Literature on Psoriatic Arthritis

Related Articles[Leflunomide-induced skin necrosis]

Ann Dermatol Venereol. 2008 Mar;135(3):205-8

Authors: Gros C, Delesalle F, Gautier S, Delaporte E

BACKGROUND: Leflunomide is prescribed in inflammatory rheumatisms. Cutaneous side effects have rarely been described. We report the case of a patient presenting skin necrosis attributed to this drug. PATIENTS AND METHODS: A 73-year-old woman had been taking leflunomide for psoriatic arthritis for one year and subsequently, developed three abdominal ulcerations and necrosis of one hallux. No immunological, vascular or neoplastic aetiology was found. Corticotherapy was started, based on a hypothesis of vasculitis, but lesions progressed, leading to amputation of the hallux. Leflunomide was stopped and the ulcerations healed completely within 12 weeks, whereas prolonged local treatment had failed to yield any improvement. DISCUSSION: Skin necrosis due to leflunomide is rare; we found seven cases in the literature. Ulcerations may occur anywhere. Potentially life-threatening glomerulonephritis with mesangial deposits may be associated. Discontinuation of leflunomide followed by wash-out with cholestyramine allows healing. Corticosteroids or cyclophosphamide are sometimes necessary. The ulcerations appear to be result from excessive immunomodulation in the skin or from an inhibiting role of leflunomide on the epidermal growth factor receptor. CONCLUSION: In the absence of any demonstrated aetiology in patients presenting ulcerations or skin necrosis, a contributory role of leflunomide must be considered, even in cases of prolonged use.

PMID: 18374852 [PubMed - indexed for MEDLINE]

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Related ArticlesA genome-wide association study of psoriasis and psoriatic arthritis identifies new disease loci.

PLoS Genet. 2008 Mar;4(3):e1000041

Authors: Liu Y, Helms C, Liao W, Zaba LC, Duan S, Gardner J, Wise C, Miner A, Malloy MJ, Pullinger CR, Kane JP, Saccone S, Worthington J, Bruce I, Kwok PY, Menter A, Krueger J, Barton A, Saccone NL, Bowcock AM

A genome-wide association study was performed to identify genetic factors involved in susceptibility to psoriasis (PS) and psoriatic arthritis (PSA), inflammatory diseases of the skin and joints in humans. 223 PS cases (including 91 with PSA) were genotyped with 311,398 single nucleotide polymorphisms (SNPs), and results were compared with those from 519 Northern European controls. Replications were performed with an independent cohort of 577 PS cases and 737 controls from the U.S., and 576 PSA patients and 480 controls from the U.K.. Strongest associations were with the class I region of the major histocompatibility complex (MHC). The most highly associated SNP was rs10484554, which lies 34.7 kb upstream from HLA-C (P = 7.8×10(-11), GWA scan; P = 1.8×10(-30), replication; P = 1.8×10(-39), combined; U.K. PSA: P = 6.9×10(-11)). However, rs2395029 encoding the G2V polymorphism within the class I gene HCP5 (combined P = 2.13×10(-26) in U.S. cases) yielded the highest ORs with both PS and PSA (4.1 and 3.2 respectively). This variant is associated with low viral set point following HIV infection and its effect is independent of rs10484554. We replicated the previously reported association with interleukin 23 receptor and interleukin 12B (IL12B) polymorphisms in PS and PSA cohorts (IL23R: rs11209026, U.S. PS, P = 1.4×10(-4); U.K. PSA: P = 8.0×10(-4); IL12B:rs6887695, U.S. PS, P = 5×10(-5) and U.K. PSA, P = 1.3×10(-3)) and detected an independent association in the IL23R region with a SNP 4 kb upstream from IL12RB2 (P = 0.001). Novel associations replicated in the U.S. PS cohort included the region harboring lipoma HMGIC fusion partner (LHFP) and conserved oligomeric golgi complex component 6 (COG6) genes on chromosome 13q13 (combined P = 2×10(-6) for rs7993214; OR = 0.71), the late cornified envelope gene cluster (LCE) from the Epidermal Differentiation Complex (PSORS4) (combined P = 6.2×10(-5) for rs6701216; OR 1.45) and a region of LD at 15q21 (combined P = 2.9×10(-5) for rs3803369; OR = 1.43). This region is of interest because it harbors ubiquitin-specific protease-8 whose processed pseudogene lies upstream from HLA-C. This region of 15q21 also harbors the gene for SPPL2A (signal peptide peptidase like 2a) which activates tumor necrosis factor alpha by cleavage, triggering the expression of IL12 in human dendritic cells. We also identified a novel PSA (and potentially PS) locus on chromosome 4q27. This region harbors the interleukin 2 (IL2) and interleukin 21 (IL21) genes and was recently shown to be associated with four autoimmune diseases (Celiac disease, Type 1 diabetes, Grave’s disease and Rheumatoid Arthritis).

PMID: 18369459 [PubMed - indexed for MEDLINE]

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Related ArticlesInhibition of PI3K/AKT and MEK/ERK pathways act synergistically to enhance antiangiogenic effects of EGCG through activation of FOXO transcription factor.

J Mol Signal. 2008;3:7

Authors: Shankar S, Chen Q, Srivastava RK

ABSTRACT: BACKGROUND: We have recently shown that epigallocatechin-3-gallate (EGCG), a polyphenolic compound from green tea, inhibits angiogenesis. However, the molecular mechanisms by which EGCG inhibits angiogenesis have never been investigated. In this study, we examined the interaction of PI3K/AKT and MEK/ERK pathways on the regulation of FOXO transcription factors, which ultimately control the antiangiogenic effects of EGCG. RESULTS: Inhibition of PI3K/AKT and MEK/ERK pathways interact synergistically to inhibit migration and capillary tube formation of HUVEC cells and further enhanced the antiangiogenic effects of EGCG. Inhibition of AKT and MEK kinases synergistically induced FOXO transcriptional activity, which was further enhanced in the presence of EGCG. Phosphorylation deficient mutants of FOXO induced FOXO transcriptional activity, inhibited HUVEC cell migration and capillary tube formation. Inhibition of FOXO phosphorylation also enhanced antiangiogenic effects of EGCG through transcriptional activation of FOXO. CONCLUSION: Inhibition of PI3K/AKT and MEK/ERK pathways act synergistically to regulate antiangiogenic effects of EGCG through activation of FOXO transcription factors. The activation of FOXO transcription factors through inhibition of these two pathways may have physiological significance in management of diabetic retinopathy, rheumatoid arthritis, psoriasis, cardiovascular diseases, and cancer.

PMID: 18355401 [PubMed - in process]

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Related ArticlesIs folic acid good for everyone?

Am J Clin Nutr. 2008 Mar;87(3):517-33

Authors: Smith AD, Kim YI, Refsum H

Fortification of food with folic acid to reduce the number of neural tube defects was introduced 10 y ago in North America. Many countries are considering whether to adopt this policy. When fortification is introduced, several hundred thousand people are exposed to an increased intake of folic acid for each neural tube defect pregnancy that is prevented. Are the benefits to the few outweighed by possible harm to some of the many exposed? In animals, a folic acid-rich diet can influence DNA and histone methylation, which leads to phenotypic changes in subsequent generations. In humans, increased folic acid intake leads to elevated blood concentrations of naturally occurring folates and of unmetabolized folic acid. High blood concentrations of folic acid may be related to decreased natural killer cell cytotoxicity, and high folate status may reduce the response to antifolate drugs used against malaria, rheumatoid arthritis, psoriasis, and cancer. In the elderly, a combination of high folate levels and low vitamin B-12 status may be associated with an increased risk of cognitive impairment and anemia and, in pregnant women, with an increased risk of insulin resistance and obesity in their children. Folate has a dual effect on cancer, protecting against cancer initiation but facilitating progression and growth of preneoplastic cells and subclinical cancers, which are common in the population. Thus, a high folic acid intake may be harmful for some people. Nations considering fortification should be cautious and stimulate further research to identify the effects, good and bad, caused by a high intake of folic acid from fortified food or dietary supplements. Only then can authorities develop the right strategies for the population as a whole.

PMID: 18326588 [PubMed - indexed for MEDLINE]

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Related ArticlesMethotrexate therapy for psoriatic arthritis: reappraisal of an old remedy.

J Rheumatol. 2008 Mar;35(3):369-71

Authors: Saketkoo LA, Cuchacovich R, Espinoza LR

PMID: 18322970 [PubMed - indexed for MEDLINE]

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Related ArticlesAutoimmune disease in individuals and close family members and susceptibility to non-Hodgkin’s lymphoma.

Arthritis Rheum. 2008 Mar;58(3):657-66

Authors: Mellemkjaer L, Pfeiffer RM, Engels EA, Gridley G, Wheeler W, Hemminki K, Olsen JH, Dreyer L, Linet MS, Goldin LR, Landgren O

OBJECTIVE: Rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Sjögren’s syndrome have been consistently associated with an increased risk of non-Hodgkin’s lymphoma (NHL). This study was initiated to evaluate the risks of NHL associated with a personal or family history of a wide range of autoimmune diseases. METHODS: A population-based case-control study was conducted that included 24,728 NHL patients in Denmark (years 1977-1997) and Sweden (years 1964-1998) and 55,632 controls. Using univariate logistic and hierarchical regression models, we determined odds ratios (ORs) of NHL associated with a personal history of hospital-diagnosed autoimmune conditions. Risks of NHL associated with a family history of the same autoimmune conditions were assessed by similar regression analyses that included 25,941 NHL patients and 58,551 controls. RESULTS: A personal history of systemic autoimmune diseases (RA, SLE, Sjögren’s syndrome, systemic sclerosis) was clearly linked with NHL risk, both for individual conditions (hierarchical odds ratios [OR(h)] ranged from 1.6 to 5.4) and as a group (OR(h) 2.64 [95% confidence interval (95% CI) 1.72-4.07]). In contrast, a family history of systemic autoimmune diseases was modestly and nonsignificantly associated with NHL (OR(h) 1.31 [95% CI 0.85-2.03]). An increased risk of NHL was found for a personal history of 5 nonsystemic autoimmune conditions (autoimmune hemolytic anemia, Hashimoto thyroiditis, Crohn’s disease, psoriasis, and sarcoidosis) (OR(h) ranged from 1.5 to 2.6) of 27 conditions examined. CONCLUSION: Overall, our results demonstrate a strong relationship of personal history of systemic autoimmune diseases with NHL risk and suggest that shared susceptibility may explain a very small fraction of this increase, at best. Positive associations were found for a personal history of some, though far from all, nonsystemic autoimmune conditions.

PMID: 18311836 [PubMed - indexed for MEDLINE]

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Related ArticlesThe abundant synovial expression of the RANK/RANKL/Osteoprotegerin system in peripheral spondylarthritis is partially disconnected from inflammation.

Arthritis Rheum. 2008 Mar;58(3):718-29

Authors: Vandooren B, Cantaert T, Noordenbos T, Tak PP, Baeten D

OBJECTIVE: Spondylarthritis (SpA) and rheumatoid arthritis (RA) have different patterns of bone damage, with more pronounced bone erosions in RA. The RANK/RANKL/osteoprotegerin (OPG) system plays a central role in bone resorption by promoting the maturation and activation of osteoclasts. To assess the potential role of this system in the distinct bone phenotype, we studied the synovial expression of these mediators in SpA and RA peripheral synovitis. METHODS: Synovial biopsy specimens were obtained from the actively inflamed peripheral joints of 35 patients with SpA and 19 patients with RA. Paired synovial biopsy samples were obtained from 24 patients with SpA after tumor necrosis factor alpha (TNFalpha) blockade. Synovial tissue sections were immunostained for RANKL, OPG, RANK, and TRAP and assessed by semiquantitative scoring and digital image analysis. RESULTS: After extensive validation of the reactivity and specificity of the antibodies, we demonstrated the abundant expression of RANKL and OPG in SpA synovitis. RANKL was expressed by both fibroblast-like synoviocytes and sublining T lymphocytes. RANK-positive osteoclast precursors but no mature TRAP-positive osteoclasts were present in the inflamed tissue. The expression of these mediators was not different between patients with nonpsoriatic SpA, patients with psoriatic SpA, and patients with RA, was not related to the degree of systemic or local inflammation, and was not significantly modulated by highly effective treatment with TNFalpha blockers. Only the subset of patients with the best systemic response to TNFalpha blockade had decreased RANKL expression in the intimal lining layer. CONCLUSION: The relative protection against bone erosions in SpA cannot be explained by qualitative or quantitative differences in the synovial expression of RANKL, OPG, and RANK. The abundant expression of these factors in SpA peripheral synovitis is largely disconnected from systemic and local inflammation.

PMID: 18311801 [PubMed - indexed for MEDLINE]

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Related Articles[Burden of illness. First routine report on socio-medical consequences of inflammatory rheumatic disease in Germany]

Z Rheumatol. 2008 Mar;67(2):157-64

Authors: Mau W, Beyer W, Ehlebracht-König I, Engel M, Genth E, Greitemann B, Jäckel WH, Zink A

A synopsis of different socio-medical consequences of inflammatory rheumatic diseases is not yet available for Germany. Therefore, the data reported during the past decade for rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, systemic sclerosis, systemic lupus erythematodes, and Wegener’s granulomatosis are summarized in this article. Apart from clinical studies, relevant data sources were the national data base of the German collaborative arthritis centres, statistical figures from the compulsory health insurance and the national pension insurance scheme.Data were mainly available for sick leave and work disability showing limitations, which frequently occurred during the early course of diseases and increased with disease duration. Furthermore, different risk factors were identified. Measures to maintain continued participation in the labour force, such as part-time employment, partial work disability instead of full work disability, were not being adequately utilized. Only few data regarding the need of help and care were available. The proportion of patients in need of help and care increased with the duration of rheumatoid arthritis to more than 50% after more than 2 decades.This review presents detailed information concerning aspects of the burden of rheumatic diseases, which are frequently not adequately taken into account. They may be useful for the advice and care of individual patients as well as for decision processes concerning the health care system.

PMID: 18299856 [PubMed - indexed for MEDLINE]

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Related ArticlesThe prevalence of psoriatic arthritis in psoriatic patients in Tehran, Iran.

Arch Iran Med. 2008 Mar;11(2):162-5

Authors: Jamshidi F, Bouzari N, Seirafi H, Farnaghi F, Firooz A

BACKGROUND: Psoriatic arthritis is an inflammatory arthritis which is associated with psoriasis. There is no general agreement in the literature regarding the epidemiology of psoriatic arthritis. In this study, we evaluated the prevalence of psoriatic arthritis in a relatively large number of psoriatic patients. METHODS: Three hundred and twenty patients with psoriasis were evaluated in a cross-sectional study. The psoriasis area and severity index, family history, demographic variables, and some other factors (e.g., clinical type and location of the disease) were assessed. The patients were examined for signs of arthropathy and the suspects were referred to a rheumatologist for further evaluation and confirmation of the diagnosis. RESULTS: Psoriatic arthritis was observed in 29 (9.1%) patients. The prevalence of Psoriatic arthritis in men (10.1%) was not statistically different from that of women (7.8%). The most common type of psoriasis in all patients, with and without psoriatic arthritis, was chronic plaque psoriasis. The mean+/-SD psoriasis area and severity index was significantly (P

PMID: 18298293 [PubMed - indexed for MEDLINE]

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Related ArticlesAdalimumab for the treatment of severe psoriasis and psoriatic arthritis.

Expert Opin Biol Ther. 2008 Mar;8(3):363-70

Authors: Papoutsaki M, Costanzo A, Chimenti MS, Chimenti S

BACKGROUND: Psoriasis is a chronic, genetically determined, immunomediated, inflammatory skin disease affecting approximately 2 - 3% of the Caucasian population. Systemic treatment is required in moderate to severe plaque-type psoriasis forms or psoriatic arthritis. However, cumulative organ toxicity, lack of efficacy over time and other underlying diseases may limit long-term use of conventional treatments. OBJECTIVES: TNF-alpha, serves a key role in potentiating inflammatory responses associated with both psoriasis and psoriatic arthritis. Adalimumab is a fully human anti-TNF-alpha monoclonal antibody; approved for the treatment of psoriatic arthritis and, more recently, for plaque-type psoriasis. Methods: This review reports the latest progresses made in the clinical use of ‘biologic’ drugs for psoriasis focusing on the clinical management of adalimumab in the treatment of plaque psoriasis and psoriatic arthritis. RESULTS: Adalimumab was shown to be effective in treating both psoriasis and psoriatic arthritis with a rapid onset of action and a good safety profile.

PMID: 18294106 [PubMed - indexed for MEDLINE]

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