cortisol results. If cortisol is within normal range of 0800 h or 1700 h, it has been considered normal, without realizing that swings, sometimes at immunosuppressive levels, might occur during its 24 h circadian rhythm. We suggest that a first step toward unveiling the role of cortisol in diseases would be to develop a standardized cortisol circadian rhythm chart that would show normal levels at any time during a 24 h period, enabling a more accurate comparison with cortisol values obtained under pathological conditions.
Mroz, Pawel; Hashmi, Javad T; Huang, Ying-Ying; Lange, Norbert; Hamblin, Michael R
Photodynamic therapy (PDT) is a rapidly developing cancer treatment that utilizes the combination of nontoxic dyes and harmless visible light to destroy tumors by generating reactive oxygen species. PDT produces tumor-cell destruction in the context of acute inflammation that acts as a ‘danger signal’ to the innate immune system. Activation of the innate immune system increases the priming of tumor-specific T lymphocytes that have the ability to recognize and destroy distant tumor cells and, in addition, lead to the development of an immune memory that can combat recurrence of the cancer at a later point in time. PDT may be also successfully combined with immunomodulating strategies that are capable of overcoming or bypassing the escape mechanisms employed by the progressing tumor to evade immune attack. This article will cover the role of the immune response in PDT anti-tumor effectiveness. It will highlight the milestones in the development of PDT-mediated anti-tumor immunity and emphasize the combination strategies that may improve this therapy. PMID:21162652
Hicks, Martin J.; Chiuchiolo, Maria J.; Ballon, Douglas; Dyke, Jonathan P.; Aronowitz, Eric; Funato, Kosuke; Tabar, Viviane; Havlicek, David; Fan, Fan; Sondhi, Dolan; Kaminsky, Stephen M.; Crystal, Ronald G.
Glioblastoma multiforme (GBM) is the most common and aggressive primary intracranial brain tumor in adults with a mean survival of 14 to 15 months. Aberrant activation of the epidermal growth factor receptor (EGFR) plays a significant role in GBM progression, with amplification or overexpression of EGFR in 60% of GBM tumors. To target EGFR expressed by GBM, we have developed a strategy to deliver the coding sequence for cetuximab, an anti-EGFR antibody, directly to the CNS using an adeno-associated virus serotype rh.10 gene transfer vector. The data demonstrates that single, local delivery of an anti-EGFR antibody by an AAVrh.10 vector coding for cetuximab (AAVrh.10Cetmab) reduces GBM tumor growth and increases survival in xenograft mouse models of a human GBM EGFR-expressing cell line and patient-derived GBM. AAVrh10.CetMab-treated mice displayed a reduction in cachexia, a significant decrease in tumor volume and a prolonged survival following therapy. Adeno-associated-directed delivery of a gene encoding a therapeutic anti-EGFR monoclonal antibody may be an effective strategy to treat GBM. PMID:27711187
Poulin, Yves; Wasel, Norman; Chan, Daphne; Bernstein, Geula; Andrew, Robin; Fraquelli, Elisa; Papp, Kim
Abstract Objective To describe practice patterns for care of Canadian patients with moderate to severe plaque psoriasis. Design Online survey of a consumer panel. Setting Participants were drawn from a population-wide Canadian consumer database. Participants To be eligible to participate, respondents had to have been diagnosed with plaque psoriasis within the past 5 years, and to have had body surface area involvement of 3% or greater in the past 5 years, or to have psoriasis on a sensitive area of the body (hands, feet, scalp, face, or genitals), or to be currently receiving treatment with systemic agents or phototherapy for psoriasis. Main outcome measures Proportion of respondents with psoriasis managed by FPs and other specialists, psoriasis therapies, comorbidities, and patient satisfaction. Results Invitations were sent to 3845 panelists with self-reported psoriasis, of which 514 qualified to complete the survey. Family physicians were reported to be the primary providers for diagnosis and ongoing care of psoriasis in all provinces except Quebec. Overall physician care was reported to be satisfactory by 62% of respondents. Most respondents receiving over-the-counter therapies (55%) or prescribed topical therapies (61%) reported that their psoriasis was managed by FPs. Respondents receiving prescription oral or injectable medications or phototherapy were mainly managed by dermatologists (42%, 74%, and 71% of respondents, respectively). Ongoing management of respondents with body surface area involvement of 10% or greater was mainly split between dermatologists (47%) and FPs (45%), compared with rheumatologists (4%) or other health care professionals (4%). Of those respondents receiving medications for concomitant health conditions, treatment for high blood pressure was most common (92%), followed by treatment for heart disease (75%) and elevated cholesterol and lipid levels (68%). Conclusion Patient-reported practice patterns for the diagnosis and management
Arcilla, John; Joe, Daniel; Kim, Johnathan; Kim, Yohanan; Truong, VuAnh N.; Jaipaul, Navin
Erythroderma is a rare potentially deadly exfoliative dermatitis characterized by diffuse cutaneous erythema which may be associated with multi-organ dysfunction. Therefore, it is imperative to recognize and treat it promptly. Erythrodermic psoriasis is the most common form of erythroderma. Management of this condition is largely based on aggressive supportive care and the use of anti-inflammatory immunosuppressive and biologic agents. We describe a case of psoriatic erythroderma which was triggered by withdrawal from systemic steroids and successfully treated with apremilast and cyclosporine. Apremilast induced atrial fibrillation limited its continued use after the initial response period. PMID:27942369
Bolge, Susan C; Eldridge, Helen M; Lofland, Jennifer H; Ravin, Caitlin; Hart, Philip J; Ingham, Michael P
Objective The objective of this study was to describe patient experience with intravenous (IV) biologics for ankylosing spondylitis, Crohn’s disease, psoriatic arthritis, psoriasis, rheumatoid arthritis, or ulcerative colitis. Methods Semi-structured telephone interviews were conducted in 405 patients with these autoimmune diseases who were receiving an IV biologic to treat their disease. Results On a 7-point scale (1= not at all satisfied; 7= very satisfied), mean satisfaction with IV medication was rated 6.1; 77% of patients rated satisfaction as 6 or 7. The most frequently perceived benefits of IV therapy were related to supervision provided by health care professionals. Most patients (82%, n=332) preferred their IV medication to subcutaneous injection. The three most common reasons for preferring IV were not wanting to self-inject (43%), less frequent dosing (34%), and preference for administration by a health care professional (24%). African–American/black patients had a stronger preference for IV administration than Caucasian/white patients (97% vs 80%, P<0.05) and a greater dislike of needles/self-injection (71% vs 40%, P<0.05). Hospital outpatient departments were not rated as well as physician in-office infusion. Only half (49%) of the patients reported that both they and their physician equally influenced the choice to switch from subcutaneous to IV therapy, and only 30% were given a choice of infusion center. Conclusion Users of IV biologics are highly satisfied with their medications and perceive the opportunity for health care provider interaction at their infusion facilities as an advantage of their regimen. These findings support continued need for IV therapeutic options and shared decision-making between patients and physicians while selecting biologic treatments. PMID:28405158
Xiao, Ting; Li, Bo; He, Chun-Di; Chen, Hong-Duo
Generalized pustular psoriasis (GPP) is an erythrodermic, generalized form of pustular psoriasis. GPP is rare in children. The present study describes a case of juvenile GPP and reviews 12 juvenile GPP inpatients treated at our hospital in the period 1978-2005.
Jalal, O; Houass, S; Laissaoui, K; Hocar, O; Charioui, S; Amal, S
Psoriasis is a frequent dermatosis, its prevalence is estimated of between 1 and 3 p. 100. The severe forms may threaten the functional and life prognosis of patients. We conducted a retrospective study on 160 cases of severe psoriasis collected between 1990 and 2001. We included patients exhibiting severe psoriasis: pustular, erythrodermic or arthropathic psoriasis, the generalized forms that had developed for more than 6 months, without positive response to treatment and the forms with a PASI greater than 50. The patients' ages ranged from 6 to 85 years with a clear male predominance (96 men, 64 women). Nine familial cases were collected. Erythroderma was noted in 87 cases, pustular psoriasis in 31, generalized psoriasis in 31 and psoriatic rheumatism in 15 (4 of which were associated with pustular psoriasis). Local treatment with topical corticosteroids or a Vitamin D derivative was recommended in respectively 41.8 and 13.75 p. 100 of cases. The administration of general treated relied on methotrexate and was required in 68.75 p. 100 of cases. Progression was usually good, relapses were often noted when treatment was stopped. Four patients died. Although the diagnosis of psoriasis is often easy, the severe forms are still difficult to treat. Treatment is complicated, sometimes disappointing and often necessitates heavy and aggressive treatments that require strict surveillance.
Baliwag, Jaymie; Barnes, Drew H; Johnston, Andrew
Psoriasis is a common inflammatory skin disease with an incompletely understood etiology. The disease is characterized by red, scaly and well-demarcated skin lesions formed by the hyperproliferation of epidermal keratinocytes. This hyperproliferation is driven by cytokines secreted by activated resident immune cells, an infiltrate of T cells, dendritic cells and cells of the innate immune system, as well as the keratinocytes themselves. Psoriasis has a strong hereditary character and has a complex genetic background. Genome-wide association studies have identified polymorphisms within or near a number of genes encoding cytokines, cytokine receptors or elements of their signal transduction pathways, further implicating these cytokines in the psoriasis pathomechanism. A considerable number of inflammatory cytokines have been shown to be elevated in lesional psoriasis skin, and the serum concentrations of a subset of these also correlate with psoriasis disease severity. The combined effects of the cytokines found in psoriasis lesions likely explain most of the clinical features of psoriasis, such as the hyperproliferation of keratinocytes, increased neovascularization and skin inflammation. Thus, understanding which cytokines play a pivotal role in the disease process can suggest potential therapeutic targets. A number of cytokines have been therapeutically targeted with success, revolutionizing treatment of this disease. Here we review a number of key cytokines implicated in the pathogenesis of psoriasis.
Baliwag, Jaymie; Barnes, Drew H.; Johnston, Andrew
Psoriasis is a common inflammatory skin disease with an incompletely understood etiology. The disease is characterized by red, scaly and well-demarcated skin lesions formed by the hyperproliferation of epidermal keratinocytes. This hyperproliferation is driven by cytokines secreted by activated resident immune cells, an infiltrate of T cells, dendritic cells and cells of the innate immune system, as well as the keratinocytes themselves. Psoriasis has a strong hereditary character and has a complex genetic background. Genome-wide association studies have identified polymorphisms within or near a number of genes encoding cytokines, cytokine receptors or elements of their signal transduction pathways, further implicating these cytokines in the psoriasis pathomechanism. A considerable number of inflammatory cytokines have been shown to be elevated in lesional psoriasis skin, and the serum concentrations of a subset of these also correlate with psoriasis disease severity. The combined effects of the cytokines found in psoriasis lesions likely explain most of the clinical features of psoriasis, such as the hyperproliferation of keratinocytes, increased neovascularization and skin inflammation. Thus, understanding which cytokines play a pivotal role in the disease process can suggest potential therapeutic targets. A number of cytokines have been therapeutically targeted with success, revolutionizing treatment of this disease. Here we review a number of key cytokines implicated in the pathogenesis of psoriasis. PMID:25585875
Armstrong, April W; Bukhalo, Michael; Blauvelt, Andrew
Many of the molecular pathways associated with psoriasis pathogenesis are also involved in host defense mechanisms that protect against common pathogens. Candida can stimulate the production of cytokines that trigger or exacerbate psoriasis, and many systemic psoriasis treatments may put patients at increased risk for developing oral, cutaneous, and genitourinary candidiasis. Therefore, dermatologists should regularly screen patients with psoriasis for signs of Candida infection, and take steps to effectively treat these infections to prevent worsening of psoriasis symptoms. This review provides an overview of candidiasis epidemiology in patients with psoriasis, followed by a primer on the diagnosis and treatment of superficial Candida infections, with specific guidance for patients with psoriasis. Candidiasis in patients with psoriasis typically responds to topical or oral antifungal therapy. While biologic agents used to treat moderate-to-severe psoriasis, such as tumor necrosis factor-α inhibitors and interleukin-17 inhibitors, are known to increase patients' risk of developing localized candidiasis, the overall risk of infection is low, and candidiasis can be effectively managed in most patients while receiving systemic psoriasis therapies. Thus, the development of candidiasis does not usually necessitate changes to psoriasis treatment regimens.
Ryan, Caitriona; Korman, Neil J; Gelfand, Joel M; Lim, Henry W; Elmets, Craig A; Feldman, Steven R; Gottlieb, Alice B; Koo, John Y M; Lebwohl, Mark; Leonardi, Craig L; Van Voorhees, Abby S; Bhushan, Reva; Menter, Alan
Over the past 2 decades, considerable progress has been made to further elucidate the complex pathogenesis of psoriasis, facilitating the development of a new armamentarium of more effective, targeted therapies. Despite these important advances, substantial deficits remain in our understanding of psoriasis and its treatment, necessitating further research in many areas. In the sixth section of the American Academy of Dermatology Psoriasis Guidelines of Care, gaps in research and care were identified. We discuss the most important gaps in research that currently exist and make suggestions for studies that should be performed to address these deficits. These encompass both basic science and clinical research studies, including large, prospective epidemiologic studies to determine the true prevalence and natural history of psoriasis; further molecular studies in patients with psoriatic and psoriatic arthritis to understand the function of psoriasis susceptibility genes and to identify novel therapeutic targets; studies to examine the role of environmental factors in the development of psoriasis; further investigation of the relationship between psoriasis and cardiometabolic disease; studies that examine the role of adjunctive therapies such as psychological interventions in appropriate patient groups; and finally, studies to identify biomarkers of disease severity and treatment response to optimize patient therapy.
Bonifati, C; Berardesca, E
Several tools have been introduced in clinical trials to quantify the severity and the response to a given therapeutic regimen of both psoriasis and psoriatic arthritis. Each method present specific advantages and limitations. Here we will discuss some of the most popular clinical outcome measures of both psoriasis (Psoriasis Severity Index, Physician Global Assessment, National Psoriasis Fundation-Psoriasis Score, Dermatology Life Quality Index) and psoriatic arthritis (American College Rheumatology response criteria, Psoriatic Arthritis Response Criteria).
Isaeva, O. G.; Osipov, V. A.
The system of partial differential equations describing tumor-immune dynamics with angiogenesis taken into account is presented. For spatially homogeneous case, the steady state analysis of the model is carried out. The effects of single photodynamic impact are numerically simulated. In the case of strong immune response we found that the photodynamic therapy (PDT) gives rise to the substantial shrinkage of tumor size which is accompanied by the increase of IL-2 concentration. On the contrary, the photodynamic stimulation of weak immune response is shown to be insufficient to reduce the tumor. These findings indicate the important role of anti-cancer immune response in the long-term tumor control after PDT.
Isaeva, O. G.; Osipov, V. A.
The system of partial differential equations describing tumor-immune dynamics with angiogenesis taken into account is presented. For spatially homogeneous case, the steady state analysis of the model is carried out. The effects of single photodynamic impact are numerically simulated. In the case of strong immune response we found that the photodynamic therapy (PDT) gives rise to the substantial shrinkage of tumor size which is accompanied by the increase of IL-2 concentration. On the contrary, the photodynamic stimulation of weak immune response is shown to be insufficient to reduce the tumor. These findings indicate the important role of anti-cancer immune response in the long-term tumor control after PDT.
Drucker, D J; Rosen, C F
Type 2 diabetes mellitus is characterised by beta cell failure, which frequently develops in the setting of insulin resistance. Inflammation contributes to the pathophysiology of type 2 diabetes by impairing insulin action in peripheral tissues and via reduction of beta cell function. Inflammation may also play an important role in the development of complications that arise in patients with type 2 diabetes. Hence, the anti-inflammatory actions of commonly used glucose-lowering drugs may contribute, indirectly, to their mechanisms of action and therapeutic benefit. Herein we highlight the anti-inflammatory actions of glucagon-like peptide-1 (GLP-1), which exerts direct and indirect actions on immune function. The observations that GLP-1 receptor agonists exert anti-inflammatory actions in preclinical studies, taken together with case reports linking improvements in psoriasis with GLP-1 receptor agonist therapy, illustrates the emerging clinical implications of non-classical anti-inflammatory actions of incretin-based therapeutics.
Kumar, Rakesh; Lal, Neena
Anti-cancer drug development is a major area of research. Monitoring of response to newer anti-cancer drugs has undergone an evolution from structural imaging modalities to targeting functional metabolic activity at cellular level to better define responsive and non-responsive cancerous tissue. This review article highlights the contribution of Positron Emission Tomography (PET) in this field. PET holds a promising role in the future by providing us information pertaining to the drugs effectiveness early in the course of therapy, so that side effects and expenses can be reduced substantially. PET has been used to measure changes in drug induced metabolism, cellular proliferation and tissue perfusion. Also changes induced by immuno-modulating drugs such as apoptosis, telomere activity, growth factor levels and many more can be studied using specific radiolabelled PET tracers whereas conventional imaging modalities which detect changes in tumor size and residual tissue histopathology may not prove useful in such scenario. In future, most PET scanners will be replaced by Hybrid PET-CT scanners, which provide functional and structural information in the same setting. In addition, PET-CT improves characterization of equivocal lesions and decreases interobserver variability. The most important recent patents concerning role of PET in drug development have been presented.
Khan, Razi; Spagnoli, Vincent; Tardif, Jean-Claude; L'Allier, Philippe L
The underlying role of inflammation in atherosclerosis has been characterized. However, current treatment of coronary artery disease (CAD) predominantly consists of targeted reductions in serum lipoprotein levels rather than combating the deleterious effects of acute and chronic inflammation. Vascular inflammation acts by a number of different molecular and cellular pathways to contribute to atherogenesis. Over the last decades, both basic studies and clinical trials have provided evidence for the potential benefits of treatment of inflammation in CAD. During this period, development of pharmacotherapies directed towards inflammation in atherosclerosis has accelerated quickly. This review will highlight specific therapies targeting interleukin-1β (IL-1β), P-selectin and 5-lipoxygenase (5-LO). It will also aim to examine the anti-inflammatory effects of serpin administration, colchicine and intravenous HDL-directed treatment of CAD. We summarize the mechanistic rationale and evidence for these novel anti-inflammatory treatments at both the experimental and clinical levels. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Baran, Anna; Myśliwiec, Hanna; Kiluk, Paulina; Świderska, Magdalena; Flisiak, Iwona
Irisin has been proposed to regulate metabolic diseases such as obesity, diabetes or metabolic syndrome which are common comorbidities in psoriasis. The aim of this study was to evaluate the serum irisin level in psoriasis and elucidate possible associations with disease activity, inflammatory or metabolic parameters and topical treatment. Thirty-seven individuals with active plaque-type psoriasis and 15 healthy controls were enrolled. Blood samples were collected before and after two weeks of therapy. Serum irisin concentrations were examined by enzyme-linked immunosorbent assay (ELISA). The results were correlated with psoriasis area and severity index (PASI), body mass index (BMI), inflammatory and biochemical markers, lipid profile and effectiveness of topical treatment. Irisin serum levels were insignificantly increased in psoriatic patients in comparison to the controls (p = 0.38). No significant correlations between investigated adipokine and several indicators of metabolic disorders, nor BMI (p = 0.37) or PASI (p = 0.5) were found. Significant positive correlations with C-reactive protein (CRP) (0.009), lipocalin-2 (p = 0.02), age (p = 0.02) and disease duration (p = 0.008) were noted. After topical treatment, serum irisin level did not significantly change (p = 0.31), despite clinical improvement. Irisin might be a marker of inflammation in psoriatic patients, but may not be a reliable indicator of metabolic conditions, severity of psoriasis nor efficacy of antipsoriatic treatment.
Rosińska, D; Wolska, H; Jablonska, S; Konca, I
Ten children, five with generalized pustular psoriasis and five with erythrodermic disease, were treated with etretinate and observed for up to seven years. In all those with pustular psoriasis, complete clearing was obtained in three weeks to four months, but in one child maintenance therapy had to be introduced twice, for one year each time. In those with erythrodermic psoriasis, the results were favorable only in two, and in two it was necessary to introduce Re-PUVA. Clinical side effects were slight, and laboratory examinations did not disclose any significant abnormalities. In one child who was treated intermittently for seven years, focal osteoporosis of one tibia was disclosed by radiography. No adverse effects on children's development were noticed.
Al-Mutairi, Nawaf; Shabaan, Dalia
Psoriasis is a chronic inflammatory disease that has been associated with an increased incidence of insulin resistance and diabetes mellitus (DM). Tumor necrosis factor (TNF) α inhibitors and IL-6 blockers, which are routinely used for the treatment of psoriasis, have been positively associated with insulin sensitivity. The aim of this study was to assess the effects of treatment with TNF-α inhibitors on insulin sensitivity in psoriatic patients with type 2 DM. This study confirms a beneficial effect of anti-TNF-α agents on insulin resistance and insulin sensitivity in psoriasis patients with type 2 DM.
Alcock, Richard F; Naoum, Chris; Aliprandi-Costa, Bernadette; Hillis, Graham S; Brieger, David B
Cardiovascular complications are important causes of morbidity and mortality in patients undergoing elective non-cardiac surgery, with adverse cardiac outcomes estimated to occur in approximately 4% of all patients. Anti-platelet therapy withdrawal may precede up to 10% of acute cardiovascular syndromes, with withdrawal in the peri-operative setting incompletely appraised. The aims of our study were to determine the proportion of patients undergoing elective non-cardiac surgery currently prescribed anti-platelet therapy, and identify current practice in peri-operative management. In addition, the relationship between management of anti-platelet therapy and peri-operative cardiac risk was assessed. We evaluated consecutive patients attending elective non-cardiac surgery at a major tertiary referral centre. Clinical and biochemical data were collected and analysed on patients currently prescribed anti-platelet therapy. Peri-operative management of anti-platelet therapy was compared with estimated peri-operative cardiac risk. Included were 2950 consecutive patients, with 516 (17%) prescribed anti-platelet therapy, primarily for ischaemic heart disease. Two hundred and eighty nine (56%) patients had all anti-platelet therapy ceased in the peri-operative period, including 49% of patients with ischaemic heart disease and 46% of patients with previous coronary stenting. Peri-operative cardiac risk score did not influence anti-platelet therapy management. Approximately 17% of patients undergoing elective non-cardiac surgery are prescribed anti-platelet therapy, the predominant indication being for ischaemic heart disease. Almost half of all patients with previous coronary stenting had no anti-platelet therapy during the peri-operative period. The decision to cease anti-platelet therapy, which occurred commonly, did not appear to be guided by peri-operative cardiac risk stratification. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
Bonciolini, Veronica; Volpi, Walter; Del Bianco, Elena; Caproni, Marzia
Curcumin is a complementary therapy that may be helpful for the treatment of psoriasis due to its anti-inflammatory, antiangiogenic, antioxidant, and antiproliferative effects. In the present study we performed a randomized, double-blind, placebo-controlled clinical trial to assess the effectiveness of a bioavailable oral curcumin in the treatment of psoriasis. Sixty-three patients with mild-to-moderate psoriasis vulgaris (PASI < 10) were randomly divided into two groups treated with topical steroids and Meriva, a commercially available lecithin based delivery system of curcumin, at 2 g per day (arm 1), or with topical steroids alone (arm 2), both for 12 weeks. At the beginning (T0) and at the end of the therapy (T12), clinical assessment and immunoenzymatic analysis of the serum levels of IL-17 and IL-22 were performed. At T12, both groups achieved a significant reduction of PASI values that, however, was higher in patients treated with both topical steroids and oral curcumin than in patients treated only with topical steroids. Moreover, IL-22 serum levels were significantly reduced in patients treated with oral curcumin. In conclusion, curcumin was demonstrated to be effective as an adjuvant therapy for the treatment of psoriasis vulgaris and to significantly reduce serum levels of IL-22. PMID:26090395
ter Brake, Olivier; Westerink, Jan-Tinus; Berkhout, Ben
RNA interference or RNAi-based gene therapy for the treatment of HIV-1 infection has recently emerged as a highly effective antiviral approach. The lentiviral vector system is a good candidate for the expression of antiviral short hairpin RNAs (shRNA) in HIV-susceptible cells. However, this strategy can give rise to vector problems because the anti-HIV shRNAs can also target the HIV-based lentiviral vector system. In addition, there may be self-targeting of the shRNA-encoding sequences within the vector RNA genome in the producer cell. The insertion of microRNA (miRNA) cassettes in the vector may introduce Drosha cleavage sites that will also result in the destruction of the vector genome during the production and/or the transduction process. Here, we describe possible solutions to these lentiviral-RNAi problems. We also describe a strategy for multiple shRNA expression to establish a combinatorial RNAi therapy.
Rahbari, Nuh N; Kedrin, Dmitriy; Incio, Joao; Liu, Hao; Ho, William W; Nia, Hadi T; Edrich, Christina M; Jung, Keehoon; Daubriac, Julien; Chen, Ivy; Heishi, Takahiro; Martin, John D; Huang, Yuhui; Maimon, Nir; Reissfelder, Christoph; Weitz, Jurgen; Boucher, Yves; Clark, Jeffrey W; Grodzinsky, Alan J; Duda, Dan G; Jain, Rakesh K; Fukumura, Dai
The survival benefit of anti-vascular endothelial growth factor (VEGF) therapy in metastatic colorectal cancer (mCRC) patients is limited to a few months because of acquired resistance. We show that anti-VEGF therapy induced remodeling of the extracellular matrix with subsequent alteration of the physical properties of colorectal liver metastases. Preoperative treatment with bevacizumab in patients with colorectal liver metastases increased hyaluronic acid (HA) deposition within the tumors. Moreover, in two syngeneic mouse models of CRC metastasis in the liver, we show that anti-VEGF therapy markedly increased the expression of HA and sulfated glycosaminoglycans (sGAGs), without significantly changing collagen deposition. The density of these matrix components correlated with increased tumor stiffness after anti-VEGF therapy. Treatment-induced tumor hypoxia appeared to be the driving force for the remodeling of the extracellular matrix. In preclinical models, we show that enzymatic depletion of HA partially rescued the compromised perfusion in liver mCRCs after anti-VEGF therapy and prolonged survival in combination with anti-VEGF therapy and chemotherapy. These findings suggest that extracellular matrix components such as HA could be a potential therapeutic target for reducing physical barriers to systemic treatments in patients with mCRC who receive anti-VEGF therapy.
Machado-Pinto, Jackson; Diniz, Michelle dos Santos; Bavoso, Nádia Couto
Psoriasis is a chronic inflammatory disease associated with several comorbidities. A few decades ago, it was considered an exclusive skin disease but today it is considered a multisystem disease. It is believed that 73% of psoriasis patients have at least one comorbidity. Studies have demonstrated the association of psoriasis with inflammatory bowel disease, uveitis, psychiatric disorders, metabolic syndrome and its components and cardiovascular diseases. The systemic inflammatory state seems to be the common denominator for all these comorbidities. This work aims at presenting a review of the current literature on some new comorbidities that are associated with psoriasis as osteoporosis, obstructive sleep apnea and chronic obstructive pulmonary disease. While there is still controversy, many studies already point to a possible bone involvement in patients with psoriasis, especially in the male group, generally less affected by osteoporosis. Psoriasis and chronic obstructive pulmonary disease present some risk factors in common as obesity, smoking and physical inactivity. Besides, both diseases are associated with the metabolic syndrome. These factors could be potential confounders in the association of the two diseases. Further prospective studies with control of those potential confounders should be developed in an attempt to establish causality. Existing data in the literature suggest that there is an association between obstructive sleep apnea and psoriasis, but studies performed until now have involved few patients and had a short follow-up period. It is, therefore, premature to assert that there is indeed a correlation between these two diseases. PMID:26982772
Gerdes, S; Mrowietz, U; Boehncke, W-H
Psoriasis is a systemic chronic inflammatory disease associated with comorbidity. Many epidemiological studies have shown that psoriasis is associated with psoriatic arthritis as well as cardiovascular and metabolic diseases. Furthermore, obesity and psychological diseases such as depression and anxiety disorders are linked with psoriasis and play a central role in its management. The association of psoriasis and its comorbidity can be partly explained by genetic and pathophysiological mechanisms. Approximately 40 psoriasis susceptibility loci have been described with the majority linked to the innate and adaptive immune system. In some associated diseases, such as psoriatic arthritis, an overlap of their genetic susceptibility exists. Pathophysiologically the "psoriatic march" is a model that describes the development of metabolic and cardiovascular diseases due to the presence of underlying systemic inflammation. Dermatologists are the gatekeepers to treatment for patients with psoriasis. The early detection and the management of comorbidity is part of their responsibility. Concepts for the management of psoriasis and tools to screen for psoriatic comorbidity have been developed in order to support dermatologists in daily practice.
Cortes, Claudia P.; Wehbe, Firas H.; McGowan, Catherine C.; Shepherd, Bryan E.; Duda, Stephany N.; Jenkins, Cathy A.; Gonzalez, Elsa; Carriquiry, Gabriela; Schechter, Mauro; Padgett, Denis; Cesar, Carina; Madero, Juan Sierra; Pape, Jean W.; Masys, Daniel R.; Sterling, Timothy R.
Background Antiretroviral therapy (ART) decreases mortality risk in HIV-infected tuberculosis patients, but the effect of the duration of anti-tuberculosis therapy and timing of anti-tuberculosis therapy initiation in relation to ART initiation on mortality, is unclear. Methods We conducted a retrospective observational multi-center cohort study among HIV-infected persons concomitantly treated with Rifamycin-based anti-tuberculosis therapy and ART in Latin America. The study population included persons for whom 6 months of anti-tuberculosis therapy is recommended. Results Of 253 patients who met inclusion criteria, median CD4+ lymphocyte count at ART initiation was 64 cells/mm3, 171 (68%) received >180 days of anti-tuberculosis therapy, 168 (66%) initiated anti-tuberculosis therapy before ART, and 43 (17%) died. In a multivariate Cox proportional hazards model that adjusted for CD4+ lymphocytes and HIV-1 RNA, tuberculosis diagnosed after ART initiation was associated with an increased risk of death compared to tuberculosis diagnosis before ART initiation (HR 2.40; 95% CI 1.15, 5.02; P = 0.02). In a separate model among patients surviving >6 months after tuberculosis diagnosis, after adjusting for CD4+ lymphocytes, HIV-1 RNA, and timing of ART initiation relative to tuberculosis diagnosis, receipt of >6 months of anti-tuberculosis therapy was associated with a decreased risk of death (HR 0.23; 95% CI 0.08, 0.66; P=0.007). Conclusions The increased risk of death among persons diagnosed with tuberculosis after ART initiation highlights the importance of screening for tuberculosis before ART initiation. The decreased risk of death among persons receiving > 6 months of anti-tuberculosis therapy suggests that current anti-tuberculosis treatment duration guidelines should be re-evaluated. PMID:24066096
Gisondi, Paolo; Del Giglio, Micol; Girolomoni, Giampiero
Psoriasis is an immune-mediated inflammatory skin disease frequently associated with metabolic disorders, including diabetes, dyslipidaemia and metabolic syndrome. Moreover, a growing number of studies confirm the association between psoriasis and obesity. It has been found that obesity, as measured by body mass index >30 kg/m(2), can double the risk of incident psoriasis. A positive correlation between different measures of adiposity and the severity of psoriasis has also been reported. Epidemiologic studies have also provided robust evidence confirming the association between obesity and psoriatic arthritis. Genetic, metabolic and environmental factors are all likely to contribute to these associations. Adipose tissue is an active endocrine and paracrine organ that has a key role in lipid and glucose metabolism as well as inflammation. Fat tissue is traditionally distributed into two main compartments with different metabolic characteristics, i.e. the subcutaneous and visceral adipose tissue. Particular attention has been devoted to visceral adiposity because of its contribution to inflammation and atherosclerosis. The association between psoriasis and obesity should be properly considered when choosing a systemic treatment, because it could exert negative effects on metabolic parameters, including liver enzymes, serum lipids and renal function. Obesity may increase the risk of liver and renal toxicity from methotrexate and cyclosporine. Moreover, obesity can compromise the effectiveness of systemic treatments for psoriasis (conventional and biological therapies). Dermatologists are also expected to promote a healthy lifestyle and weight loss for obese patients because they could improve metabolic parameters and responsiveness to psoriasis therapies.
Torres, Tiago; Sales, Rita; Vasconcelos, Carlos; Selores, Manuela
Psoriasis is a common, chronic and systemic inflammatory disease associated with several comorbidities, such as obesity, hypertension, diabetes, dyslipidaemia and metabolic syndrome, but also with an increased risk of cardiovascular disease, like myocardial infarction or stroke. The chronic inflammatory nature of psoriasis has been suggested to be a contributing and potentially independent risk factor for the development of cardiovascular comorbidities and precocious atherosclerosis. Aiming at alerting clinicians to the need of screening and monitoring cardiovascular diseases and its risk factors in psoriatic patients, this review will focus on the range of cardiometabolic comorbidities and increased risk of cardiovascular disease associated with psoriasis.
Risk of tuberculosis is higher with anti-tumor necrosis factor monoclonal antibody therapy than with soluble tumor necrosis factor receptor therapy: The three-year prospective French Research Axed on Tolerance of Biotherapies registry
Tubach, Florence; Salmon, Dominique; Ravaud, Philippe; Allanore, Yannick; Goupille, Philippe; Bréban, Maxime; Pallot-Prades, Béatrice; Pouplin, Sophie; Sacchi, Antoinette; Chichemanian, Rose Marie; Bretagne, Stéphane; Emilie, Dominique; Lemann, Marc; Lorthololary, Olivier; Mariette, Xavier
Background Tuberculosis (TB) is associated with anti-tumour necrosis factor (TNF) therapy but whether it is drug-specific remains a concern. Our objective was to describe cases of tuberculosis associated with anti-TNF therapy, identify risk factors and estimate the incidence. Methods An incidence study with the French population as reference and a case-control analysis. We collected, for 3 years, cases of TB among French patients receiving anti-TNF therapy, whatever the indication, with two controls treated with anti-TNF agents per case. Results We collected 69 cases of TB in patients treated for rheumatoid arthritis (n=40), spondylarthropathies (n=18), inflammatory colitis (n=9), psoriasis (n=1) and Behçet’s disease (n=1) treated with infliximab (n=36), adalimumab (n=28) and etanercept (n=5). None of the cases had received correct chemoprophylaxis treatment. The sex and age-adjusted incidence rate of TB was 116.7 per 100,000 patient-years. The SIR was 12.2 (95% confidence interval 9.7–15.5) and was higher for therapy with infliximab and adalimumab than for that with etanercept: 18.6 (13.4–25.8) and 29.3 (20.2–42.4) versus 1.8 (0.7–4.3), respectively. In the case-control analysis, the exposure to infliximab or adalimumab versus etanercept was an independent risk factor for TB: odds ratio=13.3 (2.6–69.0) and 17.1 (3.6–80.6), respectively. Other risk factors were age, the first year of anti-TNF treatment, and being born in an endemic area. Conclusions The risk of TB is higher for patients receiving monoclonal-antibody than soluble-receptor anti-TNF therapy. The increased risk with early anti-TNF treatment and the absence of correct chemoprophylaxis treatment favours the reactivation of latent TB. PMID:19565495
Okamoto, F; Sato, T; Umebayashi, Y; Ohtsuka, F; Hommura, S
We evaluated aqueous humor protein concentration in psoriasis using a laser flare-cell meter, which can quantify aqueous flare precisely and objectively. Psoriatic severity was evaluated on the basis of psoriasis area and severity index (PASI) score. Aqueous flare was measured in 40 eyes of 20 psoriasis patients (sixteen psoriasis vulgaris, three guttate psoriasis, and one psoriatic arthritis) and 28 eyes of 14 normal controls. Aqueous flare value was significantly higher in psoriatic patients than in normal controls (p < 0.01). There was no difference between psoriasis vulgaris and the other types of psoriasis. Aqueous flare value was higher in patients with psoriatic history longer than 10 years than in those with less than 10 years (p < 0.05), and also higher in patients with severe psoriasis (PASI score > 10) than in those with mild psoriasis (PASI score < 10) (p < 0.05). But no statistically significant differences in aqueous flare value were found among cyclosporin, etretinate, and psoralen ultra violet A therapies. These findings strongly suggest that patients suffering from psoriasis have slight damage of the blood-aqueous barrier even if they have no ocular symptoms, and that the degree of blood-aqueous barrier damage increases with time and severity of psoriasis.
Glossmann, Hartmut; Reider, Norbert
In this article we present arguments that the “antidiabetic” drug metformin could be useful as an add-on therapy to methotrexate for the treatment of psoriasis and, perhaps, for rheumatoid arthritis as well. Biochemical data suggest that both drugs may share a common cellular target, the AMP-activated protein kinase (AMPK). This enzyme is a master regulator of metabolism and controls a number of downstream targets, e.g., important for cellular growth or function in many tissues including T-lymphocytes. Clinical observations as well as experimental results argue for anti-inflammatory, antineoplastic and antiproliferative activities of metformin and a case-control study suggests that the drug reduces the risk for psoriasis. Patients with psoriasis have higher risk of metabolic syndrome, type 2 diabetes and cardiovascular mortality. Metformin has proven efficacy in the treatment of prediabetes and leads to a pronounced and sustained weight loss in overweight individuals. We expect that addition of metformin to methotrexate can lead to positive effects with respect to the PASI score, reduction of the weekly methotrexate dose and of elevated cardiovascular risk factors in patients with metabolic syndrome and psoriasis. For reasons explained later we suggest that only male, overweight patients are to be included in a pilot trial. On the other side of the coin are concerns that the gastrointestinal side effects of metformin are intolerable for patients under low dose, intermittent methotrexate therapy. Metformin has another side effect, namely interference with vitamin B12 and folate metabolism, leading to elevated homocysteine serum levels. As patients must receive folate supplementation and will be controlled with respect to their B12 status increased hematological toxicity is unlikely to result. PMID:24194965
Kouris, A; Platsidaki, E; Kouskoukis, C; Christodoulou, C
Psoriasis is a chronic, inflammatory scaling dermatosis. The marked visible appearance of the lesions have a negative impact on body image that leads to decreased self-esteem, hence seriously compromising the patient's quality of life. The clinical picture critically affects the social well-being of the patient since the disease is commonly misunderstood and feared by the social environment as being contagious. The patient feels stigmatized and this further intensifies their lack of self-confidence and self-esteem. Feelings of shame and guilt increase the tendency toward suicidal ideation. The poor quality of life of psoriatic patients has been associated with excessive alcohol consumption, increased smoking and greater use of tranquilizers, sedatives and antidepressants. As far as mental impairment is concerned, a correlation has been found between psychological stress and the clinical severity of symptoms: the more mentally affected the patient, the more severe the dermatologic lesions. Similarly, stressful life events constitute a major risk for the occurrence and recurrence, exacerbating the severity and duration of the symptoms. Depression and anxiety can worsen the disease or cause resistance to treatment or patient's indifference, which in turn can lead to expensive and prolonged treatment. Not least, the disease itself contributes to anxiety, depression and psychological stress, thus creating a "vicious circle" that is difficult to manage. Given that women seem to invest more in their personal appearance than men, it is hardly surprising that female psoriatic patients report higher levels of depression. Similarly, the risk of mental disorders is also higher in younger patients for whom body image plays an equally significant role. The severity of the disease, side effects of therapy and mental disorders are among the causes that have been attributed to sexual dysfunction reported by some psoriatic patients. At the social level, stigma, social rejection
Snell, Terry W; Johnston, Rachel K; Srinivasan, Bharath; Zhou, Hongyi; Gao, Mu; Skolnick, Jeffrey
There is great interest in drugs that are capable of modulating multiple aging pathways, thereby delaying the onset and progression of aging. Effective strategies for drug development include the repurposing of existing drugs already approved by the FDA for human therapy. FDA approved drugs have known mechanisms of action and have been thoroughly screened for safety. Although there has been extensive scientific activity in repurposing drugs for disease therapy, there has been little testing of these drugs for their effects on aging. The pool of FDA approved drugs therefore represents a large reservoir of drug candidates with substantial potential for anti-aging therapy. In this paper we employ FINDSITE(comb), a powerful ligand homology modeling program, to identify binding partners for proteins produced by temperature sensing genes that have been implicated in aging. This list of drugs with potential to modulate aging rates was then tested experimentally for lifespan and healthspan extension using a small invertebrate model. Three protein targets of the rotifer Brachionus manjavacas corresponding to products of the transient receptor potential gene 7, ribosomal protein S6 polypeptide 2 gene, or forkhead box C gene, were screened against a compound library consisting of DrugBank drugs including 1347 FDA approved, non-nutraceutical molecules. Twenty nine drugs ranked in the top 1 % for binding to each target were subsequently included in our experimental analysis. Continuous exposure of rotifers to 1 µM naproxen significantly extended rotifer mean lifespan by 14 %. We used three endpoints to estimate rotifer health: swimming speed (mobility proxy), reproduction (overall vitality), and mitochondria activity (cellular senescence proxy). The natural decline in swimming speed with aging was more gradual when rotifers were exposed to three drugs, so that on day 6, mean swimming speed of females was 1.19 mm/s for naproxen (P = 0.038), 1.20 for fludarabine (P = 0
Lu, Liming; Xuan, Meiling; Yan, Yuhong; Li, Geng; Zhou, Li; Wen, Zehuai; Lu, Chuanjian
Psoriasis vulgaris (PV) has been causing increasing concern due to its highly prevalent, harmful and therapy-resistant characteristics. The YXBCM01 (Chinese herbal medicine) for PV trial evaluates the effects of YXBCM01 on relapse rate in patients suffering from PV. As an update to the published design and method for the trial, this paper presents the statistical plan for the main publication to avoid the risk of outcome reporting bias, selective reporting, and data-driven results. This trial is a multicenter, randomized, double-blind, placebo-controlled, parallel-group clinical trial. A total of 600 PV patients (300 in each group) will be randomized to one of two arms: participants in the experimental group will receive the YXBCM01 granule 5.5 g twice daily for 12 weeks. Placebo granules are given to patients in the control group at a dose of 5.5 g twice daily for 12 weeks. The sequential topical therapy is administrated simultaneously to all eligible patients by using calcipotriol betamethasone ointment once daily (a treatment area of up to 30 % body surface area (BSA), fingertip unit is recommended) in the first 4 weeks (maximum of 100 g weekly), followed by calcipotriol betamethasone ointment once daily for the remaining 8 weeks (maximum of 100 g weekly). The primary outcome measure is relapse rate in the treatment period and follow-up period. The secondary outcome measures include time to relapse, time to onset, rebound rate, cumulative consumption of topical medicine, visual analog scale (VAS), BSA, the Dermatology Life Quality Index (DLQI) and the Medical Outcomes Study (MOS) 36-item short form health survey (SF-36). Application of this statistical analysis plan to the YXBCM01 for PV trial will facilitate unbiased evaluation of these important clinical data. This study will provide evidence regarding the value of YXBCM01 as an intervention for PV patients. Chinese Clinical Trial Registry: ChiCTR-TRC-13003233 , registered on 26 May 2013.
AbuHilal, Mohn'd; Walsh, Scott; Shear, Neil
Major advances have been made in the understanding of the pathophysiology of psoriasis. The authors review the role of interleukin (IL) 17 in the pathogenesis of psoriasis and provide updates on approved and investigational therapies targeting IL-17 and the IL-17 receptor. A PubMed search was performed for relevant literature. The IL-23/Th17 signaling pathway (including IL-17) plays a central role in the pathogenesis of psoriasis. Biologic agents that block IL-17 (secukinumab and ixekizumab) or its receptor (brodalumab) are effective and safe for the treatment of psoriasis. © The Author(s) 2016.
Sako, Eric; Famenini, Shannon; Wu, Jashin J
Research investigating psoriasis has spanned decades, and as our understanding of the disease has evolved, the focus of publications has changed. We sought to characterize the trends in original psoriasis-related research from 1960 to 2010 chronologically by decade. A literature review was performed using the keyword psoriasis in the MEDLINE database. All original psoriasis-related articles published at the beginning of each decade were searched and categorized by study type and topic. Number of articles per topic. A total of 869 original psoriasis-related articles were found. The number of publications increased 18 fold over 5 decades. The immunology and pathogenesis of psoriasis was the most frequently researched topic (36%), and retrospective studies were the most common study type (37%). Recent highly published topics included biologic therapy, genetics, and psoriasis-associated cardiovascular disease. Original psoriasis-related publications have grown substantially since 1960. Basic science research into the immunology and pathogenesis has been and continues to be the mainstay of psoriasis research. Recent research trends suggest the focus has expanded to topics such as psoriasis-associated cardiovascular disease, genetics, and biologic therapy.
Mahil, Satveer K; Capon, Francesca; Barker, Jonathan N
Psoriasis is a common and debilitating immune-mediated skin disease with a complex genetic basis. Genetic studies have provided critical insights into the pathogenesis of disease. This article focuses on the results of genetic association studies, which provide evidence that psoriasis susceptibility genes are involved in innate and adaptive immunity and skin barrier functions. The potential for disease stratification and the development of more effective treatments with fewer side effects using genetic data are highlighted.
Huang, Kun; Chen, Aijun; Zhang, Xuemei; Song, Zhixin; Xu, Hongmei; Cao, Ju; Yin, Yibing
Progranulin (PGRN) is a multi-functional protein known to be involved in inflammation. Recent studies have found that PGRN has dual roles in inflammation and exerts anti-inflammatory and pro-inflammatory function in different diseases. However, the role of PGRN in psoriasis has not been fully elucidated. Here, we detected preferential expression of PGRN in human psoriatic lesions and serum. Moreover, serum PGRN/tumour necrosis factor-α ratio was negatively correlated with disease severity. To investigate the role of PGRN in the pathogenesis of psoriasis, we used wild-type (WT) and PGRN(-/-) mice in a model of 12-O-tetradecanoylphorbol 13-acetate (TPA) -induced psoriasis-like inflammation. We demonstrated that PGRN expression was dramatically enhanced in the psoriasis-like lesions of TPA-treated WT mice, in accordance with human psoriatic lesions. Surprisingly, PGRN(-/-) mice were more sensitive to the development of TPA-induced psoriasis-like inflammation. The mechanism underlying this increased sensitivity of PGRN(-/-) mice to TPA-induced psoriasis-like inflammation was impaired differentiation of regulatory T cells in lymph nodes and decreased recruitment of these cells in the affected skin, which results in more severe inflammation. Hence, in WT mice, PGRN promotes differentiation and recruitment of regulatory T cells at the site of inflammation, which protects the skin from an exaggerated psoriasis-like inflammatory response.
Fontana, Elisa; Sclafani, Francesco; Cunningham, David
Neo-vascularization is a vital process for tumor growth and development which involves the interaction between tumor cells and stromal endothelial cells through several growth factors and membranous receptors which ultimately activate pro-angiogenic intracellular signaling pathways. Inhibition of angiogenesis has become a standard treatment option for several tumor types including colorectal cancer, glioblastoma and ovarian cancer. In gastric cancer, the therapeutic role of anti-angiogenic agents is more controversial. Bevacizumab and ramucirumab, two monoclonal antibodies, which target vascular endothelial growth factor-A and vascular endothelial growth factor receptor-2, respectively, have been demonstrated antitumor activity in patients with tumors of the stomach or esophagogastric junction. However, especially for bevacizumab, this antitumor activity has not consistently translated into a survival advantage over standard treatment in randomized trials. In this article, we provide an overview of the role of angiogenesis in gastric cancer and discuss the results of clinical trials that investigated safety and effectiveness of antiangiogenic therapies in this disease. A review of the literature has been done using PubMed, ClinicalTrials.gov website and the ASCO Annual Meeting Library. PMID:25538401
Charron, Dominique; Suberbielle-Boissel, Caroline; Tamouza, Ryad; Al-Daccak, Reem
Research on stem cell therapies for regenerative medicine is progressing rapidly. Although the use of autologous stem cells is a tempting choice, there are several instances in which they are either defective or not available in due time. Allogenic stem cells derived from healthy donors presents a promising alternative. Whether autologous or allogenic, recent advances have proven that stem cells are not as immune privileged as they were thought. Therefore understanding the interactions of these cells with the recipient immune system is paramount to their clinical application. Transplantation of stem cells induces humoral as well as cellular immune response. This review focuses on the humoral response elicited by stem cells upon their administration and consequences on the survival and maintenance of the graft. Current transplantation identifies pre- and post-transplantation anti-HLA antibodies as immune rejection and cell signaling effectors. These two mechanisms are likely to operate similarly in the context of SC therapeutics. Ultimately this knowledge will help to propose novel strategies to mitigate the allogenic barriers. Immunogenetics selection of the donor cell and immunomonitoring are key factors to allow the implementation of regenerative stem cell in the clinics. Copyright © 2012. Published by Elsevier Inc.
Papenfuss, Kerstin; Cordier, Stefanie M; Walczak, Henning
Human tumour cells are characterized by their ability to avoid the normal regulatory mechanisms of cell growth, division and death. The classical chemotherapy aims to kill tumour cells by causing DNA damage-induced apoptosis. However, as many tumour cells posses mutations in intracellular apoptosis-sensing molecules like p53, they are not capable of inducing apoptosis on their own and are therefore resistant to chemotherapy. With the discovery of the death receptors the opportunity arose to directly trigger apoptosis from the outside of tumour cells, thereby circumventing chemotherapeutic resistance. Death receptors belong to the tumour necrosis factor receptor superfamily, with tumour necrosis factor (TNF) receptor-1, CD95 and TNF-related apoptosis-inducing ligand-R1 and -R2 being the most prominent members. This review covers the current knowledge about these four death receptors, summarizes pre-clinical approaches engaging these death receptors in anti-cancer therapy and also gives an overview about their application in clinical trials conducted to date. PMID:19210756
Efficacy and safety of ixekizumab treatment for Japanese patients with moderate to severe plaque psoriasis, erythrodermic psoriasis and generalized pustular psoriasis: Results from a 52-week, open-label, phase 3 study (UNCOVER-J).
Saeki, Hidehisa; Nakagawa, Hidemi; Nakajo, Ko; Ishii, Taeko; Morisaki, Yoji; Aoki, Takehiro; Cameron, Gregory S; Osuntokun, Olawale O
Psoriasis, a chronic, immune-mediated skin disease characterized by red, scaly plaques, affects approximately 0.3% of the population in Japan. The aim of this open-label study was to evaluate the long-term efficacy and safety of ixekizumab, a humanized, anti-interleukin-17A monoclonal antibody, in Japanese patients with plaque psoriasis (n = 78, including 11 psoriatic arthritis), erythrodermic psoriasis (n = 8) and generalized pustular psoriasis (n = 5). Ixekizumab was administrated s.c. at baseline (week 0, 160 mg), from weeks 2 to 12 (80 mg every 2 weeks), and from weeks 16 to 52 (80 mg every 4 weeks). At week 52, 92.3% of patients with plaque psoriasis achieved Psoriasis Area and Severity Index (PASI) 75, 80.8% achieved PASI 90, 48.7% achieved PASI 100, and 52.6% had remission of plaques (by static Physician Global Assessment, sPGA ). Difficult to treat areas of psoriasis (nail or scalp) also responded to ixekizumab. All patients with psoriatic arthritis who were assessed (5/5) achieved an American College of Rheumatology 20 response. Most patients with erythrodermic psoriasis or generalized pustular psoriasis responded to ixekizumab and the clinical outcome was maintained over 52 weeks (75% and 60% of patients achieved sPGA [0, 1] at week 52, respectively). Mostly mild or moderate treatment-emergent adverse events were reported by 79 of 91 patients; the most common were nasopharyngitis, eczema, seborrheic dermatitis, urticaria and injection site reactions. In conclusion, 52-week ixekizumab treatment was efficacious and well tolerated in Japanese patients with plaque psoriasis. Efficacy was also observed in patients with erythrodermic psoriasis, generalized pustular psoriasis and psoriatic arthritis. © 2016 Eli Lilly Japan K.K. The Journal of Dermatology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Dermatological Association.
Zundler, Sebastian; Becker, Emily; Weidinger, Carl; Siegmund, Britta
The number of biologicals for the therapy of immunologically mediated diseases is constantly growing. In contrast to other agents that were previously introduced in rheumatologic or dermatologic diseases and only later adopted for the treatment of inflammatory bowel diseases (IBDs), the field of IBD was ground breaking for the concept of anti-adhesion blockade. Anti-adhesion antibodies selectively target integrins controlling cell homing to the intestine, which leads to reduction of inflammatory infiltration to the gut in chronic intestinal inflammation. Currently, the anti-α4β7-antibody vedolizumab is successfully used for both Crohn's disease and ulcerative colitis worldwide. In this mini-review, we will summarize the fundamental basis of intestinal T cell homing and explain the molecular groundwork underlying current and potential future anti-adhesion therapies. Finally, we will comment on noteworthy clinical aspects of anti-adhesion therapy and give an outlook to the future of anti-integrin antibodies and inhibitors.
Psoriasis is an immune-mediated chronic inflammatory skin disease with a complex etiology. The proinflammatory cytokine IL-17A is known to play key role in the pathogenesis of psoriasis, and recently anti-IL-17A antibodies have been approved for psoriasis treatment. Here, we discuss our recent findings demonstrating that IκBζ, a transcriptional co-activator, plays a crucial role in the development of psoriasis by mediating IL-17A-driven effects. These findings have significant implications as they uncover a novel crucial regulatory mechanism involved in psoriasis development, and identify IκBζ as a possible future target in the treatment of psoriasis and other IL-17A-driven diseases.
Paydary, Koosha; Khaghani, Parisa; Emamzadeh-Fard, Sahra; Alinaghi, Seyed Ahmad Seyed; Baesi, Kazem
After its identification in 1980s, HIV has infected more than 30 million people worldwide. In the era of highly active anti-retroviral therapy, anti-retroviral drug resistance results from insufficient anti-retroviral pressure, which may lead to treatment failure. Preliminary studies support the idea that anti-retroviral drug resistance has evolved largely as a result of low-adherence of patients to therapy and extensive use of anti-retroviral drugs in the developed world; however, a highly heterogeneous horde of viral quasi-species are currently circulating in developing nations. Thus, the prioritizing of strategies adopted in such two worlds should be quite different considering the varying anti-retroviral drug resistance prevalence. In this article, we explore differences in anti-retroviral drug resistance patterns between developed and developing countries, as they represent two distinct ecological niches of HIV from an evolutionary standpoint. PMID:23835806
de Oliveira, Maria de Fátima Santos Paim; Rocha, Bruno de Oliveira; Duarte, Gleison Vieira
Psoriasis is a chronic inflammatory systemic disease. Evidence shows an association of psoriasis with arthritis, depression, inflammatory bowel disease and cardiovascular diseases. Recently, several other comorbid conditions have been proposed as related to the chronic inflammatory status of psoriasis. The understanding of these conditions and their treatments will certainly lead to better management of the disease. The present article aims to synthesize the knowledge in the literature about the classical and emerging comorbidities related to psoriasis. PMID:25672294
Islam, M T; Paul, H K; Zakaria, S M; Islam, M M; Shafiquzzaman, M
A cross-sectional study was conducted on 102 cases having clinical manifestation of psoriasis with a view to evaluate the epidemiological determinants of psoriasis. Psoriasis constituted 1.49% of the total dermatological disorder. Seventy patients (68.6%) were males and thirty two (31.4%) were females with a male to female ratio of 2.18:1. The mean age was 30.76±13.17 years in male and 26.94±14.94 years in female. Sixteen (15.7%) patients had one or more family member having psoriasis with male and female in equal frequency. Regarding precipitating factors, psoriasis was developed after trauma in 4.9%, infection 3.9%, stressful life events 6.9% and drugs 2.9%; and was exacerbated after trauma in 5.9%, infection 5.9%, stressful life events 35.3% and drugs 12.7%. The disease showed improvement in summer (27.5%) and found deteriorated in winter (47.1%). Sunlight had beneficial effect in 33.3% of cases. During pregnancy improvement was observed in 50% but flare up in 22.2% of cases. Fifty percent of patients were smokers, 41.2% were non-smokers and 13.7% were ex-smokers. Forty percent had Body Mass Index (BMI) between 22 to 26 Kg/m², 40.2% had less than 22 Kg/m² and 15.7% had above 26 Kg/m². It was concluded that the prevalence of psoriasis among dermatological patients was similar to results reported in Turkey and in Northern India. The precipitating factors, such as smoking, stressful life events, infection, trauma, sunlight, pregnancy, drugs, and seasonal variations could influence the development of psoriasis and affect its clinical expression.
Armstrong, April W; Siegel, Michael P; Bagel, Jerry; Boh, Erin E; Buell, Megan; Cooper, Kevin D; Callis Duffin, Kristina; Eichenfield, Lawrence F; Garg, Amit; Gelfand, Joel M; Gottlieb, Alice B; Koo, John Y M; Korman, Neil J; Krueger, Gerald G; Lebwohl, Mark G; Leonardi, Craig L; Mandelin, Arthur M; Menter, M Alan; Merola, Joseph F; Pariser, David M; Prussick, Ronald B; Ryan, Caitriona; Shah, Kara N; Weinberg, Jeffrey M; Williams, MaryJane O U; Wu, Jashin J; Yamauchi, Paul S; Van Voorhees, Abby S
An urgent need exists in the United States to establish treatment goals in psoriasis. We aim to establish defined treatment targets toward which clinicians and patients with psoriasis can strive to inform treatment decisions, reduce disease burden, and improve outcomes in practice. The National Psoriasis Foundation conducted a consensus-building study among psoriasis experts using the Delphi method. The process consisted of: (1) literature review, (2) pre-Delphi question selection and input from general dermatologists and patients, and (3) 4 Delphi rounds. A total of 25 psoriasis experts participated in the Delphi process. The most preferred instrument was body surface area (BSA). The most preferred time for evaluating patient response after starting new therapies was at 3 months. The acceptable response at 3 months postinitiation was either BSA 3% or less or BSA improvement 75% or more from baseline. The target response at 3 months postinitiation was BSA 1% or less. During the maintenance period, evaluation every 6 months was most preferred. The target response at every 6 months maintenance evaluation is BSA 1% or less. Although BSA is feasible in practice, it does not encompass health-related quality of life, costs, and risks of side effects. With defined treatment targets, clinicians and patients can regularly evaluate treatment responses and perform benefit-risk assessments of therapeutic options individualized to the patient. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.
Bracke, S; Desmet, E; Guerrero-Aspizua, S; Tjabringa, S G; Schalkwijk, J; Van Gele, M; Carretero, M; Lambert, J
Diseases of the skin are amenable to RNAi-based therapies and targeting key components in the pathophysiology of psoriasis using RNAi may represent a successful new therapeutic strategy. We aimed to develop a straightforward and highly reproducible in vitro psoriasis model useful to study the effects of gene knockdown by RNAi and to identify new targets for topical RNAi therapeutics. We evaluated the use of keratinocytes derived from psoriatic plaques and normal human keratinocytes (NHKs). To induce a psoriatic phenotype in NHKs, combinations of pro-inflammatory cytokines (IL-1α, IL-17A, IL-6 and TNF-α) were tested. The model based on NHK met our needs of a reliable and predictive preclinical model, and this model was further selected for gene expression analyses, comprising a panel of 55 psoriasis-associated genes and five micro-RNAs (miRNAs). Gene silencing studies were conducted by using small interfering RNAs (siRNAs) and miRNA inhibitors directed against potential target genes such as CAMP and DEFB4 and miRNAs such as miR-203. We describe a robust and highly reproducible in vitro psoriasis model that recapitulates expression of a large panel of genes and miRNAs relevant to the pathogenesis of psoriasis. Furthermore, we show that our model is a powerful first step model system for testing and screening RNAi-based therapeutics.
Sauzullo, I; Mengoni, F; Marocco, R; Potenza, C; Skroza, N; Tieghi, T; Lichtner, M; Vullo, V; Mastroianni, C M
Screening for latent tuberculosis infection (LTBI) is mandatory in patients with psoriasis prior to starting on tumour necrosis factor (TNF) blockers. To investigate the longitudinal changes of interferon (IFN)-γ response to Mycobacterium tuberculosis-specific antigens by serial QuantiFERON-TB Gold In-Tube (QFT-GIT) testing in patients with psoriasis during long-term anti-TNF therapy. The direct in vitro effect of adalimumab on IFN-γ secretion was also evaluated. In total, 148 patients with psoriasis designated to start anti-TNF treatment were enrolled. We performed a tuberculin skin test at screening, and QFT-GIT at baseline and serially for 24 months after TNF antagonist onset. At screening, QFT-GIT was positive in 22.3% of the patients, negative in 73.6% and indeterminate in 4%. The IFN-γ response following isoniazid therapy declined and became QFT-GIT negative in 8% of 26 patients with LTBI; in 69% of subjects with LTBI the QFT-GIT remained persistently positive with a significant increase of IFN-γ levels during the follow-up, even if no cases of active tuberculosis were found. Variations of IFN-γ levels were observed also in 7% of 27 patients without LTBI who switched to positive QFT-GIT after 12 or 18 months of biologic therapy, suggesting a new occurrence or reactivation of LTBI. In vitro data showed that in the presence of adalimumab the IFN-γ levels were significantly reduced in a dose-dependent manner (P < 0.05). Fluctuations of IFN-γ release may occur in patients with psoriasis treated with TNF antagonists. The clinical use of repeated blood tests and the correct interpretation of individual IFN-γ changes could be useful in identifying possible cases of LTBI reactivation or newly acquired tuberculosis infection during long-term anti-TNF treatment. © 2013 British Association of Dermatologists.
Okasha, Ebtsam F; Bayomy, Naglaa A; Abdelaziz, Eman Z
Psoriasis is a chronic inflammatory skin disease that affects about 1%-3% of the world's population. Black seed oil, i.e., the oil extracted from black seeds (Nigella sativa seeds), possesses a broad spectrum of pharmacological actions including anti-inflammatory, immunostimulatory, and antioxidant properties. This study aimed to investigate the effect of black seed oil on imiquimod (IMQ) induced psoriasis-like skin lesions. To this end, 30 male albino rats were divided into three groups: group I, control group; group II, psoriasis-induced group receiving daily topical applications of IMQ cream (5%) on the shaved back skin for 10 consecutive days; and group III, black seed oil group receiving a daily topical dose of black seed oil 5 mg/kg body weight for 10 days after induction of psoriasis. Animals of all groups were sacrificed and specimens obtained from the skin of the central part of the back were processed for histological and immunohistochemical staining with proliferating cell nuclear antigen (PCNA). IMQ application led to epidermal inflammation, hyperplasia and alterations in the normal appearance of keratinocytes with degenerative changes observed at both light and electron microscopic levels. Collagenous fibers were abundant in the dermis and PCNA-positive cells were detected in all layers of the epidermis. However, topical use of black seed oil strongly inhibited IMQ-induced psoriasis-like inflammation and alleviated all epidermal and dermal changes observed after IMQ application, allowing us to conclude that black seed oil can be used as an adjuvant topical therapy for treating psoriasis. Anat Rec, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.
Deng, Yaxiong; Chang, Christopher; Lu, Qianjin
Psoriasis is a chronic inflammatory autoimmune disease characterized by an excessively aberrant hyperproliferation of keratinocytes. The pathogenesis of psoriasis is complex and the exact mechanism remains elusive. However, psoriasis is thought to result from a combination of genetic, epigenetic, and environmental influences. Recent studies have identified that epigenetic factors including dysregulated DNA methylation levels, abnormal histone modification and microRNAs expressions are involved in the development of psoriasis. The interplay of immune cells and cytokines is another critical factor in the pathogenesis of psoriasis. These factors or pathways include Th1/Th2 homeostasis, the Th17/Treg balance and the IL-23/Th17 axis. Th17 is believed particularly important in psoriasis due to its pro-inflammatory effects and its involvement in an integrated inflammatory loop with dendritic cells and keratinocytes, contributing to an overproduction of antimicrobial peptides, inflammatory cytokines, and chemokines that leads to amplification of the immune response. In addition, other pathways and signaling molecules have been found to be involved, including Th9, Th22, regulatory T cells, γδ T cells, CD8(+) T cells, and their related cytokines. Understanding the pathogenesis of psoriasis will allow us to develop increasingly efficient targeted treatment by blocking relevant inflammatory signaling pathways and molecules. There is no cure for psoriasis at the present time, and much of the treatment involves managing the symptoms. The biologics, while lacking the adverse effects associated with some of the traditional medications such as corticosteroids and methotrexate, have their own set of side effects, which may include reactivation of latent infections. Significant challenges remain in developing safe and efficacious novel targeted therapies that depend on a better understanding of the immunological dysfunction in psoriasis.
Kluger, Nicolas; Bessis, Didier; Guillot, Bernard; Girard, Céline
Generalized pustular and/or erythrodermic psoriasis may have severe or even lethal complications. A peculiar noninfectious acute respiratory distress syndrome (so-called "sterile pneumonitis") has been described in generalized pustular psoriasis and/or erythrodermic psoriasis. We report a new case in a 14-year-old girl with a long history of pustular psoriasis and review the published work on this complication. The girl developed sterile pneumonitis during a disease flare-up, and high-dose corticosteroid therapy was quickly initiated. Within a few days, her clinical and radiological status was dramatically improved. The pathogenesis of aseptic pneumonitis is unknown, but various proinflammatory cytokines have been implicated, especially tumor necrosis factor-alpha, which could play a role in the recruitment of leukocytes to the lung. This complication has rarely been reported but should be more widely known as the differential diagnoses include congestive heart failure, acute lung infection related or unrelated to immunosuppressive therapy, and drug hypersensitivity reaction. Early recognition would avoid delays in the correct management of this potentially lethal complication, which requires high-dose systemic corticosteroid therapy. Copyright © 2009 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.
Zhang, Hong; Hou, Wenhong; Henrot, Laurence; Schnebert, Sylvianne; Dumas, Marc; Heusèle, Catherine; Yang, Jin
We present a computational model to study the spatio-temporal dynamics of epidermis homoeostasis under normal and pathological conditions. The model consists of a population kinetics model of the central transition pathway of keratinocyte proliferation, differentiation and loss and an agent-based model that propagates cell movements and generates the stratified epidermis. The model recapitulates observed homoeostatic cell density distribution, the epidermal turnover time and the multilayered tissue structure. We extend the model to study the onset, recurrence and phototherapy-induced remission of psoriasis. The model considers psoriasis as a parallel homoeostasis of normal and psoriatic keratinocytes originated from a shared stem cell (SC) niche environment and predicts two homoeostatic modes of psoriasis: a disease mode and a quiescent mode. Interconversion between the two modes can be controlled by interactions between psoriatic SCs and the immune system and by normal and psoriatic SCs competing for growth niches. The prediction of a quiescent state potentially explains the efficacy of multi-episode UVB irradiation therapy and recurrence of psoriasis plaques, which can further guide designs of therapeutics that specifically target the immune system and/or the keratinocytes. © 2015 The Author(s) Published by the Royal Society. All rights reserved.
Zhang, Hong; Hou, Wenhong; Henrot, Laurence; Schnebert, Sylvianne; Dumas, Marc; Heusèle, Catherine; Yang, Jin
We present a computational model to study the spatio-temporal dynamics of epidermis homoeostasis under normal and pathological conditions. The model consists of a population kinetics model of the central transition pathway of keratinocyte proliferation, differentiation and loss and an agent-based model that propagates cell movements and generates the stratified epidermis. The model recapitulates observed homoeostatic cell density distribution, the epidermal turnover time and the multilayered tissue structure. We extend the model to study the onset, recurrence and phototherapy-induced remission of psoriasis. The model considers psoriasis as a parallel homoeostasis of normal and psoriatic keratinocytes originated from a shared stem cell (SC) niche environment and predicts two homoeostatic modes of psoriasis: a disease mode and a quiescent mode. Interconversion between the two modes can be controlled by interactions between psoriatic SCs and the immune system and by normal and psoriatic SCs competing for growth niches. The prediction of a quiescent state potentially explains the efficacy of multi-episode UVB irradiation therapy and recurrence of psoriasis plaques, which can further guide designs of therapeutics that specifically target the immune system and/or the keratinocytes. PMID:25566881
Psoriasis is one of the most common chronic inflammatory human skin diseases. Though clinically well characterized, the exact etiological and pathogenic mechanisms are still not known in detail. Current knowledge indicates distinct overlap to other inflammatory as well as autoimmune disorders. However, the one or more relevant autoantigens could not be characterized so-far. On the other side, several autoimmune diseases were shown to be associated with psoriasis. In addition, serological autoimmune phenomena, namely diverse circulating specific autoantibodies could be demonstrated in the past. A matter of current debate is if psoriasis is a primary autoimmune disease or secondarily evolving into autoimmunity as seen in other chronic inflammatory diseases. Related to this aspect is the concept of autoinflammation versus autoimmunity where psoriasis shares mechanisms of both entities. Though T-cells remain among the most important cellular players in the pathogenesis of psoriasis and current therapeutic strategies successfully target these cells or their products irrespective of these concepts, autoimmunity if relevant will add to the treatment armamentarium by using protective and prophylactic antigen-specific modalities.
Wahl, Astrid K; Robinson, Hilde S; Langeland, Eva; Larsen, Marie H; Krogstad, Anne-Lene; Moum, Torbjørn
Knowledge of illness perception may aid the identification of groups of patients with a higher risk of coping poorly with the demands of their illness. This study aims to investigate associations between illness perception, clinical characteristics, patient knowledge, quality of life and subjective health in persons with psoriasis. The present study was based on cross-sectional data from patients awaiting climate therapy in Gran Canaria. We included 254 eligible patients (74%) who completed a questionnaire including the revised Illness Perception Questionnaire, the Psoriasis Knowledge Questionnaire, and the Dermatological Life Quality Index. Disease severity was measured using the Psoriasis Area and Severity Index. Several statistically significant associations between clinical characteristics, knowledge and various illness perception dimensions were found. Illness perception was also significantly related to disease-specific quality of life and subjective health. These findings contradict previous findings, which suggested that objective disease factors are not relevant to illness perception in psoriasis.
Grozdev, Ivan; Korman, Neil; Tsankov, Nikolai
Psoriasis is an inflammatory immune-mediated disease that affects the skin and has pathogenic effects with systemic impact. The relationship between psoriasis and comorbidities remains controversial. The hypothesis of a causative role of psoriasis in its cardiovascular and metabolic comorbidities is based on pathophysiologic concepts establishing a link between chronic inflammation in psoriasis, endothelial dysfunction, formation of atherosclerotic plaques, and the different compounds of metabolic syndrome. Psoriasis management has to be multidisciplinary. It implicates identification and treatment of psychological disorders, addictions, and associated cardiovascular and metabolic diseases, together with improvement of quality of life of patients.
Simpson, Cory L; McCausland, Drew; Chu, Emily Y
Novel direct anti-viral agents are emerging as effective treatments for hepatitis C virus (HCV) and provide an alternative to the year-long standard therapy with interferon and ribavirin. However, cutaneous side effects from these new medications, including rash, pruritus and photosensitivity, are among the most commonly reported adverse events and have resulted in therapy discontinuation in some cases. Here, we report two cases of a photo-distributed lichenoid eruption that occurred within 1 month of starting anti-viral therapy with simeprevir and sofosbuvir without interferon or ribavirin. This report provides the first histologic description of the cutaneous eruption associated with direct anti-viral therapy for HCV and highlights the importance of recognizing and treating the often intolerable dermatologic side effects of these novel medications, the incidence of which is likely to increase as direct anti-viral agents may become the standard of care for HCV.
Ribeiro, Camila Ferrari; Siqueira, Elisa Beatriz Dalledone; Holler, Ana Paula; Fabrício, Lincoln; Skare, Thelma Larocca
Nailfold capillaroscopy is a useful technique for evaluating changes in microcirculation. To investigate changes at nailfold capillaroscopy in psoriatic patients compared with controls. Nailfold capillaroscopy was performed in 46 psoriatic patients and 50 controls to assess microscopic morphological changes, capillary density and the presence of areas with devascularization. Patients with psoriasis had lower capillary density (p=0.0005), increased avascular areas (p=0.0035) and an increased number of morphologically abnormal capillaries (coiled, p<0.0001) compared to controls. No association was found between capillary density and the duration of the disease (p = 0.92) or the extent of skin involvement, as measured by the psoriasis area and severity index (PASI) score (p = 0.59). The presence of avascular areas was more common in psoriatic individuals whose nails were affected by the condition (p = 0.047). Patients with psoriasis have decreased capillary density and a greater presence of morphologically abnormal capillaries when compared to controls.
Romaní de Gabriel, J
Darwinian medicine, or evolutionary medicine, regards some pathological conditions as attempts by the organism to solve a problem or develop defense mechanisms. At certain stages of human evolution, some diseases may have conferred a selective advantage. Psoriasis is a high-penetrance multigenic disorder with prevalence among whites of up to 3%. Psoriatic lesions have been linked with enhanced wound-healing qualities and greater capacity to fight infection. Leprosy, tuberculosis, and infections caused by viruses similar to human immunodeficiency virus have been postulated as environmental stressors that may have selected for psoriasis-promoting genes in some human populations. The tendency of patients with severe psoriasis to develop metabolic syndrome may reflect the body's attempt to react to environmental stresses and warning signs by triggering insulin resistance and fat storage.
Nasimi, M; Abedini, R; Azizpour, A; Nikoo, A
Linear psoriasis (LPs) is considered a rare clinical presentation of psoriasis, which is characterized by linear erythematous and scaly lesions along the lines of Blaschko. We report the case of a 20-year-old man who presented with asymptomatic linear and S-shaped erythematous, scaly plaques on right side of his trunk. The plaques were arranged along the lines of Blaschko with a sharp demarcation at the midline. Histological examination of a skin biopsy confirmed the diagnosis of psoriasis. Topical calcipotriol and betamethasone dipropionate ointments were prescribed for 2 months. A good clinical improvement was achieved, with reduction in lesion thickness and scaling. In patients with linear erythematous and scaly plaques along the lines of Blaschko, the diagnosis of LPs should be kept in mind, especially in patients with asymptomatic lesions of late onset. © 2016 British Association of Dermatologists.
Keijsers, Romy R M C; Joosten, Irma; van Erp, Piet E J; Koenen, Hans J P M; van de Kerkhof, Peter C M
Psoriasis is a common chronic inflammatory skin disease that results from interplay between the immune system and the epithelium. In the light of very successful anticytokine therapies for psoriasis, the focus has been directed towards the adaptive immune system. Expression studies, genetic studies and treatments specifically targeting players of the IL-23/IL-17 pathway, point at an important role for IL-17 in the pathogenesis of psoriasis. IL-17 stimulates the keratinocytes to produce psoriasis-associated molecules, eventually leading to chronic skin inflammation. The current opinion is that IL-17 is mainly produced by T cells, so-called T-helper 17 (Th17) cells, in psoriasis. However, evidence is accumulating that cells of the innate immune system, like neutrophils, mast cells, γδ T cells and innate lymphoid cells are the main source of IL-17 in psoriasis, rather than T cells. The paradigm in this field of research is shifting. With this viewpoint article, we will address this novel concept by critically summarizing the current literature on this subject. In psoriatic arthritis and atherosclerosis, important conditions related to psoriasis, it was also found that the majority of IL-17 is associated with cells of the innate immune system. This new concept changes our view of IL-17. Blocking IL-17 with targeted treatments might be more far-reaching than previously thought; not only IL-17 production by T cells but also by innate immune cells is blocked. Furthermore, therapies specifically targeting IL-17 may not only improve psoriasis, but also comorbidity that is associated with the IL-17 pathway, hereby preventing serious complications on the long term. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Stepanova, A; Zschau, H; Küster, W
An erythrodermic skin disease occurring in a patient with an already existing erythroderma of different cause is a rare phenomenon. A 13 year old girl with congenital lamellar ichthyosis suffered from both erythroderma and generalized scaling. Probably at the age of 11, a clinically not recognized psoriatic erythroderma appeared associated with a pustular palmoplantar psoriasis of the Barber-Königsbeck type as well as a psoriatic osteoarthropathy. The identification off such overlapping disorders is of great importance for proper therapy.
Kolbinger, Frank; Loesche, Christian; Valentin, Marie-Anne; Jiang, Xiaoyu; Cheng, Yi; Jarvis, Philip; Peters, Thomas; Calonder, Claudio; Bruin, Gerard; Polus, Florine; Aigner, Birgit; Lee, David M; Bodenlenz, Manfred; Sinner, Frank; Pieber, Thomas Rudolf; Patel, Dhavalkumar D
IL-17A is a key driver of human autoimmune diseases, particularly psoriasis. We sought to determine the role of IL-17A in psoriasis pathogenesis and to identify a robust and measurable biomarker of IL-17A-driven pathology. We studied 8 healthy subjects and 8 patients with psoriasis before and after administration of secukinumab, a fully human anti-IL-17A mAb, and used a combination of classical techniques and a novel skin microperfusion assay to evaluate the expression of 170 proteins in blood, nonlesional skin, and lesional skin. For validation, we also tested stored sera from 601 patients with a variety of autoimmune diseases. IL-17A was specifically expressed in lesional compared with nonlesional psoriatic skin (9.8 vs 0.8 pg/mL, P < .001). Proteomic and gene transcription analyses revealed dysregulated antimicrobial peptides, proinflammatory cytokines, and neutrophil chemoattractants, levels of which returned to normal after treatment with secukinumab. β-Defensin 2 (BD-2) was identified as a biomarker of IL-17A-driven pathology by comparing protein expression in patients with psoriasis versus that in healthy subjects (5746 vs 82 pg/mL in serum, P < .0001; 2747 vs <218 pg/mL in dermis, P < .001), responsiveness to secukinumab therapy, and synergistic induction by IL-17A and TNF-α in epidermal keratinocytes. In a validation set of sera from 601 patients with autoimmune diseases thought to be IL-17A driven, we found that BD-2 levels are most highly increased in patients with psoriatic skin lesions, and in patients with psoriasis, BD-2 levels correlated well with IL-17A levels (r = 0.70, n = 199, P < .001) and Psoriasis Area and Severity Index scores (r = 0.53, n = 281, P < .001). IL-17A is a primary driver of skin pathology in patients with psoriasis, and serum BD-2 is an easily measurable biomarker of IL-17A-driven skin pathology. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
Mroz, Pawel; Castano, Ana P.; Wu, Mei X.; Kung, Andrew L.; Hamblin, Michael R.
Anti-tumor immunity is stimulated after PDT due a number of factors including: the acute inflammatory response caused by PDT, release of antigens from PDT-damaged tumor cells, priming of the adaptive immune system to recognize tumor-associated antigens (TAA), and induction of heat-shock proteins. The induction of specific CD8+ T-lymphocyte cells that recognize major histocompatibility complex class I (MHC-I) restricted epitopes of TAAs is a highly desirable goal in cancer therapy as it would allow the treatment of tumors that may have already metastasized. The PDT killed tumor cells may be phagocytosed by dendritic cells (DC) that then migrate to draining lymph nodes and prime naÃve T-cells that recognize TAA epitopes. We have carried out in vivo PDT with a BPD-mediated vascular regimen using a pair of BALB/c mouse colon carcinomas: CT26 wild type expressing the naturally occurring retroviral antigen gp70 and CT26.CL25 additionally expressing beta-galactosidase (b-gal) as a model tumor rejection antigen. PDT of CT26.CL25 cured 100% of tumors but none of the CT26WT tumors (all recurred). Cured CT26.CL25 mice were resistant to rechallenge. Moreover mice with two bilateral CT26.CL25 tumors that had only one treated with PDT demonstrated spontaneous regression of 70% of untreated contralateral tumors. T-lymphocytes were isolated from lymph nodes of PDT cured mice that recognized a particular peptide specific to b-gal antigen. T-lymphocytes from LN were able to kill CT26.CL25 target cells in vitro but not CT26WT cells as shown by a chromium release assay. CT26.CL25 tumors treated with PDT and removed five days later had higher levels of Th1 cytokines than CT26 WT tumors showing a higher level of immune response. When mice bearing CT26WT tumors were treated with a regimen of low dose cyclophosphamide (CY) 2 days before, PDT led to 100% of cures (versus 0% without CY) and resistance to rechallenge. Low dose CY is thought to deplete regulatory T-cells (Treg, CD4+CD25+foxp
The exact association between psoriasis and arthritis remains an enigma. Some investigators consider that the two disorders constitute a disease entity, psoriatic arthritis, while others support the thesis that psoriasis and arthritis are common diseases and occur simultaneously by chance. The author upholds the latter view as viable. To underscore his viewpoint he presents a comprehensive overview of the controversial opinions through an historical perspective as well as reporting on his epidemiologic and clinical findings from large population studies in the Netherlands. Therapeutic regimens for the management of both skin and joint problems are presented.
Guinea-Viniegra, Juan; Jiménez, María; Schonthaler, Helia B; Navarro, Raquel; Delgado, Yolanda; Concha-Garzón, María José; Tschachler, Erwin; Obad, Susanna; Daudén, Esteban; Wagner, Erwin F
Psoriasis is a common inflammatory skin disease with limited treatment options that is characterized by a complex interplay between keratinocytes, immune cells, and inflammatory mediators. MicroRNAs (miRNAs) are regulators of gene expression and play critical roles in many human diseases. A number of miRNAs have been described to be up-regulated in psoriasis, but their causal contribution to disease development has not been demonstrated. We confirm that miR-21 expression is increased in epidermal lesions of patients with psoriasis and that this leads to reduced epidermal TIMP-3 (tissue inhibitor of matrix metalloproteinase 3) expression and activation of TACE (tumor necrosis factor-α-converting enzyme)/ADAM17 (a disintegrin and metalloproteinase 17). Using patient-derived skin samples and mouse models of psoriasis, we demonstrate that increased miR-21 may be a consequence of impaired transcriptional activity of Jun/activating protein 1 (AP-1), leading to activation of the interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (Stat3) pathway. Inhibition of miR-21 by locked nucleic acid (LNA)-modified anti-miR-21 compounds ameliorated disease pathology in patient-derived psoriatic skin xenotransplants in mice and in a psoriasis-like mouse model. Targeting miR-21 may represent a potential therapeutic option for the treatment of psoriasis.
Shear, N H; Hartmann, M; Toledo-Bahena, M E; Gilbert, M; Katsambas, A; Yao, R; Popmihajlov, Z
We evaluated the effect of plaque-type psoriasis on health-related quality of life (HRQoL) of patients who received infliximab (IFX) in real-world clinical settings. REALITY was a prospective, observational, open-label study of the efficacy and safety of up to 98 weeks of IFX (5 mg/kg infused at weeks 0, 2, 6, and every 8 weeks thereafter) in patients with moderate-to-severe plaque-type psoriasis. Patients with ≥25 % Psoriasis Area Severity Index (PASI) improvement (PASI 25) at week 50 were eligible for the Extended Treatment Phase (treatment to week 98). Inclusion criteria were diagnosis of plaque-type psoriasis, age ≥18 years, decision to start IFX, and patient consent. Key secondary efficacy outcomes included the Dermatologic Life Quality Index (DLQI; mean DLQI scores, attainment of DLQI 0/1), which was analyzed over 98 weeks. Post hoc analyses examined improvement in DLQI and the relationship between PASI and DLQI. In the Treatment Phase, patients (n = 516, 66.0 % men, mean age 46.4 years) had a mean baseline PASI of 18.1. Mean DLQI improved from 12.7 at baseline to 4.7 [mean change (95 % CI); -8.0 (-8.9, -7.1)] at week 50; 64.0 % (229/358) of patients improved by ≥5 DLQI points. At week 50 (n = 362), 37.6 % (95 % CI; 32.7, 42.7) achieved a DLQI of 0. In the Extended Treatment Phase, patients (n = 167, 68.3 % men, mean age 46.6 years) had a mean baseline PASI of 20.4. Mean DLQI improved from 12.3 at baseline to 2.8 at week 98 [mean change (95 % CI); -9.4 (-10.8, -8.0)]; 68.6 % (96/140) of patients improved by ≥5 DLQI points. At week 98 (n = 141), 47.5 % (95 % CI; 39.4, 55.7) achieved a DLQI of 0. Patients with plaque-type psoriasis who received treatment with IFX for 50 weeks or up to 98 weeks reported substantial HRQoL improvement.
Wang, Hong-Yu; He, Shuai-Bing; Wang, Hui-Hui; Fu, Xu-Yan; Zhang, Yi; Zheng, Rao; Wang, Yun
Many studies have shown that anti-aging treatment has value to prevention and treatment of some diseases. For the treatment of Parkinson' s disease, clinical and experimental researches have proved the potential value of anti-aging treatment, yet the mechanism remains unclear. For this reason, this work used the anti-aging prescriptions of Buyang Huanwu decoction in traditional Chinese medicines example to discover the anti-aging treatment mechanism on Parkinson's disease. The results showed that the mechanism of mitochondrial damage, apoptosis, free radicals and oxidative stress could contribute to the treatment of Parkinson' s disease. Buyang Huanwu decoction is more than as the carrier in this article, the discovered anti-aging treatment mechanism Parkinson's disease is not confined to Buyang Huanwu decoction, could also be used to understand the anti-aging treatment mechanism using other prescription. The main contribution of this paper is to clarify the mechanism of anti-aging treatment of Parkinson's disease, and provide a new strategy for the treatment and prevention of Parkinson's disease. Copyright© by the Chinese Pharmaceutical Association.
Fluhr, Joachim W; Cavallotti, Claudia; Berardesca, Enzo
Emollients, moisturizers, and keratolytic agents are essential in the topical treatment of psoriasis. They are adjuvants for classic treatments and help to reduce the scale load of individual patients. The major role for emollients and moisturizers is the supportive role in normalizing hyperproliferation, differentiation, and apoptosis; furthermore, they exert anti-inflammatory effects, for example, through physiologic lipids. Subsequently, an improved barrier function and stratum corneum hydration makes the epidermis more resistant to external stressors and reduces the induction of Koebner phenomena. Most of the emollients are lipid-rich (sometimes oily). The keratolytic agents, especially salicylic acid, and higher concentration of urea should be used in the initial keratolytic phase, whereas moisturizing products and emollients are especially suitable in the intermediate phase and the chronic/remission phase of psoriasis. They should be combined with bath oils.
Takeshita, Junko; Wang, Shuwei; Shin, Daniel B.; Mehta, Nehal N.; Kimmel, Stephen E.; Margolis, David J.; Troxel, Andrea B.; Gelfand, Joel M.
Importance Hypertension is prevalent among patients with psoriasis. The effect of psoriasis and its severity on hypertension control is unknown. Objective To determine the association between uncontrolled blood pressure and psoriasis, both overall and according to objectively measured psoriasis severity, among patients with diagnosed hypertension. Design, Setting, and Participants Population-based cross-sectional study nested in a prospective cohort drawn from The Health Improvement Network (THIN), an electronic medical records database broadly representative of the general population in the United Kingdom. The study population included a random sample of patients with psoriasis (n = 1322) between the ages of 25 and 64 years in THIN who were included in the Incident Health Outcomes and Psoriasis Events prospective cohort and their age- and practice-matched controls without psoriasis (n = 11 977). All included patients had a diagnosis of hypertension; their psoriasis diagnosis was confirmed and disease severity was classified by their general practitioners. Main outcomes and measures Uncontrolled hypertension was defined as a systolic blood pressure of 140 mm Hg or higher or a diastolic blood pressure of 90 mm Hg or higher based on the blood pressure recorded closest in time to the assessment of psoriasis severity. Results There was a significant positive dose-response relationship between uncontrolled hypertension and psoriasis severity as objectively determined by the affected body surface area in both unadjusted and adjusted analyses that controlled for age, sex, body mass index, smoking and alcohol use status, presence of comorbid conditions, and current use of antihypertensive medications and nonsteroidal anti-inflammatory drugs (adjusted odds ratio [aOR], 0.97; 95% CI, 0.82-1.14 for mild psoriasis; aOR, 1.20; 95% CI, 0.99-1.45 for moderate psoriasis; and aOR, 1.48; 95% CI, 1.08-2.04 for severe psoriasis; P = .01 for trend). The likelihood of uncontrolled
Zhou, Zhen-Xing; Chen, Jian-Kui; Hong, Yan-Ying; Zhou, Ru; Zhou, Dong-Mei; Sun, Li-Yun; Qin, Wen-Li; Wang, Tian-Cheng
Psoriasis is a chronic and recurrent inflammatory skin disease. Previous studies have shown that bilirubin has anti-inflammation and antioxidant effects. However, the various roles of bilirubin in psoriasis patients are still unclear. To investigate the serum total bilirubin (TB) level in the individuals with psoriasis vulgaris and further evaluate the relationship between serum TB concentration and C-reactive protein (CRP) to clarify the effect of bilirubin on inflammation. A total of 214 patients with psoriasis vulgaris and 165 age- and gender-matched healthy control subjects were recruited. The peripheral leukocyte count (white blood cell, WBC) and differential, serum biochemical and immunologic indexes including serum TB, immunoglobulin (Ig) G, IgA, IgM, complement C3 and C4 , as well as serum CRP concentrations were measured. Results showed that the serum TB level decreased significantly and peripheral WBC, neutrophil, and serum CRP concentrations increased significantly in patients with psoriasis vulgaris. Meanwhile, the serum CRP was negatively correlated with serum TB levels but positively correlated with peripheral WBC and the Psoriasis Area and Severity Index (PASI). Logistic regression analysis showed that the serum TB was a protective factor for psoriasis vulgaris. The present study suggests that lower serum TB is associated with the enhancement of the inflammatory response in psoriasis vulgaris. Therefore, lower serum TB has a prognostic significance for worsening psoriasis vulgaris. Bilirubin may play a crucial role in inflammation by contributing to the inhibition of the inflammatory response. © 2016 Wiley Periodicals, Inc.
Swaika, Abhisek; Hammond, William A; Joseph, Richard W
Immunotherapy for the treatment of cancer is rapidly evolving from therapies that globally and non-specifically simulate the immune system to more targeted activation of individual components of the immune system. The net result of this targeted approach is decreased toxicity and increased efficacy of immunotherapy. More specifically, therapies that inhibit the interaction between programmed death ligand 1 (PD-L1), present on the surface of tumor or antigen-presenting cells, and programmed death 1 (PD-1), present on the surface of activated lymphocytes, are generating much excitement and enthusiasm, even in malignancies that are not traditionally considered to be immunogenic. Herein, we review the current landscape of anti-PD-1 and anti-PD-L1 therapies in the world of oncology. We have performed a comprehensive literature search on the data available through PubMed, Medline, Scopus, the ClinicalTrials.gov registry, and abstracts from major oncology meetings in order to summarize the clinical data of anti-PD-1/PD-L1 therapies.
Uva, Luís; Miguel, Diana; Pinheiro, Catarina; Antunes, Joana; Cruz, Diogo; Ferreira, João; Filipe, Paulo
Psoriasis is a lifelong, chronic, and immune-mediated systemic disease, which affects approximately 1–3% of the Caucasian population. The different presentations of psoriasis require different approaches to treatment and appropriate prescriptions according to disease severity. The use of topical therapy remains a key component of the management of almost all psoriasis patients, and while mild disease is commonly treated only with topical agents, the use of topical therapy as adjuvant therapy in moderate-to-severe disease may also be helpful. This paper focuses on the cutaneous mechanisms of action of corticosteroids and on the currently available topical treatments, taking into account adverse effects, bioavailability, new combination treatments, and strategies to improve the safety of corticosteroids. It is established that the treatment choice should be tailored to match the individual patient's needs and his/her expectations, prescribing to each patient the most suitable vehicle. PMID:23213332
Combination of nitric oxide therapy, anti-oxidative therapy, low level laser therapy, plasma rich platelet therapy and stem cell therapy as a novel therapeutic application to manage the pain and treat many clinical conditions
Halasa, Salaheldin; Dickinson, Eva
From hypertension to diabetes, cancer to HIV, stroke to memory loss and learning disorders to septic shock, male impotence to tuberculosis, there is probably no pathological condition where nitric oxide does not play an important role. Nitric oxide is an analgesic, immune-modulator, vasodilator, anti-apoptotic, growth modulator, angiogenetic, anti-thrombotic, anti-inflammatory and neuro-modulator. Because of the above actions of nitric oxide, many clinical conditions associated with abnormal Nitric oxide (NO) production and bioavailability. Our novel therapeutic approach is to restore the homeostasis of nitric oxide and replace the lost cells by combining nitric oxide therapy, anti-oxidative therapy, low level laser therapy, plasma rich platelet therapy and stem cell therapy.
There is a growing public awareness and concern among individuals regarding the condition of their skin, with a concomitant desire to use natural products to treat skin conditions. The increased interest in these products has spurred scientific and clinical studies evaluating the composition and clinical usefulness of natural products in the treatment of inflammatory skin dermatoses. There are numerous natural ingredients that have been demonstrated to possess anti-inflammatory properties that make formulations containing these ingredients attractive treatment options. This article summarizes the active ingredients, anti-inflammatory properties, clinical effects, and therapeutic potential of colloidal oatmeal, feverfew, licorice, aloe vera, chamomile, and turmeric. Potential therapeutic indications include erythema induced by ultraviolet light, rosacea, atopic dermatitis, sensitive and irritated skin, drug-induced skin eruptions, and psoriasis. These products may be particularly well suited as alternatives to pharmacologic therapies in chronic conditions for which long-term use is required.
Kwon, Hyuck Hoon; Na, Sun Jae; Jo, Seoung Jin; Youn, Jai Il
Few epidemiological studies of pediatric patients with moderate to severe psoriasis have been available despite there being no approved systemic therapy for these patients. The aim of the present study was to elucidate clinical features of pediatric psoriasis in a tertiary referral psoriasis clinic. We analyzed the clinical data of 358 patients under 18 years of age referred to our clinic from other private clinics and medical centers. Our data showed a male :female ratio of 1.06:1 and a peak age of onset of 10-11 years. Of the patients, 32.4% had a positive family history. The most prevalent phenotype was plaque type (67.3%) and the mean Psoriasis Area and Severity Index score was 17.2 ± 12.7. The most frequently affected body part was the trunk (69.5%), followed by the legs (65.3%). Exposure to sunlight and summer season improved psoriatic lesions, while stress and winter season aggravated the clinical course. Only 26.0% of patients received systemic therapy or phototherapy during the therapeutic course. Oral acitretin (11.2%) was most frequently used followed by ultraviolet B phototherapy (7.3%). The childhood group (<13 years) showed higher prevalence of guttate and generalized pustular phenotypes and more severe clinical course compared with the adolescent group (13-18 years). In conclusion, our patients showed distinctive features in clinical phenotypes, disease severity and affected body parts compared with previous reports. We also found that clinical application of systemic therapies were limited considering the severe disease state of our patients, demanding a need for more research on treatment of pediatric psoriasis.
Taniguchi, Hiroya; Komori, Azusa; Narita, Yukiya; Kadowaki, Shigenori; Ura, Takashi; Andoh, Masashi; Yatabe, Yasushi; Komori, Koji; Kimura, Kenichi; Kinoshita, Takashi; Muro, Kei
Both bevacizumab and anti-epithelial growth factor receptor (EGFR) agents (e.g. cetuximab and panitumumab) are sequentially used for metastatic colorectal cancer (mCRC). Their co-administration as a first-line treatment does not improve outcome, indicating that there are negative interactions between these agents. A long-term pharmacokinetics study demonstrated serum persistence of bevacizumab following termination of bevacizumab 6 months after the last administration. This prompted us to investigate the impact of short intervals between bevacizumab and anti-EGFR antibody on the efficacy of subsequent anti-EGFR therapy. We retrospectively reviewed consecutive patients with KRAS exon 2 wild-type mCRC who underwent anti-EGFR therapy after the failure of fluoropyrimidines, oxaliplatin and irinotecan. We divided patients into two groups (Group A: the interval between bevacizumab and anti-EGFR agent< 6 months; Group B: the interval >6 months). Of the 114 included patients (median age, 63 years), 78 (68%) were male. Most patients (88%) were treated with cetuximab plus irinotecan. Groups A and B consisted of 74 and 40 patients, respectively. There were no significant differences in patient characteristics. Group B patients had significantly longer progression-free survival (4.2 vs. 6.6 months; HR, 0.65; 95% CI, 0.43-0.98; P = 0.038) and longer overall survival (11.6 vs. 14.3 months; HR, 0.63; 95% CI, 0.41-0.98, P = 0.039). The response rate was 24.3% in Group A and 47.5% in Group B (P = 0.012). A short interval between bevacizumab and anti-EGFR antibody treatment may interfere with the efficacy of subsequent anti-EGFR therapy. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: firstname.lastname@example.org.
Vine, Kathleen; Votava, Henry J; Smith, Barry L
Generalized pustular psoriasis of Zambusch is a unique and challenging skin condition to successfully manage. Patients often encounter potentially high recurrence rates of pustular eruptions despite multidrug treatment regimens with high morbidity as a consequence. We report a case of generalized pustular psoriasis of Zambusch in a patient whose disease initially flared following early treatment with the anti-tumor necrosis factor alpha (anti-TNF-alpha) inhibitor etanercept but was later successfully managed with cyclosporine and reintroduction of etanercept. We also discuss therapeutic management options for generalized pustular psoriasis.
McIntyre, Alan; Harris, Adrian L
Anti-angiogenic therapy has increased the progression-free survival of many cancer patients but has had little effect on overall survival, even in colon cancer (average 6–8 weeks) due to resistance. The current licensed targeted therapies all inhibit VEGF signalling (Table1). Many mechanisms of resistance to anti-VEGF therapy have been identified that enable cancers to bypass the angiogenic blockade. In addition, over the last decade, there has been increasing evidence for the role that the hypoxic and metabolic responses play in tumour adaptation to anti-angiogenic therapy. The hypoxic tumour response, through the transcription factor hypoxia-inducible factors (HIFs), induces major gene expression, metabolic and phenotypic changes, including increased invasion and metastasis. Pre-clinical studies combining anti-angiogenics with inhibitors of tumour hypoxic and metabolic adaptation have shown great promise, and combination clinical trials have been instigated. Understanding individual patient response and the response timing, given the opposing effects of vascular normalisation versus reduced perfusion seen with anti-angiogenics, provides a further hurdle in the paradigm of personalised therapeutic intervention. Additional approaches for targeting the hypoxic tumour microenvironment are being investigated in pre-clinical and clinical studies that have potential for producing synthetic lethality in combination with anti-angiogenic therapy as a future therapeutic strategy. PMID:25700172
Farber, E.M.; Nall, L. )
Prevention and detection screening programs as a public health service in curtailing the ever-increasing incidence of all forms of skin cancer are reviewed. The effect of solar and artificial ultraviolet radiation on the general population and persons with psoriasis is examined. 54 refs.
Lowes, Michelle A.; Suárez-Fariñas, Mayte; Krueger, James G.
The skin is the front line of defense against insult and injury and contains many epidermal and immune elements that comprise the skin-associated lymphoid tissue (SALT). The reaction of these components to injury allows an effective cutaneous response to restore homeostasis. Psoriasis vulgaris is the best-understood and most accessible human disease that is mediated by T cells and dendritic cells. Inflammatory myeloid dendritic cells release IL-23 and IL-12 to activate IL-17-producing T cells, Th1 cells, and Th22 cells to produce abundant psoriatic cytokines IL-17, IFN-γ, TNF, and IL-22. These cytokines mediate effects on keratinocytes to amplify psoriatic inflammation. Therapeutic studies with anticytokine antibodies have shown the importance of the key cytokines IL-23, TNF, and IL-17 in this process. We discuss the genetic background of psoriasis and its relationship to immune function, specifically genetic mutations, key PSORS loci, single nucleotide polymorphisms, and the skin transcriptome. The association between comorbidities and psoriasis is reviewed by correlating the skin transcriptome and serum proteins. Psoriasis-related cytokine-response pathways are considered in the context of the transcriptome of different mouse models. This approach offers a model for other inflammatory skin and autoimmune diseases. PMID:24655295
Strik, A S; Bots, S J A; D'Haens, G; Löwenberg, M
After the introduction of anti-tumor necrosis factor (anti-TNF) agents, the clinical outcome of patients with Inflammatory Bowel Disease (IBD) has improved significantly. However, use of anti-TNF therapy is complicated by loss of response. In order to maintain remission, adequate serum levels are required. Hence, therapeutic drug monitoring (TDM) is important in order to optimize serum drug levels, especially in patients with loss of response to these agents. Optimization of anti-TNF therapy by applying TDM enables clinicians to regain response to TNF blockers in a significant proportion of patients. It is important to use anti-TNF agents in their most optimal way, since these therapeutic agents are expensive and the medical options after failing anti-TNF therapy are limited. Here, we will discuss how to optimize treatment with anti-TNF agents in IBD patients in order to improve treatment efficacy, prevent anti-drug antibody formation, reduce side effects, discontinue unnecessary treatment and manage costs.
Xie, Xi; Li, Fen; Chen, Jin-Wei; Wang, Jia
Anti-tumor necrosis factor-α (TNF-α) biological agents, including soluble TNF-α receptors and anti-TNF-α monoclonal antibodies, bring new hope for treating rheumatic diseases such as rheumatoid arthritis, but also increase the risk of infection, especially tuberculosis (TB) infection. Recent findings have shown that the physiological TNF-mediated signaling was somehow impaired by TNF antagonists, leading to the exacerbation of chronic infection associated with aberrant granuloma formation and maintenance. Although both receptor and antibody agents appear to pose an equally high risk in causing development of new TB infections, monoclonal anti-TNF-α antibody seems more inclined to reactivate latent TB infection. This review is focused on the underlying mechanisms that cause the TB risk in the anti-TNF-α therapy and also the strategies to deal with it, with the aim of reducing the TB incidence during anti-TNF-α biological therapies.
Gisondi, P; Farina, S; Giordano, M V; Zanoni, M; Girolomoni, G
The aim of this paper was to investigate beliefs and preferences towards treatment of patients with psoriasis attending Comano SPA (Trentino, Italy) in comparison to patients referring to the University Hospital of Verona. Patient with psoriasis referring to Comano SPA and to the University Hospital of Verona were visited, their clinical data were collected and they were administered a questionnaire investigating their knowledge about psoriasis, as well as their attitude and preferences towards conventional therapies and SPA treatments. [Corrected] A total of 288 patients with chronic plaque psoriasis were recruited, 169 from Comano SPA and 119 from Verona Hospital. There were no differences regarding demographic data, severity of psoriasis, impact on quality of life and prevalence of cardio-metabolic comorbidities between the two groups. SPA patients more rarely believed that pharmacological treatments are safe and effective (6.5% vs. 21.8% P=0.001), had less trust in physician (32.5% vs. 67.2%; P=0.001) and preferred alternative therapies like balneotherapy compared to hospital patients (55.6% vs. 30.3%; P=0.0001), because they assumed they were more safe and effective than systemic drugs (37.3% vs. 1.7%; P=0.001). SPA patients preferred living with psoriasis rather than taking drugs to treat it more commonly than hospital patients (26.6% vs. 5%; P=0.001). Patients attending a SPA centre tend to trust conventional drug treatments less often than those attending a hospital clinic, and prefer balneotherapy as a dedicated alternative therapy. Fear of adverse events is a major concern among patients with psoriasis, especially those attending a SPA center.
González-Lara, Leire; Batalla, Ana; Coto, Eliecer; Gómez, Juan; Eiris, Noemí; Santos-Juanes, Jorge; Queiro, Rubén; Coto-Segura, Pablo
Genetic factors are involved not only in the overall risk of suffering psoriasis, but also in their clinical characteristics and eventually in drug outcome. Biological therapies have dramatically improved the prognosis of Psoriasis. However, these treatments are very expensive and patients often exhibit a heterogeneous response that could be partially attributed to their genetic background. Thus, the research for genetic markers in psoriatic patients that could predict a poor response to biological therapies is an important issue. Our aim was to evaluate the effect of DNA variants at the "TNFα pathway" that could affect the risk of developing Psoriasis or the response to biological therapies among these patients. The genetic association study included a total of 518 Psoriatic patients and 480 healthy controls. Ninety of these patients received biological treatment and based on the change in the PASI score after 24 weeks were classified as good (PASI score ≥75%), intermediate (PASI 50-75), and non-responders (PASI <50). Next generation sequencing (NGS) with semiconductor-array technology was used to identify the nucleotide variants in the TNF α, TNFRSF1A and TNFRSF1B, and we only found three missense amino acid changes, all in TNFRSF1B. Interestingly, we found a significantly higher frequency of rs1061622 G carriers among CW6-positive patients (p = 0.004; OR = 1.69, 95% CI = 1.18-2.41). Allele G (p.196R) carriers were significantly more frequent in the non-responder group (56%) (p = 0.05). In conclusion, we report a significant association between the TNFRSF1B p.M196R variant and the risk for psoriasis and the response to treatment with anti-TNF or anti-Il-12/Il-23. The genotyping of this polymorphism could help to optimize the treatment by identifying patients with a likely poor response to biological drugs.
Dassopoulos, Themistocles; Sninsky, Charles A
Randomized trials support the use of the thiopurines and anti-TNF monoclonal antibodies in treating Crohn disease. New therapeutic approaches and laboratory assays have helped optimize the use of these agents. Thiopurine methyltransferase activity should always be determined to avoid thiopurines in individuals with absent enzyme activity. The role of metabolite-adjusted dosing when initiating thiopurines is not settled. Measuring metabolites helps guide management in patients failing therapy. Loss of response to anti-TNF therapy is mitigated by maintenance therapy and concomitant immunomodulators. When loss of response to infliximab occurs, management is guided by the serum concentrations of infliximab and antibodies to infliximab.
Huang, Zhuochun; Yang, Bin; Shi, Yunying; Cai, Bei; Li, Yi; Feng, Weihua; Fu, Yang; Luo, Limei; Wang, Lanlan
Anti-TNF-α therapies have been applied in RA treatment, but the regulatory effect of the drug on immune system is not clear. In this study, we included 33 active RA patients and divided them into two groups. One group received anti-TNF-α mAb+methotrexate for 24 weeks, the other group got placebo+methotrexate for the first 12 weeks and anti-TNF-α mAb+methotrexate for another 12 weeks. Circulatory regulatory T cell (Treg) and effector T cell (Teff) frequency was analyzed pre-therapy and week 12 and week 24 for both group patients by flowcytometry. Our results indicated significantly elevated Treg and decreased Teff at week 24 compared with pre-therapy and week 12 for both group patients, and a little higher Treg and lower Teff frequency in anti-TNF-α therapy group than in placebo therapy patients. Our results demonstrated anti-TNF-α therapy has regulatory effect on immune system of RA patients by promoting Treg proportion increase and suppressing Teff.
Garzorz-Stark, Natalie; Krause, Linda; Lauffer, Felix; Atenhan, Anne; Thomas, Jenny; Stark, Sebastian P; Franz, Regina; Weidinger, Stephan; Balato, Anna; Mueller, Nikola S; Theis, Fabian J; Ring, Johannes; Schmidt-Weber, Carsten B; Biedermann, Tilo; Eyerich, Stefanie; Eyerich, Kilian
Novel specific therapies for psoriasis and eczema have been developed, and they mark a new era in the treatment of these complex inflammatory skin diseases. However, within their broad clinical spectrum, psoriasis and eczema phenotypes overlap making an accurate diagnosis impossible in special cases, not to speak about predicting the clinical outcome of an individual patient. Here, we present a novel robust molecular classifier (MC) consisting of NOS2 and CCL27 gene that diagnosed psoriasis and eczema with a sensitivity and specificity of >95% in a cohort of 129 patients suffering from (i) classical forms; (ii) subtypes; and (iii) clinically and histologically indistinct variants of psoriasis and eczema. NOS2 and CCL27 correlated with clinical and histological hallmarks of psoriasis and eczema in a mutually antagonistic way, thus highlighting their biological relevance. In line with this, the MC could be transferred to the level of immunofluorescence stainings for iNOS and CCL27 protein on paraffin-embedded sections, where patients were diagnosed with sensitivity and specificity >88%. Our MC proved superiority over current gold standard methods to distinguish psoriasis and eczema and may therefore build the basis for molecular diagnosis of chronic inflammatory skin diseases required to establish personalized medicine in the field. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Prieto-Pérez, Rocío; Cabaleiro, Teresa; Daudén, Esteban; Ochoa, Dolores; Roman, Manuel; Abad-Santos, Francisco
Psoriasis is a chronic inflammatory disease of the skin. The causes of psoriasis are unknown, although family and twin studies have shown genetic factors to play a key role in its development. The many genes associated with psoriasis and the immune response include TNFα, IL23, and IL12. Advances in knowledge of the pathogenesis of psoriasis have enabled the development of new drugs that target cytokines (e.g., etanercept, adalimumab, and infliximab, which target TNFα, and ustekinumab, which targets the p40 subunit of IL23 and IL12). These drugs have improved the safety and efficacy of treatment in comparison with previous therapies. However, not all patients respond equally to treatment, possibly owing to interindividual genetic variability. In this review, we describe the genes associated with psoriasis and the immune response, the biological drugs used to treat chronic severe plaque psoriasis, new drugs in phase II and III trials, and current knowledge on the implications of pharmacogenomics in predicting response to these treatments. PMID:24069534
Soleymani, Teo; Hung, Tracy; Soung, Jennifer
Psoriasis is a common, chronic autoimmune inflammatory skin disorder, which has potential systemic complications and is clinically defined by sharply demarcated, erythematous patches and plaques covered by a characteristic silvery white scale. Topical corticosteroids have widely been regarded as the mainstay first line of treatment. Recently, topical vitamin D analogs have been added to the first-line treatment repertoire as well, either as monotherapy or in combination with topical steroids due to synergistic, complementary effectiveness. In this paper, we review the role of vitamin D in the pathophysiology and treatment of psoriasis. A comprehensive search of the Cochrane Library, MEDLINE, and PUBMED databases were performed to identify relevant basic science and clinical trial literature investigating the role of vitamin D in psoriasis. Primary endpoints in clinical trials were largely based on clinical improvement as assessed by the psoriasis area severity index score or physician's global assessment. The role of vitamin D in psoriasis is complex and extensive. Oral and topical vitamin D therapies provide comparable efficacies to corticosteroids when used as monotherapy and may be superior when used in combination with a potent topical steroid. Additionally topical vitamin D analogs demonstrate a favorable safety profile with "steroid-sparing" effects. Thus, topical vitamin D derivatives should be considered an indispensable component of the current physician's arsenal in the treatment of psoriasis. © 2015 The International Society of Dermatology.
Perera, Gayathri K; Ainali, Chrysanthi; Semenova, Ekaterina; Hundhausen, Christian; Barinaga, Guillermo; Kassen, Deepika; Williams, Andrew E; Mirza, Muddassar M; Balazs, Mercedesz; Wang, Xiaoting; Rodriguez, Robert Sanchez; Alendar, Andrej; Barker, Jonathan; Tsoka, Sophia; Ouyang, Wenjun; Nestle, Frank O
Cytokines are critical checkpoints of inflammation. The treatment of human autoimmune disease has been revolutionized by targeting inflammatory cytokines as key drivers of disease pathogenesis. Despite this, there exist numerous pitfalls when translating preclinical data into the clinic. We developed an integrative biology approach combining human disease transcriptome data sets with clinically relevant in vivo models in an attempt to bridge this translational gap. We chose interleukin-22 (IL-22) as a model cytokine because of its potentially important proinflammatory role in epithelial tissues. Injection of IL-22 into normal human skin grafts produced marked inflammatory skin changes resembling human psoriasis. Injection of anti-IL-22 monoclonal antibody in a human xenotransplant model of psoriasis, developed specifically to test potential therapeutic candidates, efficiently blocked skin inflammation. Bioinformatic analysis integrating both the IL-22 and anti-IL-22 cytokine transcriptomes and mapping them onto a psoriasis disease gene coexpression network identified key cytokine-dependent hub genes. Using knockout mice and small-molecule blockade, we show that one of these hub genes, the so far unexplored serine/threonine kinase PIM1, is a critical checkpoint for human skin inflammation and potential future therapeutic target in psoriasis. Using in silico integration of human data sets and biological models, we were able to identify a new target in the treatment of psoriasis.
Falcao, Claudio Borges
with half of the concentration needed for G3139 alone in CL to reduce the cell viability by 40%. Also, it was found greater apoptotic signal in cells treated with CLs containing D-(KLAKLAK)2/G3139 complexes than CLs with G3139 only. In vivo, D-(KLAKLAK) 2/G3139 complexes in CL significantly inhibited tumor growth compared to the saline treated group, through apoptosis induction. However, the mechanism involved in cell death by apoptosis seems to be independent of reduction of bcl-2 protein levels. PEG2000 at 1% mol could significantly reduce activity of PCL formulation towards B16(F10) cells compared to CLs. After pre-incubation at pH 7.4, PCL and pH-PCL had decreased activity compared to CL towards B16(F10) cells. After pre-incubation at pH 5.0, while CL and PCL had the same activity with the cells as in neutral pH, pH-PCL formulation had its PEG cleaved and its cytotoxicity was restored against the melanoma cells. Thus, D-(KLAKLAK)2/G3139 complexes in CL had enhanced anti-cancer therapy, through apoptosis, than G3139 alone in CL in vitro and in vivo. In vitro, PCL and pH-PCL particles obtained can have a prolonged blood residence time, and, once a tumor tissue is reached, pH-PCL can have its cytotoxicity restored because of hydrolysis of cleavable PEG at a lowered pH.
Psoriasis is a common, chronic, relapsing/remitting, immune-mediated skin disease that causes itchy skin with silvery scales. It is characterized by thickened red erythematous plaques covered with silvery scales. Biological therapies have been recently introduced for patients with psoriasis in India. The biological therapies contain protein biomolecules which can be employed to target specific immune or genetic mediator of a pathophysiological process. Here, we share our clinical experience of managing 20 patients with moderate to severe psoriasis by itolizumab a humanized IgG1 monoclonal antibody. Eighteen patients achieved Psoriasis Area and Severity Index (PASI) 75 response after receiving 10 infusion of itolizumab (at the completion of treatment). Out of 18 patients 4 patients had achieved PASI 95 response and 10 patients had achieved PASI 90 response. There was no adverse event reported during the treatment period. Itolizumab was found effective and safe in the treatment of moderate to severe psoriasis patients.
Psoriasis is a common, chronic, relapsing/remitting, immune-mediated skin disease that causes itchy skin with silvery scales. It is characterized by thickened red erythematous plaques covered with silvery scales. Biological therapies have been recently introduced for patients with psoriasis in India. The biological therapies contain protein biomolecules which can be employed to target specific immune or genetic mediator of a pathophysiological process. Here, we share our clinical experience of managing 20 patients with moderate to severe psoriasis by itolizumab a humanized IgG1 monoclonal antibody. Eighteen patients achieved Psoriasis Area and Severity Index (PASI) 75 response after receiving 10 infusion of itolizumab (at the completion of treatment). Out of 18 patients 4 patients had achieved PASI 95 response and 10 patients had achieved PASI 90 response. There was no adverse event reported during the treatment period. Itolizumab was found effective and safe in the treatment of moderate to severe psoriasis patients. PMID:28050487
Wei, Kai-Che; Lai, Ping-Chin
Severe forms of psoriasis that are refractory to conventional therapies are often difficult to manage. The mammalian target of rapamycin (mTOR) inhibitors potentially have versatile effects toward putative psoriatic pathologic pathways. Therefore, mTOR inhibitors may offer a range of new therapeutic options for patients with psoriasis. We describe a 55-year-old male renal transplant patient with refractory psoriasis. We adjusted his antirejection regimen and put him on everolimus (Certican(®); Novartis, Basel, Switzerland; a semisynthetic macrolide, belonging to the mTOR inhibitors family) with low-dose tacrolimus. This combination regimen maintained his graft function and successfully controlled his psoriasis. His skin lesions never recurred in the next 18 months. To our knowledge, this is the first report showing that the combination of everolimus and tacrolimus could be used to treat recalcitrant psoriasis. The relative benefit-risk profiles of such therapies worth further investigation.
Mukherjee, Manali; Sehmi, Roma; Nair, Parameswaran
Airway inflammation is considered to be the primary component contributing to the heterogeneity and severity of airway disorders. Therapeutic efficacies of diverse novel biologics targeting the inflammatory pathways are under investigation. One such target is IL-5, a type-1 cytokine that is central to the initiation and sustenance of eosinophilic airway inflammation. Over the past decade, anti-IL5 molecules have been documented to have mixed therapeutic benefits in asthmatics. Post hoc analyses of the trials reiterate the importance of identifying the IL-5-responsive patient endotypes. In fact, the currently available anti-IL5 treatments are being considered beyond asthma management; especially in clinical complications with an underlying eosinophilic pathobiology such as hypereosinophilic syndrome (HES) and eosinophilic granulomatosis and polyangitis (EGPA). In addition, closer analyses of the available data indicate alternative mechanisms of tissue eosinophilia that remain uncurbed with the current dosage and delivery platform of the anti-IL5 molecules.
Chackartchi, T; Sachar Helft, S; Findler, M
Surgical intra-oral treatment for patients under antithrombotic therapy presents a challenge for the dental team. Within the last few years evidence based systematic reviews established new clinical guidelines for wide groups of patients which need to use antithrombotic treatment. The expected increase in use of antithrombotic treatment forced the pharmaceutical industry to provide new treatments. The former anticoagulant and anti-platelets aggregation groups of drugs were limited to small variety of medication. The search for the new treatments with ideal properties led to newly invented groups of drugs. In this article we will describe the new advancements in anti-thrombotic treatments. The article will summarize the limited knowledge of surgical management of patients under the new anti-thrombotic medications and the recommended approach for oral surgical procedures.
Singh, Rasnik K; Lee, Kristina M; Ucmak, Derya; Brodsky, Merrick; Atanelov, Zaza; Farahnik, Benjamin; Abrouk, Michael; Nakamura, Mio; Zhu, Tian Hao; Liao, Wilson
Erythrodermic psoriasis (EP) is a rare and severe variant of psoriasis vulgaris, with an estimated prevalence of 1%–2.25% among psoriatic patients. The condition presents with distinct histopathologic and clinical findings, which include a generalized inflammatory erythema involving at least 75% of the body surface area. The pathogenesis of EP is not well understood; however, several studies suggest that the disease is associated with a predominantly T helper 2 (Th2) phenotype. Given the morbidity and potential mortality associated with the condition, there is a need for a better understanding of its pathophysiology. The management of EP begins with a comprehensive assessment of the patient's presentation and often requires multidisciplinary supportive measures. In 2010, the medical board of the US National Psoriasis Foundation published consensus guidelines advocating the use of cyclosporine or infliximab as first-line therapy in unstable cases, with acitretin and methotrexate reserved for more stable cases. Since the time of that publication, additional information regarding the efficacy of newer agents has emerged. We review the latest data with regard to the treatment of EP, which includes biologic therapies such as ustekinumab and ixekizumab. PMID:28856115
Reddy, Shivani P; Martires, Kathryn; Wu, Jashin J
The risk of melanoma and hematologic cancers in patients with psoriasis is controversial. We sought to assess the risk of melanoma and hematologic cancers in patients with psoriasis, and the association with different treatments. We used case-control and retrospective cohort designs to determine melanoma or hematologic cancer risk in patients with psoriasis. Risk with treatment type was assessed using Fisher exact test. Patients with psoriasis had 1.53 times greater risk of developing a malignancy compared with patients without psoriasis (P < .01). There were no significant differences in malignancy risk among patients treated with topicals, phototherapy, systemics, or biologic agents. Patients with psoriasis and malignancy did not have significantly worse survival than patients without psoriasis. It is possible that patients developed malignancy subsequent to the follow-up time included in the study. Patients with psoriasis may experience an elevated risk of melanoma and hematologic cancers, compared with the general population. The risk is not increased by systemic or biologic psoriasis therapies. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.
Singh, Priyanka A; Cassel, Kerry P; Moscati, Ronald M; Eckersley, David
We report a case of erythrodermic pustular psoriasis associated with initiation of bupropion/naltrexone (Contrave®; Orexigen Therapeutics, La Jolla, CA) in a patient with no history of psoriasis. A 55-year-old woman was transferred to our tertiary medical center from a community hospital for possible Stevens-Johnson syndrome 3 weeks after initiation of bupropion/naltrexone. The patient was admitted to the burn unit for wound treatment and hydration. She received intravenous cyclosporine during the admission that resulted in acute kidney injury and the therapy was discontinued. The skin biopsy ruled out Stevens-Johnson syndrome and was more consistent with generalized pustular psoriasis. After discharge, the patient followed up with her dermatologist. She was diagnosed with acute generalized and erythrodermic psoriasis and the patient was restarted on cyclosporine 100 mg twice a day. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Few case reports of bupropion-induced generalized pustular psoriasis and erythrodermic psoriasis in patients with a history of psoriasis have been reported. To our knowledge, acute generalized erythrodermic pustular psoriasis associated with bupropion/naltrexone has not been reported in a patient without history of psoriasis. Due to increases in obesity and increases in prescribing of bupropion/naltrexone SR, health care providers should be aware of this possible severe adverse reaction. Published by Elsevier Inc.
Chen, Tao; Fu, Li-Xin; Zhang, Li-Wen; Yin, Bin; Zhou, Pei-Mei; Cao, Na; Lu, Yong-Hong
Psoriasis is one of the most common immune-mediated chronic inflammatory skin disorders, characterized by hyperproliferation of keratinocytes, dilation and growth of dermal capillary vasculature, and cellular infiltration of T cells, dendritic cells (DCs), and neutrophils. Paeoniflorin (PF), the principal component of total glucosides of paeony (TGP), displays anti-inflammatory and antioxidant properties in several animal models. In this study, we investigated the anti-inflammatory effects and mechanisms of PF in imiquimod (IMQ)-induced psoriasis-like mouse model. The effects of PF on inflammatory cytokine expression in peripheral blood mononuclear cells (PBMCs) from patients with psoriasis vulgaris were also observed. Our results indicated that PF effectively attenuated the clinical and histopathologic changes in IMQ-induced psoriasis-like mouse model. Furthermore, PF reduced the infiltration of T cells, CD11c(+)DCs, and neutrophils in lesional skin. In addition, PF also significantly decreased the mRNA expression of inflammatory cytokines, such as IL-17, INF-γ, IL-6, and TNF-α, in IMQ-induced psoriasis-like mouse model and PBMCs from patients with psoriasis vulgaris. Hence, our data suggest that PF can inhibit leukocyte infiltration and decrease the expression of inflammatory cytokines such as IL-17, INF-γ, IL-6, and TNF-α. PF might be a candidate drug for the treatment of psoriasis.
Veale, D; Ritchlin, C; FitzGerald, O
Psoriatic arthritis (PsA) is characterised by several unique clinical features that differentiate it from rheumatoid arthritis (RA). Attempts to identify immunopathological mechanisms, some shared with psoriasis, that underlie these differences from RA have been most challenging. Recent research studies, however, highlight novel findings in PsA at the molecular, cellular, and tissue levels that form the basis for a new understanding of this relatively common form of inflammatory arthritis. In particular, the availability of new, biological antitumour necrosis factor α therapies have allowed further insight into the immunopathology of psoriasis and PsA. This brief review focuses on immunohistological studies in psoriatic skin, PsA synovium, and bone to demonstrate how these data advance our knowledge of disease pathogenesis. PMID:15708930
Takeshita, Junko; Grewal, Sungat; Langan, Sinéad M; Mehta, Nehal N; Ogdie, Alexis; Van Voorhees, Abby S; Gelfand, Joel M
Psoriasis is a common chronic inflammatory disease of the skin that is increasingly being recognized as a systemic inflammatory disorder. Psoriatic arthritis is a well-known comorbidity of psoriasis. A rapidly expanding body of literature in various populations and settings supports additional associations between psoriasis and cardiometabolic diseases, gastrointestinal diseases, kidney disease, malignancy, infection, and mood disorders. The pathogenesis of comorbid disease in patients with psoriasis remains unknown; however, shared inflammatory pathways, cellular mediators, genetic susceptibility, and common risk factors are hypothesized to be contributing elements. As additional psoriasis comorbidities continue to emerge, education of health care providers is essential to ensuring comprehensive medical care for patients with psoriasis. Copyright © 2016 American Academy of Dermatology, Inc. All rights reserved.
Interleukin-22 (IL-22) is an IL-10 family cytokine that was recently discovered to be released by T helper 17 (Th17) cells, Th22 cells, etc. Recently, there is emerging evidence that IL-22 is involved in the development and pathogenesis of psoriasis. For instance, IL-22 can inhibit keratinocyte terminal differentiation and can induce psoriasis-like epidermis alterations; serum IL-22 levels were correlated with the disease severity of psoriasis patients, and IL-22 mRNA was positively expressed in the psoriatic skin lesions, but negatively expressed in the normal controls. All these findings suggest that IL-22 may be implicated in psoriasis; therapeutics targeting IL-22 may have promise as a potential therapeutic target for treating psoriasis. In the present review, we summarize recent advances on the role of IL-22 in the pathogenesis and treatment of psoriasis.
Ali, Tauseef; Kaitha, Sindhu; Mahmood, Sultan; Ftesi, Abdul; Stone, Jordan; Bronze, Michael S
Biologics such as antitumor necrosis factor (anti-TNF) drugs have emerged as important agents in the treatment of many chronic inflammatory diseases, especially in cases refractory to conventional treatment modalities. However, opportunistic infections have become a major safety concern in patients on anti-TNF therapy, and physicians who utilize these agents must understand the increased risks of infection. A literature review of the published data on the risk of bacterial, viral, fungal, and parasitic infections associated with anti-TNF therapy was performed and the clinical presentation, diagnostic tests, management, and prevention of opportunistic infections in patients receiving anti-TNF therapy were reviewed. Awareness of the therapeutic potential and associated adverse events is necessary for maximizing therapeutic benefits while minimizing adverse effects from anti-TNF treatments. Patients should be adequately vaccinated when possible and closely monitored for early signs of infection. When serious infections occur, withdrawal of anti-TNF therapy may be necessary until the infection has been identified and properly treated. PMID:23569399
Piktel, Ewelina; Niemirowicz, Katarzyna; Wątek, Marzena; Wollny, Tomasz; Deptuła, Piotr; Bucki, Robert
The rapid development of nanotechnology provides alternative approaches to overcome several limitations of conventional anti-cancer therapy. Drug targeting using functionalized nanoparticles to advance their transport to the dedicated site, became a new standard in novel anti-cancer methods. In effect, the employment of nanoparticles during design of antineoplastic drugs helps to improve pharmacokinetic properties, with subsequent development of high specific, non-toxic and biocompatible anti-cancer agents. However, the physicochemical and biological diversity of nanomaterials and a broad spectrum of unique features influencing their biological action requires continuous research to assess their activity. Among numerous nanosystems designed to eradicate cancer cells, only a limited number of them entered the clinical trials. It is anticipated that progress in development of nanotechnology-based anti-cancer materials will provide modern, individualized anti-cancer therapies assuring decrease in morbidity and mortality from cancer diseases. In this review we discussed the implication of nanomaterials in design of new drugs for effective antineoplastic therapy and describe a variety of mechanisms and challenges for selective tumor targeting. We emphasized the recent advantages in the field of nanotechnology-based strategies to fight cancer and discussed their part in effective anti-cancer therapy and successful drug delivery.
Tsygankov, Alexander Y
Since the introduction of highly active retroviral therapy (HAART) in 1996, dramatic improvements in therapeutic treatment modalities for HIV type 1 (HIV-1) infection have occurred. Potent drug combinations in HAART regimens efficiently block HIV-1 replication in most patients; however, multiple shortcomings of HAART are apparent and require novel treatments that can be utilized in combination with HAART or as stand-alone therapies. Gene therapy of HIV-1 represents one such treatment and several strategies are currently under development. This review focuses on advancements in the gene therapy of HIV/AIDS by highlighting the progress made in selecting new therapeutic targets and developing novel tools to exert an effect on these targets. In addition, new trends emerging from this progress are summarized. This review is based primarily on literature published between 2006 and 2008.
Ciombor, Kristen K.; Goldberg, Richard M.
Angiogenesis is a complex biologic process critical to growth and proliferation of colorectal cancer. The safety and efficacy of various anti-angiogenic agents have been investigated in many treatment settings. Bevacizumab, an anti-vascular endothelial growth factor agent, has efficacy in both the first-line setting and beyond progression in metastatic colorectal cancer. The decoy vascular endothelial growth factor receptor aflibercept has been approved in combination with 5-fluorouracil, leucovorin and irinotecan-based chemotherapy in metastatic colorectal cancer patients whose disease has progressed on a prior oxaliplatin-based chemotherapy regimen. The multikinase inhibitor regorafenib is modestly effective in the refractory colorectal cancer setting but confers significant toxicity. Ramucirumab, an anti-vascular endothelial growth factor receptor 2 molecule, has efficacy in combination with 5-fluorouracil, leucovorin and irinotecan after disease progression on a first-line bevacizumab-, oxaliplatin- and fluoropyrimidine-containing regimen. Questions regarding optimal treatment setting, predictive biomarkers of response, and cost effectiveness of these anti-angiogenic agents and others are as yet unanswered. PMID:27551256
In this issue of Blood, Cooke et al demonstrate the potential of a fully human anti-hepcidin antibody as a novel therapeutic for iron-restricted anemias such as anemia of inflammation, cancer, or chronic kidney disease (formerly known as “anemia of chronic diseases”).
Ohlmann, C-H; Kamradt, J; Stöckle, M
The identification of intracellular androgen synthesis by prostate cancer cells has led to the identification of new targets and the development of third generation drugs for the therapy of castration-resistant prostate cancer. Inhibitors of androgen synthesis and more potent androgen receptor antagonists, such as abiraterone acetate, MDV3100, TAK-700 and TOK-001, will improve treatment by prolongation of survival and palliation. A significant reduction of tumor-associated pain and a survival advantage of 4.6 months compared to placebo following docetaxel-based chemotherapy has already been shown for abiraterone in a phase III study. Further phase III studies with abiraterone, MDV3100 and TAK-700 before and after docetaxel-based chemotherapy are currently running. TOK-001 is the first of the new drugs which combines the therapeutic use of androgen synthesis inhibition and androgen receptor antagonism in a single drug. The first clinical studies with this therapy are currently being carried out and it remains to be seen whether this combination leads to increased effectiveness. With an increase in therapy options for prostate-resistant cancer, one of the projects in the coming years will be to integrate the present therapies into therapy concepts. In addition to an effective sequence of the individual medications, a combination with already established therapies, such as cytostatic agents, could also prove to be useful. Altogether, the development of new antihormonal therapies is a considerable expansion of the therapy options for patients which could contribute to an improvement of the quality of life and the prognosis of patients.
Abreu, José Luís Pio Da Costa; Reis, José Pedro Gaspar Dos; Figueiredo, Américo Manuel Da Costa
Introduction and objective: Psoriasis is a chronic skin disease with a high impact on self-esteem and patients’ health-related quality of life. In the last decades some studies have pointed out mental disorders associated with psoriasis and the etiopathogenic mechanisms behind that co-existence. This work compiles psychopathology associated with psoriasis and further analyzes the etiopathogenesis of psoriasis and mental disorders. Methods: A systematic review of the literature was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and using the “5S” levels of organization of evidence from healthcare research, as previously described. Results: Psoriasis is linked with many mental disorders, both in the psychotic and neurotic sprectrum. Chronic stress diminishes hypothalamic-pituitary-adrenal axis and upregulates sympathetic-adrenal-medullary responses, stimulating pro-inflammatory cytokines. Then, it maintains and exacerbates psoriasis and some of its mental disorders. High levels of pro-inflammatory cytokines connect psoriasis, psychiatric conditions, and other comorbidities of psoriasis (such as atherosclerosis) within a vicious cycle. Furthermore, the etiopathogenesis of the link between each psychiatric comorbidity and psoriasis has its own subtleties, including the cooccurrence of other comorbidities, the parts of the body affected by psoriasis, treatments, and biological and psychosocial factors. Conclusion: The study of psychopathology can amplify our understanding about the etiopathogenesis of psoriasis and associated mental disorders. Patients would benefit from a psychodermatologic approach. The adequate treatment should take into account the mental disorders associated with psoriasis as well as the circumstances under which they occur. PMID:27386050
Boehncke, W H
Co-existing inflammation and epidermal hyperproliferation characteristic for psoriasis have been shown to be reproducible in several animal models utilizing a variety of different strategies. These models highlight some points of the multicausal pathogenesis of psoriasis. Based on observations made in the animal models, a hypothesis is proposed for the pathogenesis of psoriasis, the elements of which can be tested in a recently established xenogeneic transplantation model.
Kalomoiris, Stefanos; Lawson, Je'tai; Chen, Rachel X; Bauer, Gerhard; Nolta, Jan A; Anderson, Joseph S
As HIV continues to be a global public health problem with no effective vaccine available, new and innovative therapies, including HIV gene therapies, need to be developed. Due to low transduction efficiencies that lead to low in vivo gene marking, therapeutically relevant efficacy of HIV gene therapy has been difficult to achieve in a clinical setting. Methods to improve the transplantation of enriched populations of anti-HIV vector-transduced cells may greatly increase the in vivo efficacy of HIV gene therapies. Here we describe the development of preselective anti-HIV lentiviral vectors that allow for the purification of vector-transduced cells to achieve an enriched population of HIV-resistant cells. A selectable protein, human CD25, not normally found on CD34+ hematopoietic progenitor cells (HPCs), was incorporated into a triple combination anti-HIV lentiviral vector. Upon purification of cells transduced with the preselective anti-HIV vector, safety was demonstrated in CD34+ HPCs and in HPC-derived macrophages in vitro. Upon challenge with HIV-1, improved efficacy was observed in purified preselective anti-HIV vector-transduced macrophages compared to unpurified cells. These proof-of-concept results highlight the potential use of this method to improve HIV stem cell gene therapy for future clinical applications.
Ebihara, Shin; Date, Fumiko; Dong, Yupeng; Ono, Masao
Ankylosis is a major pathological manifestation of spondyloarthropathy. The aim of this study was to evaluate the effects of anti-IL-17 therapy on spontaneous ankylosing enthesitis in mice. In this study, we used male DBA/1 mice as a spontaneous ankylosis model. Serum IL-17 concentrations were determined using enzyme-linked immunosorbent assay. Male DBA/1 mice from different litters were mixed and caged together preceding the treatment at 10 weeks (wk) of age (prophylaxis) or 21 wk of age (intervention). Treatment with anti-IL-17 antibodies or saline was initiated after caging in groups of mice and administered weekly. The onset of tarsal ankylosis was assessed by ankle swelling and histopathological examination. Pathological changes and mRNA expression levels were assessed in joints and ears obtained at the experimental end-point. We found that circulating IL-17 increased with the onset of ankylosis in male DBA/1 mice, coinciding with the onset of dermatitis. The symptoms of dermatitis corresponded to the pathological characteristics of psoriasis: acanthosis with mild hyperkeratosis, scaling, epidermal microabscess formation and augmented expression of K16, S100A8 and S100A9. Prophylactic administration of anti-IL-17 antibodies significantly prevented the development of both ankylosis and dermatitis in male DBA/1 mice caged together. On the other hand, administration of anti-IL-17 antibodies after disease onset had a lesser but significant effect on ankylosis progression but did not affect dermatitis progression. In conclusion, IL-17 is a key mediator in the pathogenic process of tarsal ankylosis and psoriasis-like dermatitis in male DBA/1 mice caged together. Thus, IL-17 is a potential therapeutic target in ankylosing enthesitis and psoriasis in humans.
Pfeffer, J; Kaufmann, R; Boehncke, W-H
Psoriasis is characterized by a complex phenotype and pathogenesis along with polygenic determination. Several psoriasis animal models have only been able to incompletely reproduce the disease. A xenogeneic transplantation approach, grafting skin from psoriatic patients onto mice with a severe combined immunodeficiency (SCID), was the first to meet the criteria for a psoriasis model. During the last 10 years, this psoriasis SCID-mouse model not only allowed telling experiments focusing on pathogenetic aspects, but also proved being a powerful tool for drug discovery with a good predictive value.
Thurber, Marzieh; Feasel, Adrienne; Stroehlein, John; Hymes, Sharon R
Pustular psoriasis is an uncommon variant of psoriasis characterized by widespread pustules on an erythematous background. Recent reports document the efficacy of immunobiologic agents such as infliximab in the treatment of pustular psoriasis. We present a patient that developed cutaneous and pathologic changes consistent with pustular psoriasis while receiving treatment with infliximab for chronic ulcerative colitis. More long-term studies need to be conducted in order to fully understand this paradoxical reaction as well as the mechanism of action and side effect profiles of infliximab and other immunobiologic agents.
Swindell, William R.; Johnston, Andrew; Xing, Xianying; Voorhees, John J.; Elder, James T.; Gudjonsson, Johann E.
Background Whole-genome expression profiling has been used to characterize molecular-level differences between psoriasis lesions and normal skin. Pathway analysis, however, is complicated by the fact that expression profiles have been derived from bulk skin biopsies with RNA derived from multiple cell types. Results We analyzed gene expression across a large sample of psoriatic (PP) and uninvolved/normal (PN) skin biopsies (n = 215 patients). We identified 1975 differentially expressed genes, including 8 associated with psoriasis susceptibility loci. To facilitate pathway analysis, PP versus PN differences in gene expression were analyzed with respect to 235 gene modules, each containing genes with a similar expression pattern in keratinocytes and epidermis. We identified 30 differentially expressed modules (DEMs) biased towards PP-increased or PP-decreased expression. These DEMs were associated with regulatory axes involving cytokines (e.g., IFN-γ, IL-17A, TNF-α), transcription factors (e.g., STAT1, NF-κB, E2F, RUNX1) and chromatin modifiers (SETDB1). We identified an interferon-induced DEM with genes encoding anti-viral proteins (designated “STAT1-57”), which was activated in psoriatic epidermis but repressed following biologic therapy. Genes within this DEM shared a motif near the transcription start site resembling the interferon-stimulated response element (ISRE). Conclusions We analyzed a large patient cohort and developed a new approach for delineating epidermis-specific pathways and regulatory mechanisms that underlie altered gene expression in psoriasis. Our findings highlight previously unrecognized “transcription circuits” that can provide targets for development of non-systemic therapies. PMID:24260178
Lin, Yin-Ku; Yen, Hung-Rong; Wong, Wen-Rou; Yang, Sien-Hung; Pang, Jong-Hwei Su
The treatment of psoriasis in children is still an intractable problem and demands a long-term therapy with prolonged efficacy that is free from serious adverse events. Many modes of therapy are currently in use but the disease is often resistant to treatment owing to the unacceptable toxicity that leads to poor compliance. Therefore, to develop an alternative treatment is indispensable. Traditional Chinese medicine has been documented for over 1000 years to provide various effective treatments for inflammatory skin diseases. Herein, we report an 8-year-old boy with recalcitrant pediatric psoriasis who, after multiple treatment failures with conventional antipsoriatic medications, showed remarkable clinical improvement with 8 weeks of topical treatment with Indigo naturalis composite ointment. Remission has lasted for over 2 years until now. Our patient's response suggests that topical Indigo naturalis composite ointment may provide a safe and effective alternative treatment for pediatric psoriasis.
Fu, Lisa Wenyang; Vender, Ronald
The novel discovery of the systemic role of vitamin D in the modulation of the immune system especially the Type 1 helper T cell (Th1) pathway reveals its potential for treating Th1 inflammatory diseases. Psoriasis has been recently established to be a systemic disease centered on inflammation and involvement of cytokines of the Th1 pathway. There is an increased prevalence of metabolic syndrome in patients with psoriasis. Metabolic syndrome also involves a proinflammatory state. This paper proposes the idea of the potential use of oral vitamin D to treat psoriasis and metabolic syndrome concurrently. We propose there is merit in more clinical trials investigating the use of vitamin D to treat both psoriasis and metabolic syndrome through its anti-inflammatory effects. On application to psoriasis management and prognosis, the goal is to decrease the risk for cardiovascular disease and decrease disease morbidity and mortality.
Schmitt, Jochen; Wozel, Gottfried
The prodrug leflunomide is an immunomodulatory agent whose M1 metabolite inhibits the proliferation of T- and B-lymphocytes. The efficacy of leflunomide in rheumatoid arthritis suggests it may be useful psoriasis arthritis. Two patients with psoriasis arthritis in whom NSAIDs, glucocorticosteroids, sulfasalazine, cyclosporine and methotrexate were not as effective as expected were treated with leflunomide for 18 and 27 months. At regular visits examination of the joints (according to the ACR criteria) and the skin (PASI), the visual analogue scale for pain, and the quality of life (HAQ) were assessed. In both patients progression of the joint disease was arrested, pain reduced and quality of life improved. The cutaneous findings did not change, even though topical therapy was continued. Leflunomide is a long-term treatment option for patients with predominantly joint disease. In case of insufficient response, combination with other anti-inflammatory drugs, e.g. methotrexate, is possible. As leflunomide has little effect on psoriatic skin lesions, additional topical therapy is necessary.
Pirlet, Charles; Legrand, Victor; Nyssen, Astrid; Pierard, Luc; Gach, Olivier
Dual anti-platelet therapy is prescribed in the setting of coronary heart disease for the prevention of stent thrombosis and acute thrombotic events. The optimal duration of dual anti-platelet therapy is still under debate as numerous trials have shown non-inferiority of a strategy of early cessation of one of the agents as compared to the standard practice whereas two larger trials have demonstrated benefit of prolonging dual anti-platelet therapy.
Yang, Yunlong; Zhang, Yin; Iwamoto, Hideki; Hosaka, Kayoko; Seki, Takahiro; Andersson, Patrik; Lim, Sharon; Fischer, Carina; Nakamura, Masaki; Abe, Mitsuhiko; Cao, Renhai; Skov, Peter Vilhelm; Chen, Fang; Chen, Xiaoyun; Lu, Yongtian; Nie, Guohui; Cao, Yihai
The impact of discontinuation of anti-VEGF cancer therapy in promoting cancer metastasis is unknown. Here we show discontinuation of anti-VEGF treatment creates a time-window of profound structural changes of liver sinusoidal vasculatures, exhibiting hyper-permeability and enlarged open-pore sizes of the fenestrated endothelium and loss of VE-cadherin. The drug cessation caused highly leaky hepatic vasculatures permit tumour cell intravasation and extravasation. Discontinuation of an anti-VEGF antibody-based drug and sunitinib markedly promotes liver metastasis. Mechanistically, host hepatocyte, but not tumour cell-derived vascular endothelial growth factor (VEGF), is responsible for cancer metastasis. Deletion of hepatocyte VEGF markedly ablates the ‘off-drug'-induced metastasis. These findings provide mechanistic insights on anti-VEGF cessation-induced metastasis and raise a new challenge for uninterrupted and sustained antiangiogenic therapy for treatment of human cancers. PMID:27580750
Yang, Yunlong; Zhang, Yin; Iwamoto, Hideki; Hosaka, Kayoko; Seki, Takahiro; Andersson, Patrik; Lim, Sharon; Fischer, Carina; Nakamura, Masaki; Abe, Mitsuhiko; Cao, Renhai; Skov, Peter Vilhelm; Chen, Fang; Chen, Xiaoyun; Lu, Yongtian; Nie, Guohui; Cao, Yihai
The impact of discontinuation of anti-VEGF cancer therapy in promoting cancer metastasis is unknown. Here we show discontinuation of anti-VEGF treatment creates a time-window of profound structural changes of liver sinusoidal vasculatures, exhibiting hyper-permeability and enlarged open-pore sizes of the fenestrated endothelium and loss of VE-cadherin. The drug cessation caused highly leaky hepatic vasculatures permit tumour cell intravasation and extravasation. Discontinuation of an anti-VEGF antibody-based drug and sunitinib markedly promotes liver metastasis. Mechanistically, host hepatocyte, but not tumour cell-derived vascular endothelial growth factor (VEGF), is responsible for cancer metastasis. Deletion of hepatocyte VEGF markedly ablates the 'off-drug'-induced metastasis. These findings provide mechanistic insights on anti-VEGF cessation-induced metastasis and raise a new challenge for uninterrupted and sustained antiangiogenic therapy for treatment of human cancers.
Ribeiro, Lara Beatriz Prata; Rego, Juliana Carlos Gonçalves; Estrada, Bruna Duque; Bastos, Paula Raso; Piñeiro Maceira, Juan Manuel; Sodré, Celso Tavares
Biologic drugs represent a substantial progress in the treatment of chronic inflammatory immunologic diseases. However, its crescent use has revealed seldom reported or unknown adverse reactions, mainly associated with anti-tumor necrosis factor (anti-TNF). Psoriasiform cutaneous reactions and few cases of alopecia can occur in some patients while taking these drugs. Two cases of alopecia were reported after anti-TNF therapy. Both also developed psoriasiform lesions on the body. This is the second report about a new entity described as 'anti-TNF therapy-related alopecia', which combines clinical and histopathological features of both alopecia areata and psoriatic alopecia. The recognition of these effects by specialists is essential for the proper management and guidance of these patients. PMID:25830994
Ribeiro, Lara Beatriz Prata; Rego, Juliana Carlos Gonçalves; Estrada, Bruna Duque; Bastos, Paula Raso; Piñeiro Maceira, Juan Manuel; Sodré, Celso Tavares
Biologic drugs represent a substantial progress in the treatment of chronic inflammatory immunologic diseases. However, its crescent use has revealed seldom reported or unknown adverse reactions, mainly associated with anti-tumor necrosis factor (anti-TNF). Psoriasiform cutaneous reactions and few cases of alopecia can occur in some patients while taking these drugs. Two cases of alopecia were reported after anti-TNF therapy. Both also developed psoriasiform lesions on the body. This is the second report about a new entity described as 'anti-TNF therapy-related alopecia', which combines clinical and histopathological features of both alopecia areata and psoriatic alopecia. The recognition of these effects by specialists is essential for the proper management and guidance of these patients.
Kitchen, Scott G.; Shimizu, Saki; An, Dong Sung
Human stem cell-based therapeutic intervention strategies for treating HIV infection have recently undergone a renaissance as a major focus of investigation. Unlike most conventional antiviral therapies, genetically engineered hematopoietic stem cells possess the capacity for prolonged self-renewal that would continuously produce protected immune cells to fight against HIV. A successful strategy therefore has the potential to stably control and ultimately eradicate HIV from patients by a single or minimal treatment. Recent progress in the development of new technologies and clinical trials sets the stage for the current generation of gene therapy approaches to combat HIV infection. In this review, we will discuss two major approaches that are currently underway in the development of stem cell-based gene therapy to target HIV: One that focuses on the protection of cells from productive infection with HIV, and the other that focuses on targeting immune cells to directly combat HIV infection. PMID:21247612
Agrawal, Gaurav; Borody, Thomas; Turner, Robert; Leis, Sharyn; Campbell, Jordana
Background: Fistulizing Crohn's disease (CD) presents a therapeutic challenge as fistulae are notoriously difficult to heal. Mycobacterium avium ss paratuberculosis (MAP) treatment in CD is gaining attention. Aim: We evaluated healing of CD fistula(e) using a novel combination therapy. Study: Nine consecutive patients who failed to heal fistulae on conventional treatment including anti-TNF, were treated with at least three doses of infliximab, 18–30 courses of hyperbaric oxygen therapy and anti-MAP antibiotics comprising rifabutin, clarithromycin and clofazimine. Results: All patients achieved complete healing of fistulae by 6–28 weeks and follow-up for mean 18 months. Conclusion: Combining infliximab, hyperbaric oxygen therapy and anti-MAP, seems to enable healing of recalcitrant fistulae and although a small case series, all nine patients achieved complete healing. PMID:28031926
Teo, Kelvin Yi Chong; Ng, Wei Yan; Lee, Shu Yen; Cheung, Chui Ming Gemmy
Myopic choroidal neovascularization (mCNV) is the second most common form of CNV after age-related macular degeneration (AMD). It is a sight-threatening complication of pathologic myopia (PM) and often affects patients in their working years causing significant impact on quality of life. Previous therapies such as photodynamic therapy with verteporfin have shown limited success. Due to the similarities in pathogenesis of mCNV and AMD CNV, anti-vascular endothelial growth factor therapy (anti-VEGF), which has so far been the mainstay of treatment for AMD CNV, has been shown to be effective in the treatment of mCNV and has become the first-line treatment of choice. This article aims to examine briefly the epidemiology and pathophysiology of mCNV, as well as review the evidence for efficacy, safety, and clinical use of anti-VEGF treatment for mCNV.
Zarrabi, Kevin; Fang, Chunhui; Wu, Shenhong
Angiogenesis is a critical process in the progression of advanced renal cell carcinoma. Agents targeting angiogenesis have played a primary role in the treatment of metastatic renal cell carcinoma. However, resistance to anti-angiogenesis therapy almost always occurs, and major progress has been made in understanding its underlying molecular mechanism. Axitinib and everolimus have been used extensively in patients whom have had disease progression after prior anti-angiogenesis therapy. Recently, several new agents have been shown to improve overall survival in comparison with everolimus. This review provides an in-depth summary of drugs employable in the clinical setting, the rationale to their use, and the studies conducted leading to their approval for use and provides perspective on the paradigm shift in the treatment of renal cell carcinoma. Highlighted are the newly approved agents cabozantinib, nivolumab, and lenvatinib for advanced renal cell carcinoma patients treated with prior anti-angiogenesis therapy.
Erer, Burak; Yilmaz, Gulsen; Yilmaz, Fatma Meric; Koklu, Seyfettin
Anti-TNF-alpha agents are increasingly used in rheumatoid arthritis (RA) treatment and that is known to increase the risk of tuberculosis (TB) reactivation. Adenosine deaminase (ADA) levels are shown to increase to high levels in TB patients. Our aim is to investigate the serum ADA levels in RA patients being treated with anti-TNF-alpha and to compare the results with the patients on DMARD therapy. The study groups comprised of 56 RA patients (45 female, mean age 49) who were treated either with two or three DMARDs, 32 RA patients with anti-TNF-alpha treatment (26 female, mean age 46) and 20 healthy controls (10 female, mean age 48). All patients fulfilled the 1987 ACR criteria for RA. DAS28 score was calculated for all subjects. When compared to healthy controls, ADA levels were measured statistically higher both in patient groups (P = 0.046, 0.002). ADA levels in anti-TNF-alpha group were similar to conventional therapy (11.3 +/- 2.7, 10.9 +/- 4.01; P = 0.76). PPD was positive in 17 RA patients in the anti-TNF-alpha treatment group (%53). The ADA levels were found to be similar in the anti-TNF-alpha group when compared according to the PPD positivity (positive, 12.4 +/- 3.7; negative, 10.5 +/- 2.1; P = 0.02). No correlation was found between the ADA levels and age, disease duration, ESR, CRP, DAS 28 and HAQ score. In this study, we observed that RA patients at remission taking DMARD or anti-TNF-alpha therapy have similar levels of serum ADA. Although serum ADA levels during TB infection increase much higher, in our study, ADA levels of all RA patients were lower than 15 IU/L. Elevated ADA levels may be a clue for diagnosis of TB in patients who were on anti-TNF-alpha therapy.
Batycka-Baran, Aleksandra; Besgen, Petra; Wolf, Ronald; Szepietowski, Jacek C; Prinz, Joerg C
Psoriasis is a common, chronic immune-mediated inflammatory disease. The inflammatory process in psoriasis has systemic effects and may influence the development of psoriatic comorbidities. The systemic action of phototherapy in patients with psoriasis has been so far poorly elucidated. We aimed to investigate the expression of genes encoding selected psoriasis-related cytokines in peripheral blood mononuclear cells (PBMCs) isolated from patients with psoriasis before and after treatment with phototherapy. 17 patients with mild to moderate plaque psoriasis were treated with narrow band-UVB (NB-UVB), 8 patients with moderate to severe plaque psoriasis with bath-psoralen-ultraviolet A therapy (PUVA). PBMCs were isolated by Ficoll gradient density centrifugation. Expression of genes encoding TNF-α, IL-17A, IL-6, IL-1 β, INF-γ, and IL-10 in PBMCs of patients with psoriasis before and after phototherapy was analyzed with quantitative RT-PCR. Treatment with NB-UVB therapy led to a significant decrease in IL-17A, TNF-α, and IL-6 mRNA levels in PBMCs (p=0.003; p=0.042; p=0.019, respecti