Genetics, autoantibodies and clinical features in understanding and predicting rheumatoid arthritis

This thesis investigated the association between several genetic factors and autoantibodies and the development of undifferentiated arthritis (UA) and rheumatoid arthritits (RA). Second, this thesis described a prediction model that estimates the chance to progress from UA to RA. The most important genetic risk factor for RA are the HLA-Class II alleles that encode for a common amino acid sequence, called the ‘Shared Epitope’. Investigating the progression to RA from UA revealed that the HLA-Shared Epitope alleles are not primarily a risk factor for RA but for the presence of anti-CCP antibodies, that are known to be specific for RA. Smoking in the presence of HLA-Shared Epitope alleles particularly increased the risk on anti-CCP-positive RA.. The HLA-DR3 alleles were associated with anti-CCP-negative RA. The presence of HLA-alleles encoding for D70ERAA correlated with a lower risk on RA and a less severe disease course. The presence of the PTPTN22 T-allele conferred an increased risk for both UA and RA. The knowledge on risk factors for RA-development was translated in a model that estimates the chance to progress to RA in patients that present with UA by using 9 clinical variables. The discriminative ability was high and this model allows individualized treatment decisions in UA.​​​​​​​LEI Universiteit LeidenKlinische evaluatie en behandeling van reumatische ziekte

Het veranderende gezicht van reumatoïde artritis

Oratie uitgesproken door Prof.dr. A.H.M. Van der Helm-van Mil bij de aanvaarding van het ambt van hoogleraar op het gebied van Reumatologie, in het bijzonder Vroege Artritis aan de Universiteit Leiden op vrijdag 14 oktober 2016Oratie uitgesproken door Prof.dr. A.H.M. Van der Helm-van Mil bij de aanvaarding van het ambt van hoogleraar op het gebied van Reumatologie, in het bijzonder Vroege Artritis aan de Universiteit Leiden op vrijdag 14 oktober 201

The earlier, the better or the worse? Towards accurate management of patients with arthralgia at risk for RA

The favourable long-term results of early treatment in patients with classified rheumatoid arthritis have resulted in an increasing interest in the diseases phases preceding clinical arthritis. The hypothesis to test is that an intervention in these early phases may better prevent or reduce disease persistence than an intervention when arthritis has become clinically manifest. While several placebo-controlled trials are still ongoing, to date there is no firm evidence that this hypothesis truly holds. Therefore, it is important to reflect on the current status of arthralgia preceding clinical arthritis. Inherent to every new field of research, attitudes are conflicting, with opinions propagating innovation (based on the fear of undertreatment) on the one hand, and critical sounds pleading for more restraint (fear of overtreatment) on the other hand. In this Viewpoint, we will examine these divergent opinions, relate them to a preferred ultimate scenario and provide considerations for future studies and daily practice

Response to: "does ACPA-negative RA consist of subgroups related to sustained DMARD-free remission and serological markers at disease presentation" by Masi and Fleischmann

Pathophysiology and treatment of rheumatic disease

What is the prevalence of MRI-detected inflammation and erosions in small joints in the general population? A collation and analysis of published data

Introduction: MRI sensitively depicts erosions, bone marrow edema (BME) and synovitis in rheumatoid arthritis (RA). Recently developed European League Against Rheumatism (EULAR) recommendations stated that MRI is valuable to improve the certainty of a considered diagnosis and to detect structural damage at an early time point. However, these recommendations were mainly based on the data of patients with RA; prevalences of MRI features in the general population were not extensively explored. We reviewed the literature on MRI studies including symptom-free persons to assess the occurrence of MRI features.Methods: Medical literature databases up to September 2013 were systematically reviewed for symptom-free persons with MRI data on metacarpophalangeal, wrist and metatarsophalangeal joints. Data were extracted and summarised. When allowed because of comparable scanning and scoring protocols, a mean frequency of features was calculated.Results: Of the 338 articles screened, 31 studies evaluated MRI findings in symptom-free persons (n=516 in total). Both the imaging techniques (= 1 T, with/without contrast enhancement) and the scoring methods (non-validated or RA MRI score (RAMRIS)) varied widely, prohibiting direct comparisons of the results of many studies. 15 studies scored data according to RAMRIS; combining data of similar joint regions showed that erosions (RAMRIS >= 1) were present in 33-52% of symptom-free persons. Similarly, synovitis was present in 27% and BME in 0-16% of symptom-free persons. The prevalence of MRI-detected erosions increased with age.Conclusions: MRI features, erosions in particular, occur frequently in symptom-free persons. Before MRI can be implemented in the diagnostic process, larger studies should be conducted determining the degree and combination of MRI features that are disease specific

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

Validity of the rheumatoid arthritis MRI score applied to the forefeet using the OMERACT filter: a systematic literature review

Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas