Literature on Psoriatic Arthritis

Related ArticlesInosine 5′-monophosphate dehydrogenase inhibitors for the treatment of autoimmune diseases.

Curr Opin Drug Discov Devel. 2006 Sep;9(5):595-605

Authors: Ratcliffe AJ

Inosine 5′-monophosphate dehydrogenase (IMPDH) is a key enzyme in the de novo biosynthesis of guanine nucleotides. Proliferation of T- and B-lymphocytes, a hallmark of many autoimnunne diseases, is heavily dependent on access to a large pool of guanine nucleotides. To support this activity IMPDH is upregulated. The clinical benefit observed with mnycophenolic acid, a potent IMPDH inhibitor, in a number of autoimmune diseases, including those associated with organ transplantation, rheumatoid arthritis, psoriasis, systemic lupus erythenmatosus and inflammatory bowel disease, has validated IMPDH as an immunosuppressive target, and triggered the search from the pharmaceutical industry for IMPDH inhibitors with best-in-class status. This review will highlight recent advances in the IMPDH field, with a focus on the discovery and development of non-nucleoside IMPDH inhibitors.

PMID: 17002220 [PubMed - indexed for MEDLINE]

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Related Articles[Vascular development in inflammatory bowel disease]

Gastroenterol Hepatol. 2006 Aug-Sep;29(7):414-21

Authors: Pousa ID, Gisbert JP, Maté J

There are 4 major concepts in vascular development: vasculogenesis (formation of blood vessels from angioblasts), angiogenesis (formation of vascular sprouts from preexisting vessels), arteriogenesis (thickening and development of vessels) and lymphangiogenesis (formation of lymphatic vessels). In the last decade, these concepts, especially angiogenesis and lymphangiogenesis, have acquired major importance due to their role in tumoral growth and metastatic dissemination. Moreover, the activity of various diseases that involve chronic inflammation, such as asthma, psoriasis and rheumatoid arthritis, has been associated with vascular development. Several growth factors and cytokines are involved in this process and consequently investigation into these elements, both in peripheral blood and their expression in affected tissues, could elucidate the role of vascular development in diseases whose pathogenesis involves chronic inflammation, such as inflammatory bowel disease. The presence of distinct molecules involved in vascular development processes, such as vascular endothelial growth factor (VEGF), basic fibroblastic growth factor and placental growth factor, among others, has been studied in both ulcerative colitis and Crohn’s disease, although not extensively. It has been suggested that the phenomena of vasculogenesis, angiogenesis and lymphangiogenesis play a critical, although not exclusive, role in the inflammation that characterizes inflammatory bowel disease. In general, the results obtained to date suggest that new vascular formation is involved in the pathogenesis of these diseases.

PMID: 16938258 [PubMed - indexed for MEDLINE]

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Related ArticlesProblems encountered during anti-tumour necrosis factor therapy.

Best Pract Res Clin Rheumatol. 2006 Aug;20(4):757-90

Authors: Desai SB, Furst DE

Worldwide, over 400,000 patients have been treated with tumour necrosis factor (TNF)-alpha antagonists for indications that include rheumatoid arthritis, juvenile rheumatoid arthritis, inflammatory bowel disease, psoriatic arthritis and ankylosing spondylitis. Since their approval, concerns regarding safety have been raised. There is a risk of re-activation of granulomatous diseases, especially tuberculosis, and measures should be taken for detection and treatment of latent tuberculosis infections. Preliminary data suggest that anti-TNF therapy may be safe in chronic hepatitis C. However, TNF-alpha antagonists have resulted in re-activation of chronic hepatitis B if not given concurrently with antiviral therapy. Solid tumours do not appear to be increased with anti-TNF therapy. Variable rates of increased lymphoma risk have been described with anti-TNF therapy compared with the general population, although no increased risk was found compared with a rheumatoid arthritis population. Large phase II and III trials with TNF-alpha antagonists in advanced heart failure have shown trends towards a worse prognosis, and should therefore be avoided in this population. Both etanercept and infliximab are associated with the formation of autoantibodies, and these autoantibodies are rarely associated with any specific clinical syndrome. Rare cases of aplastic anaemia, pancytopenia, vasculitis and demyelination have been described with anti-TNF therapy. This chapter will discuss the safety profile and adverse events of the three commercially available TNF-alpha antagonists: etanercept, infliximab and adalimumab. The data presented in this review have been collected from published data, individual case reports or series, package inserts, the Food and Drug Administration postmarketing adverse events surveillance system, and abstracts from the American College of Rheumatology and European Congress of Rheumatology meetings for 2005.

PMID: 16979537 [PubMed - indexed for MEDLINE]

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Related ArticlesEmerging peptide therapeutics for inflammatory diseases.

Curr Pharm Biotechnol. 2006 Aug;7(4):241-6

Authors: Vally M, Seenu S, Pillarisetti S

Steroids are the best known anti-inflammatory drugs and have been in use for more than 50 years. Their chronic use however was limited by safety concerns. Non-steroidal anti-inflammatory drugs (NSAIDs) including COX-2 inhibitors although devoid of steroid side effects often possess gastrointestinal side effects. In addition recent data suggest that chronic use of some Cox inhibitors is associated with cardiovascular risk. Currently biologics represent the best option for many inflammatory diseases where TNFalpha is the main culprit. These include rheumatoid arthritis, ulcerative colitis, inflammatory bowel disease and psoriasis. A wealth of information is now available on the role of different cytokines and adhesion molecules in the origin and progression of inflammatory diseases. With the success of protein therapeutics such as Etanercept (Enbrel), which binds TNFalpha and inhibits its activity, research has been focused on developing small peptides that can interfere with cytokines or specific cell surface molecules and inhibit the inflammatory reactions. Here we review these peptides that are in discovery and development phases and their potential in the treatment of inflammatory diseases.

PMID: 16918401 [PubMed - indexed for MEDLINE]

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Related ArticlesSafety of etanercept in psoriasis: a critical review.

Drug Saf. 2006;29(8):675-85

Authors: Sánchez Carazo JL, Mahiques Santos L, Oliver Martinez V

Conventional systemic treatments for patients with psoriasis are associated with multiple adverse effects that require continuous monitoring. The introduction of new biological agents such as etanercept, a fully human fusion protein, has permitted individualisation of patients’ treatment according to disease stage. The drug is a competitive inhibitor of tumour necrosis factor-alpha (TNFalpha) that prevents interaction between this cytokine and its cell surface receptors. Etanercept also modulates the activity of other inflammatory cytokines and does not induce complement-mediated cell lysis in vitro. The main source of information regarding etanercept safety comes from studies in patients with rheumatoid arthritis. The most common adverse effect during drug administration is mild injection site reactions. There is no increase in the overall incidence of infections compared with placebo, although there have been several reports of infections caused by intracellular organisms (Mycobacterium tuberculosis, Listeria monocytogenes, and Mycobacterium avium intracellulare). Therefore, combination of this drug with corticosteroids must be carefully monitored and should be avoided in patients with established sepsis. There are no data showing that treatment with etanercept results in an increase in the occurrence of malignant neoplasms. However, caution is recommended in use of etanercept in patients with a current or past history of demyelinating disease. Etanercept must be used with extreme caution in patients with heart failure because of several reports indicating a worsening or de novo occurrence of congestive heart failure while receiving the drug. Monitoring of autoantibodies is not currently considered necessary as they do not predict response, toxicity or autoimmune events. The presence of non-neutralising antibodies to the TNF receptor fragment or other protein components of etanercept has not been related to a decrease in drug response or adverse reactions. Etanercept does not generally modify the course of inflammatory bowel disease. When combined with other systemic therapies for psoriasis, current data do not show an increase in adverse events. In patients with hepatitis C viral infection, etanercept does not increase transaminase levels or viral load and in some instances has allowed the concomitant use of interferon which had previously been discontinued because of a worsening of psoriasis. Etanercept is rated as a US FDA category B drug in pregnancy. However, its use is not recommended in pregnant women unless the benefit-risk ratio greatly favours its use. Etanercept is not recommended for use in lactating women. Etanercept represents a relevant treatment for psoriasis, efficacious over many weeks and safe but special care should be taken to avoid the potential risks.

PMID: 16872241 [PubMed - indexed for MEDLINE]

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Related ArticlesModulating TNF-alpha signaling with natural products.

Drug Discov Today. 2006 Aug;11(15-16):725-32

Authors: Paul AT, Gohil VM, Bhutani KK

Natural products have been, and continue to be, a major source of pharmacologically active substances from which drugs can be developed. Currently, tumor necrosis factor-alpha (TNF-alpha) inhibitors from natural origins are being advanced for the treatment of inflammatory disorders. Elevated TNF-alpha synthesis has been associated with the development of diabetes, septic shock, tumorigenesis, rheumatoid arthritis, psoriatic arthritis and inflammatory bowel disease. Currently, only protein-based drugs are available for the clinical inhibition of TNF-alpha activity. Small-molecule drugs that can regulate TNF-alpha levels or activity might provide a cost-effective alternative to protein-based therapeutics. This review briefly highlights the physiological and pathological roles of TNF-alpha, and covers those natural compounds capable of interfering with TNF-alpha activity.

PMID: 16846800 [PubMed - indexed for MEDLINE]

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Related ArticlesTargeting cytosolic phospholipase A2 by arachidonyl trifluoromethyl ketone prevents chronic inflammation in mice.

Eur J Pharmacol. 2006 Jun 13;539(3):195-204

Authors: Malaviya R, Ansell J, Hall L, Fahmy M, Argentieri RL, Olini GC, Pereira DW, Sur R, Cavender D

Cytosolic phospholipase A(2) (cPLA(2)) plays a pivotal role in inflammation by catalyzing the release of arachidonic acid, a substrate for lipoxygenase and cyclooxygenase enzymes, from membrane phospholipids. In the present study we examined the role of cPLA(2) in inflammatory responses through the use of a specific inhibitor of the enzyme, cPLA(2), arachidonyl trifluoromethyl ketone (AACOCF3). Interestingly, we observed that AACOCF3 is an inhibitor of chronic but not acute inflammatory responses. Specifically, AACOCF3 inhibited phorbol 12-myristate 13-acetate (PMA)-induced chronic ear edema in mice. Additionally, oral treatment of ovalbumin-sensitized/ovalbumin-challenged BALB/c mice with 20 mg/kg AACOCF3 prevented the development of airway hyper-responsiveness in a model of asthma. Furthermore, AACOCF3 decreased cellular recruitment in the airway lumen and airway inflammation after the ovalbumin challenge. Taken together, these results suggest that a potent and specific chemical inhibitor of cPLA(2) may be useful for the treatment of chronic inflammatory diseases including rheumatoid arthritis, inflammatory bowel disease, psoriasis, and asthma.

PMID: 16712837 [PubMed - indexed for MEDLINE]

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Related ArticlesConcepts and epidemiology of spondyloarthritis.

Best Pract Res Clin Rheumatol. 2006 Jun;20(3):401-17

Authors: Sieper J, Rudwaleit M, Khan MA, Braun J

The term ’spondyloarthritides’ (SpA) comprises ankylosing spondylitis (AS), reactive arthritis, arthritis/spondylitis with inflammatory bowel disease, and arthritis/spondylitis with psoriasis. The main links between these diseases are an association with HLA-B27 and a similar clinical picture. Patients normally present with chronic low back pain or asymmetrical arthritis, predominantly of the lower limbs, and an overlap of these symptoms often occurs. AS is regarded as the most severe subtype. Recent attention has focused on earlier diagnosis of AS among patients with chronic low back, and this is becoming more important as effective therapies for early treatment have become available. AS is a disease of young people, normally starting in the third decade of life. The incidence and prevalence rates of AS, and of SpA as a whole, are strongly dependent and are directly correlated to the prevalence of HLA-B27 in a given population. Incidence rates of 0.5-8.2/100 000 population and prevalence rates of 0.2-1.2% have been described for AS, and about double these figures have been reported for SpA.

PMID: 16777573 [PubMed - indexed for MEDLINE]

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Related ArticlesPatients with psoriatic arthritis have an increased number of lymphocytes in the duodenal mucosa in comparison with patients with psoriasis vulgaris.

J Rheumatol. 2006 May;33(5):924-7

Authors: Lindqvist U, Kristjánsson G, Pihl-Lundin I, Hagforsen E, Michaëlsson G

OBJECTIVE: To determine if there is evidence of inflammation in the duodenal mucosa in patients with psoriatic arthritis (PsA) and to compare the results with those in patients with psoriasis vulgaris (PsV). METHODS: Nineteen consecutive patients with PsA underwent gastroduodenoscopy, and biopsy specimens were taken from the duodenal and gastric mucosa. In addition to routine processing, the duodenal mucosal specimens were stained for CD3+, CD8+ and CD4+ T lymphocytes, tryptase-positive mast cells, and EG2-positive eosinophil granulocytes. The results were compared with those in duodenal mucosal specimens from patients with PsV and patients with irritable bowel syndrome. RESULTS: Compared with PsV patients (without antibodies against gliadin), patients with PsA had a highly significant increase in intraepithelial CD3+ and CD8+ lymphocytes and also in CD4+ lymphocytes in the lamina propria in the villi. The lymphocyte increase was not related to presence of IgA antibodies against gliadin, endomysium, or transglutaminase, or to concomitant gastritis. Patients with PsA and PsV showed a pronounced increase in mast cells and eosinophil granulocytes. CONCLUSION: The increased lymphocyte infiltration in the duodenal mucosa in PsA, but not in PsV, might indicate different pathogenetic mechanisms in these psoriasis variants.

PMID: 16541478 [PubMed - indexed for MEDLINE]

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Related ArticlesCutaneous psoriasis in a military flight surgeon.

Aviat Space Environ Med. 2006 Feb;77(2):140-4

Authors: Hagen AD, Sulit DJ, Sulit AK

Cutaneous psoriasis is a common, non-infectious, hyperproliferative, papulosquamous, inflammatory skin disease whose pathogenesis is unknown. The course of psoriasis is typically chronic and unpredictable. Psoriasis can range from a small, local pathological area of skin to widespread dermatologic disease, such as generalized pustular psoriasis and erythroderma. Symptoms can range from mildly symptomatic to life threatening. Complications can range from psychological problems to systemic medical disease, such as psoriatic arthritis and inflammatory bowel disease. Treatment options can have adverse side effects which negatively affect multiple organ systems such as the hematological, neurological, and immunological systems. Therefore, psoriasis is a dermatologic disease that should be taken seriously in military aviation. The disease, its complications, and its therapies can interfere with concentration, mission accomplishment, the ability to operate aircraft safely, and compliance with safety equipment use. In this case report, we present the case of a naval flight surgeon who presented with inverse psoriasis and plaque psoriasis, which ultimately became well controlled with topical medications. The flight surgeon was recommended for military aeromedical waivers for psoriasis and chronic medication use. We also review the medical literature on cutaneous psoriasis, discuss its complications, and review its aeromedical implications in military aviation.

PMID: 16491582 [PubMed - indexed for MEDLINE]

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