Literature on Psoriatic Arthritis

Related ArticlesOnset or exacerbation of cutaneous psoriasis during TNFalpha antagonist therapy.

Joint Bone Spine. 2008 May;75(3):315-8

Authors: Wendling D, Balblanc JC, Briançon D, Brousse A, Lohse A, Deprez P, Humbert P, Aubin F

The widespread use of TNFalpha antagonists in recent years has led to the recognition of paradoxical adverse effects, defined as the onset or exacerbation of disorders that are usually improved by TNFalpha antagonists. Cutaneous psoriasis is an example, of which several cases have been reported. OBJECTIVE: To identify cases of psoriasis onset or exacerbation during TNFalpha antagonist therapy and to look for potential predictive factors. METHODS: We retrospectively reviewed cases of psoriasis onset or exacerbation during TNFalpha antagonist therapy. For each case we recorded the following data: age, sex, underlying disease, nature of the TNFalpha antagonist, effectiveness in improving the underlying disease, history of psoriasis in the patient or family, time to psoriasis development, type of psoriasis (confirmed by an experienced dermatologist), concomitant treatments, whether the TNFalpha antagonist was stopped or continued, and the outcome of the psoriasis. These data were compared to those in the literature. RESULTS: We identified 12 patients, six men and six women, with a mean age of 45.5 years. The TNFalpha antagonist was adalimumab in four patients, etanercept in six patients, and infliximab in two patients. The underlying disease was ankylosing spondylitis in six cases, rheumatoid arthritis in four, and psoriatic arthritis in two. Mean time from treatment initiation to psoriasis was 4.1 months (range, 1-15 months). A previous history of psoriasis in the patient was noted in six cases, including four of the six patients taking etanercept. TNFalpha antagonist therapy was effective on the underlying disease in 11 of the 12 patients. The drug was discontinued in five patients, of whom four experienced resolution of their psoriasis. In the remaining seven patients, the drug was continued and the skin lesions remained unchanged. Most of the patients had psoriasis vulgaris (plaque psoriasis); palmoplantar pustulosis was a feature in five patients. DISCUSSION: Over 40 cases of psoriasis onset or exacerbation during TNFalpha antagonist therapy have been reported in the literature. The prevalence of this adverse effect has been estimated at 1.5-5% of patients taking TNFalpha antagonists. The findings from our case series are consistent with data in the literature. Psoriasis is a class effect that has been reported with all the currently available TNFalpha antagonists. The skin lesions develop within the first few months of therapy. Patients with a wide range of underlying diseases can be affected. Palmoplantar pustulosis is a common feature. A previous history of psoriasis seems more common in patients who experience psoriasis onset or exacerbation during etanercept therapy (four of six patients in our study and 55% in the literature); thus, previous psoriasis may be a risk factor for psoriasis exacerbation during etanercept therapy.

PMID: 18329935 [PubMed - indexed for MEDLINE]

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Related ArticlesDetailed analysis of contrast-enhanced MRI of hands and wrists in patients with psoriatic arthritis.

Skeletal Radiol. 2008 May;37(5):433-42

Authors: Tehranzadeh J, Ashikyan O, Anavim A, Shin J

OBJECTIVE: The objective was to perform detailed analysis of the involved soft tissues, tendons, joints, and bones in the hands and wrists of patients with psoriatic arthritis (PsA). MATERIALS AND METHODS: We reviewed 23 contrast-enhanced MR imaging studies (13 hands and 10 wrists) in 10 patients with the clinical diagnosis of PsA. We obtained clinical information from medical records and evaluated images for the presence of erosions, bone marrow edema, joint synovitis, tenosynovitis, carpal tunnel, and soft tissue involvement. Two board-certified musculoskeletal radiologists reviewed all images independently. Differences were resolved during a subsequent joint session. RESULTS: The average duration of disease was 71.3 months, ranging from 1 month to 25 years. Eight of the 10 wrists (80%) and 6 of the 13 hands demonstrated bone erosions. Bone marrow abnormalities were shown in 5 of the 10 wrists (50%) and 4 of the 14 hands (31%). Triangular fibrocartilage tears were seen in 6 of the 10 wrists (60%). Wrist and hand joint synovitis were present in all studies (67 wrist joints and 101 hand joints). Wrist soft tissue involvement was detected in 9 of the 10 wrists (90%) and hand soft tissue involvement was present in 12 of the 13 wrists (92%). Findings adjacent to the region of soft tissue involvement included synovitis (4 wrists) and tenosynovitis (3 wrists). Bone marrow edema adjacent to the region of soft tissue involvement was seen in one wrist. Bulge of the flexor retinaculum was seen in 4 of the 10 wrists (40%) and median nerve enhancement was seen in 8 of the 10 wrists (80%). Tenosynovitis was seen in all studies (all 10 of the hands and all 13 of the wrists). The “rheumatoid” type of distribution of bony lesions was common in our study. Interobserver agreement for various findings ranged from 83% to 100%. CONCLUSION: Contrast-enhanced MRI unequivocally demonstrated bone marrow edema, erosions, tendon and soft-tissue disease, and median nerve involvement, with good interobserver reliability in patients with PsA of the hands and wrists. Disease was more extensive in the wrists than in the hands.

PMID: 18286282 [PubMed - indexed for MEDLINE]

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Related ArticlesNoncompetitive antagonism and inverse agonism as mechanism of action of nonpeptidergic antagonists at primate and rodent CXCR3 chemokine receptors.

J Pharmacol Exp Ther. 2008 May;325(2):544-55

Authors: Verzijl D, Storelli S, Scholten DJ, Bosch L, Reinhart TA, Streblow DN, Tensen CP, Fitzsimons CP, Zaman GJ, Pease JE, de Esch IJ, Smit MJ, Leurs R

The chemokine receptor CXCR3 is involved in various inflammatory diseases, such as rheumatoid arthritis, multiple sclerosis, psoriasis, and allograft rejection in transplantation patients. The CXCR3 ligands CXCL9, CXCL10, and CXCL11 are expressed at sites of inflammation, and they attract CXCR3-bearing lymphocytes, thus contributing to the inflammatory process. In this study, we characterize five nonpeptidergic compounds of different chemical classes that block the action of CXCL10 and CXCL11 at the human CXCR3, i.e., the 3H-pyrido[2,3-d]pyrimidin-4-one derivatives N-1R-[3-(4-ethoxy-phenyl)-4-oxo-3,4-dihydro-pyrido[2,3-d]pyrimidin-2-yl]-ethyl-N-pyridin-3-ylmethyl-2-(4-fluoro-3-trifluoromethyl-phenyl)-acetamide (VUF10472/NBI-74330) and N-1R-[3-(4-ethoxy-phenyl)-4-oxo-3,4-dihydro-pyrido[2,3-d]pyrimidin-2-yl]-ethyl-N-pyridin-3-ylmethyl-2-(4-trifluoromethoxy-phenyl)-acetamide (VUF10085/AMG-487), the 3H-quinazolin-4-one decanoic acid {1-[3-(4-cyano-phenyl)-4-oxo-3,4-dihydro-quinazolin-2-yl]-ethyl}-(2-dimethylamino-ethyl)-amide (VUF5834), the imidazolium compound 1,3-bis-[2-(3,4-dichloro-phenyl)-2-oxo-ethyl]-3H-imidazol-1-ium bromide (VUF10132), and the quaternary ammonium anilide N,N-dimethyl-N-[4-[[[2-(4-methylphenyl)-6,7-dihydro-5H-benzocyclohepten-8-yl]-carbonyl]amino]benzyl] tetrahydro-2H-pyran-4-aminium chloride (TAK-779). To understand the action of these CXCR3 antagonists in various animal models of disease, the compounds were also tested at rat and mouse CXCR3, as well as at CXCR3 from rhesus macaque, which was cloned and characterized for the first time in this study. Except for TAK-779, all compounds show slightly lower affinity for rodent CXCR3 than for primate CXCR3. In addition, we have characterized the molecular mechanism of action of the various antagonists at the human CXCR3 receptor. All tested compounds act as noncompetitive antagonists at CXCR3. Moreover, this noncompetitive behavior is accompanied by inverse agonistic properties of all five compounds as determined on an identified constitutively active mutant of CXCR3, CXCR3 N3.35A. It is interesting to note that all compounds except TAK-779 act as full inverse agonists at CXCR3 N3.35A. TAK-779 shows weak partial inverse agonism at CXCR3 N3.35A, and it probably has a different mode of interaction with CXCR3 than the other two classes of small-molecule inverse agonists.

PMID: 18270317 [PubMed - indexed for MEDLINE]

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