Autoimmune Rheumatic Diseases: Diagnosis and Management 

Autoimmune rheumatic diseases (ARDs) are a diverse group of conditions that primarily affect the joints, bones, muscle, and connective tissue (see Sidebar).1 They can be especially challenging to diagnose during early stages, often presenting with nonspecific symptoms and signs that may flare and remit. However, early diagnosis is important to improve outcomes for patients.

This article will review ARDs and the importance of early and accurate diagnosis. It will discuss the importance of laboratory testing for autoantibodies and how antibody panels can help to rule in or rule out common autoimmune diseases. Also discussed is the importance of laboratory testing before and after biologic drugs are administered for treatment of ARDs.

Characteristics of ARDs

The ARDs are characterized by an abnormal immune response to normal cells and tissues.1,2 They can lead to severe, debilitating pain and progressive disease. Some are associated with increased morbidity and mortality. The abnormal immune response can be directed at a specific part of the body, such as the joints in rheumatoid arthritis (RA).2 The abnormal response can also be more general and systemic, affecting multiple organs and tissues as with systemic lupus erythematosus (SLE).2 The majority of rheumatic diseases are due to an autoimmune response,1 whereas others (eg, gout and osteoarthritis) have different pathophysiology.

Scope and Causes

The overall prevalence of autoimmunity in the general population is approximately 3% to 5%.2 Women get autoimmune diseases at a rate more than twice that of men (6.4% of women compared to 2.7% of men).3 Different autoimmune diseases can occur at different times in a person’s life. However, women are most commonly diagnosed with an autoimmune disease when they are between 14 and 44 years old.3

Some ARDs, such as SLE, have a genetic component, and can also be triggered by infections or environmental factors.2 However, the cause of an ARD in a specific individual usually cannot be determined.

Diagnosis of ARDs

Diagnosis of ARDs may be delayed because initial signs and symptoms can be nonspecific. If diagnosis is delayed, irreversible joint or organ damage may ensue. Early diagnosis and treatment provides an opportunity to prevent or mitigate this damage, control symptoms, and improve chances for remission.2,4

Signs and Symptoms

Some ARDs have characteristic findings that can aid in diagnosis. For example, the primary symptoms of Sjögren syndrome are dry mouth and dry eyes.5 Other ARDs have characteristic radiographic findings.6-8

However, pathognomonic signs are the exception rather than the rule. The early symptoms of autoimmune diseases may flair and remit and may overlap with those of other conditions, including other ARDs. They may include2,4
  • Muscle aches
  • Fatigue
  • Swelling and redness over the joints
  • Mild fever
  • Trouble concentrating
  • Rashes
  • Hair loss
  • Numbness and tingling in the hands and feet

Autoantibody testing

Autoantibody testing is an important aid in the diagnosis of ARDs.2,9 Almost all ARDs have specific autoantibody profiles (eg, myositis- and systemic sclerosis-specific antibodies). As such, testing for specific autoantibodies can help rule in or rule out specific ARDs. Testing using antibody panels (testing for a number of autoantibodies at the same time) can improve efficiency over sequential testing, expedite diagnosis and treatment, and improve outcomes for patients. Testing patients with risk factors for certain ARDs is also valuable. For example, SLE autoantibodies can be detected many years before a patient becomes symptomatic.10

Management

No single therapy exists for ARDs. Treatments include nonsteroidal anti-inflammatory drugs, immunosuppressants, and cytokine antagonists.2 In general, autoimmune conditions are not cured; treatments are aimed at minimizing symptoms, inhibiting inflammation, slowing progression, and/or inducing remission.2

Biologics and Biosimilars

Many ARDs are treated with biologics or biosimilars. A biologic is a drug that contains components of a living organism or is manufactured in a living system, such as microorganisms, plant cells, or animal cells.11 Many biologics are produced using recombinant DNA technology; others are monoclonal antibodies, including adalimumab, ustekinumab, and infliximab.12-14 A biosimilar is a biologic medical product that is an almost identical copy of an original product.11 Examples include Inflectra™ and Renflexis™, which are biosimilars of Remicade® (infliximab).

Biologics and biosimilars alter the function of the immune system, and alterations of immune function can result in certain latent infections becoming active.14 Thus, laboratory testing for certain infections is essential prior to treatment. Medical professional organization guidelines recommend testing for hepatitis B virus (HBV), hepatitis C virus (HCV), and/or tuberculosis prior to beginning treatment with a biologic or biosimilar.12,15







References
  1. van der Heijde D, Daikh DI, Betteridge N, et al. Common language description of the term rheumatic and musculoskeletal diseases (RMDs) for use in communication with the lay public, healthcare providers and other stakeholders endorsed by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). Ann Rheum Dis. 2018;77:829-832.
  2. Wang L, Wang FS, Gershwin ME. Human autoimmune diseases: a comprehensive update. J Intern Med. 2015;278:369-395.
  3. Hayter SM, Cook MC. Updated assessment of the prevalence, spectrum and case definition of autoimmune disease. Autoimmun Rev. 2012;11:754-765.
  4. Goldblatt F, O'Neill SG. Clinical aspects of autoimmune rheumatic diseases. Lancet. 2013;382:797-808.
  5. Shiboski CH, Shiboski SC, Seror R, et al. 2016 American College of Rheumatology/European League Against Rheumatism classification criteria for primary Sjögren's syndrome: a consensus and data-driven methodology involving three international patient cohorts. Ann Rheum Dis. 2017;76:9-16.
  6. Rudwaleit M, van der Heijde D, Landewé R, et al. The development of Assessment of SpondyloArthritis International Society classification criteria for axial spondyloarthritis (part II): validation and final selection. Ann Rheum Dis. 2009;68:777-783.
  7. Statement on sarcoidosis: joint statement of the American Thoracic Society (ATS), the European Respiratory Society (ERS) and the World Association of Sarcoidosis and Other Granulomatous Disorders (WASOG) adopted by the ATS Board of Directors and by the ERS Executive Committee, February 1999. Am J Respir Crit Care Med. 1999;160:736-755.
  8. Leavitt RY, Fauci AS, Bloch DA, et al. The American College of Rheumatology 1990 criteria for the classification of Wegener's granulomatosis. Arthritis Rheum. 1990;33:1101-1107.
  9. Birtane M, Yavuz S, Taştekin N. Laboratory evaluation in rheumatic diseases. World J Methodol. 2017;7:1-8.
  10. Arbuckle MR, McClain MT, Rubertone MV, et al. Development of autoantibodies before the clinical onset of systemic lupus erythematosus. N Engl J Med. 2003;349:1526-1533.
  11. McCamish M, Yoon W, McKay J. Biosimilars: biologics that meet patients' needs and healthcare economics. Am J Manag Care. 2016;22(suppl 13):S439-S442.
  12. Singh JA, Furst DE, Bharat A, et al. 2012 update of the 2008 American College of Rheumatology recommendations for the use of disease-modifying antirheumatic drugs and biologic agents in the treatment of rheumatoid arthritis. Arthritis Care Res (Hoboken). 2012;64:625-639.
  13. Abreu C, Sarmento A, Magro F. Screening, prophylaxis and counselling before the start of biological therapies: a practical approach focused on IBD patients. Dig Liver Dis. 2017;49:1289-1297.
  14. Henrickson SE, Ruffner MA, Kwan M. Unintended immunological consequences of biologic therapy. Curr Allergy Asthma Rep. 2016;16:46. doi:10.1007/s11882-016-0624-7
  15. Lichtenstein GR, Loftus EV, Isaacs KL, et al. ACG Clinical Guideline: management of Crohn's disease in adults. Am J Gastroenterol. 2018;113:481-517.

Examples of Autoimmune Rheumatic Diseases

  • Rheumatoid arthritis (RA)
  • Systemic lupus erythematosus (SLE)
  • Sjögren syndrome
  • Polymyositis/dermatomyositis
  • Systemic sclerosis
  • Mixed connective tissue disease (MCTD)
  • CREST (calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia) syndrome
  • Neuropsychiatric SLE
How the Laboratory Can Help

Diagnosis

Quest Diagnostics offers tests for the many different antibodies that are associated with ARDs and other autoimmune diseases. The ANAlyzeR™ ANA, IFA with Reflex Titer/Pattern, Systemic Autoimmune Panel 1 (test code 36378) screens for antinuclear antibodies (ANA), which are common to many ARDs. The panel reflexes to ANA titer and simultaneously tests for an additional 24 markers associated with rheumatic and related diseases.

This panel is suitable for individuals with signs and symptoms associated with autoimmune disease(s), and can help to rapidly rule in or rule out autoimmune and coexisting conditions. For example, a positive result for rheumatoid factor (IgA, IgG, IgM), cyclic citrullinated peptide (CCP) antibody (IgG), or 14-3-3η protein generally supports a diagnosis of RA. Quest also offers more limited but focused panels for diagnosis of ARDs. See TestDirectory.QuestDiagnostics.com for more information.

Pretreatment

The Quest Pre-biologic/biosimilar Screen Panel, HCV/HBV with Reflexes and QFT 1 Tube (test code 37616) provides screening for HCV, HBV, and latent TB. This testing is recommended before beginning a biologic or biosimilar to treat an autoimmune disease.11 The panel includes 
  • Hepatitis C Antibody with Reflex to HCV RNA, PCR w/Reflex to Genotype, LiPA® (test code 94345)
  • Hepatitis B Surface Antigen with Reflex Confirmation (test code 498)
  • Hepatitis B Surface Antibody Immunity, Quantitative (test code 8475)
  • Hepatitis B Core Antibody, Total, with Reflex to IgM (test code 37676)
  • QuantiFERON®-TB Gold Plus, 1 Tube (test code 36970)
A screening panel (test code 37620) that includes QuantiFERON-TB Gold Plus, 4 Tubes, Draw Site Incubated (test code 36971) is also available.

Panel components can be ordered separately.

Quest also offers testing for other infectious diseases such as HIV, herpes, chicken pox, and fungal infections, and biochemical testing (eg, tests of liver and kidney function), which is also important before beginning a patient on a biologic or biosimilar. 

Treatment Monitoring

Quest also offers tests to monitor drug levels for patients being treated for ARDs. For example, tests are available to monitor adalimumab levels, to help ensure that patients are receiving a therapeutic dosage (test code 36299), to detect the presence of antidrug antibodies (test code 36295), or both (test code 36297). Infliximab treatment can be similarly monitored (test codes 36310, 36302, 36312).

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Content reviewed 4/2020