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Current concepts in rheumatology 

Current concepts in rheumatology
Current concepts in rheumatology

Philip Helliwell

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date: 19 June 2019

Epidemiology of rheumatic disease

Musculoskeletal disorders represent a significant proportion of the conditions contributing to the global burden of disease (1). Mostly, this is the so-called degenerative disorders: osteoarthritis and mechanical low back and neck pain. Together they cause significant morbidity. In the UK, low back and neck pain are the leading causes of disability-adjusted life years, with other musculoskeletal disorders coming in sixteenth (2). Globally, musculoskeletal disorders have an equivalent impact to depressive and behavioural disorders (3). However, there remain significant epidemiological challenges. Firstly, classification criteria for rheumatic diseases are evolving as new knowledge is accrued. Secondly, the ways in which criteria are applied across communities where a host of problems may be at work—language, geography, access, and politics are just some of the barriers. The World Health Organization (WHO) has, for some years, been supporting epidemiological studies in areas of the world where only rudimentary data are available. The Community-Oriented Program for Control of Rheumatic Diseases (COPCORD) initiative has provided valuable data on rheumatic disease prevalence in many previously uncharted communities (

Osteoarthritis and other mechanical soft-tissue disorders are by far the most common cause of foot pain in the UK. Their management varies from resigned acceptance and self-modification of footwear to skilled intervention by health professionals. However, it is the less common inflammatory conditions that receive most attention in secondary care and that are the main focus of much of this book. In parallel, the majority of patients presenting to primary care physicians with musculoskeletal pain have osteoarthritis or soft-tissue disorders while the majority of patients seen in secondary care clinics have inflammatory musculoskeletal disorders (IMDs). Why should this be so when the burden of disease and disability is overwhelmingly with osteoarthritis and soft-tissue disorders? Essentially, IMDs are more likely to be destructive locally, to be polyarticular, and to have systemic features, thus requiring more complex medical management. Furthermore, diseases causing synovial inflammation, such as rheumatoid arthritis, commonly affect the foot, with over 90% of cases having foot involvement (4).

The concept of early treatment and the window of opportunity

Generally, and including the foot and ankle, it is believed there is a ‘window of opportunity’ in early inflammatory disease where aggressive early treatment might abort the processes that are causing inflammation, thus preventing joint damage and the chronic cycle of inflammatory change that might occur (5). The classic paradigm here is with rheumatoid arthritis where early and targeted treatment leads to better outcomes, but the same is likely true for other inflammatory diseases such as psoriatic arthritis (6). This trend to earlier treatment is reflected by the widespread adoption of early arthritis clinics, where the aim is to see and treat people before the disease becomes too established.

This concept has been nicely illustrated in the foot by Helliwell et al (Figure 1.1). The foot and ankle may well be a special case in terms of early intervention, as continued loading of inflamed structures may lead to early damage and deformity. This was illustrated by one of the first randomized controlled trials of functional foot orthoses in rheumatoid arthritis in a population who did not have particularly early disease but who had established, and partly reversible, deformity (7). As ever, the concept of joint protection in the foot is difficult to apply but should be acknowledged at an early stage.

Figure 1.1 ‘Window of opportunity’ in early inflammatory disease. The course of deformity (Y1) is plotted against time (X) from disease onset alongside treatment strategy (Y2). Patients who develop severe deformity within 5 years from disease onset (pathway C) have only a short time period in which to initiate preventative management. Others may develop progressive deformity (pathway B) following repeated inflammatory attacks (hence the ‘saw-tooth’ appearance). Finally, a smaller group (pathway A) resist cumulative damage and deformity until the later stages of disease and then rapid development of deformity occurs following some acute incident (perhaps rupture of tibialis posterior tendon). RA, Rheumatoid arthritis.

Figure 1.1 ‘Window of opportunity’ in early inflammatory disease. The course of deformity (Y1) is plotted against time (X) from disease onset alongside treatment strategy (Y2). Patients who develop severe deformity within 5 years from disease onset (pathway C) have only a short time period in which to initiate preventative management. Others may develop progressive deformity (pathway B) following repeated inflammatory attacks (hence the ‘saw-tooth’ appearance). Finally, a smaller group (pathway A) resist cumulative damage and deformity until the later stages of disease and then rapid development of deformity occurs following some acute incident (perhaps rupture of tibialis posterior tendon). RA, Rheumatoid arthritis.

Reproduced from Helliwell P, Woodburn J, Redmond A, Turner D, Davys H. The Foot and Ankle in Rheumatoid Arthritis: A Comprehensive Guide. London: Churchill Livingstone: Elsevier; 2007.

There may be several reasons why delays occur before effective treatment can be given. The patient may not consult for a variety of reasons, including low expectations, poor availability of appropriate care, and a hope that things may settle with time. Once people consult, there may be disincentives to refer early, both financial and educational, and initial treatment may be symptomatic only. People consult a wide spectrum of health professionals and sorting out those who need early referral and treatment from those who don’t is a challenge. A few simple ‘rules’ have been suggested (Box 1.1) (8). Whatever set of guidance is used, a low threshold of referral is necessary for treatment to be started early enough—within 3–6 months of symptom onset.

Information sourced from Emery P, Breedveld FC, Dougados M, Kalden JR, Schiff MH, Smolen JS. Early referral recommendation for newly diagnosed rheumatoid arthritis: evidence based development of a clinical guide. Annals of the Rheumatic Diseases. 2002;61(4):290.

Delays at the secondary care institution could be minimized by appropriate triage and availability of clinic appointments. The development of new classification criteria, designed to permit earlier identification and treatment, may well help earlier identification and treatment in this disease (Table 1.1) (9).

Table 1.1 The 2010 classification criteria for rheumatoid arthritis. These criteria apply to people who have at least one joint with synovitis and no other plausible explanation for the condition (e.g., someone with psoriatic arthritis)

Add scores of categories A to D. Interpretation: a score of ≥6 indicates that this person can be classified as having rheumatoid arthritis

A. Joint involvement



1 large joint (hip, knee, ankle, shoulder, elbow)


2–10 large joints


1–3 small joints (excludes distal interphalangeal joints, first carpometacarpal joint, and first metatarsophalangeal joint)


4–10 small joints


>10 joints (includes at least one small joint)


B. Serology



Negative rheumatoid factor (RF) and negative anti-citrullinated protein antibody (ACPA)


Low positive RF or low positive ACPA


High positive RF or high positive ACPA


C. Acute phase reactants



Normal C-reactive protein (CRP) and normal erythrocyte sedimentation rate (ESR)


Abnormal CRP and abnormal ESR


D. Duration of symptoms



<6 weeks


≥6 weeks


Reproduced from Aletaha D, Neogi T, Silman AJ et al. 2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Annals of the Rheumatic Diseases. 2010;69(9):1580–8 with permission from Wiley.

If a true biologic marker was available diagnosis would be much more straightforward for all concerned. A biologic marker usually has pathological relevance, and for some time it was thought that rheumatoid factor fulfilled this role in rheumatoid arthritis. However, it later became clear that rheumatoid factor is present in only about 75% of cases of rheumatoid arthritis. Further biologic markers have been sought. Antibodies to keratin, in particular anti-citrullinated protein antibodies (ACPAs), have been found to be more specific (95%) for rheumatoid arthritis than rheumatoid factor. However, this occurs at the cost of lower sensitivity (67%) (10). This test may, however, be of more use in situations where it is desired to have a very low rate of false positives. Are new ways of imaging helpful? For example, magnetic resonance imaging (MRI) is a very sensitive technique for detecting inflammation. Joints not inflamed clinically may, nevertheless, show extensive inflammation on MRI. The same is true for ultrasound (US), especially power Doppler US. Both these techniques are discussed in Chapter 12. The point to be made here is that using these new techniques may change the way we diagnose and treat inflammatory diseases such as rheumatoid arthritis. MRI is costly but US is cheaper, is becoming widely available, and may permit much earlier diagnosis.

Treatment approaches: pharmacological therapies

The treatment of IMDs has seen many significant changes over the past 15 years, with the concept of tight control and the introduction of biologic drugs. The biologic drugs, the logical end-product of the science of inflammation, have transformed the treatment of inflammatory disease, and may even yet be found to be of use in other musculoskeletal disorders. With the advent of biologic drugs has come an escalation of costs, making the rheumatology department one of the most expensive in the hospital setting. However, traditional approaches must not be forgotten. Small molecules such as hydroxychloroquine, methotrexate, and corticosteroids remain the cornerstone of treatment and are cheap and readily available across all societies. Biologic drugs, given systemically, may be ‘rationed’ (, accessed 25 January 2016) but are generally widely available in the UK, if needed. It is also worth remembering that IMDs are still potentially chronic disabling disorders, without a cure, and that treatment of patients with these conditions should involve much more than just pharmacotherapy, although that does provide the starting point. The multidisciplinary team, consisting of physicians, nurses, physiotherapists, occupational therapists, podiatrists, pharmacists, and psychologists, is still important to the patient in the delivery of their care.

Tumour necrosis factor (TNF) inhibitors have proven to be the benchmark of biologic therapies across the disease spectrum, particularly in rheumatoid arthritis and the spondyloarthropathies. Clearly TNF is a key cytokine in the process of inflammation and abrogation of this molecule will result in significant, and often life-changing, improvements for patients. The initial fears of adverse events—and in particular neoplasm and infection—have been less prominent than expected but, of course, remain a threat and can be catastrophic for some patients. TNF inhibitors probably work better for spondyloarthropathy than rheumatoid arthritis, for which they were initially designed, but there is a significant proportion of patients in whom the drug does not work and in whom the drug does work but subsequently becomes ineffective. In the latter group it may help to switch to another TNF inhibitor, but there is little benefit in so doing with the former group. Those who never respond to TNF inhibitors may be driven by other cytokines—interleukin (IL)-17, for example—and an alternative approach to disease management is required in this group.

Other cytokine inhibitors that are now available or becoming available are inhibitors of IL-6, the IL-17 inhibitors, the IL-12/23 (and IL-23 alone) inhibitors, and there are a host of others in development. The cytokines (IL-17 and IL-23) are clearly more important in spondyloarthropathy and will in time completely change our treatment options for these disorders. IL-17 inhibition may work for TNF-resistant rheumatoid arthritis, but early results are not promising. For rheumatoid arthritis IL-6 seems to be important and this is now an important alternative treatment for patients with rheumatoid arthritis who have never responded to TNF inhibitors or for whom several have failed.

There are other biologic drugs targeted not at cytokines but at cell lines or cell–cell interaction. Of these, rituximab, targeting a surface molecule on B cells (which produce antibodies and autoantibodies such as rheumatoid factor and ACPA), has proven to be very effective in rheumatoid arthritis and systemic lupus. Abatacept, targeting T cell surface molecules, is an alternative treatment of rheumatoid arthritis and has been used in psoriatic arthritis. Other ways of selectively blocking inflammatory pathways are under development or are about to be introduced and we can expect new, and biosimilar, drugs to appear regularly in the future. Indeed, new small molecules have been developed that target immune cellular pathways. Of these the Janus kinase (JAK) inhibitors and inhibitors of phosphodiesterase-4 look promising.

For all these powerful disease-modifying drugs it is worth remembering that the normal immune system also uses these pathways so that lowered immunity means that infection is a constant risk. If infection occurs, it can spread locally extremely fast and become a systemic infection with all the gravity of that situation. As clinicians we should keep a low threshold of detection and management of infection, particularly in the foot, in people on any antirheumatic drug, but particularly biologic drugs. The patient should be advised to stop the drug and seek immediate treatment for the infection—usually a combination of local and systemic therapy (Box 1.2) (11).

Adapted from Williams A. et al. Guidelines for the management of foot health problems associated with rheumatoid arthritis. Musculoskelet Care. 2011;9:86–92 with permission from Wiley.

Treatment approaches: non-pharmacological therapies

As noted above, although biologic therapies may have a dramatic impact, there is much more to the delivery of care. In recent years the importance of the multidisciplinary team in disease management has been highlighted in the UK by the National Institute of Health and Care Excellence (NICE) and by the Arthritis and Musculoskeletal Alliance (ARMA) ( and There is evidence that this model has not been widely adopted from the point of view of podiatry care ( To what extent is the multidisciplinary approach to care evidence-based? There is burgeoning evidence for individual contributions: nursing, podiatry, occupational therapy, physiotherapy (7, 12, 13)—and for education provided across the multidisciplinary team (14).

Care may effectively be delivered in the context of a combined multidisciplinary clinic (15, 16). Such a method of delivering care has been described for the foot across a spectrum of disease, providing anecdotal evidence of improved outcomes and cost savings (15). This approach is not always practical, though: an alternative might be a weekly multidisciplinary meeting to discuss problems and approaches to management of shared patients. Even this approach may provide a challenge in some situations. What is clear is that lines of communication should be established between members of the team so that patient management can be shared—one approach in Bradford, UK is to have a single electronic record shared between the primary and secondary care teams, and to which all relevant parties can contribute.

Economic impact and treatment cost-effectiveness

In most healthcare systems there are finite resources. In the National Health Service typical cost savings of up to 20% have to be made year on year. At the same time, wages are rising, technology and the drugs we use are becoming more expensive. Arguments have been made that the cost/benefit analysis should be wider than just at the individual and local level. In societal terms, the introduction of effective, but expensive, treatments, such as TNF inhibitors, will not only alleviate individual suffering but prevent work loss and increase productivity, to the benefit of the wider community. Nevertheless, in the UK, there is ‘rationing’ of a subtle kind, and this rationing may vary from location to location (the so-called post code lottery). The UK entrusts the guidance on the use of biologics and other new drugs and technologies to NICE. The process by which such judgements are made is a thorough and fair appraisal of the cost/benefit equation. NICE have an unstated threshold of about £30,000 per quality-adjusted life year (QALY). The means by which this is calculated and the projections made in the modelling may have some uncertainties but, equally, the quality of the data provided for the assessments may not always be appropriate. More collaboration between trialists and bodies such as NICE might overcome some of these difficulties, as might new approaches to economic modelling.

The changing role of the multidisciplinary team

With the emergence of new data, foot health management has moved into an evidence-based specialty, and this has in turn led to more prominence in the infrastructure and pathways for treating rheumatic diseases ( At the same time, the treatment paradigm has become aligned with that of rheumatology in general: early detection and treatment prevents subsequent deformity and disability. This has meant that the podiatrist is now much more proactive and treats to prevent rather than to react. Of course, there are still situations where ‘reaction’ is important and treatment of established inflammatory and degenerative diseases will still be a large part of podiatry care.

This early intervention role is mirrored by the approaches taken. There is now much more assessment of the foot as a complex biomechanical structure and less emphasis, especially in early disease, on the skin and nails. Gait analysis, from qualitative assessment to full quantitative studies performed in the laboratory, is an essential part of the role, as well as an appreciation of the contribution of the different soft-tissue structures to the normal function of the foot. Many health professionals are also now becoming skilled at US, so that more precise assessments of ligamentous stability and inflammatory activity can be made, as well as targeted injections.

The podiatrist is also now, as a member of the multidisciplinary team, thinking beyond the foot to the disease as a whole, albeit inflammatory or non-inflammatory. In particular, podiatrists perform an important role in surveillance for potential infection for patients on biologics and for ulceration in rheumatoid arthritis and connective tissue disease. As the role develops it is likely that more and more podiatrists will partake in integrated care in outpatient settings with seamless communication and education links to primary care teams. This role will of course be extended into the wider multidisciplinary team providing care across different settings. Podiatrists will no longer gaze at feet, and never stray above the ankle, but will look beyond to the rest of the patient, as physicians must learn to look below the upper limb to the feet.


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