Early inflammatory arthritis is common, with an. Diagnosis of early arthritis: outcomes of a nurse-led clinic
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1 Diagnosis of early arthritis: outcomes of a nurse-led clinic Y El Miedany, D Palmer, M El Gaafary Abstract Recent data suggest that early treatment of inflammatory arthritis can improve patient outcomes. While rheumatologists recognized this need for early evaluation and treatment, the current load on the rheumatology service nationwide may limit the capacity for timely evaluation. The authors developed a protocol to be applied through a specialized early arthritis clinic that is able to discriminate between different categories of early arthritis, to shortening the time taken to reach the correct diagnosis and provide the appropriate management. A total of 108 patients have been reviewed in the early arthritis clinic over 12 months. It took 3 weeks for the patients to be fully assessed in the rheumatology clinic instead of 16 weeks. Completing the clinic proforma helped the assessor to cover all causes of arthritis/ arthralgia. Disease-modifying antirheumatic drug (DMARD) therapy was initiated within a few weeks (2 5 weeks) once diagnosis was confirmed, instead of 8 10 months previously. This early arthritis clinic model helped to shorten the referral lag time (duration between symptoms onset and first rheumatologist assessment) as well as lag time to DMARD therapy (duration between symptom onset and the institution of DMARD therapy). Key words: Arthritis Nurse-led services Drug therapy Early inflammatory arthritis is common, with an estimated prevalence range between 30% and 50% (Wolfe et al, 1993; Van der Horst-Bruinsma et al, 1998) of patients presenting to the rheumatology clinic. Early arthritis has been defined in several ways, but the diagnosis is usually one of exclusion, based on the failure to satisfy classification criteria for the well-recognized rheumatic conditions (e.g. rheumatoid arthritis (RA) and psoriatic arthritis). In general, patients with early arthritis are defined as those with the potential to develop persistent inflammatory arthritis, but in whom a recognized clinical pattern does not exist. In some of these patients, the disease Yasser El Miedany is Consultant Rheumatologist, Head of Rheumatology Department; Deborah Palmer is Rheumatology Specialist Nurse, Rheumatology Department, Darent Valley Hospital, Dartford, Kent; and Maha El Gaafary is Lecturer of Community, Environmental and Occupational Medicine, Faculty of Medicine, Ain Shams University, Cairo, Egypt Accepted for publication: February 2006 evolves into other rheumatic conditions, while in many cases the disease regresses (Wolfe et al, 1993). From the clinical perspective, if effective therapy could be introduced prior to the development of presumed irreversible damage, outcomes could be improved. This was fuelled by the window of opportunity hypothesis for therapeutic intervention in RA (Masi et al, 1976). The hypothesis was based on the existence of a time frame within which there is potential for a disproportionate response to therapy, resulting in long-term benefits, or more importantly, the chance of a cure. Initially, early arthritis clinics (EACs) were confined to clinical research units. However, there is a big difference between clinic-oriented and research-oriented services. Hence, in the late 1990s EACs emerged as part of general rheumatology services worldwide (Emery and Gough, 1991; Quinn and Emery, 2005). An EAC should, by definition, offer early assessment of patients with either signs or symptoms of inflammatory arthritis, i.e. patients with the potential to develop RA. Ideally the clinic should be able to offer assessment of patients within a short time of referral to the clinic and almost as importantly, offer early review to assess response to intervention. Over the past decade, nursing in the UK has undergone major changes in the expansion of its role and responsibilities with the introduction of nurse specialists. In rheumatology the role of the specialist nurse has evolved to include drug monitoring and supervision of day-to-day management of rheumatic diseases. As most of the work carried out by the rheumatology nurse specialists involves assessment and management of inflamed joints, they would be good assets to share in the assessment of early arthritis patients. The aim of this work was to develop a protocol to be applied through a specialized EAC that is able to discriminate between different categories of early arthritis, to shorten the time taken to reach the correct diagnosis and to provide the appropriate management. Patients and methods Starting from September 2004, GPs within the Trust were asked to refer patients presenting with joint pains and a clinical picture suggestive of early arthritis. Patients with early arthritis were defined as those with clinical picture suggestive of inflammatory disorder (joint pain or swelling, limited range of motion and morning stiffness), but in whom a specific rheumatic disease has not been diagnosed. Patients satisfying the American College of Rheumatology classification criteria for RA (Arnett et al, 1988) and the 394 British Journal of Nursing, 2006, Vol 15, No 7 BJN_15_7_394_9_arthritis.indd 2 5/4/06 11:32:06
2 Nurse-led clinic European Study Group for Spondyloarthropathy (Dougados et al, 1991) were excluded, as were those with a specific rheumatic diagnosis. The aims and objectives of the service, which was supplemented by local lectures, was detailed in a letter to local GPs outlining guidelines for referral to the clinic. Guidelines for referral included: n Synovitis: defined as the presence of at least two of the following three clinical criteria: joint swelling, joint tenderness or decreased range of motion n Symmetrical symptoms n Metacarpophalangeal (MCP) and metatarsophalangeal (MTP) joint involvement n Positive squeeze test on the MCP and/or MTP joints n Significant early morning stiffness (>30 minutes) n Relatively good response to NSAIDs n Family history of rheumatoid arthritis. The senior rheumatologist screened the patients referral letters. An appointment was then made to assess the appropriate patients. Disease assessment Patients were assessed in a dedicated specialized nurse-led EAC. A proforma specific for the EAC was developed by the senior rheumatologist (El Miedany et al, 2005), designed to document the history of present illness, assess the possibility of having other rheumatologic causes of joint pain as well as review of the other body systems (Box 1). The proforma was designed such that minimal writing was required and ticking the appropriate box was applied for most of the points. Physical examination of the upper and lower limb joints was carried out for signs of joint inflammation, tender and swollen joint counts. Patient s and physician s global assessments, pain score and grip strength were walso assessed. The patient s data were recorded in the proforma. To assess functional disability, the patient completed the health assessment questionnaire in the first visit. Laboratory examinations included: full blood count, blood chemistry, inflammatory markers (erythrocyte sedimentation rate and C-reactive protein), thyroid function tests, creatinine kinase (CK), bone profile, rheumatoid factor, anti-nuclear antibodies (ANAs), extractable nuclear antigen (ENA) (if ANA positive). An X-ray of the affected joints, as well as chest X-rays were requested. The rheumatologist assessed the patient clinically after reviewing the patient s proforma and clinical findings reported by the nurse. The referring physician was notified. Non-steroidal anti-inflammatory drug (NSAID) therapy is usually prescribed as initial therapy and the patient was asked to come again for reassessment by the specialist nurse as well as the rheumatologist. A shorter follow-up proforma that summarized the clinical data, laboratory results and X-ray findings was also designed to be completed by the assessor. If the patient had evidence of active synovial inflammation, an ultrasound or magnetic resonance image (MRI) of the joint was carried out and the patient was treated according to the approved protocol of management of early arthritis. If the patient is not considered to have a rheumatologic condition, then the patient is returned to the care of the referring physician. Treatment A standard step-up treatment protocol was followed: 1. NSAIDs 2. Single dose of corticosteroids either intramuscularly or intraarticularly 3. DMARD therapy. This protocol was chosen on the basis of previous research in oligoarthritis and early mild polyarthritis (Green et al, 2001). Therapy was escalated at the discretion of the assessing physician (according to initial therapeutic response and clinical presentation), the primary aim being to eliminate the presence of synovitis and induce remission. Patients in whom toxicity or inefficacy with NSAIDs had previously been demonstrated began therapy with the second step of the protocol. Outcome and data assessment Proformas of the clinic were audited to assess for the form s ability to discriminate between early inflammatory arthritis and other causes of joint pains. Data were described as mean and standard deviation or number and percentages. Student t-test was used to compare the new and former referral and therapy lag times. Correlation between clinical variables was studied using Spearman s correlation. A p- value less than 0.05 was graded as statistically significant. All data manipulation and analysis were performed using SPSS, version Results The clinic has been ongoing for 12 months and a total of 108 patients have been seen. There were 99 patients with rheumatologic diagnosis: 69 early arthritis less than 1- year duration, 6 rheumatoid arthritis (Figure 1), 5 psoriatic arthritis (Figure 2), 10 osteoarthritis (Figure 3), 7 gouty arthritis (Figure 4). There were 11 patients with nonrheumatic causes: diabetes mellitus, thyroid dysfunction, hepatitis, hyperlipidemia and soft tissue rheumatism. The average time to complete the proforma was 7.2 minutes. Comparing the provision with the final diagnosis (Table 1), the proforma helped in considering the proper diagnosis in most of the patients (95/108, 87.96%). The average time for the patient to be assessed in the clinic dropped from 12 weeks to 3.4 weeks, (p=<0.001) (Table 2). DMARD therapy was initiated within 2 5 weeks once diagnosis was confirmed, instead of 8 10 months previously (p<0.001). Table 1. Comparison between the provisional diagnosis based on the proforma versus final diagnosis Condition Provisional diagnosis Final diagnosis Early arthritis Rheumatoid arthritis 3 6 Psoriatic arthritis 5 5 Osteoarthritis Gouty arthritis 3 7 Diabetes mellitus 1 2 Soft tissue rheumatism 3 3 Thyroid disease 1 4 Hepatitis 0 1 Hyperlipidemia 0 1 British Journal of Nursing, 2006, Vol 15, No BJN_15_7_394_9_arthritis.indd 3 5/4/06 11:32:06
3 Box 1. Proforma for early arthritis clinic Early Arthritis Clinic Patient s Name: Date of Birth: / / Hospital Number: Address: Post Code: GP: Date: / / Age: Complaint: Duration (start of symptoms): Course: stationary/progressive/regressive Joint pain: Yes/No Joint swelling: Yes/No Which joints: Morning stiffness: Yes/No Duration: Subcutaneous swelling: Yes/No Have medications been given: Yes/No What are the medications prescribed?: Response to these medications: History of similar/other joint pain: Skin rash: Yes/No Site: Diagnosis: Psoriasis: Yes/No Duration: Treatment: History of fever: Yes/No Pattern: Dry eye: Yes/No Schirmer s Test: Positive/Negative Dry mouth: Yes/No Mouth ulcers: Yes/No Occasional/frequent Painful/painless Genital ulcers: Yes/No Treatment: Eye complaint (inflammation/infection): Yes/No Diagnosis: Raynaud s Phenomenon: Yes/No Treatment: Lower back pain: Yes/ No Back morning stiffness: Yes/No Duration: minute(s) Does it radiate to lower limb: Yes/No LL Tingling/numbness in lower limb: Yes/No Thyroid: euthyroid/hypo/hyperthyroidism Thyroxin dose: µgm History of hepatitis: Yes/No Hep. A/Hep. B/Hep. C Diabetes mellitus: Yes/No Hypertension: Yes/No History of gouty arthritis: Yes/No Diuretics: Yes/No History of hyperlipidemia: Yes/No Recent loss of body weight: Yes/No How many stones/pounds: Over: Chest symptoms: dyspnoea/cough/infection/wheezes/other: Heart/CVS (cardiovascular system): dyspnoea/palpitation/stroke/uncontrolled hypertension/ischaemic heart disease/angina/ myocardial infarction/deep vein thrombosis/other: Genitourinary: diarrhoea/constipation/heart burn/ulcers/bleeding per rectum/haematemesis (vomiting of blood)/endoscopy irritable bowel syndrome/ulcerative colitis/crohn s Disease/Whipple s Disease/coeliac disease/other: Urinary tract: renal colic/burning sensation/stones/difficulty of initiation/precipitancy/others: Central nervous system: headache/increased cranial tension/fits, epilepsy/tingling, numbness/nerve injury: Family history: Provisional diagnosis: Investigations requested: Yes No Rheumatology blood profile: n n Lipid profile: n n Rheumatoid factor and anti-nuclear antibody (RF & ANA): n n Extractable nuclear antigen (ENA): n n Anti-cyclic citrullinated protein (a-ccp): n n X-ray: n n Ultrasonography: n n MRI: n n Bone Scan: n n Dual energy X-ray absorptiometry (DXA) scan: n n Medications suggested: Parameters of disease activity: TJC SJC PGH Pain PhGA MS HAQ Grip Strength (R & L) ESR CRP RF a-ccp X-ray MRI Disease Activity Score: Date: / / Recommendations: CRP = C-reactive protein; ESR = Erythrocyte sedimentation rate; HAQ = Health assessment questionnaire; MS = Morning stiffness; PGH = Patient global health assessment; PhGH = Physician global health assessment; PS = Pain score; SJC = Swollen joint count; TJC = Tender joint count 396 British Journal of Nursing, 2006, Vol 15, No 7 BJN_15_7_394_9_arthritis.indd 4 5/4/06 11:32:07
4 nurse-led clinic Table 2 shows the demographic data regarding the patients diagnosed to have early arthritis (n=69), while Table 3 shows the clinical characteristics of this group of patients. Pain in the hand joints, symmetrical arthritis, positive squeeze test of the metacarpophalangeal joints and long duration of morning stiffness were the most common clinical parameters among patients presenting with persistent inflammatory arthritis. Inflammatory markers were negative predictors of persistent inflammatory arthritis (Table 4). At baseline, the mean health assessment questionnaire (HAQ) score was Comparing the patients whose early arthritis went into self-remission with the group of patients who developed persistent inflammatory arthritis, there was no significant difference between baseline HAQ scores. In group I, the mean HAQ score was 0.743, whereas the mean HAQ score in group II was (p>0.05). However, by the end of the year one, there was a significant difference between both groups: HAQ in group I was (p>0.05), and group II was (p<0.01). The patients characteristics that were significant in predicting the HAQ change were disease activity score, tender joint count and progression of the functional abilities (p<0.001). Discussion The assessment of patients with early arthritis is associated with a number of inherent difficulties. Because the classic features of RA may not be apparent, classification criteria may not be useful (Harrison et al, 1998; Green et al, 1999). In the meantime, management of inflammatory arthritis based on suppression of synovitis to minimize damage would seem to be the appropriate aim of therapy in this patient group. In the current work, in which management was based on such a concept, a step-up treatment algorithm was used with DMARD therapy as a surrogate marker for significant persistent inflammatory disease. Rheumatoid arthritis Table 2. Demographic data of all patients included in this study Number of patients assessed in the early arthritis clinic 108 Number of patients diagnosed as early arthritis 69 Female:male ratio 60:9 Mean age (years) Disease duration (symptom-assessment) (mean) 6.1 months Referral lag time (GP-assessment) (mean) 3.4 weeks Number of patients on non-steroidal anti-inflammatory drugs 65/69 Number of patients on steroid therapy 4/69 The authors presented in this work an example of an early arthritis clinic established in a busy district general hospital. The exact structure and services offered at such clinics are varied and frequently determined by availability of resources. Several models exist including the Birmingham (Gough, 1993), Leeds (Quinn et al, 2003) and Swedish (Karolinska) set-ups (Klareskog et al, 2001). Each offers a slightly different approach based around a unifying concept of early case definition and intervention. The Birmingham system was the original model, much copied and altered. The service allowed direct referral via long-range pager to a rheumatologist for all patients with possible inflammatory arthritis. Urgent patients could be seen on the same or next working day, and all patients could be seen within 2 weeks of referral. Assessment was undertaken in a purpose-built ward with staff including the head rheumatologist, trainee rheumatologists, a specialist nurse, a physiotherapist and an occupational therapist and Modest firm swellings of proximal interphalangeal joints (Bouchard's nodes) Psoriatic arthritis Heberden's nodes of the distal interphalangeal joints Squaring of thumb owing to disease of carpometacarpal joint Eroded bone synovial membrane Excess synovial fluid inflamed capsule Thinning cartilage Resembles rheumatoid arthritis but tends to affect the fingers and toes, often with accompanying skin lesions Eroded bone Thinning cartilage Figure 1. Rheumatoid arthritis. Figure 2. Psoriatic arthritis. British Journal of Nursing, 2006, Vol 15, No BJN_15_7_394_9_arthritis.indd 5 5/4/06 11:32:10
5 Osteoarthritis Osteophytes (spurs) synovial membrane Joint deformity Figure 3. Osteoarthritis. Gouty arthritis Uric acid (tophi) in joint space Uric acid crystals in tissues surrounding joint Figure 4. Gouty arthritis. inflamed capsule Small amount of remaining cartilage inflamed capsule with the capacity to use medical students and GPs for educational purposes. The Leeds system further developed the Birmingham model with an increased emphasis on imaging, with the addition of ultrasound and MRI assessments of the joints. The Karolinska system in Sweden is based on a day-patient programme where all patients receive comprehensive assessments and education by a junior doctor, physiotherapist, social worker, occupational therapist and co-coordinating nurse prior to a prognostic and therapeutic decision from the senior physician. Such protocols are nearly impossible to be applied in a district general hospital, and the authors believe that their model is easy to apply, is not time- nor space-consuming, does not exhaust resources and is a good example that can be applied in similar hospitals. Results of this work revealed that the clinic proforma has enabled the specialist nurse to discriminate between early arthritis cases and other subclinical conditions that might be causing joint pain. Good documentation with accurate detailing of distribution of symptomatic joints, duration of morning stiffness, response to NSAIDs, any prodromal illness, family and past medical histories are important for every case of arthritis. As the particular symptoms may be the presenting manifestation of many infections, inflammatory or malignant condition documentation should include description of any skin rash, weight loss, urine analysis and blood pressure. Completing the proforma took only 7 minutes on average, giving more time for clinical examination. Data recording was also feasible and reproducible with minimal time needed. Results of this work helped to put the accuracy of diagnosis at 87.9% of the patients, indicating that the clinic and the clinical proforma allowed earlier and successful diagnosis. Results of the study done by Van der Horst-Bruinsma et al (1998) showed that just 70% of all patients seen were accurately diagnosed within 2 weeks of assessment. Of principal importance is the relationship with primary care and awareness of the service provided. Results of this audit have shown the importance of using such guidelines. Unless guidance was offered, EAC services may have been exploited for non-urgent cases, especially where conventional waiting lists are lengthy. This may, in turn, compromise the quality of care offered to true inflammatory patients where early intervention has the greatest potential for benefit. The principal objective of the EAC is to improve patient assessment and outcome. One of the key delays in assessing patients with inflammatory arthritis was time to referral to secondary care. Results of this audit showed that the clinic has managed to cut the waiting time for patients with early arthritis to be assessed and the lag time for the patients to start their DMARD therapy. A review of primary trial data from 14 randomized controlled trials of DMARD therapies in RA indicated disease duration as a significant determinant of response to therapy: patients with short disease duration had a more favourable response (Anderson et al, 2000). Patients presenting with a disease duration of less than 1 year showed response in 53% of cases, whereas patients presenting with a disease duration 398 British Journal of Nursing, 2006, Vol 15, No 7 BJN_15_7_394_9_arthritis.indd 6 5/4/06 11:32:12
6 nurse-led clinic of 1 2 years, 2 5 years, 5 10 years and more than 10 years showed diminished response with time. This emphasizes the importance of early intervention (Irvine et al, 1999). Another study compared the performance of a routine clinic with an early arthritis clinic and demonstrated a median reduction in referral time to a rheumatologist of at least 13 months (Van der Horst-Bruinsma et al, 1998). Conclusion As the body of evidence for early intervention and assessment in early arthritis continues to grow, and is driven by the EAC experience, gains to the nurse practitioners and rheumatologists include better understanding of prognostic factors and improved outcome in terms of function in this group of patients. This EAC model was formulated and utilized in a busy rheumatology centre. The clinic proforma ensured that all causes of arthritis/arthralgia were covered. Access to specialized rheumatology care was reduced from 3 months to 3 weeks. Treatment was initiated within a few weeks of final diagnosis. Without this clinic, these patients would have had to wait longer to be assessed, and would have seen delayed treatment for their disease. BJN Anderson JJ, Wells G, Verhoeven AC, Felson DT (2000) Factors predicting response to treatment in rheumatoid arthritis. The importance of disease duration. Arthritis Rheum 43(1): 22 9 Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31(3): Dougados M, Van der Linden S, Juhlin R, Huitfeldt B, Amor B, Calin A (1991) The European Spondyloarthropathy Study Group preliminary criteria for the classification of spondyloarthropathy. Arthritis Rheum 34(10): El Miedany YM, Youssef SS, Mehanna AN, El Gaafary M (2005) Establishment of a specialized early arthritis clinic using a systemic and specific protocol for referral and management. Arthritis Rheum 52(9): S121 Emery P, Gough A (1991) Why early arthritis clinics? Br J Rheumatol 30(4): Gough AKS (1993) Disease severity and prediction of outcome in early rheumatoid arthritis, thesis. London Green M, Marzo-Ortega H, McGonagle D, Wakefield R, Proudman S, Conaghan P (1999) Persistence of mild, early inflammatory arthritis: the importance of disease duration, rheumatoid factor and the shared epitope. Arthritis Rheum 42(10): Green M, Marzo-Ortega H, Wakefield RJ, Astin P, Proudman S, Conaghan PG (2001) Predictors of outcome in patients with oligoarthritis: results of a protocol of intra-articular corticosteroids to all clinically active joints. Arthritis Rheum 44(5): Harrison BJ, Symmons DP, Barrett EM, Silman AJ (1998) The performance of the 1987 ARA classification criteria for rheumatoid arthritis in a population based cohort of patients with early inflammatory arthritis. J Rheumatol 25(12): Irvine S, Munro R, Porter D (1999) Early referral, diagnosis and treatment of rheumatoid arthritis: evidence for changing medical practice. Ann Rheum Dis 58(8): Klareskog L, Nordmark B, Lindblad S (2001) On the organization of an early arthritis clinic. Best Pract Res Clin Rheumatol 15(1): 1 15 Masi AT, Maldonado-Cocco JA, Kaplan SB, Feigenbaum SL, Chandler RW (1976) Prospective study of the early course of rheumatoid arthritis in young adults: comparison of patients with and without rheumatoid factor positivity at entry and identification of variables correlating with outcome. Semin Arthritis Rheum 4(4): Quinn M, Emery P (2005) Are early arthritis clinics necessary? Best Pract Res Clin Rheumatol 19(1): 1-17 Quinn MA, Green MJ, Emery P (2003) Evaluation and management of early inflammatory polyarthritis. In: Hochberg MC, Silman AJ, Smolen JS, Weinblatt ME, Weisman MH, eds. Practical Rheumatology. 3rd edn. Mosby, St Louis Van der Horst-Bruinsma I, Speyer I, Visser H, Breedveld FC, Hazes JM (1998) Diagnosis and course of early onset arthritis: results of a special early arthritis clinic compared to routine care. Br J Rheumatol 37(10): Wolfe F, Ross K, Hawley F, Roberts F, Cathey M (1993) The prognosis of rheumatoid arthritis and undifferentiated polyarthritis syndrome in the clinic: a study of 1141 patients. J Rheumatol 20: Table 3. Clinical characteristics of the patients suffering from early arthritis assessed. Variable Number (%) Patients presenting with hand joint pain 67/69 (97.1%) Patients presenting with joint pain >3 joints 64/69 (92.8%) Symmetric arthritis 34/69 (49.3%) Positive compression test MCP joints 47/69 (68.1%) Positive compression test MTP joints 31/69 (44.9%) Duration of morning stiffness (mean) minutes Subcutaneous nodules 0/69 Baseline HAQ Hand erosions by X-ray 0/69 Rheumatoid factor positive 25/69 (36.23%) ESR (mean) 23 mm/hour CRP (mean) 8.56 mg/litre ESR = Erythrocyte sedimentation rate; CRP = C-reactive protein; HAQ = Health assessment questionnaire; MCP = Metacarpophalangeal; MTP = Metatarsophalangeal Table 4. Correlation between the disease activity parameters in the patients with early arthritis TJC 0.831** 0.303* 0.305* 0.709** 0.623** 0.622** 0.358* SJC * 0.421* 0.415* PGH 0.562** ** 0.975** PS 0.421** ** PhGH 0.560** ESR * CRP MS CRP ESR PhGH PS PGH SJC **p<0.001; *p<0.05; MS = Morning stiffness; CRP = C-reactive protein; ESR = Erythrocyte sedimentation rate; PGH = Patient global health assessment; PhGH = Physician global health assessment; PS = Pain score; SJC = Swollen joint count; TJC = Tender joint count Key Points n Rheumatology nurse specialists can be a good asset in the assessment of patients with early arthritis. n The early arthritis clinic model helps to shorten the referral lag time as well as lag time to start disease-modifying antirheumatic drug therapy. n The clinic proforma enabled the specialist nurse to discriminate between early arthritis cases and other subclinical conditions that might cause joint pain. British Journal of Nursing, 2006, Vol 15, No BJN_15_7_394_9_arthritis.indd 7 5/4/06 11:32:13
J. van Aken* H. van Dongen* S. le Cessie F.C. Breedveld T.W.J. Huizinga. * both authors contributed equally
CHAPTER Comparison of long term outcome of patients with rheumatoid arthritis presenting with undifferentiated arthritis or with rheumatoid arthritis: an observational cohort study J. van Aken* H. van
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