Rheumatology specialist care delivered at the Southern QLD Centre of Excellence in Aboriginal and Torres Strait Islander Primary Health Care.

BACKGROUND: There is limited literature on the prevalence of rheumatologic conditions in Australian First Nations people. Existing evidence suggests a high disease burden with poorer outcomes. In 2016 a rheumatology clinic was established at The Southern Queensland Centre of Excellence in Aboriginal and Torres Strait Islander Primary Health Care (CoE). AIMS: To improve knowledge of rheumatic diseases presentations in an urban First Nations cohort and to assess the effectiveness of the CoE clinic. METHODS: Data on attendance, diagnosis, treatment and demographics were obtained retrospectively from clinical records at the CoE from 2016 to 2020. Administrative attendance data for the largest public general rheumatology clinic in the region for the 4 years preceding the establishment of the CoE clinic were used as a historic cohort control. RESULTS: A cohort of 93 patients was seen at the CoE with 439 appointments compared to 207 in the historical control. Common diagnoses were osteoarthritis (24%), seropositive rheumatoid arthritis (17%), gout (13%) and spondyloarthropathies (10%). Forty per cent of the cohort at CoE were treated with at least one disease-modifying antirheumatic drug (DMARD) and 12% with a biologic or targeted synthetic DMARD. Seventy-five per cent of appointments were attended versus 71% in control group. Adjusted odds ratio of attendance was 1.35 (P = 0.07). CONCLUSIONS: Provision of rheumatology specialty care in an urban primary health setting aimed specifically at the needs of First Nations people led to increased uptake and engagement. A broad range of rheumatologic diagnoses was made and significant DMARD treatments commenced.

Dynamics of Patient-Based Benefit-Risk Assessment of Medicines in Chronic Diseases: A Systematic Review.

Background: A critical gap exits in understanding the dynamics of patient-based benefit-risk assessment (BRA) of medicines in chronic diseases during the disease journey. Purpose: To systematically review and synthesize current evidence on the changes of patients' preferences about the benefits and risks of medicines during their disease journey including the influence of disease duration and severity, and previous treatment experience. Methods: A systematic review of studies identified in PubMed and Embase, from inception to November 2020, was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. Articles were eligible if they analyzed adult patient-based BRA of medicines with a chronic disease, based on at least one of the pre-specified dimensions: disease severity, disease duration, or previous treatment experience. Results: A total of 26,228 articles were identified and 105 were eligible for inclusion. Of these, 85 detected a variation in patient-based BRA of medicines with at least one of the pre-specified criteria. Patients with higher disease severity and more treatment experience have increased risk tolerance. It remains inconclusive whether disease duration directly affects the relative importance of a patient's preference. Conclusion: Factors important for patients' BRA of their medicines during a chronic disease journey vary more with their clinical situation and previous treatment experience than with time since diagnosis. Due to the importance of these factors on patients' perspectives and potential impact on their decision-making and eventually their clinical outcomes, there is a need for more studies to assess the dynamics of patients' BRA in every disease.

Patient-based benefit-risk assessment of medicines: development, refinement, and validation of a content search strategy to retrieve relevant studies.

Introduction: Poor indexing and inconsistent use of terms and keywords may prevent efficient retrieval of studies on the patient-based benefit-risk assessment (BRA) of medicines. We aimed to develop and validate an objectively derived content search strategy containing generic search terms that can be adapted for any search for evidence on patient-based BRA of medicines for any therapeutic area. Methods: We used a robust multistep process to develop and validate the content search strategy: (1) we developed a bank of search terms derived from screening studies on patient-based BRA of medicines in various therapeutic areas, (2) we refined the proposed content search strategy through an iterative process of testing sensitivity and precision of search terms, and (3) we validated the final search strategy in PubMed by firstly using multiple sclerosis as a case condition and secondly computing its relative performance versus a published systematic review on patient-based BRA of medicines in rheumatoid arthritis. Results: We conceptualized a final search strategy to retrieve studies on patient-based BRA containing generic search terms grouped into two domains, namely the patient and the BRA of medicines (sensitivity 84%, specificity 99.4%, precision 20.7%). The relative performance of the content search strategy was 85.7% compared with a search from a published systematic review of patient preferences in the treatment of rheumatoid arthritis. We also developed a more extended filter, with a relative performance of 93.3% when compared with a search from a published systematic review of patient preferences in lung cancer.

Use of telemedicine for rheumatology practice in Queensland, Australia: experiences before and during the COVID-19 pandemic.

BACKGROUND: In Australia there is a shortage of rheumatologists potentially translating to poorer outcomes. A possible solution in this setting is telemedicine (TM). AIMS: To examine the utilisation and provider perceptions of TM in rheumatology in Queensland and explore the challenges faced when using TM before and during COVID-19. METHODS: A sequential mixed-methods study design was used. Rheumatologists completed a questionnaire on demographics, clinical practice, TM uptake, models of care and clinician perceptions of TM. The qualitative phase utilised purposeful sampling of active users of TM through in-depth semi-structured interviews. RESULTS: Thirty rheumatologists participated, with 76.7% identifying as active TM users. Use of TM was limited prior to COVID-19 with 80.9% examining less than five patients per week. Patient populations served by TM included capital city (53.3%), regional (63.3%) and rural/remote (23.3%). Most rheumatologists prescribed conventional or biological disease modifying agents (90% and 55%) through TM consultations. Barriers to TM use included low confidence in joint assessments, limited distribution of technology, access to administrative and peripheral clinical staff and lack of financial incentives. During the COVID-19 pandemic, a significant expansion of TM via telephone calls occurred and rheumatologists reported low confidence and satisfaction with this model. CONCLUSIONS: Familiarity with TM exists in this rheumatologist cohort; however, its use in routine practice is limited due to multiple barriers. The COVID-19 pandemic highlighted low confidence in telephone calls as a form of TM underlining the need for appropriate TM models of care for rheumatology practice.

A patient-centered knowledge translation tool for treat-to-target strategy in rheumatoid arthritis: Patient and rheumatologist perspectives.

AIM: Implementation of treat-to-target (T2T) for rheumatoid arthritis (RA) presents many challenges and an evidence-practice gap has emerged. This study assessed clinician and patient barriers to the implementation of an RA-T2T strategy and developed a knowledge translation (KT) tool for use in "real-life" clinical settings. METHODS: Surveys of patients and rheumatologists measured agreement with RA-T2T recommendations and use in daily practice. Patient knowledge and perceptions were assessed as was clinician willingness to alter practice and barriers to RA-T2T using visual analog scales. An electronic KT-tool was developed and a two-phase usability trial undertaken to assess use in clinical interactions. RESULTS: Ninety-one percent of patients had no prior knowledge of RA-T2T but agreed with the recommendations showing mean level agreement scores (8.39-9.54, SD 2.37-1.54). Ninety percent were willing to try RA-T2T, 49% felt their treatment could be improved and 28% wanted more involvement in treatment decisions. Rheumatologists agreed with RA-T2T recommendations (7.30-9.27, SD 2.59-0.91). Barriers to implementation identified by rheumatologists included time, appointment availability and perceived patient reluctance to escalate medications. Usability experiences with the KT-tool were tracked and clinicians reported it was easy to use (100%), resulted in a discussion of RA-T2T (73%) and a target being set for 63% of consults. Patients reported they read (92%) and understood (87%) the information in the KT-tool, and that a target was set in 62% of interactions. CONCLUSIONS: RA-T2T uptake in clinical practice may be improved through understanding local clinician and patient barriers and an implementation strategy utilizing a patient-driven KT-tool.

Streptococcus species enriched in the oral cavity of patients with RA are a source of peptidoglycan-polysaccharide polymers that can induce arthritis in mice.

OBJECTIVES: Analysis of oral dysbiosis in individuals sharing genetic and environmental risk factors with rheumatoid arthritis (RA) patients may illuminate how microbiota contribute to disease susceptibility. We studied the oral microbiota in a prospective cohort of patients with RA, first-degree relatives (FDR) and healthy controls (HC), then genomically and functionally characterised streptococcal species from each group to understand their potential contribution to RA development. METHODS: After DNA extraction from tongue swabs, targeted 16S rRNA gene sequencing and statistical analysis, we defined a microbial dysbiosis score based on an operational taxonomic unit signature of disease. After selective culture from swabs, we identified streptococci by sequencing. We examined the ability of streptococcal cell walls (SCW) from isolates to induce cytokines from splenocytes and arthritis in ZAP-70-mutant SKG mice. RESULTS: RA and FDR were more likely to have periodontitis symptoms. An oral microbial dysbiosis score discriminated RA and HC subjects and predicted similarity of FDR to RA. Streptococcaceae were major contributors to the score. We identified 10 out of 15 streptococcal isolates as S. parasalivarius sp. nov., a distinct sister species to S. salivarius. Tumour necrosis factor and interleukin 6 production in vitro differed in response to individual S. parasalivarius isolates, suggesting strain specific effects on innate immunity. Cytokine secretion was associated with the presence of proteins potentially involved in S. parasalivarius SCW synthesis. Systemic administration of SCW from RA and HC-associated S. parasalivarius strains induced similar chronic arthritis. CONCLUSIONS: Dysbiosis-associated periodontal inflammation and barrier dysfunction may permit arthritogenic insoluble pro-inflammatory pathogen-associated molecules, like SCW, to reach synovial tissue.

Real-world questions and concerns about disease-modifying antirheumatic drugs (DMARDs): a retrospective analysis of questions to a medicine call center.

BACKGROUND: Disease-modifying antirheumatic drugs (DMARDs) have transformed the treatment of numerous autoimmune and inflammatory diseases but their perceived risk of harm may be a barrier to use. METHODS: In a retrospective mixed-methods study, we analysed conventional (c) and biologic (b) DMARDs-related calls and compared them with rest of calls (ROC) from consumers to an Australian national medicine call center operated by clinical pharmacists from September 2002 to June 2010. This includes the period where bDMARDs became available on the Pharmaceutical Benefits Scheme, the government-subsidized prescription medicines formulary. We compared caller and patient demographics, enquiry types and motivation to information-seek for both cDMARDs and bDMARDs with ROC, using a t-test for continuous data and a chi-square test for categorical data. We explored call narratives to identify common themes. RESULTS: There were 1547 calls involving at least one DMARD. The top three cDMARD enquiry types were side effects (27.2%), interactions (21.9%), and risk versus benefit (11.7%). For bDMARDs, the most common queries involved availability and subsidized access (18%), mechanism and profile (15.8%), and side effects (15.1%). The main consumer motivations to information-seek were largely independent of medicines type and included: inadequate information (44%), wanting a second opinion (23.6%), concern about a worrying symptom (18.8%), conflicting information (6.9%), or information overload (2.3%). Question themes common to conventional and biological DMARDs were caller overemphasis on medication risk and the need for reassurance. Callers seeking information about bDMARDs generally overestimated effectiveness and focused their attention on availability, cost, storage, and medicine handling. CONCLUSION: Consumers have considerable uncertainty regarding DMARDs and may overemphasise risk. Patients cautiously assess the benefits and risks of their DMARDs but when new treatments emerge, they tend to overestimate their effectiveness.

A rare form of dermatomyositis associated with muscle weakness and normal creatine kinase level.

We present a case study of a 61-year-old Vietnamese woman who presents with features of dermatomyositis (DM), including Gottron's papules, heliotrope rash, cutaneous ulcers, generalised weakness and pain, and weight loss with normal levels of creatine kinase (CK). She demonstrated features of interstitial lung disease and subsequently tested positive for anti-melanoma differentiation-associated gene 5 and anti-small ubiquitin-like modifier 1 activating enzyme antibodies, which belong to a DM subtype known as clinically amyopathic dermatomyositis and do not present with raised CK. She received standard treatment for DM, including oral prednisolone, hydroxychloroquine, mycopheonlate and topical betamethasone. The treatment successfully reversed skin changes; however, the patient remained generally weak and unable to carry out her activities of daily living.

Tele-Rheumatology to Regional Hospital Outpatient Clinics: Patient Perspectives on a New Model of Care.

Background: Telehealth has the potential to improve access to specialist rheumatology services. The timely and appropriate delivery of care to those living with rheumatological diseases is crucial to ensuring excellent long-term outcomes. Introduction: The outcomes of a tele-rheumatology service delivered to regional hospital outpatient clinics were evaluated with patient perspectives and acceptability analyzed. Materials and Methods: A tele-rheumatology clinic was commenced in Australia from a metropolitan hospital to five regional clinics. The model of care included a trained nurse at the spoke site linked to a rheumatologist from the hospital hub site for follow-up consultations of stable review patients using videoconferencing. Surveys assessing perspectives on the tele-rheumatology encounter were completed and a subsample participated in focus groups to further explore acceptability. Results: Forty-eight patients with a diverse range of conditions participated. Patient travel was reduced on average by 95 km and 42% avoided time off work. Eighty-eight to 100% of participants agreed/strongly agreed with statements relating to acceptability, quality of physician-patient interaction, and nurse involvement. Twenty-nine percent expressed the need for a physical examination by a specialist rheumatologist and 25% felt that an in-person consultation would establish better patient-physician rapport. Qualitatively, participants viewed tele-rheumatology as equivalent to in-person care after an initial adjustment period. Discussion: Tele-rheumatology through videoconferencing for follow-up of patients with established disease is acceptable to patients and demonstrates the potential to improve time, travel, and cost burdens placed on patients who live remotely compared with traditional, face-to-face rheumatology care. Conclusions: Implementation of sustainable and patient acceptable models of tele-rheumatology care may allow timely access to all patients living with rheumatological conditions.

The effect of glucocorticoids on Thrombospondin-1, Osteocalcin and the Thrombospondin-1:Osteocalcin ratio in humans.

OBJECTIVE: Thrombospondin-1 (TSP1), a matricellular protein, and Osteocalcin (OCN), a noncollagenous protein secreted by osteoblasts, are known to be up- and down-regulated, respectively, by glucocorticoids. The aim of this study was to determine whether a ratio between TSP1:OCN was altered by changes in glucocorticoid activity in humans. DESIGN: Prospective observational study. SETTING: Tertiary university hospital in Queensland, Australia. PATIENTS AND MEASUREMENTS: Patients with Cushing's syndrome (CS, n = 19), asthma or giant cell arteritis on chronic prednisolone treatment (PRED, n = 13), adrenal insufficiency (AI, n = 16) and healthy volunteers (HV, n = 20). Plasma TSP1 and serum total OCN were measured by immunoassay at 0800h, 1200h and 1600h in patients with CS, patients with AI taking replacement glucocorticoids, HV before and after 4 mg dexamethasone and PRED patients predose at 800 and 4 hours post-dose at 1200 hours. RESULTS: Plasma TSP1 in CS was higher (P < .0001), and serum OCN was lower (P < .0001) than HV. The TSP1:OCN ratio in HV increased significantly after 4 mg dexamethasone (P < .0001) and in AI after taking their hydrocortisone replacement therapy (P < .001). PRED patients had a higher TSP1:OCN ratio compared with HV at both 800 and 1200 hours (both P < .001), but no significant change occurred from pre- to post-dose. A TSP1:OCN ratio of >73 at 800 hours differentiated CS from HV with a sensitivity of 95% and a specificity of 100%. CONCLUSIONS: The TSP1:OCN ratio is elevated in patients on prednisolone and in patients with CS compared with healthy volunteers. It may be a useful biomarker of total body glucocorticoid activity in humans.

Treat-to-target in rheumatoid arthritis: Evaluating the patient perspective using the Patient Opinion Real-Time Anonymous Liaison system: The RA T2T PORTAL study.

OBJECTIVES: To determine the level of agreement among patients with rheumatoid arthritis (RA) with the principles and recommendations of the treat-to-target (T2T) initiative in New Zealand (NZ) and to further explore specific patient opinions via online iterative surveys. METHODS: Participants with RA were recruited from rheumatology clinics in NZ and invited to receive and reply to surveys administered via the Patient Opinion Real-Time Anonymous Liaison (PORTAL) system. An enrolment survey recorded demographics, disease duration and treatment and then RA T2T surveys were administered weekly. A Likert scale 1-5 measured agreement with the principles and recommendations and further surveys explored responses of interest identified by investigators from each prior survey. RESULTS: One hundred and ninety patients consented to participate in PORTAL and 132 in the RA T2T surveys. Level of agreement with RA T2T principles was: 93.3% to 99.3% and to the recommendations: 77.3%-100%. The lowest level of agreement 77.3% was with recommendation 8, 3 monthly treatment adjustment, and the highest was 100% agreement with recommendation 10, shared decision-making. Patients agreed less with low disease activity as the target compared with remission (91.4% and 98%). Despite high-level agreement for the use of a disease activity score (95.7%), 23% did not feel the individual components reflected their disease control. Patients rated difficulty coping, erosions on imaging, health-related quality of life and pain all significantly higher than C-reactive protein as indicators of worsening arthritis. CONCLUSIONS: Despite a high level of patient agreement with RA T2T this study highlights the importance of patient engagement in the RA T2T process to individualize therapy adjustments, make shared decisions and decide on targets that accurately reflect disease control according to patients.

Treatment delays for patients with new-onset rheumatoid arthritis presenting to an Australian early arthritis clinic.

BACKGROUND: Early treatment ensures optimal outcomes in rheumatoid arthritis (RA) yet there are limited data in Australia quantifying treatment delays in clinical practice. AIMS: To quantify treatment delays in new RA patients and to explore factors influencing delay and resultant patient outcomes. METHODS: Data were obtained for 88 patients presenting with a new diagnosis of RA to an early arthritis clinic (EAC) in Australia between 2008 and 2015. Date and details of symptom onset, initial general practitioner (GP) presentation, GP referral and review at EAC were collected. Patient demographics and clinical features were analysed for outcomes and features predictive of delay. RESULTS: Median overall delay from symptom onset to rheumatology review was 26.4 weeks. Patient delay (8.7 weeks) was the longest delay and predicted overall delay. Delays in GP referral and time to EAC review were 4 and 8.4 weeks respectively. Increased overall delay was predicted by lower fatigue and disease activity scores (DAS28) and increased tender joint counts (TJC). Patient delay was increased by socioeconomic disadvantage. Increased GP delay was associated with lower DAS28 and higher TJC and ESR. Patients seen within 16 weeks had greater improvement in DAS28 and probability of remission at 6 months. CONCLUSIONS: In this Australian EAC setting, patient delay was the greatest contributor to RA treatment delay. Delays in treatment were associated with lower disease severity and socioeconomic disadvantage. Remission was more likely after prompt initiation of treatment.

What will it take? Pathways, time and funding: Australian medical students' perspective on clinician-scientist training.

BACKGROUND: Clinician-scientists are in decline worldwide. They represent a unique niche in medicine by bridging the gap between scientific discovery and patient care. A national, integrated approach to training clinician-scientists, typically programs that comprise a comprehensive MD-PhD pathway, are customary. Such a pathway is lacking in Australia. The objective was to gather perceptions from Australian medical students on factors they perceive would influence their decision to pursue clinician-scientist training. METHODS: A cross-sectional mixed methods design used quantitative and qualitative questions in an online self-report survey with medical students from a four-year MD program. Quantitative measures comprised scaled response questions regarding prior experience and current involvement in research, and short- and long-term opinions about factors that influence their decisions to undertake a research higher degree (RHD) during medical school. Qualitative questions gathered broader perceptions of what a career pathway as a clinician-scientist would include and what factors are most conducive to a medical student's commitment to MD-PhD training. RESULTS: Respondents (N = 418; 51% female) indicated Time, Funding and Pathway as the major themes arising from the qualitative data, highlighting negative perceptions rather than possible benefits to RHD training. The lack of an evident Pathway was inter-related to Time and Funding. Themes were supported by the quantitative data. Sixty percent of students have previous research experience of varying forms, and 90% report a current interest, mainly to improve their career prospects. CONCLUSIONS: The data emphasise the need for an MD-PhD pathway in Australia. A model that provides an early, integrated, and exclusive approach to research training pathways across all stages of medical education is suggested as the best way to rejuvenate the clinician-scientist. A national pathway that addresses factors influencing career decision making throughout the medical education continuum should include an appropriate funding structure, and provide early and continuing advice and mentoring. It should be flexible, gender equitable, and include post-graduate training. The implications of implementing MD-PhD programs represent a substantial investment. However this should not be a deterrent to Australia's commitment to an MD-PhD pathway, but rather a challenge to help ensure our future healthcare is guided by highly trained and competent clinician-scientists.

Patterns in use and costs of conventional and biologic disease-modifying anti-rheumatic drugs in Australia.

OBJECTIVES: The aim of this study was to characterise the use and costs of subsidising conventional disease-modifying anti-rheumatic drugs (DMARDs) and biologic DMARDs in Australia from 2004-2014 through pharmaceutical benefits schemes. METHODS: Dispensing and expenditure data on conventional and biologic DMARDs were extracted from Medicare Australia and temporal trends were analysed. Medicine use was standardised in terms of the defined daily dose (DDD) per 1,000 population per day (DDD/1,000 population/day). RESULTS: Conventional and biologic DMARD use increased 74% over the study period (4.86 to 8.46 DDD/1,000 population/day; average annual increase 6.7%). Conventional DMARDs accounted for the vast majority of total use and increased 55% (4.81 to 7.43 DDD/1,000 population/day), while biologic DMARD use increased 1,784% (0.055 to 1.030 DDD/1,000 population/day). The most frequently used conventional DMARD was methotrexate (56% total conventional DMARD use) and use increased 95%. Hydroxychloroquine and leflunomide use increased marginally while sulfasalazine use declined 4.2%. Etanercept was the most commonly used biologic DMARD in 2004 and adalimumab in 2014. Conventional DMARD expenditure decreased 4.2% to AUD$33.3 million but biologic DMARD expenditure increased 2,089% to AUD$585.4 million. CONCLUSIONS: The use of conventional and biologic DMARDs increased substantially over a decade in Australia. Patterns of use of conventional DMARDs have changed, and costs have decreased. In contrast a significant escalation in both the use and cost of biologic DMARDs has occurred. Further research is required to address cost-effectiveness, regulation and quality use of these medicines in clinical practice.

WNT ligands contribute to the immune response during septic shock and amplify endotoxemia-driven inflammation in mice.

Improved understanding of the molecular mechanisms underlying dysregulated inflammatory responses in severe infection and septic shock is urgently needed to improve patient management and identify new therapeutic opportunities. The WNT signaling pathway has been implicated as a novel constituent of the immune response to infection, but its contribution to the host response in septic shock is unknown. Although individual WNT proteins have been ascribed pro- or anti-inflammatory functions, their concerted contributions to inflammation in vivo remain to be clearly defined. Here we report differential expression of multiple WNT ligands in whole blood of patients with septic shock and reveal significant correlations with inflammatory cytokines. Systemic challenge of mice with lipopolysaccharide (LPS) similarly elicited differential expression of multiple WNT ligands with correlations between WNT and cytokine expression that partially overlap with the findings in human blood. Molecular regulators of WNT expression during microbial encounter in vivo are largely unexplored. Analyses in gene-deficient mice revealed differential contributions of Toll-like receptor signaling adaptors, a positive role for tumor necrosis factor, but a negative regulatory role for interleukin (IL)-12/23p40 in the LPS-induced expression of Wnt5b, Wnt10a, Wnt10b, and Wnt11. Pharmacologic targeting of bottlenecks of the WNT network, WNT acylation and ß-catenin activity, diminished IL-6, tumor necrosis factor, and IL-12/23p40 in serum of LPS-challenged mice and cultured splenocytes, whereas IL-10 production remained largely unaffected. Taken together, our data support the conclusion that the concerted action of WNT proteins during severe infection and septic shock promotes inflammation, and that this is, at least in part, mediated by WNT/ß-catenin signaling.

The intestinal microbiome in human disease and how it relates to arthritis and spondyloarthritis.

Humans and microbes have developed a symbiotic relationship over time, and alterations in this symbiotic relationship have been linked to several immune mediated diseases such as inflammatory bowel disease, type 1 diabetes and spondyloarthropathies. Improvements in sequencing technologies, coupled with a renaissance in 16S rRNA gene based community profiling, have enabled the characterization of microbiomes throughout the body including the gut. Improved characterization and understanding of the human gut microbiome means the gut flora is progressively being explored as a target for novel therapies including probiotics and faecal microbiota transplants. These innovative therapies are increasingly used for patients with debilitating conditions where conventional treatments have failed. This review discusses the current understanding of the interplay between host genetics and the gut microbiome in the pathogenesis of spondyloarthropathies, and how this may relate to potential therapies for these conditions.

Role of genetics in infection-associated arthritis.

Genetic discoveries in arthritis and their associated biological pathways spanning the innate and adaptive immune system demonstrate the strong association between susceptibility to arthritis and control of exogenous organisms. The canonical theory of the aetiology of immune-mediated arthritis and other immune-mediated diseases is that the introduction of exogenous antigenic stimuli to a genetically susceptible host sets up the environment for an abnormal immune response manifesting as disease. A disruption in host-microbe homeostasis driven by disease-associated genetic variants could ultimately provide the source of exogenous antigen triggering disease development. We discuss genetic variants impacting the innate and adaptive arms of the immune system and their relationship to microbial control and arthritic disease. We go on to consider the evidence for a relationship between HLA-B27, infection and arthritis, and then emerging evidence for an interaction between microbiota and rheumatoid arthritis.