Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
21744755 Quadriplegia due to pachymeningitis, vasculitis and sepsis in a patient with rheumatoid ar 2011 May We report the case of a 84-year-old man, with history of rheumatoid arthritis, admitted the Hospital for a fall and complaining of dysaesthesia and pain located to the cervical spine and arms. Within a few hours after admission, fever and acute, progressive, ascendant quadriplegia became evident. Magnetic resonance imaging (MRI) of cervical spine showed spinal canal stenosis between C4-C6 with spinal cord compression. Hemocultures resulted positive for Staphylococcus aureus. The clinical picture rapidly evolved to sepsis with a fatal multi-organ failure. An autopsy found a osteosclerosis narrowing the neurocanal at the level of C3-C6, and recent cervical medulla infarction. A histological exam revealed the presence of a suppurative pachymeningitis with local phenomenas of periradiculitis, vasculitis and thrombosis of the anterior medullar artery, associated with coagulative necrosis of the neural tissue.
22532632 Adiponectin isoforms: a potential therapeutic target in rheumatoid arthritis? 2012 Oct OBJECTIVES: Several clinical studies have suggested the adipocytokine adiponectin is involved in the progression of rheumatoid arthritis (RA). From this point of view, adiponectin might present a new therapeutic target. However, as adiponectin also exerts beneficial effects in the human organism, a strategy that would allow its detrimental effects to be abolished while maintaining the positive effects would be highly favourable. To elucidate such a strategy, the authors analysed whether the different adiponectin isoforms induce diverging effects, especially with regard to rheumatoid arthritis synovial fibroblasts (RASF), a central cell type in RA pathogenesis capable of invading into and destroying cartilage. METHODS: Affymetrix microarrays were used to screen for changes in gene expression of RASF. Messenger RNA levels were quantified by real-time PCR, protein levels by immunoassay. The migration of RASF and primary human lymphocytes was analysed using a two-chamber migration assay. RESULTS: In RASF, the individual adiponectin isoforms induced numerous genes/proteins relevant in RA pathogenesis to clearly different extents. In general, the most potent isoforms were the high molecular weight/middle molecular weight isoforms and the globular isoform, while the least potent isoform was the adiponectin trimer. The chemokines secreted by RASF upon adiponectin stimulation resulted in an increased migration of RASF and lymphocytes. CONCLUSION: The results clearly suggest a pro-inflammatory and joint-destructive role of all adiponectin isoforms in RA pathophysiology, indicating that in chronic inflammatory joint diseases the detrimental effects outweigh the beneficial effects of adiponectin.
22760475 Association between tumor necrosis factor-α (TNF-α) promoter -308 G/A and response to TN 2013 May OBJECTIVES: Tumor necrosis factor (TNF)-α promoter -308G/A polymorphism has been shown to be associated with high TNF-α production and poor response to anti-TNF-α treatment. However, not all patients show a good response to TNF-α antagonists, so this association remains controversial. This study was designed to investigate whether TNF-α promoter -308 G/A polymorphism is associated with responsiveness to anti-TNF therapy in rheumatoid arthritis (RA) patients. The 28-joint count Disease Activity Score (DAS) 28 or the American College of Rheumatology (ACR) improvement criteria 20 were used to measure patient response. METHODS: A meta-analysis was performed. Pooled ORs and 95 % CIs were calculated by both dominant and recessive genetic models. RESULTS: Fifteen studies with a total of 2127 patients were included in this meta-analysis. The results showed that patients with the G allele responded better to the treatment (OR = 1.87, 95 % CI 1.26-2.79). A subanalysis showed similar results. CONCLUSIONS: Based on the results of this meta-analysis, RA patients with the TNF-α promoter -308 G allele respond better to TNF-α antagonist treatment, suggesting that this allele plays a major role in anti-TNF-alpha treatment response.
21936614 Differences in activity limitation, pain intensity, and global health in patients with rhe 2011 Nov OBJECTIVE: In this study we compared activity limitations, pain intensity, and global health in patients with rheumatoid arthritis (RA) in Sweden and the USA and aimed to determine whether nationality is associated with these outcomes. METHODS: We used longitudinal data from the 'Swedish TIRA project' (n = 149) and the University of California, San Francisco (UCSF) RA panel study (n = 85). Data were collected annually concerning use of medications [disease-modifying anti-rheumatic drugs (DMARDs), biologics, and corticosteroids], morning stiffness, number of swollen joints, and number of painful joints. Three self-reported outcome measures were examined: pain intensity measured on a 0-100 visual analogue scale (VAS), activity limitation according to the Health Assessment Questionnaire (HAQ), and global health. To analyse the data, the Student's t-test, the χ(2)-test, and the generalized estimating equation (GEE) method were used. RESULTS: Nationality was significantly related to HAQ score and pain intensity, even after adjustment for covariates. The patients in the TIRA cohort reported a lower HAQ score and a higher pain intensity than the patients in the UCSF cohort. Nationality was not related to global health. CONCLUSION: Patients with RA should be assessed with awareness of the psychosocial and cultural context because disability seems to be affected by nationality. Further knowledge to clarify how a multinational setting affects disability could improve the translation of interventions for patients with RA across nationalities.
21484221 Microvascular function is preserved in newly diagnosed rheumatoid arthritis and low system 2011 Aug Rheumatoid arthritis (RA) is associated with increased cardiovascular morbidity and mortality. Microvascular function has been linked to several risk factors for cardiovascular disease and may be affected in RA. It is, however, presently unknown at what point in the disease course the abnormalities in microvascular function occur. We determined whether microvascular function is already disturbed in early disease-modifying antirheumatic drugs (DMARD)-naive RA patients with low systemic inflammation. Fifteen consecutive RA patients with a median symptom duration of 5 months, a C-reactive protein level of ≤20 mg/l and without a history of cardiovascular disease, and age 15 and sex-matched healthy controls were recruited. Endothelium-dependent and endothelium-independent vasodilatation in skin was evaluated with laser Doppler fluxmetry after iontophoresis of acetylcholine and sodium nitroprusside, respectively. Videomicroscopy was used to measure recruitment of skin capillaries after arterial occlusion. CRP and ESR levels were mildly, but significantly elevated in patients compared to controls. No differences in both endothelium-dependent vasodilatation and capillary recruitment were observed between groups [709% (95% CI, 457-961%) vs 797% (95% CI, 556-1,037%), P = 0.59 and 37% (95% CI, 26-47%) vs 41% (95% CI, 31-50%), P=0.59, respectively]. Skin microvascular function is preserved in early, DMARD-naive RA patients with moderately active RA but low systemic inflammatory activity. Both the extent of the systemic inflammation and disease duration, therefore, may be important determinants of microvascular dysfunction and subsequent increased risk for cardiovascular disease.
21295983 Foot and ankle joint kinematics in rheumatoid arthritis cannot only be explained by altera 2011 Mar Rheumatoid arthritis (RA) manifests itself in the foot and ankle of RA patients. The foot and ankle joint kinematics of these patients differ from that of healthy subjects. However, the factors that lead to these differences are not yet fully understood. The aim of this study was to analyse the effect of walking speed and the disease process on foot and ankle joint kinematics of RA subjects. Gait recordings of 23 RA and 14 age-matched healthy subjects were performed and their foot and ankle joint kinematics were analysed during the stance phase of the gait cycle. Stance phase characteristics of the group of RA subjects and of the group of healthy subjects were compared. The healthy subjects walked at 100% (Vc), 75% (V75) and 50% (V50) of their comfortable walking speed. In a multi-level linear model significant differences between the two groups due to the factors walking speed and the disease process were analysed. The ankle dorsi-flexion, medial arch and hallux abduction motion at single-stance and toe-off were only influenced by the walking speed. The hallux maximum flexion at toe-off and the midfoot supination at single-stance were influenced by both the walking speed and the disease process. The hindfoot eversion motion at single-stance was only influenced by the disease process. In conclusion, the reduction of walking speed of RA subjects compared to healthy subjects does not explain all of the observed foot and ankle kinematics differences.
21295822 Treatment of early rheumatoid arthritis: concepts in management. 2011 Apr OBJECTIVES: The early diagnosis and treatment of rheumatoid arthritis (RA) are important goals for rheumatologists. This article provides a review of the literature describing evolving concepts in the treatment of early RA, studies that evaluate treatment strategies using a predefined target, and methods to identify patients who are at higher risk for progressive joint damage. METHODS: We conducted a PubMed search for randomized trials using the terms "early rheumatoid arthritis" and subsequently "tight control" to compare the outcomes of studies using early intervention with biologics and disease-modifying antirheumatic drugs (DMARDs) in early RA and also to compare outcomes of strategies of treatment using a predefined target. RESULTS: The study designs and outcomes of clinical trials of DMARDs and biologic agents in early RA are presented. Early, prompt therapy with combination DMARDs or biologics combined with methotrexate leads to improved outcomes for patients with early RA. In studies where treatment was targeted to a specific outcome, such as remission, the target was achieved more often with targeted treatment than when patients received routine care. Patients who are more likely to experience a rapid disease course that is associated with joint destruction can be identified based on clinical and laboratory variables shown to be predictors of rapid progression. CONCLUSIONS: Early assessment and close monitoring of patients with early RA, targeting remission where possible, are important to optimize long-term outcomes. Specific treatment can be selected from among the many proven therapies to obtain the best results for the individual patient.
22308630 Methotrexate and post operative complications in patients with rheumatoid arthritis underg 2011 Dec In the 1990's there were concerns that methotrexate might increase the risk of post operative complications following elective orthopaedic surgery; as a result many Units initiated policies to discontinue methotrexate prior to elective orthopaedic surgery. In 2001 we carried out a controlled study of complications after elective surgery in rheumatoid arthritis (RA) patients who either continued or discontinued methotrexate prior to surgery. In this study we showed that continuation of methotrexate therapy prior to orthopaedic surgery did not increase the risk of infection or surgical complication occurring in patients with RA within one year of surgery. The limitation of this study was that complications later than one year were not studied. Sixty-five patients have been followed up. Thirty-one were fully assessed in clinic and 34 underwent a structured telephone interview. There were no incidences of deep bone infection in any patient group so that there is no evidence that continued methotrexate therapy in the perioperative period increases the risk of late deep infections. We adhere to our original advice that in the absence of renal failure or sepsis, methotrexate therapy should not be stopped before elective orthopaedic surgery in patients with RA whose disease is controlled by the drug before surgery.
21981268 Lack of association of IL6R rs2228145 and IL6ST/gp130 rs2228044 gene polymorphisms with ca 2011 Dec Interleukin-6 (IL-6) is a key mediator of inflammation in rheumatoid arthritis (RA) and its actions may be controlled by the IL-6 receptor (IL-6R). IL-6 transducer (IL-6ST/ gp130) is the signal transducing subunit of the IL-6R. We assessed the influence of the IL6R and the IL6ST/gp130 genes in the risk of cardiovascular (CV) disease in RA. For this purpose, 1250 Spanish patients with RA were genotyped for the IL6R rs2228145 and IL6ST/gp130 rs2228044 functional gene polymorphisms. Patients were stratified according to the presence or absence of CV events. Also, a subgroup of patients without CV events was assessed for the presence of subclinical atherosclerosis using two surrogate markers of atherosclerosis (flow-mediated endothelium-dependent vasodilatation and carotid intima-media thickness). No significant differences in the genotype and allele frequencies for both gene polymorphisms between patients with and without CV events were observed. It was also the case when values of surrogate markers of atherosclerosis were compared according to IL6R and IL6ST genotype frequencies. In conclusion, our results do not confirm an association of IL6R rs2228145 and IL6ST/gp130 rs2228044 polymorphisms with CV disease in RA.
20671021 Changes in disease characteristics and response rates among patients in the United Kingdom 2011 Jan OBJECTIVES: Anti-TNF therapy has significantly improved outcomes for patients with severe RA. In the UK, changing financial restrictions and increasing experience with their use may have resulted in changes to the way physicians use anti-TNF therapies. The aim of this analysis was to examine changes in disease characteristics and response rates among patients starting anti-TNF therapy for RA over an 8-year period. METHODS: A total of 11 216 RA patients registered between 2001 and 2008 with the British Society for Rheumatology Biologics Register were included and stratified according to year of first anti-TNF prescription. Baseline characteristics and treatment response were compared year on year using logistic and linear regression models. RESULTS: Mean RA disease activity and severity of new anti-TNF-treated patients decreased between 2001 and 2008. The mean disease duration remained high (11 years in 2008) although the proportion of patients having disease duration<5 years increased significantly (2001: 9%; 2008: 29%; P<0.001). The majority of patients had failed three DMARDs on average before the first anti-TNF prescription. There was an increase in both the proportion of EULAR good responders at 1 year (2001: 18%; 2008: 30%; P<0.001) and in the number of patients achieving remission (2001: 8%; 2008: 17%; P<0.001). Drug survival remained relatively stable over the study years. CONCLUSIONS: There is a significant trend towards earlier use of anti-TNF therapies in patients with less severe disease, although the mean disease duration at first treatment remains high. This has correlated with improvements in outcome. These results support the earlier use of anti-TNF therapies in RA.
23087182 MiR-20a regulates ASK1 expression and TLR4-dependent cytokine release in rheumatoid fibrob 2013 Jun OBJECTIVE: To evaluate whether miR-20a belonging to the cluster miR-17-92 is a negative regulator of inflammation in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) by modulating expression of apoptosis signal-regulating kinase (ASK) 1, a key component of the toll-like receptors 4 pathway, upstream of p38 mitogen-activated protein kinase. METHODS: Evaluation of miR-20a and ASK1 mRNA was performed by RT-qPCR. ASK1 protein expression was assessed by western blotting. Overexpression of miR-20a was performed by transfection of RA FLS and THP-1 cells with miR-20a mimics. Interleukin (IL)-6, CXCL-10, IL-1β and TNF-α release were measured by ELISA. The role of miR-20a in vivo was assessed by IL-6 release from macrophages obtained from mice injected intraperitoneally with vectorised miR-20a mimics. RESULTS: We showed that stimulation of RA FLS with lipopolysacharide (LPS) and bacterial lipoproteins (BLP) induces a drop in expression of miR-20a and that this decrease is associated with an upregulation of ASK1 expression. Using transfection of Ask1 3'UTR reporters, we demonstrate that Ask1 is a direct target of miR-20a. Overexpression of miR-20a led to a global decrease in ASK1 protein in BLP- and LPS-activated cells indicating that miR-20a regulates the expression of ASK1 at the translational level. Transfection of miR-20a mimics decreases IL-6 and CXCL10 release by RA FLS and IL-1β and TNF-α by activated THP-1 cells but only in response to LPS. Last, injection of vectorised miR-20a mimics to mice led to a global decrease in ASK1 protein expression and IL-6 secretion in LPS-activated macrophages. CONCLUSIONS: Our data point toward an important role for miR-20a in the regulation of pro-inflammatory cytokines release, by controlling ASK1 expression in RA FLS.
21990370 Periarticular osteoporosis: a useful feature in the diagnosis of early rheumatoid arthriti 2011 Dec OBJECTIVES: To identify regions of interest (ROIs) relevant to periarticular osteoporosis in RA with low precision error and sufficient inter-rater reliability and to test diagnostic validity for RA. METHODS: Periarticular BMD was measured using dual-energy X-ray absorptiometry (DXA). Five ROIs were defined around MCP and/or PIP joints II-V, II-IV and mid-metacarpal to mid-phalangeal. They were evaluated for precision using the root mean square coefficient of variation (RMS-CV) and the intra-class correlation coefficient (ICC) for inter-reader reliability. To test validity, established RA patients (n = 25) and early arthritis patients (n = 25) were compared with healthy controls (n  = 37) matched on sex, age and menopausal status using paired t-tests, ROC curves and scatterplots. RESULTS: The RMS-CV was 0.45-1.07%. The ICC was 0.99. Mean BMDs of the five ROIs ranged from 0.321 to 0.372 g/cm(2) in established RA, from 0.321 to 0.382 g/cm(2) in early arthritis and from 0.342 to 0.401 g/cm(2) in healthy controls. Mean differences ranged from 0.012 to 0.032 g/cm(2) for established RA and from 0.023 to 0.033 g/cm(2) for early arthritis patients compared with matched controls, with P < 0.05 for ROIs 1-5 in early arthritis and the whole hand in established RA. ROC curves indicated low discriminative power, with an area under the curve (AUC) of 0.61-0.64, and scatterplots showed great overlap between BMD values of patients and controls. CONCLUSIONS: Periarticular BMD measured with DXA seems not to be a useful diagnostic feature due to strong overlap of BMD values between healthy controls, established RA patients and early arthritis patients.
22045835 Effectiveness of statins on total cholesterol and cardiovascular disease and all-cause mor 2012 Jan OBJECTIVE: There is increasing prevalence of hypercholesterolemia among patients with osteoarthritis (OA) and rheumatoid arthritis (RA). We examined the effectiveness of statins on total cholesterol (TC), cardiovascular (CV) morbidity, and mortality in patients with OA or RA. METHODS: A population-based cohort study was done using a record-linkage database in Tayside, Scotland. In total, 2024 OA or RA patients who had at least 2 separate TC measurements between 1993 and 2007 were studied. They were categorized into statin-exposed and statin-unexposed groups according to statin use status during followup. The main outcomes were TC concentration change from baseline, CV events, and all-cause mortality during the followup. Multivariate Cox regression models with a time-dependent variable for statins were employed to assess the risk of outcomes. RESULTS: Statin-associated TC concentrations in OA decreased by 15% in patients without CV disease (primary prevention, n = 1269) and 7% in patients with CV disease (secondary prevention, n = 247) from baseline of 5.30 mmol/l and 4.54 mmol/l, respectively. Correspondingly, in RA TC was reduced by 16% (n = 430) and 15% (n = 78) with baselines of 5.54 mmol/l and 4.95 mmol/l. In primary prevention, statins were associated with reduced CV events and all-cause mortality in RA patients [adjusted HR 0.45 (95% CI 0.20-0.98) and 0.43 (95% CI 0.20-0.92), respectively] and all-cause mortality in OA patients [adjusted HR 0.43 (95% CI 0.25-0.72)]. Statins were not associated with reduced risk of CV events or all-cause mortality in the secondary prevention of RA or OA patients [adjusted HR 0.68 (95% CI 0.30-1.54) and 0.52 (95% CI 0.20-1.34) for OA patients, and HR 0.58 (95% CI 0.07-4.79) and 0.79 (95% CI 0.18-3.53) for RA patients]. CONCLUSION: Statins reduced TC concentrations between 7% and 16% in patients with OA or RA. Statins were associated with reduced CV events and mortality in RA and mortality in OA in primary prevention.
23211585 Great artists with rheumatoid arthritis. What did their disease and coping teach? Part II. 2012 Dec Raoul Dufy (1877-1953) and Niki de Saint Phalle (1930-2002) were 2 famous artists who suffered from rheumatoid arthritis (RA). Both artists represent an additional outstanding example of successful coping with RA in former times when, for the first time, corticosteroids were available, but nevertheless treatment was very limited in the pre-biological era. Dufy was one of the earliest patients with RA who received corticosteroids and regained his creativity to paint for a few additional years, but finally he died of massive intestinal hemorrhages, the adverse event of the combination of corticosteroid plus aspirin. Niki de Saint Phalle, a self-taught French painter and sculptor, was one of the most significant and unconventional female artists of the 20th century. Her eventful life was full of emotional burdens and lifelong lung disease in addition to RA. Niki de Saint Phalle came out from each physical and emotional crisis with new forces and new artistic ideas. Interestingly, it has been suggested that the occupational exposure to colors contributed to the development of RA in artists, which used significantly more bright and clear colors based on toxic heavy metals such as Renoir and Dufy. Moreover, these 2 were cigarette smokers, a recently described risk factor for developing RA and increasing the severity once it does develop. Niki de Saint Phalle produced her sculptures made of plastic material without protection while she assumed that exposition to polyester and toxic fumes of polystyrene caused severe damage to her lungs, resulting in recurrent health problems.
22885430 Use of infliximab in a patient with rheumatoid arthritis and chronic hepatitis B. 2012 Aug Anti-TNF-α agents have emerged as a potent treatment for patients with rheumatoid arthritis unresponsive to conventional disease-modifying antirheumatic drugs. Increased susceptibility to infections induced by these drugs is the main complication of their use. Reactivation of hepatitis B virus (HBV) is one of the most worrisome side effects in patients with HBV infection receiving anti-TNF-α. We report the case of a 56-year-old male patient with stable hepatitis B and good response to the antiviral combination of lamivudine and tenofovir when infliximab was started. The patient went into remission. During the 30-month treatment with the biologic, his liver function remained stable, with no HBV reactivation.
22854174 Usage problems and social barriers faced by persons with a wheelchair and other aids. Qual 2013 Jan OBJECTIVE: The objective of this study was to identify the usage and accessibility problems faced by the disabled (whether in pain or not) users of assistive devices (conventional wheelchairs), identify physical barriers that limit their mobility, and recognize the socio-cultural practices excluding them from the design process of such devices. Another main purpose of this paper is to improve the ergonomic criteria that influence the design and manufacture of assistive devices. STUDY POPULATION: 15 patients with any of the following diagnoses: ankylosing spondylitis, rheumatoid arthritis, or amputees using wheelchairs in Mexico and Colombia. DESIGN: Qualitative study. Thematic analysis with a theoretical industrial design approach to employing usability testing for ergonomic analysis. RESULTS: We identified 6 issues associated with usability problems from the patient's standpoint: barriers for use of wheelchairs (usability and acceptability), creative adaptations, potential use of technical devices, independence, body perception and assistive devices, and architectural barriers. The ergonomic and usability requirements and the resulting level of independence vary across wheelchair users with chronic pain and those whose disability does not involve pain. The latter are more independent in their movements and decisions. CONCLUSIONS: User input is essential in the design of assistive devices. The proposal of "design from and for the user" must rely on both engineering and medical perspective on the ergonomy as well as the user interpretation of the environment and the experience of the disease. Thus we can arrive at a "user-centered design".
22449398 Mining functional gene modules linked with rheumatoid arthritis using a SNP-SNP network. 2012 Feb The identification of functional gene modules that are derived from integration of information from different types of networks is a powerful strategy for interpreting the etiology of complex diseases such as rheumatoid arthritis (RA). Genetic variants are known to increase the risk of developing RA. Here, a novel method, the construction of a genetic network, was used to mine functional gene modules linked with RA. A polymorphism interaction analysis (PIA) algorithm was used to obtain cooperating single nucleotide polymorphisms (SNPs) that contribute to RA disease. The acquired SNP pairs were used to construct a SNP-SNP network. Sub-networks defined by hub SNPs were then extracted and turned into gene modules by mapping SNPs to genes using dbSNP database. We performed Gene Ontology (GO) analysis on each gene module, and some GO terms enriched in the gene modules can be used to investigate clustered gene function for better understanding RA pathogenesis. This method was applied to the Genetic Analysis Workshop 15 (GAW 15) RA dataset. The results show that genes involved in functional gene modules, such as CD160 (rs744877) and RUNX1 (rs2051179), are especially relevant to RA, which is supported by previous reports. Furthermore, the 43 SNPs involved in the identified gene modules were found to be the best classifiers when used as variables for sample classification.
22736093 How early in the course of rheumatoid arthritis does the excess cardiovascular risk appear 2012 Oct Rheumatoid arthritis (RA) is a chronic inflammatory disease which is associated with an increased cardiovascular (CV) burden. Whether the risk is already present at the time of RA diagnosis remains a key area of debate. The aim of this review was to evaluate the existence of both subclinical CV changes, including endothelial dysfunction and atherosclerosis, CV risk factors, as well as CV disease manifestations such as coronary heart disease, myocardial infarction, congestive heart failure and CV death prior to RA diagnosis and during the first few years of the disease. The state of the endothelial function remains controversial in patients with newly diagnosed RA. Studies with impaired brachial artery vasodilatory responses at baseline showed a reversal of the dysfunction after 6-12 months of anti-inflammatory therapy. Morphological evidence of arterial wall atherosclerosis, measured by carotid artery intima-media thickness or the prevalence of carotid plaques, was already present during the first year following RA diagnosis. The risk of coronary heart disease and myocardial infarction is increased even prior to and, at the latest, within 1 year of the clinical onset of RA. The prevalence of hypertension was similar among patients with RA and controls. CV mortality may not increase within the first years of RA diagnosis. In conclusion, the CV risk seems to increase sooner after the RA diagnosis than previously thought. In addition to systematic CV risk assessment, patients with early RA might benefit from being targeted with stricter than conventional CV risk prevention and intervention.
22741935 Management of neutrophilic dermatoses. 2012 Mar Neutrophilic dermatoses, including Sweet's syndrome, pyoderma gangrenosum, and rheumatoid neutrophilic dermatitis, are inflammatory conditions of the skin often associated with underlying systemic disease. These are characterized by the accumulation of neutrophils in the skin. The associated conditions, potential for systemic neutrophilic infiltration, and therapeutic management of these disorders can be similar. Sweet's syndrome can often be effectively treated with a brief course of systemic corticosteroids. Pyoderma gangrenosum, however, can be recurrent, and early initiation of a steroid-sparing agent is prudent. Second-line treatment for both of these conditions includes medications affecting neutrophil function, in addition to immunosuppressant medications.
21906522 [Establishment of a rat model of rheumatoid arthritis with kidney deficiency syndrome]. 2011 Sep OBJECTIVE: To establish a rat model of rheumatoid arthritis (RA) with kidney deficiency syndrome. METHODS: A total of 110 six-week-old specific pathogen-free male and female Sprague-Dawley rats were randomly divided into normal control group, sham-operated group, collagen-induced arthritis (CIA) control group, castration plus CIA group and hydroxyurea plus CIA group. Testiculus or ovary of rats in the castration plus CIA group was cut off, respectively. Rats in the hydroxyurea plus CIA group were given 375 mg/(kg·d) hydroxyurea by gavage administration for 17 d. Then rats in the CIA control group, castration plus CIA group and hydroxyurea plus CIA group were subcutaneously injected with mixture of type II collagen and incomplete Freund's adjuvant to induce rheumatoid arthritis. General state, arthritis index and joint swelling of the rats were observed to evaluate the onset of CIA. Contents of anti-type II collagen antibody, interleukin-6 (IL-6), IL-10, interferon-γ (IFN-γ) and corticosterone (CORT) in plasma were detected by enzyme-linked immunosorbent assay, and adrenal cyclic adenylic acid (cAMP) and cyclic guanylic acid (cGMP) levels were detected by radioimmunoassay. RESULTS: Compared with the CIA control group, the degrees of joint swelling and joint damage were significantly increased in the kidney-deficiency CIA rats (castration plus CIA group and hydroxyurea plus CIA group), with kidney deficiency syndrome similar to human clinical symptoms, such as depressed, bowed back, dullness, reduced diet and perianal contamination; the rats in those two groups were noted with a significantly decreased ratio of cAMP/cGMP; the content of CORT was increased in male rats while decreased in female rats, with an obvious increase in the content of anti-type II collagen antibody; the contents of IFN-γ, IL-6 and IL-10 were obviously increased in the castration plus CIA group. CONCLUSION: The rat model of RA with kidney deficiency syndrome has both obvious kidney deficiency syndrome and characteristics of RA and can reflect part of the patient's characteristics. However, castration is more suitable for inducing RA with kidney deficiency syndrome in rats.