The course of clinically suspect arthralgia and early rheumatoid arthritis : clinical features, imaging and genetics

The field of rheumatoid arthritis (RA) is moving into identification of patients as early as possible and the ultimate aim is to prevent RA becoming a chronic disease. To this end, we studied the phase of Clinically Suspect Arthralgia (CSA). Patients with arthralgia that were considered by the rheumatologist to have an increased risk to progress to RA (CSA) had indeed an increased risk of RA. In addition, subclinical MRI-inflammation preceded clinical arthritis with a few months. Future research will shed more light on processes underlying progression from CSA to RA and effectiveness of treatment initiation in the CSA phase. The severity of the course of RA is variable between patients and this cannot be yet accurately predicted. In this thesis, we performed studies that contributed to the understanding of these differences in severity. Three genetic risk factors for more severe joint damage progression (two non-HLA and one HLA variation) and one for arthritis persistence were identified. Further research on functional implications of the identified variants and whether they might be useful as biomarkers to guide treatment decisions is needed.Reumafonds, Stichting MCH en Bronovo-Nebo, Pfizer BV, AbbVie BV, UCB Pharma BV en Chipsoft.LUMC / Geneeskund

Kokemuksia Oman muotoinen koti -hankkeesta nuorten silmin

Opinnäytetyön tilaaja on Helsingin kaupungin nuorisoasiainkeskuksen Oman muotoinen koti -hanke. Hanke on aloitettu 2015 ja se tarjoaa nuorille eri asumiskokeilujen avulla ratkaisua haastaviin asumistilanteisiin Helsingissä. Oman muotoinen koti -hankkeessa nuoret muuttivat 2017 vuoden alussa asumaan Kannelmäkeen. Asunnon lisäksi nuorille avautui mahdollisuus tehdä töitä 20 tuntia kuukaudessa yhdessä mietittyjen tehtävien parissa. Opinnäytetyön idea oli seurata neljän nuoren alkuvaihetta Oman muotoinen koti -hankkeessa. Opinnäytetyöni tavoite oli keskittyä nuorten kokemusten taltiointiin hankkeen edetessä, mistä saatu tieto auttaisi hankkeen kehittämisessä tilaajaa. Sain tilaajalta vapaat kädet opinnäytetyön toteuttamiseen. Valitsin nuorten kokemusten taltioimiseen teemahaastattelun menetelmän. Haastateltavien keski-ikä oli 20 vuotta, joista osa oli maahanmuuttajataustaisia ja osa kantasuomalaisia. Kaikki haastateltavat olivat erilaisia, tein haastatteluun kysymysrungon, mutta annoin tilaa haastattelussa nuorille kertoa valitsemasta aiheesta enemmän. Äänitin haastattelut ja litteroin ne. Haastattelun teemat vaihtelivat haastateltavan kanssa. Vaikka kysymykset olivat samat, tunsi osa nuorista tarvetta puhua enemmän toisesta teemasta. Tein haastattelut hankkeen alkuvaiheessa, joten haastattelujen tulokset puhuvat vain hankkeen alkuvaiheen tunnelmista. Opinnäytetyön teoreettisessa viitekehyksessä käsittelen asunnottomuuden lisäksi nuorten työllisyyttä. Pohdin mikä motivoi nuoria työllistymiseen ja mitkä keinot auttavat nuoria löytämään sopivaa työtä ja mitkä asiat voivat vaikuttaa nuorten työllistymiseen. Aineiston analyysiosiossa avaan nuorten ajatuksia hankkeesta ja työnteosta. Yhdistän teoreettista viitekehystä omaan pohdintaan. Oman muotoinen koti hankkeen alkuvaiheen aineiston analyysin perusteella, hankkeelle on kova tarve ja sitä olisi hyvä laajentaa isommaksi eri puolille pääkaupunkiseutua. Hanke tukee nuorten hankalaa asumistilannetta ja työllistymistä alati muuttuvassa työelämässä.The thesis focuses on City of Helsinki’s youth Departments Home That Fits Project. The project started at the beginning of 2015 and its objective is to provide solution for the housing crisis among the youth population in Helsinki. Home That Fits project’s youth moved to shared apartment in Kannelmäki at the beginning of 2017. Apart from housing the youth were provided with opportunity to work 20 hours a month in a agreed contract between all the partners involved. The thesis goal was to follow four young people in the project’s early stage. The main focus was to understand on how the project can be develop through the experiences of the young participants in the Home That Fits project. From the young people’s experiences I did choose with the cooperation of the parties involved a particular themes that we could base our questions on. The interviewee’s average age was early 20’s. All the participants shared their experiences differently. The interview’s theme changed from time to time although the questions stayed the same. Some of the youth felt the need to talk more about other subject than the agreed themes. The interviews were conducted at the early stages of the project. Therefore the results are based on that. The Thesis theory part deals with the youth's employment: What motivates young people to seek employment , what are the mechanisms that have been created to help the youth find the right work and the issues that can affect youth employment. The findings shows that there is a certain need for Home That Fits project in the Helsinki area of Kannelmäki and it could expand to other parts of Helsinki metropolitan area

Improving our understanding of the paradoxical protective effect of obesity on radiographic damage: a large magnetic resonance imaging-study in early arthritis

ObjectiveObesity conveys a risk for RA development, while paradoxically, associating with less radiographic progression after RA diagnosis. Using MRI we can study this surprising association in detail from MRI-detected synovitis and osteitis to MRI-detected erosive progression, which precedes radiographic progression. Previous research suggested obesity associates with less osteitis and synovitis. We therefore aimed to (i) validate the previously suggested association between BMI and MRI-detected osteitis/synovitis; (ii) study whether this is specific for ACPA-positive or ACPA-negative RA or also present in other arthritides; (iii) study whether MRI-detected osteitis associates with MRI-detected erosive progression; and (iv) study whether obesity associates with MRI-detected erosive progression.MethodsWe studied 1029 early arthritis patients (454 RA, 575 other arthritides), consecutively included in Leiden Early Arthritis Clinic. At baseline patients underwent hand-and-foot MRI that were RAMRIS-scored, and 149 RA patients underwent follow-up MRIs. We studied associations between baseline BMI and MRI-detected osteitis/synovitis (using linear regression), and erosive progression (using Poisson mixed models).ResultsIn RA, higher BMI associated with less osteitis at disease onset (β = 0.94; 95% CI: 0.93, 0.96) but not with synovitis. Higher BMI associated with less osteitis in ACPA-positive RA (β = 0.95; 95% CI: 0.93, 0.97), ACPA-negative RA (β = 0.97; 95% CI: 0.95, 0.99) and other arthritides (β = 0.98; 95% CI: 0.96, 0.99). Over 2 years, overweight and obesity associated with less MRI-detected erosive progression (P = 0.02 and 0.03, respectively). Osteitis also associated with erosive progression over 2 years (P ConclusionsHigh BMI relates to less osteitis at disease onset, which is not confined to RA. Within RA, high BMI and less osteitis associated with less MRI-detected erosive progression. This suggests that the protective effect of obesity on radiographic progression is exerted via a path of less osteitis and subsequently fewer MRI-detected erosions.Pathophysiology and treatment of rheumatic disease

Improvement of symptoms in clinically suspect arthralgia and resolution of subclinical joint inflammation: a longitudinal study in patients that did not progress to clinical arthritis

INTRODUCTION: Arthralgia and MRI-detected subclinical inflammation can precede the development of clinically evident rheumatoid arthritis (RA). However, part of the patients presenting with clinically suspect arthralgia (CSA) do not progress to RA. In these 'non-progressors', we aimed to study the frequencies of spontaneous improvement of arthralgia and its relation with the course of subclinical inflammation. METHODS: Between April 2012 and April 2015, 241 patients were considered at risk for RA based on the clinical presentation and included in the CSA cohort. One hundred fifty-two patients with complete data on clinical follow-up did not develop clinical arthritis, of which 98 underwent serial 1.5T MRI scans (wrist, MCP2-5, and MTP1-5 joints) at baseline and after 2 years. MRI scans were scored for synovitis, tenosynovitis, and bone marrow oedema (summed: MRI inflammation score). MRI scores were compared to scores of symptom-free persons. RESULTS: After a 2-year follow-up, 33% of the 'non-progressors' had complete resolution of symptoms; 67% had no symptom resolution and were diagnosed as persistent CSA (44%), osteoarthritis (10%), and tendinomuscular complaints (13%). With symptom-free controls as a reference, patients without resolution did not have increased MRI scores at any time point. However, patients achieving resolution of symptoms had increased MRI inflammation scores at baseline (4.0 vs. 2.6, p = 0.037), but not after 2 years (3.0 vs. 2.6; p = 0.57), and during follow-up, their MRI inflammation score decreased significantly (p = 0.036). CONCLUSIONS: A subgroup of CSA patients that did not progress to RA had spontaneous improvement of symptoms and resolution of subclinical joint inflammation. This time relationship suggests that symptoms and inflammation were causally related in these patients. Further research is needed to identify the mechanisms underlying the resolution of inflammation

Moderate use of alcohol is associated with lower levels of C reactive protein but not with less severe joint inflammation: a cross-sectional study in early RA and healthy volunteers

Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

Development of clinically apparent synovitis: A longitudinal study at the joint level during progression to inflammatory arthritis

Introduction Subclinical inflammation, detected by MRI, in patients with arthralgia is predictive for development of inflammatory arthritis (IA). However, within patients that develop IA, the course of inflammation at the joint level during this transition is unknown. This longitudinal study assessed progression of inflammation at the joint level. Methods 350 joints (unilateral metacarpophalangeals (MCPs), wrist, metatarsophalangeal (MTP) joints) of 35 patients presenting with clinically suspect arthralgia (CSA) that progressed to IA were studied at presentation with CSA and subsequently when clinical synovitis was first identified at joint examination (median time interval 17 weeks). At both time points, subclinical inflammation (bone marrow oedema, synovitis, tenosynovitis) was evaluated with MRI and joint examination was performed. Results At presentation with CSA, 71 joints showed subclinical inflammation. During progression to IA, 20% of these joints had resolution of inflammation, 60% had persistent inflammation and 20% progressed to clinical synovitis. Of all joints that had developed clinical synovitis (n = 45), no prior subclinical inflammation was detected in 69%. Similar results were observed for anticitrullinated protein antibodies (ACPA)-positive and ACPA-negative patients. Conclusions This longitudinal study demonstrated moderate correlations between joints with subclinical inflammation and joints that developed clinical synovitis. These data imply that IA development is a more systemic rather than a locally outgrowing process

Sequence of joint tissue inflammation during rheumatoid arthritis development

OBJECTIVE: Subclinical joint inflammation in patients with arthralgia is predictive for progression to rheumatoid arthritis (RA). However, the time course of progression for bone marrow edema (osteitis), synovitis, and/or tenosynovitis is unsettled. This longitudinal study assessed the course of magnetic resonance imaging (MRI)-detected subclinical joint inflammation during progression to RA. METHODS: Patients that progressed from clinically suspect arthralgia (CSA) to RA underwent 1.5-T MRI of the metacarpophalangeal (MCP), wrist, and metatarsophalangeal (MTP) joints at presentation with arthralgia and at first identification of synovitis assessed through physical examination (n = 31). MRIs were evaluated for osteitis, synovitis, tenosynovitis, and erosions by two readers, blinded for clinical data and order in time. To estimate changes in MRI scores between the asymptomatic state and CSA onset, scores of MRI features at CSA baseline were compared with scores from age-matched symptom-free persons. RESULTS: At presentation with CSA, synovitis and tenosynovitis scores were higher than scores from age-matched symptom-free persons (p = 0.004 and p = 0.001, respectively). Anti-citrullinated protein antibody (ACPA)-positive arthralgia patients also had increased osteitis scores (p = 0.04). Median duration between presentation with arthralgia and RA development was 17 weeks. During progression to RA, synovitis and osteitis increased significantly (p = 0.001 and p = 0.036, respectively) in contrast to tenosynovitis and erosion scores. This pattern was similar in both ACPA subsets, although statistical significance was reached for synovitis and osteitis in ACPA-negative but not ACPA-positive RA. CONCLUSION: Increased tenosynovitis and synovitis scores at CSA onset and the increase in synovitis and osteitis during progression to RA suggest an 'outside-in' temporal relationship of arthritis development, in particular for ACPA-negative RA. For ACPA-positive RA, further studies are needed

Interosseous tendon inflammation in the hands of patients with clinically suspect arthralgia: analysis of MRI data from a prospective cohort study

Background Inflammation around the tendons of interosseous muscles of the hand (interosseous tendon inflammation) was recently observed with MRI for the first time in patients with rheumatoid arthritis and in at-risk individuals with detectable anti-citrullinated protein antibodies, generating the hypothesis that interosseous tendon inflammation precedes clinical arthritis. To better understand the role of interosseous tendon inflammation during the development of rheumatoid arthritis, we studied the frequency of interosseous tendon inflammation in healthy individuals and in those with arthralgia that was suspected of progressing to rheumatoid arthritis (ie, clinically suspect arthralgia) and the association of interosseous tendon inflammation with other symptoms of inflamed joint tissues and with clinical arthritis development.Methods Adult (age >= 18 years) patients who presented with clinically suspect arthralgia and symptom-free (control) individuals underwent contrast-enhanced hand MRI. MRIs were evaluated for interosseous tendon inflammation on the radial and ulnar sides of the second to fifth metacarpophalangeal joints, and for synovitis, tenosynovitis, and osteitis using the rheumatoid arthritis MRI scoring system. Patients with clinically suspect arthralgia were followed up for clinical arthritis development. The presence of local tenosynovium was examined using immunohistochemistry for anti-CD55 and anti-CD68 on tissue from the hands of three embalmed bodies donated for scientific research. The primary outcome for the cross-sectional part of the study was the presence of interosseous tendon inflammation on MRI. The primary outcome for the longitudinal part of the study was development of clinical arthritis.Findings Between April 3, 2012, and May 20, 2020, 667 patients with clinically suspect arthralgia (mean age 44 years [SD 13], 504 [76%] were women and 163 [24%] were men) underwent contrast-enhanced hand MRI. Between Nov 1, 2013, and Nov 30, 2014, 193 symptom-free controls were recruited (mean age 50 years [SD 16], 136 [70%] were women and 57 [30%] were men). Two (1%) of 193 symptom-free controls had interosseous tendon inflammation. Immunohistochemistry of cadaveric hand tissues showed no tenosynovium surrounding interosseous tendons. At inclusion, 67 (10%) of 667 patients with clinically suspect arthralgia had interosseous tendon inflammation (p<00001 vs symptom-free controls). Interosseous tendon inflammation occurred more frequently if synovitis (odds ratio [OR] 22 [95% CI 12-42]), or tenosynovitis (OR 97 [55-170]), was present at metacarpophalangeal joints. A three-dimensional MRI reconstruction suggested confluency of interosseous tendon inflammation with metacarpophalangeal-flexor-tenosynovitis. 91 (16%) of 558 patients with clinically suspect arthralgia developed clinical arthritis during follow-up (median total follow-up 253 months [95% CI 251-255]). Patients with clinically suspect arthralgia with interosseous tendon inflammation had a higher risk of developing clinical arthritis (hazard ratio [HR] 45 [28-72]), which was attenuated but still significant after adjusting for concomitant synovitis, tenosynovitis, or osteitis (HR 17 [102-28]).Interpretation Interosseous tendon inflammation is almost absent in symptom-free individuals but occurs in people with clinically suspect arthralgia, in whom it correlates with symptoms and is associated with the development of clinical arthritis. The absence of local tenosynovium suggests that interosseous tendon inflammation arises from expanding local subclinical inflammation in the pre-arthritis phase of rheumatoid arthritis.Pathophysiology and treatment of rheumatic disease

Does information on novel identified autoantibodies contribute to predicting the progression from undifferentiated arthritis to rheumatoid arthritis: A study on anti-CarP antibodies as an example

Background: The presence of autoantibodies is considered an important characteristic of rheumatoid arthritis (RA); therefore, both anticitrullinated protein antibodies (ACPA) and rheumatoid factor (RF) are included in the 2010 classification criteria for rheumatoid arthritis (RA). However, a considerable number of RA patients lack both these autoantibodies. Recently, several novel autoantibodies have been identified but their value for the classification of RA patients is unclear. Therefore, we studied the value of novel autoantibodies using the presence of anticarbamylated protein (anti-CarP) antibodies as an example for predicting RA development in patients with undifferentiated arthritis (UA). Methods: There were 1352 UA patients included in the Leiden Early Arthritis Clinic (EAC) cohort according to the 1987 criteria. When the 2010 criteria were used, there were 838 UA patients. Of these, we evaluated whether they fulfilled the 1987 or 2010 criteria after 1 year, respectively. Logistic regression analyses were performed with RA as outcome and ACPA, RF, and anti-CarP antibodies as predictors. Analyses were repeated after stratification for ACPA and RF. Results: Thirty-three percent of the 1987-UA patients and 6% of the 2010-UA patients progressed to RA during the first year of follow-up. For the 1987-UA patients, anti-CarP antibodies were associated with progression to RA, an association which remained when a correction was made for the presence of ACPA and RF (odds ratio (OR) 1.7, 95% confidence interval (CI) 1.2-2.4). After stratification for ACPA and RF, anti-CarP antibodies were associated with progression to RA only for ACPA- and RF-negative patients (OR 2.1, 95% CI 1.3-3.7). For the 2010-UA patients, anti-CarP antib