9The course of established rheumatoid arthritis
Introduction
In 1992, an article in this series of reviews summarised existing opinions on the course of rheumatoid arthritis (RA).1 There have been many developments in the intervening period, including new diagnostic tests, novel imaging modalities, better understanding and assessment of disability and quality of life, and many therapeutic innovations. Yet not everything has changed; patients with RA continue to have a disabling and often severe disease and much remains to be done before the disease can be considered to have been cured. Consequently, it is both timely and relevant to look once again at the course of RA from the perspective of current clinical practice, and to consider what has changed in the last couple of decades.
Studying the course of a disease is only of major relevance in long-term medical conditions. Acute self-limiting diseases or disorders that are rapidly fatal are not usually considered from such a viewpoint. The course of a chronic disease is synonymous with the concept of its natural history. This approach to medical practice can be traced back to Pliny the Elder and classical Rome, which was the source of the concept of ‘natural history’. In modern day terms, the natural history of RA falls into a number of areas, which although broadly inter-related, are nevertheless relatively independent.
Three general themes define the course of RA and contribute to its understanding. The first theme is the impact of joint inflammation; the extent and severity of these inflammatory changes varies, depending on both factors caused by the disease itself and by the impact of anti-rheumatic drugs. The second theme is the effect of RA on general health, including both extra-articular disease and associated comorbidities. The third theme is its effect on joint damage. These different aspects of RA combine and cause disability and reduce quality of life.
Cutting across these general themes are three other issues, which are important but somewhat different. One of these is the effect of RA on subsets of patients, such as different age groups and different racial groups. A second is the existence of variants of rheumatoid arthritis, an example being fibromyalgic RA. Third, there are issues related to prognostic factors; in particular identifying patients with RA who will do well or badly based on pre-existing genetic risks.
This multiplicity of factors means that there is no single or simple way to summarise the natural history of RA in an individual patient or even in a group of patients. The overall natural history of RA remains complex and its different components need to be described independently. A consequence of the variability in the clinical features of RA is that some clinicians believe it is not a single disease but a collection of separate disorders collected under a ‘flag of convenience’. Heterogeneity in both the genotypes and phenotypes of RA might favour the presence of such disease diversity, but the arguments favouring disease splitting or disease lumping are probably true for most chronic disorders.
Virtually no patients with RA are untreated nowadays, although many choose not to take all the treatments recommended to them. It is very difficult to assess the impacts of different forms of treatment in the long term, beyond the impacts identified in randomised controlled trials. Consequently, in this chapter we will not consider the impact or effects of specific forms of therapy in RA. Clearly, this restriction has limitations. For example, patients treated before the current era of biologics received very different patterns of therapy from those that are now widely used, making it difficult to compare treatment across different eras. Nevertheless, the experiences of these earlier years still have some valuable lessons for current times.
Section snippets
General description of the disease course
The classic descriptions of disease course by Short and Bauer, conceived over 50 years ago, suggested three broad patterns – progressive, intermittent and ‘malignant’ RA.2, 3, 4 In progressive disease, which occurred in 70% of cases, there was an invariable trend towards progression, with fluctuations in severity. In intermittent disease, which occurred in 25% of cases, attacks of arthritis were followed by intermissions for variable periods; in many cases, these remissions lasted for more than
Classic polyarticular disease
Our present understanding the natural history of classic polyarticular RA has been advanced by large, prospective, observational studies of early disease followed-up for prolonged periods. The best example is the Norfolk Arthritis Register (NOAR), which was set up in 1989 and has now enrolled over 3000 patients with early inflammatory arthritis.7 One important finding from NOAR is that the 1987 American College of Rheumatology (ACR) criteria for RA are not ideal.8 Some patients met the criteria
Definitions
Although remission is an important outcome of treatment, it is defined in many different ways and no single set of criteria is predominant. Many studies use the American Rheumatism Association (ARA) criteria; these are strict and require patients to satisfy five criteria on two consecutive months, including: morning stiffness lasting 15 minutes; no fatigue; no joint pain by history; no joint tenderness or pain on motion; no soft tissue swelling in joints or tendon sheaths; and ESR < 30 mm/h for men
Assessments
Disability can be measured using generic measures, like the SF-36 and Nottingham Health Profile (NHP), or disease-specific measures, like the Health Assessment Questionnaire (HAQ) or the Arthritis Impact Measurement Score (AIMS).52 Historically, simple classifications systems were used such as the Steinbrocker Functional Class.53 The most detailed information has come from studies using the HAQ. Disability increases with disease duration with an average annual increase of 1–2% in patients
Assessment
Outcome studies evaluate joint damage using plain X-rays and focus on joint-space loss and juxta-articular bone erosions, usually in the hands and feet. These X-rays are generally evaluated using semiquantitative methods, particular Larsen's and Sharp's scores, together with a number of variations in these approaches.82 As these methods have different scales, changes in damage have been expressed as percent maximal damage.
Changes in damage
We have identified 15 studies that have assessed changes in joint damage
Assessment
Disease activity can be assessed in terms of individual measures, such as joint counts, the ESR or as composite measures; the most well-known composite measure is the disease activity score (DAS). Joint counts can include an extended 66/68 joint count, the Ritchie articular index and the reduced 28-joint count. There is no advantage in examining large numbers of joints, and therefore the 28-joint count has been widely adopted.98 The DAS can be used with 28-joint counts.99 It is widely
Definitions
There are many different types of comorbidity in RA. Some of these, such as lung disease and vasculitis, are extra-articular manifestations of the disease process. Others, such as gastrointestinal ulcers and liver damage, might be a consequence of medication. A third group is disease-associated comorbidities, the best example of which is ischaemic heart disease. Finally, comorbidities might be unrelated to the disease process and could have occurred for other reasons. These various types of
Potential extent
Genetic polymorphisms have the potential to influence joint inflammation, joint damage and extra-articular disease, thus profoundly affecting the course of RA. Associated comorbidities such as cardiovascular disease are now well recognised as being complex diseases themselves, with specific genetic risk factors; these can affect the outcome of RA either directly or indirectly, via interactions with the rheumatoid disease process itself. To make matters more complicated, the effects of treatment
Conclusions
There is no single approach to assessing the course of RA. Patients can have problems in a variety of domains and although patients with severe disease are likely to fare less well overall, not all patients will do poorly in all areas. The variability of RA with time and across different aspects of patients' lives makes it very difficult to capture its overall course in a single individual.
One key issue is whether the various subtypes of RA, such as fibromyalgic and polymyalgic disease, are
Acknowledgements
The authors' ongoing research in rheumatoid arthritis is supported by the Arthritis Research Campaign and we are grateful for their continuing help.
References (144)
- et al.
The course of rheumatoid arthritis
Baillieres Clinical Rheumatology
(1992) Rheumatoid arthritis: types of course and prognosis
Medical Clinics of North America
(1968)- et al.
The systemic lesions of malignant rheumatoid arthritis
The American Journal of Medicine
(1954) Articular patterns in the early course of rheumatoid arthritis
The American Journal of Medicine
(1983)- et al.
The clinical features of rheumatoid arthritis
European Journal of Radiology
(1998) - et al.
Late onset rheumatoid arthritis: clinical and laboratory comparisons with younger onset patients
Archives of Gerontology and Geriatrics
(2006) - et al.
Elderly-onset rheumatoid arthritis
Rheumatic Diseases Clinics of North America
(2000) - et al.
Genes, environment and immunity in the development of rheumatoid arthritis
Current Opinion in Immunology
(2006) - et al.
Remission in rheumatoid arthritis: wishful thinking or clinical reality?
Seminars in Arthritis and Rheumatism
(2005) - et al.
Predictive factors in early arthritis: long-term followup
Seminars in Arthritis and Rheumatism
(2004)
Long-term outcome of treating rheumatoid arthritis: results after 20 years
Lancet
Longitudinal radiographic analysis of rheumatoid arthritis in the hand and wrist
The Journal of Hand Surgery
The course of rheumatoid arthritis in patients receiving simple medical and surgical measures
New England Journal of Medicine
Rheumatoid Arthritis
Aspects of early arthritis. What determines the evolution of early undifferentiated arthritis and rheumatoid arthritis? An update from the Norfolk Arthritis Register
Arthritis Research & Therapy
The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis
Arthritis and Rheumatism
The NOAR Damaged Joint Count (NOAR-DJC): a clinical measure for assessing articular damage in patients with early inflammatory polyarthritis including rheumatoid arthritis
Rheumatology (Oxford)
Ten year outcome in a cohort of patients with early rheumatoid arthritis: health status, disease process, and damage
Annals of the Rheumatic Diseases
How to diagnose rheumatoid arthritis early: a prediction model for persistent erosive) arthritis
Arthritis and Rheumatism
Palindromic rheumatism: part of or apart from the spectrum of rheumatoid arthritis
The American Journal of Medicine
The role of anti-cyclic citrullinated peptide antibodies in predicting progression of palindromic rheumatism to rheumatoid arthritis
The Journal of Rheumatology
Prevalence and clinical significance of anti-cyclic citrullinated peptide and antikeratin antibodies in palindromic rheumatism. An abortive form of rheumatoid arthritis?
Rheumatology Oxford
The prevalence and meaning of fatigue in rheumatic disease
The Journal of Rheumatology
Fatigue in rheumatoid arthritis reflects pain, not disease activity
Rheumatology (Oxford)
Severe rheumatoid arthritis (RA), worse outcomes, comorbid illness, and sociodemographic disadvantage characterize ra patients with fibromyalgia
The Journal of Rheumatology
Diagnosing late onset rheumatoid arthritis, polymyalgia rheumatica, and temporal arteritis in patients presenting with polymyalgic symptoms. A prospective longterm evaluation
The Journal of Rheumatology
Does the age of onset of rheumatoid arthritis influence phenotype? a prospective study of outcome and prognostic factors
Rheumatology (Oxford)
Elderly onset rheumatoid arthritis: clinical aspects
Clinical and Experimental Rheumatology
Early rheumatoid arthritis patients: relationship of age
Rheumatology International
Outcome of late-onset rheumatoid arthritis
Clinical Rheumatology
Aging, autoimmunity and arthritis: T-cell senescence and contraction of T-cell repertoire diversity - catalysts of autoimmunity and chronic inflammation
Arthritis Research & Therapy
The multiple facets of premature aging in rheumatoid arthritis
Arthritis and Rheumatism
Hypothalamic-pituitary-adrenocortical and gonadal functions in rheumatoid arthritis
Annals of the New York Academy of Sciences
Rheumatoid cachexia: metabolic abnormalities, mechanisms and interventions
Rheumatology (Oxford)
Impact of age and comorbidities on the criteria for remission and response in rheumatoid arthritis
Annals of the Rheumatic Diseases
Remitting seronegative symmetrical synovitis with pitting edema. RS3PE syndrome
Journal of the American Medical Association
Remitting, seronegative, symmetrical synovitis with pitting edema—13 additional cases
The Journal of Rheumatology
The syndrome of seronegative symmetrical synovitis with pitting edema (RS3 PE syndrome): a unique form of arthritis in the elderly? Report of 4 additional cases
The Journal of Rheumatology
Remitting seronegative symmetrical synovitis with pitting edema of the hands: ultrasound, color doppler ultrasound, and magnetic resonance imaging findings
Arthritis and Rheumatism
Remitting seronegative symmetrical synovitis with pitting edema syndrome: followup for neoplasia
The Journal of Rheumatology
Refining the complex rheumatoid arthritis phenotype based on specificity of the HLA-DRB1 shared epitope for antibodies to citrullinated proteins
Arthritis and Rheumatism
Correlation between disease phenotype and genetic heterogeneity in rheumatoid arthritis
The Journal of Clinical Investigation
Outcome in patients with early rheumatoid arthritis treated according to the ‘sawtooth’ strategy
Arthritis and Rheumatism
Remission in a prospective study of patients with rheumatoid arthritis. American Rheumatism Association preliminary remission criteria in relation to the disease activity score
British Journal of Rheumatology
Utility of disease modifying antirheumatic drugs in ‘sawtooth’ strategy. A prospective study of early rheumatoid arthritis patients up to 15 years
Annals of the Rheumatic Diseases
Early inflammatory polyarthritis: results from the Norfolk Arthritis Register with a review of the literature. II. Outcome at three years
Rheumatology (Oxford)
How does functional disability in early rheumatoid arthritis (RA) affect patients and their lives? Results of 5 years of follow-up in 732 patients from the Early RA Study (ERAS)
Rheumatology (Oxford)
Prognostic factors for remission in early rheumatoid arthritis: a multiparameter prospective study
Annals of the Rheumatic Diseases
Rheumatoid arthritis in Spain: occurrence of extra-articular manifestations and estimates of disease severity
Annals of the Rheumatic Diseases
The influence of sex on rheumatoid arthritis: a prospective study of onset and outcome after 2 years
The Journal of Rheumatology
Cited by (79)
The relationship between major dietary patterns and disease activity of rheumatoid arthritis
2022, Clinical Nutrition ESPENCitation Excerpt :Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes joint erosion and systemic inflammation. RA affects 0.5–1% of the world's population [1]. Inflammatory cascades are activated, and pro-inflammatory indicators such as interleukin-1 (IL-1) and interleukin-6 (IL-6) are elevated in the synovium, increasing protease activity and promoting joint erosion.
Descriptive epidemiology of hip and knee replacement in rheumatoid arthritis: An analysis of UK electronic medical records
2020, Seminars in Arthritis and RheumatismCitation Excerpt :The progressive and often permanent nature of radiographic joint damage, in conjunction with associated pain, loss of function and failure to adequately respond to therapeutic options are strong indications for eventual joint replacement surgery [2,3]. While progression of structural damage in RA has been well described [4,5], long-term clinical outcomes such as the incidence of joint replacement remains less well studied [6]. Estimates from the US National Inpatient Sample from 2002–2012 indicate that of approximately 2.7 million total hip replacements (THR) and 5.7 million total knee replacements (TKR), approximately 3% were carried out in patients with prevalent RA.
Joint disease
2019, Ortner's Identification of Pathological Conditions in Human Skeletal Remains