Elsevier

The Lancet

Volume 382, Issue 9894, 31 August–6 September 2013, Pages 797-808
The Lancet

Series
Clinical aspects of autoimmune rheumatic diseases

https://doi.org/10.1016/S0140-6736(13)61499-3Get rights and content

Summary

Multisystem autoimmune rheumatic diseases are heterogeneous rare disorders associated with substantial morbidity and mortality. Efforts to create international consensus within the past decade have resulted in the publication of new classification or nomenclature criteria for several autoimmune rheumatic diseases, specifically for systemic lupus erythematosus, Sjögren's syndrome, and the systemic vasculitides. Substantial progress has been made in the formulation of new criteria in systemic sclerosis and idiopathic inflammatory myositis. Although the autoimmune rheumatic diseases share many common features and clinical presentations, differentiation between the diseases is crucial because of important distinctions in clinical course, appropriate drugs, and prognoses. We review some of the dilemmas in the diagnosis of these autoimmune rheumatic diseases, and focus on the importance of new classification criteria, clinical assessment, and interpretation of autoimmune serology. In this era of improvement of mortality rates for patients with autoimmune rheumatic diseases, we pay particular attention to the effect of leading complications, specifically cardiovascular manifestations and cancer, and we update epidemiology and prognosis.

Introduction

Autoimmune diseases form a range of disorders from organ-specific (eg, Hashimoto's thyroiditis) to systemic disorders with multi-organ involvement. Disorders that mainly, but not exclusively, affect joints and muscles are grouped together as the autoimmune rheumatic diseases, and include rheumatoid arthritis, systemic lupus erythematosus, primary Sjögren's syndrome, systemic sclerosis (scleroderma), idiopathic inflammatory myositis, and the systemic vasculitides. These multisystem autoimmune rheumatic diseases are heterogeneous disorders associated with substantial morbidity and mortality. Although these diseases can present classically, which makes diagnosis simple, they also share many common features, including constitutional disturbance, arthralgia and arthritis, myalgia, sicca symptoms, and pulmonary, renal, and neurological involvement, which can make differentiation between the diseases difficult.

Up to 50% of patients with an apparent autoimmune rheumatic disease cannot be readily diagnosed with a specific disorder in the first 12 months of follow-up.1 The term undifferentiated connective tissue disease is often used to describe this group of patients. Some patients with this presentation will progress to a defined autoimmune rheumatic disease during 5 years of follow-up, a smaller proportion resolve completely, and most remain symptomatic but undefined.2, 3, 4 Patients who remain symptomatic generally have a good prognosis, although the persistent symptoms and uncertainty about the diagnosis can lead to substantial patient frustration and morbidity. Less common is when convincing features of two autoimmune rheumatic diseases are present, and terms such as rhupus (rheumatoid arthritis and systemic lupus erythematosus) or overlap syndrome (eg, scleroderma-lupus overlap) are often used. Management is largely guided by the dominant clinical phenotype. A more specific diagnosis can be reached by review with an experienced clinician, effective use and judicious interpretation of immunopathological tests, together with careful follow-up, thereby helping to inform treatment decisions and prognosis.

Rheumatology is entering an exciting time; several revised classification criteria of autoimmune rheumatic diseases are available to help with diagnostic challenges and expanding treatment opportunities. This Review summarises recent advances in understanding the clinical features of systemic lupus erythematosus, Sjögren's syndrome, systemic sclerosis, idiopathic inflammatory myositis, and the systemic vasculitides, in particular concentrating on developments in classification criteria, epidemiology, and prognosis, many as a result of international collaboration, and the long-term follow-up of dedicated cohorts of patients over several decades. Further articles in this Series will assess pathogenesis and treatment of the autoimmune rheumatic diseases.

Section snippets

Use of autoantibodies in diagnosis

Attempts to refine classification criteria for various autoimmune rheumatic diseases show the dilemma faced by clinicians in establishing early diagnosis and prognosis. Although diagnosis can be straightforward when characteristic features of specific diseases are present, patients ultimately diagnosed with an autoimmune rheumatic disease are often a diagnostic challenge. Many of the early symptoms are prodromal features of constitutional disturbance that are clinically indistinguishable

Recent advances in disease definitions and classification

Clinicians need to recognise the important distinctions between nomenclature systems, classification criteria, and diagnostic criteria. Diagnostic criteria are intended for clinical use to confirm the presence of a disease. Nomenclature systems, such as those discussed in reference to systemic vasculitis, specify the name to be used once a specific diagnosis is made. Classification criteria are findings that allow the classification of a patient into a particular category for further study and

Epidemiology

Changes in classification criteria pose several challenges to understanding the epidemiology of the autoimmune rheumatic diseases. The changes make historic comparisons difficult, and the use of different criteria in different parts of the world further restricts assessment of the global burden of these diseases. The rarity of individual autoimmune rheumatic diseases also contributes to the difficulties in the creation of accurate data on incidence and prevalence. Although improved

Selected clinical outcomes

In the past 30–40 years, mortality rates for patients with autoimmune rheumatic diseases have mainly fallen and causes of morbidity have changed. Reasons for these improvements are multifactorial, but are most probably attributable to earlier diagnosis and diagnosis of milder disease, availability of immunosuppressives and biological treatments, and improvements in supportive regimens. Consequently, alternative causes for morbidity and death have become more predominant in many of the

Cardiovascular disease

Atherosclerotic cardiovascular disease is an inflammatory disease.56 Premature death from cardiovascular disease was reported in patients with systemic lupus erythematosus in the 1970s,57 and the risk of death from cardiovascular disease and thrombotic events has not improved in recent years.58, 59 Traditional cardiovascular risk factors do not explain the increased burden of cardiovascular disease in systemic lupus erythematosus,60, 61 and inflammation, treatment side-effects, and factors

Cancer

The risk of cancer is increased in patients with various autoimmune rheumatic diseases, most clearly documented with non-Hodgkin lymphoma.70, 71, 72 The association suggests that disordered immune function contributes to the pathogenesis of various cancers, but has also raised concerns about the contribution of immunosuppressive drugs. Conversely, most clearly in the case of idiopathic inflammatory myositis, the association suggests that cancer contributes to the development of autoimmunity.

One

Disease damage and mortality

In patients with systemic lupus erythematosus, survival in western nations has improved from around 50% at 5 years in the 1950s, to between 80 and 90% at 10 years in many cohorts since the 1980s.59, 82, 83 This improvement is partly attributable to diagnosis of milder disease and improvements in treatment of renal disease and infection. Predictors of mortality vary across cohorts; renal disease, damage accrual, hypertension, and corticosteroid use are associated in several reports.58, 83, 84

Conclusions

Classification criteria for autoimmune rheumatic diseases have been the source of considerable debate as rheumatologists strive to ensure appropriate identification of disease and thereby apply targeted treatments to improve patient outcomes. In the past 10 years, large-scale international cooperation has resulted in the continuing development of comprehensive classification and nomenclature criteria for the autoimmune rheumatic diseases. These new approaches mirror our present understanding of

Search Strategy and selection criteria

We searched the Cochrane Library and Medline from Jan 1, 1990, to Dec 31, 2012, with the search terms “systemic lupus erythematosus”, “SLE”, “Sjögren's syndrome”, “systemic sclerosis”, “scleroderma”, “inflammatory myositis”, “dermatomyositis”, “polymyositis”, “inclusion body myositis”, “systemic vasculitis”, “giant cell arteritis”, “temporal arteritis”, “Takayasu's arteritis”, “polyarteritis nodoa”, “Wegener's granulomatosis”, “granulomatosis with polyangiitis”, “Churg Strauss syndrome”,

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