Browse

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

ID PMID Title PublicationDate abstract
23566317 Why is epigenetics important in understanding the pathogenesis of inflammatory musculoskel 2013 Apr 3 In its widest sense, the term epigenetics describes a range of mechanisms in genome function that do not solely result from the DNA sequence itself. These mechanisms comprise DNA and chromatin modifications and their associated systems, as well as the noncoding RNA machinery. The epigenetic apparatus is essential for controlling normal development and homeostasis, and also provides a means for the organism to integrate and react upon environmental cues. A multitude of functional studies as well as systematic genome-wide mapping of epigenetic marks and chromatin modifiers reveal the importance of epigenomic mechanisms in human pathologies, including inflammatory conditions and musculoskeletal disease such as rheumatoid arthritis. Collectively, these studies pave the way to identify possible novel therapeutic intervention points and to investigate the utility of drugs that interfere with epigenetic signalling not only in cancer, but possibly also in inflammatory and autoimmune diseases.
25039084 Neural control of the immune system. 2014 Jun Neural reflexes support homeostasis by modulating the function of organ systems. Recent advances in neuroscience and immunology have revealed that neural reflexes also regulate the immune system. Activation of the vagus nerve modulates leukocyte cytokine production and alleviates experimental shock and autoimmune disease, and recent data have suggested that vagus nerve stimulation can improve symptoms in human rheumatoid arthritis. These discoveries have generated an increased interest in bioelectronic medicine, i.e., therapeutic delivery of electrical impulses that activate nerves to regulate immune system function. Here, we discuss the physiology and potential therapeutic implications of neural immune control.
24707273 Certolizumab-induced uveitis: a case report and review of the literature. 2014 Jan We report the case of a 64-year-old woman with rheumatoid arthritis and bilateral visual deterioration. The patient had been treated with certolizumab, a new tumor necrosis factor alpha (TNFα) antagonist, and her findings were consistent with bilateral uveitis, suggestive of sarcoidosis. Here, we review the literature on TNFα antagonist-induced sarcoidosis and report the first case of uveitis induced by certolizumab. Awareness of the possibility of this unique complication is important for both rheumatologists and ophthalmologists who treat patients with this new agent.
24504969 High-purity neutrophil isolation from human peripheral blood and saliva for transcriptome 2014 The oral cavity is a source of readily available neutrophils and can be used as a model to better understand the role of neutrophils in chronic inflammatory diseases such as rheumatoid arthritis, bronchitis, periodontitis, and inflammatory bowel disease. In this chapter we describe reproducible methods to obtain highly purified neutrophil samples from blood and saliva in humans to enable cell analysis using whole-genome microarrays.
24697038 [Diabetes mellitus and periodontal disease]. 2013 Scientific studies confirm correlation between periodontitis and systemic diseases such as: arteriosclerosis, diabetes, heart diseases, stroke, diseases of the respiratory system, kidney diseases, osteoporosis, rheumatoid arthritis, premature birth and low birth weight. The interaction between periodontitis and diabetes mellitus is described, based on the literature.
25017470 Analytical method for lipoperoxidation relevant reactive aldehydes in human sera by high-p 2014 Nov 1 A validated, simple and sensitive HPLC method was developed for the simultaneous determination of lipoperoxidation relevant reactive aldehydes: glyoxal (GO), acrolein (ACR), malondialdehyde (MDA), and 4-hydroxy-2-nonenal (HNE) in human serum. The studied aldehydes were reacted with 2,2'-furil to form fluorescent difurylimidazole derivatives that were separated on a C18 column using gradient elution and fluorescence detection at excitation and emission wavelengths of 250 and 355nm, respectively. The method showed good linearity over the concentration ranges of 0.100-5.00, 0.200-10.0, 0.200-40.0, and 0.400-10.0nmol/mL for GO, ACR, HNE, and MDA, respectively, with detection limits ranging from 0.030 to 0.11nmol/mL. The percentage RSD of intraday and interday precision did not exceed 5.0 and 6.2%, respectively, and the accuracy (%found) ranged from 95.5 to 103%. The proposed method was applied for monitoring the four aldehydes in sera of healthy, diabetic, and rheumatic human subjects with simple pretreatment steps and without interference from endogenous components. By virtue of its high sensitivity and accuracy, our method enabled detection of differences between analytes concentrations in sera of human subjects under different clinical conditions.
24882804 IL-32γ induces chemotaxis of activated T cells via dendritic cell-derived CCL5. 2014 Jul 18 Interleukin (IL)-32 has been associated with a variety of inflammatory diseases including rheumatoid arthritis, vasculitis and Crohn's disease. We have previously reported that IL-32γ, the IL-32 isoform with the highest biological activity, could act as an immune modulator through regulation of dendritic cell (DC) functions in immune responses. Cell locomotion is crucial for induction of an effective immune response. In this study, we investigated the effect and underlying mechanisms of IL-32γ on recruitment of T cells. IL-32γ upregulated the expression of several chemokines including CCL2, CCL4, and CCL5 in the DCs. In particular, IL-32γ significantly increased CCL5 expression in a dose-dependent manner. Treatment with JNK and NF-κB inhibitors suppressed IL-32γ-induced CCL5 expression in DCs, indicating that IL-32γ induced CCL5 production through the JNK and NF-κB pathways. Furthermore, supernatants from IL-32γ-treated DCs showed chemotactic activities controlling migration of activated CD4(+) and CD8(+) T cells, and these activities were suppressed by addition of neutralizing anti-CCL5 antibody. These results show that IL-32γ effectively promotes migration of activated T cells via CCL5 production in DCs. The chemotactic potential of IL-32γ may explain the pro-inflammatory effects of IL-32 and the pathologic role of IL-32 in immune disorders such as rheumatoid arthritis.
24705690 Reverse shoulder arthroplasty with a short metaphyseal humeral stem. 2014 Jun PURPOSE: Reverse shoulder prostheses have been gaining popularity in recent years. A short metaphyseal stem design will allow bone stock preservation and minimize stem related complications. We examined the clinical and radiographic short-term outcome of a short metaphyseal stem reverse shoulder arthroplasty. METHODS: Thirty-one patients, with a mean follow-up of 36 months (24-52), were evaluated clinically with the Constant-Murley score, patient satisfaction and pain relief scores. The fixation of the glenoid and humeral components, subsidence and notching were evaluated on radiographs. The indications were cuff tear arthropathy (22), fracture sequelae (five) and rheumatoid arthritis (four). RESULTS: The average Constant score improved from 12.7 (range two to 31) pre-operatively to 56.2 (range 17-86) postoperatively. It rose from 13.5 to 58.3 in patients with Cuff arthropathy, from 15.8 to 62.0 in revision arthroplasty, from 10.2 to 47.4 in those with fracture sequelae, and from 11.5 to 55.3 in patients with rheumatoid arthritis. The overall mean patient satisfaction score improved from 2.4/10 to 8.5/10 and mean pain score improved from 0.8/15 to 12.5/15. We found an overall improvement in active forward flexion from 46.8 to 128.5° and from 41.6 to 116.5° in abduction. No humeral loosening or subsidence was observed. Two cases of grade 1-2 glenoid notching were reported. Overall there were three intra-operative fractures that did not affect the operation and healed without affecting the good results. There were five late traumatic periprosthetic fractures, only one of them required a revision surgery to a stemmed implant and the rest healed without surgery. There were two early dislocations that had to be revised. CONCLUSIONS: The clinical and radiographic evaluation of a bone preserving metaphyseal humeral component in reverse shoulder arthroplasty is promising, with good clinical results, no signs of loosening or subsidence.
25258545 Adherence and resource use among patients treated with biologic drugs: findings from BEETL 2014 OBJECTIVES: Systemic administration of anti-tumor necrosis factor alpha (anti-TNF alpha) leads to an anti-inflammatory and joint protective effect in pathologies such as rheumatoid arthritis, psoriasis, and Crohn's disease. The aim of this study was to assess adherence to therapy, persistence in treatment (no switches or interruptions), and consumption of care resources (drugs, outpatient services, hospitalizations). METHODS: We conducted an observational retrospective cohort analysis using the administrative databases of five local health units. Patients filling at least one prescription for anti-TNF alpha between January 1, 2009 and December 31, 2011 were included and followed up for 1 year. Patients were defined as adherent if >80% of the follow-up period was covered by drugs dispensation. RESULTS: A total of 1,219 patients were analyzed (mean age 49.6±14.6, male 47%). Among enrolled patients, 36% were affected by rheumatoid arthritis, and 31% and 10% were affected by psoriasis and Crohn's disease, respectively; other indications remained below these percentages. Thirty-four percent of patients (420) were treated with adalimumab, 51% (615) with etanercept, and 15% (184) with infliximab. Among the 94% of patients who did not switch, those treated with infliximab had a higher rate of adherence across all indications (51% overall) when compared to that observed in patients treated with etanercept (27%) or adalimumab (23%). The mean annual nonpharmacological expenditure for each patient in analysis was €988 for adherent and €1,255 for nonadherent patients. Infliximab was associated with the lowest cost for all indications as determined by the multivariate generalized linear model. CONCLUSIONS: Patients treated with infliximab were associated with higher adherence and persistence in treatment and lower costs, as compared to those treated with adalimumab or etanercept.
24561021 Systemic diseases and biotherapies: understanding, evaluating, and preventing the risk of 2014 Dec Hepatitis B virus (HBV) reactivation can occur in chronic carriers of the HBV surface antigen (HBsAg) and constitutes a well-known complication of immunosuppressive therapy. HBV reactivation has also been reported after contact with the HBV. The increasing use of biological agents (TNFα antagonists, rituximab, abatacept, and tocilizumab) to treat systemic diseases has resulted in numerous publications about the risk of HBV reactivation. The relevant scientific societies have issued recommendations designed to prevent HBV reactivation. The main measures consist of screening for markers indicating chronic HBV infection (HBsAg) or HBV infection in the distant past (antibodies to the HBV core antigen) before initiating biological therapies, vaccinating marker-negative patients, and considering close follow-up or antiviral treatment before immunosuppressive treatment initiation or in the event of HBV reactivation. Here, we discuss the pathophysiological mechanisms underlying HBV reactivation during biological treatments, most notably in patients with occult HBV infection or markers for remote HBV infection, whose hepatocyte nuclei may contain a resistance form of HBV DNA known as covalently closed circular DNA (cccDNA). Assessment of the risk of reactivation relies on the HBV status, drugs used, and data from the literature. Finally, we discuss the various recommendations and modalities for HBV vaccination, preemptive treatment, and patient management, according to the level of risk and to the circumstances in which reactivation occurs.
24500264 Durable remission of pemphigus with a fixed-dose rituximab protocol. 2014 Jul IMPORTANCE: Rituximab induces B-lymphocyte apoptosis by targeting CD20 antigen and has shown efficacy in antibody-mediated autoimmune disease. Rituximab is increasingly being acknowledged as an effective and safe treatment option for pemphigus. OBJECTIVE: To assess the clinical response of patients with pemphigus to rituximab using a modified fixed-dose rheumatoid arthritis protocol (1 g intravenously on days 1 and 15, followed by 500 mg intravenously if clinically warranted at 6-month intervals or repeated full dosing). DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study was conducted using records from a tertiary referral center for autoimmune bullous disorders. Participants included 92 patients (pemphigus vulgaris, 84 [91%], and pemphigus foliaceus, 8 [9%]) who received rituximab treatment between May 1, 2006, and August 30, 2012. MAIN OUTCOMES AND MEASURES: The primary outcomes were time to relapse and achievement of a complete response with or without treatment at the end of the study. RESULTS: Median time to relapse after the first treatment cycle was 15 months (95% CI, 10.3-19.7). All patients experienced improvement. Complete remission rates with or without adjuvant treatment at final follow-up were 89% (56 patients [61%] were in complete remission without treatment and 26 patients [28%] were in complete remission during adjuvant treatment). No serious infectious adverse events occurred. CONCLUSIONS AND RELEVANCE: The fixed-dose, modified rheumatoid arthritis protocol for rituximab was efficacious and well tolerated in patients with pemphigus. Patients who do not achieve remission after 1 cycle or patients who experience relapse benefit from further cycles of rituximab. Our results need to be confirmed in larger and controlled trials.
23938103 "They just scraped off the calluses": a mixed methods exploration of foot care access and 2013 Aug 13 BACKGROUND: There is little indication that foot health services in Australia are meeting modern day recommendations for Rheumatoid Arthritis (RA) patients. The overall objective of this study was to explore the current state of foot health services for patients with RA with an emphasis on identifying barriers to the receipt of appropriate foot care in South-West Sydney, New South Wales, Australia. METHODS: A mixed (quantitative and qualitative) approach was adopted. Indications for appropriate access to foot care were determined by comparing the foot health, disease and socio-demographic characteristics of patients with unmet foot care demands, foot care users and patients with no demands for foot care. Perceptions of provision of, and access to, foot care were explored by conducting telephone-based interviews using an interpretative phenomenology approach with thematic analysis. RESULTS: Twenty-nine participants took part in the cross-sectional quantitative research study design, and 12 participants took part in the interpretative phenomenological approach (qualitative study). Foot care access appeared to be driven predominantly by the presence of rearfoot deformity, which was significantly worse amongst participants in the foot care user group (p = 0.02). Five main themes emerged from the qualitative data: 1) impact of disease-related foot symptoms, 2) footwear difficulties, 3) medical/rheumatology encounters, 4) foot and podiatry care access and experiences, and 5) financial hardship. CONCLUSIONS: Foot care provision does not appear to be driven by appropriate foot health characteristics such as foot pain or foot-related disability. There may be significant shortfalls in footwear and foot care access and provision in Greater Western Sydney. Several barriers to adequate foot care access and provision were identified and further efforts are required to improve access to and the quality of foot care for people who have RA. Integration of podiatry services within rheumatology centres could resolve unmet needs of people with RA by permitting rapid access to expert-led multidisciplinary foot care for people with RA.
23631580 Periodontitis and systemic diseases: a record of discussions of working group 4 of the Joi 2013 Apr BACKGROUND: There has been an explosion in research into possible associations between periodontitis and various systemic diseases and conditions. AIM: To review the evidence for associations between periodontitis and various systemic diseases and conditions, including chronic obstructive pulmonary disease (COPD), pneumonia, chronic kidney disease, rheumatoid arthritis, cognitive impairment, obesity, metabolic syndrome and cancer, and to document headline discussions of the state of each field. Periodontal associations with diabetes, cardiovascular disease and adverse pregnancy outcomes were not discussed by working group 4. RESULTS: Working group 4 recognized that the studies performed to date were largely cross-sectional or case-control with few prospective cohort studies and no randomized clinical trials. The best current evidence suggests that periodontitis is characterized by both infection and pro-inflammatory events, which variously manifest within the systemic diseases and disorders discussed. Diseases with at least minimal evidence of an association with periodontitis include COPD, pneumonia, chronic kidney disease, rheumatoid arthritis, cognitive impairment, obesity, metabolic syndrome and cancer. The working group agreed that there is insufficient evidence to date to infer causal relationships with the exception that organisms originating in the oral microbiome can cause lung infections. CONCLUSIONS: The group was unanimous in their opinion that the reported associations do not imply causality, and establishment of causality will require new studies that fulfil the Bradford Hill or equivalent criteria. Precise and community-agreed case definitions of periodontal disease states must be implemented systematically to enable consistent and clearer interpretations of studies of the relationship to systemic diseases. The members of the working group were unanimous in their opinion that to develop data that best inform clinicians, investigators and the public, studies should focus on robust disease outcomes and avoid surrogate endpoints. It was concluded that because of the relative immaturity of the body of evidence for each of the purported relationships, the field is wide open and the gaps in knowledge are large.
24669186 Genistein suppresses tumor necrosis factor α-induced inflammation via modulating reactive 2014 AIMS: Genistein, an isoflavone derivative found in soy, is known as a promising treatment for rheumatoid arthritis (RA). However, the detailed molecular mechanism of genistein in suppression of proinflammatory cytokine production remains ambiguous. The aim of this work was to evaluate the signal pathway by which genistein modulates inflammatory cytokine expression. MATERIALS AND METHODS: MH7A cells were stimulated with tumor necrosis factor (TNF)-α and incubated with genistein, and interleukin (IL)-1β, IL-6, and IL-8 production was measured by enzyme-linked immunosorbent assay. Nuclear translocation of nuclear factor (NF)-κB was measured by a confocal fluorescence microscopy. The intracellular accumulation of reactive oxygen species (ROS) was monitored using the fluorescent probe 5-6-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate. Signal-transduction protein expression was measured by Western blot. RESULTS: Genistein decreased the secretion of IL-1β, IL-6, and IL-8 from TNF-α-stimulated MH7A cells in a dose-dependent manner. Genistein prevented TNF-α-induced NF-κB translocation as well as phosphorylation of IκB kinase-α/β and IκBα, and also suppressed TNF-α-induced AMPK inhibition. The production of IL-1β, IL-6, and IL-8 induced by TNF-α was decreased by the phosphatidylinositol-3 kinase inhibitor LY294002, suggesting that inhibition of Akt activation might inhibit IL-1β, IL-6, and IL-8 production induced by TNF-α. In addition, we also found that pretreatment with the adenosine monophosphate-activated protein kinase (AMPK) agonist 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside obviously inhibited TNF-α-induced proinflammatory cytokine production. These observations suggest that the inhibitory effect of genistein on TNF-α-induced proinflammatory cytokine production is dependent on AMPK activation. CONCLUSION: These findings indicate that genistein suppressed TNF-α-induced inflammation by inhibiting the ROS/Akt/NF-κB pathway and promoting AMPK activation in MH7A cells.
25101341 Etanercept-induced cystic acne. 2014 Jul Tumor necrosis factor α antagonists are potent biologics used to treat a variety of autoimmune disorders such as rheumatoid arthritis, ankylosing spondylitis, Crohn disease, psoriasis, and psoriatic arthritis. These medications are known to have many side effects (eg, infusion reactions, cytopenia, risk for infection, heart failure); however, only a few cases of acne vulgaris have been associated with the use of these biologics, particularly infliximab and adalimumab. We report a rare case of etanercept-induced cystic acne.
23412245 Classifications of glenoid dysplasia, glenoid bone loss and glenoid loosening: a review of 2013 Apr So far, glenoid implantation still remains a challenge and is technically demanding even for an experienced shoulder surgeon. Each shoulder pathology has its own evolution. In primary glenohumeral osteoarthritis, glenoid involvement and proper morphology vary considerably. Erosion is more posterior and inferior. In rheumatoid arthritis, glenoid erosion is more medial with a very weak and soft bone. In eccentric arthritis, glenoid erosion is most of the time superior. Glenoid component loosening has been recognized as one of the common indications for revision surgery after total shoulder arthroplasty. Scapular notching is specific to the reverse shoulder arthroplasty. Moreover, there is concern about the high frequency of glenoid components that demonstrate radiographic periprosthetic lucencies. There is little information available to guide clinical decision making regarding glenoid surgery. Placement or replacement with a standard glenoid component is usually possible. In some instances, bone graft reconstruction or the use of augmented or custom components can be an option. The purpose of this study is to evaluate the main glenoid erosion classifications.
23201918 The role of Fc receptors and complement in autoimmunity. 2013 Apr Autoantibodies interact with the innate immune system, including the complement network and Fc receptors (FcRs) bearing effector cells, resulting in the induction of tissue injury. It was suggested that these two pro-inflammatory pathways might mediate distinct effector responses, and that only one or the other effector arm may usually dominate an inflammatory response. Recent studies, however, support the notion that autoantibody-induced tissue injury may depend on both, FcRs and selected pathways of the complement network. This review summarizes our current knowledge on the interactions between autoantibodies, FcRs and complement components as essential triggers of tissue injury in autoimmune diseases like rheumatoid arthritis, anti-glomerular basement membrane glomerulonephritis and subepidermal blistering diseases. Manipulation of these connective pathways might be of therapeutic use to control antibody-mediated autoimmune diseases.
25589459 A systematic review of post-surgical pyoderma gangrenosum: identification of risk factors 2015 Mar BACKGROUND: Post-surgical pyoderma gangrenosum (PSPG) presents as a rapidly expanding cutaneous ulcer at a site of surgery with potentially devastating consequences. We systematically reviewed the English and foreign language literature to identify risk factors for PSPG and propose a management strategy. METHODS: A systematic review was completed in PubMed, Medline, Embase, and Cochrane Database for all published reports of PSPG from January 1946 to June 2013. We manually examined bibliographies for relevant references and used Google Translate for articles in foreign languages, including Italian, Japanese, German, Dutch, Turkish, Spanish, Chinese, Dutch, Russian, Portuguese, and Czech. RESULTS: We identified 220 cases of PSPG (mean age 52.8 years, range 5-85 years). Thirty-seven patients (16.8%) had a history of pyoderma gangrenosum, nineteen (8.6%) had a hematologic disorder such as leukemia or lymphoma, thirteen (5.9%) had inflammatory bowel disease, and eight (3.6%) had rheumatoid arthritis. PSPG occurred most commonly after breast (25%), cardiothoracic (14%), abdominal (14%), and obstetric (13%) surgeries. The most common breast procedures were bilateral reduction mammoplasty (45%), breast reconstruction (25%), and lumpectomy or mastectomy (11%). Signs of wound complication occurred on average 7.0 days after surgery. Nineteen patients (8.6%) at risk for PSPG received perioperative corticosteroids during skin grafting or later surgeries with a favorable outcome. CONCLUSIONS: Patients with a history of pyoderma gangrenosum, rheumatoid arthritis, inflammatory bowel disease, or hematologic malignancy who are undergoing breast, cardiothoracic, or abdominal surgeries should be carefully observed for post-operative ulceration at incision sites. Debridement should not be performed before dermatologic consultation to assess for PSPG. Patients at risk of PSPG undergoing breast surgery may benefit from perioperative prednisone to prevent PSPG which can lead to destructive wound enlargement and significant scarring.
24038004 Acute exacerbation in rheumatoid arthritis-associated interstitial lung disease: a retrosp 2013 Sep 13 OBJECTIVES: To investigate the risk factors and prognosis associated with acute exacerbation (AE) in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). DESIGN: A retrospective case-control study. SETTING: A single academic hospital. PARTICIPANTS: 51 consecutive patients diagnosed with RA-ILD between 1995 and 2012. All patients fulfilled the diagnostic criteria of the American College of Rheumatology for RA. ILD was diagnosed on the basis of clinical presentation, pulmonary function tests, high-resolution CT (HRCT) findings and lung biopsy findings. MAIN OUTCOME MEASURES: Overall survival and cumulative AE incidence were analysed using Kaplan-Meier method. Cox hazards analysis was used to determine significant variables associated with AE occurrence and survival status. RESULTS: A total of 11 patients (22%) developed AE, with an overall 1-year incidence of 2.8%. Univariate analysis revealed that older age at ILD diagnosis (HR 1.11; 95% CI 1.02 to 1.21; p=0.01), usual interstitial pneumonia (UIP) pattern on HRCT (HR 1.95; 95% CI 1.07 to 3.63; p=0.03) and methotrexate usage (HR 3.04; 95% CI 1.62 to 6.02; p=0.001) were associated with AE. Of 11 patients who developed AE during observation period, 7 (64%) died of initial AE. In survival, AE was a prognostic factor for poor outcome (HR 2.47; 95% CI 1.39 to 4.56; p=0.003). CONCLUSIONS: In patients with RA-ILD, older age at ILD diagnosis, UIP pattern on HRCT and methotrexate usage are associated with the development of AE. Furthermore, AE has a serious impact on their survival.
23777809 Guidelines for the management of people with foot health problems related to rheumatoid ar 2013 Jun 18 BACKGROUND: In the last decade there has been a significant expansion in the body of knowledge on the effects of rheumatoid arthritis (RA) on the foot and the management of these problems. Aligned with this has been the development of specialist clinical roles for podiatrists. However, despite being recommended by national guidelines, specialist podiatrists are scarce. In order to inform non-specialist podiatrists of the appropriate interventions for these foot problems, management guidelines have been developed and disseminated by a group of specialist podiatrists. The aim of this survey was to investigate the use of these guidelines in clinical practice. METHOD: Following ethical approval an online questionnaire survey was carried out. The questions were formulated from a focus group and comprised fixed response and open response questions. The survey underwent cognitive testing with two podiatrists before being finalised. An inductive approach using thematic analysis was used with the qualitative data. RESULTS: 245 questionnaires were completed (128-non-specialist working in the private sector, 101 non-specialists working in the NHS and 16 specialist podiatrists). Overall, 97% of the non-specialists (n = 222) had not heard of the guidelines. The non-specialists identified other influences on their management of people with RA, such as their undergraduate training and professional body branch meetings. Three main themes emerged from the qualitative data: (i) the benefits of the foot health management guidelines, (ii) the barriers to the use of guidelines generally and (iii) the features of useable clinical guidelines. CONCLUSIONS: This study has revealed some crucial information about podiatrists' level of engagement with the foot health management guidelines and the use of guidelines in general. Specifically, the non-specialist podiatrists were less likely to use the foot health management guidelines than the specialist podiatrists. The positive aspects were that for the specialist practitioners, the guidelines helped them to identify their professional development needs and for the few non-specialists that did use them, they enabled appropriate referral to the rheumatology team for foot health management. The barriers to their use included a lack of understanding of the risk associated with managing people with RA and that guidelines can be too long and detailed for use in clinical practice. Suggestions are made for improving the implementation of foot health guidelines.