Extra-articular (systemic) manifestations of rheumatoid arthritis

A comprehensive examination includes tests aimed at determining circulating autoantibodies and various biochemical markers of the acute phase of inflammation. Joint pain can be a sign of arthritis, including rheumatoid arthritis, arthrosis, osteoarthritis, gout, chondrocalcinosis, ankylosing spondylitis and other diseases. Allows you to identify a possible cause, as well as differentiate various forms of arthritis.

What tests are included in this complex:

· Clinical blood test (with leukocyte formula);

· Erythrocyte sedimentation rate (ESR);

· Fibrinogen;

· Antistreptolysin O;

· Uric acid in serum;

· C-reactive protein, quantitative (method with normal sensitivity);

· Rheumatoid factor (RF);

· Antinuclear factor on HEp-2 cells;

· Antibodies to extractable nuclear antigen (ENA screen).

What biomaterial can be used for research?

Deoxygenated blood.

Research method

· Flow cytometry: Clinical blood test (with leukocyte formula);

· Capillary photometry method: ESR;

· Clotting method (detection of side light scattering, determination of percentage by end point): Fibrinogen;

· Immunoturbidimetry: Antistreptolysin O, C-reactive protein, Rheumatoid factor;

· Enzymatic colorimetric method: Uric acid;

· Indirect immunofluorescence reaction: Antinuclear factor on HEp-2 cells;

· Enzyme immunoassay: Antibodies to extractable nuclear antigen (ENA screen).

How to properly prepare for research?

• During the day before the test, do not drink alcohol or take medications (as agreed with your doctor);
• Do not eat for 12 hours before the test;
• Avoid physical and emotional stress for 24 hours before the test;
• Do not smoke 3 hours before the test

General information about the study

Joint pain can be a sign of arthritis, including rheumatoid arthritis, arthrosis, osteoarthritis, gout, chondrocalcinosis, ankylosing spondylitis and other diseases.

Inflammation of the joints can also be caused by infectious or systemic diseases: influenza, scarlet fever, tuberculosis, gonorrhea, chlamydia, as well as a chronic focus of infection caused by staphylococci or streptococci. The basis of many joint diseases is the inflammatory process, which causes mobility impairments in the musculoskeletal system.

Inflammation is a biochemical protective reaction of the body in response to tissue damage; it can be both acute and chronic. For example, in rheumatoid arthritis, the process of systemic chronic inflammation is accompanied by an increase in erythrocyte sedimentation rate (ESR) and the concentration of acute-phase proteins such as fibrinogen and C-reactive protein. Fibrinogen is one of the factors known as “rheumatic tests”. The level of fibrinogen increases sharply in the blood when there is inflammation or tissue damage.

Antistreptolysin-O is one of the laboratory markers of rheumatism; it is used for the differential diagnosis of rheumatism and rheumatoid arthritis (in the case of RA, the level of antistreptolysin-O is much lower). An increase in this indicator indicates sensitization of the body to streptococcal antigens.

Elevated uric acid levels are one of the signs of gout, rheumatism, arthritis and other disorders. If the rate of synthesis of uric acid exceeds the rate of its elimination from the body, the process of purine metabolism is disrupted. The retention of this substance in the body affects the activity of the kidneys, renal failure develops, leading to inflammation of the joints, in which uric acid crystals are deposited in the joint (synovial) fluid.

Rheumatoid factor (RF) is one of the standard criteria for rheumatoid arthritis established by the American Association of Rheumatology (AAR). It is detected in 75-80% of patients with rheumatoid arthritis, but is not specific for rheumatoid arthritis, but indicates the presence of suspicious autoimmune activity. It is also found in Sjögren's syndrome, scleroderma, dermatomyositis, hyperglobulinemia, and B-cell lymphoproliferative diseases. About 30% of patients with systemic lupus erythematosus (SLE) who do not have signs of rheumatoid arthritis are RF-positive. The sensitivity of RF for rheumatoid arthritis is only 60-70%, and the specificity is 78%.

Rheumatoid factor is an antibody against immunoglobulin G (IgG) fragments. More often (up to 90% of cases) these antibodies belong to class M immunoglobulins (IgM); IgG, IgA, and IgE are rare. Despite its low specificity, the presence of RF is considered an important prognostic sign for the outcome of rheumatoid arthritis.

Antinuclear antibodies (another name is antinuclear factor) are a heterogeneous group of antibodies that react with various components of the cell nucleus. A healthy person with normal immunity should not have antinuclear antibodies in the blood or their level should not exceed the established reference values. The loss of a number of readily soluble components from the nucleus of HEp-2 cells (standardized cells used in the analysis) or their redistribution into the cytoplasm may be the reason for the detection of low titers of antinuclear factor in the HEp-2 cell line.

It is advisable to use, together with the determination of antinuclear factor, the determination of the specificity of antinuclear antibodies, which avoids false negative results in systemic rheumatic diseases. The definition of “specificity of antinuclear antibodies” refers to the determination of autoantibodies to specific antigens, for which the determination of extractable nuclear antigen (ENA screen) is used. ENA is a readily soluble component of the cell nucleus. This test includes the antigens RNP-70, RNP/Sm, SS-A, SS-B, Scl-70, centromeric protein B and Jo-1, and a number of them are produced recombinantly.

Due to its high sensitivity of 95-98%, the combined use of two tests allows for both early diagnosis of systemic diseases and clarification of the diagnosis of systemic diseases in the case of an unclear clinical picture.

The specificity of ENA screening is somewhat inferior to the specificity of testing for antibodies of the ENA group using the immunoblot method. This fact is of particular importance in the case of examination of persons suspected of having systemic lupus erythematosus, as well as mixed connective tissue disease. Taking this into account, if the result of ENA screening is positive, an additional confirmatory study is performed - immunoblot.

Detection of antibodies indicates the presence of an autoimmune disorder, but does not indicate a specific disease because the test is a screening test. The goal of any screening is to identify people at increased risk of a particular disease.

What is the research used for?

• Differential diagnosis of arthritis;
• Diagnosis of systemic autoimmune diseases;
• To diagnose rheumatoid arthritis and Sjögren's syndrome, and to distinguish them from other forms of arthritis and diseases with similar symptoms.

When is the study scheduled?

• For symptoms of an autoimmune disease (prolonged fever, joint pain, fatigue, weight loss, skin changes);
• When identifying changes characteristic of systemic connective tissue diseases (increased ESR, level of C-reactive protein, circulating immune complexes);
• For rheumatoid arthritis (determining the activity of the process, prognosis and control of treatment of the disease);
• If you suspect gout (the main symptom is pain in the joints, most often in the big toe);
• If you have morning stiffness or joint stiffness.

What do the study results mean?

To make a diagnosis, it is important to use a comprehensive examination, which includes laboratory diagnostics, clinical data and modern methods of instrumental examination of joints: CT, MRI, ultrasound.

Clinical blood test (with leukocyte formula)

Reference values: decoding of the general blood test (see detailed description)

The leukocyte formula is usually interpreted depending on the total number of leukocytes. If it deviates from the norm, then focusing on the percentage of cells in the leukocyte formula can lead to erroneous conclusions. In these situations, the assessment is made based on the absolute number of each type of cell (in a liter - 1012 / l - or microliter - 109 / l).

More details about the results: https://www.helix.ru/kb/item/02-005#subj12

Erythrocyte sedimentation rate (ESR)

Reference values:

In arthritis, the inflammatory picture of the blood is clearly expressed with a sharp increase in ESR to 40-80 mm.

More details about the results: https://www.helix.ru/kb/item/02-007#subj12

Fibrinogen

Reference values: 1.8 - 3.5 g/l

More details about the results: https://www.helix.ru/kb/item/03-011#subj12

Antistreptolysin O

Reference values:

More details about the results: https://www.helix.ru/kb/item/06-007#subj12

Serum uric acid

Reference values:

More details about the results: https://www.helix.ru/kb/item/06-033#subj12

C-reactive protein, quantitative (method with normal sensitivity)

Reference values: 0 - 5 mg/l

More details about the results: https://www.helix.ru/kb/item/06-182#subj12

CRP more than 10 mg/l indicates acute inflammation, chronic disease, injury, etc. For viral infections, metastases, sluggish chronic and some systemic rheumatic diseases, the concentration of CRP is 10-30 mg/l; for bacterial infections, exacerbation of some chronic inflammatory diseases (for example, rheumatoid arthritis) and tissue damage (surgery, acute myocardial infarction) - 40-100 mg/l (sometimes 200 mg/l), for severe generalized infections, burns and sepsis - up to 300 mg/l or more.

Rheumatoid factor

Reference values:

More details about the results: https://www.helix.ru/kb/item/13-020#subj12

Antinuclear factor on HEp-2 cells

Reference values: antibody titer not exceeding 1:160 is considered negative

Positive result: antibody titer 1:320 or more

• A negative result in a patient with signs of an autoimmune process does not exclude the presence of an autoimmune disease;
• ANAs are detected in 3-5% of healthy people (10-37% over the age of 65 years);
• If the test for antinuclear antibodies is positive, it is necessary to perform an immunoblot of antinuclear antibodies to clarify the type of autoimmune disease and make a diagnosis.

More details about the results: https://www.helix.ru/kb/item/13-045#subj12

Antibodies to extractable nuclear antigen (ENA screen)

Reference values: negative

When immunosuppressive therapy is prescribed, the test result may be negative.

More details about the results: https://www.helix.ru/kb/item/13-046#subj12

What can influence the result?

• Uremia may result in a false-negative ANA test result;
• Many drugs are associated with the development of drug-induced lupus and the appearance of ANA in the blood;
• Some drugs lower fibrinogen levels: anabolic steroids, phenobarbital, streptokinase, urokinase, and valproic acid;
• False-negative results in the analysis of antistreptolysin O can be observed in nephrotic syndrome, as well as treatment with corticosteroids and some antibiotics; hypercholesterolemia and liver diseases lead to overestimated indicators;
• Stress, intense physical activity, a diet rich in purines, anabolic steroids, niacin, epinephrine, thiazide diuretics, beta blockers, furosemide and some other drugs can lead to falsely elevated uric acid levels;
• The rate of false-positive rheumatoid factor test results increases with patient age.

What does an elevated ESR level indicate?

An increased ESR in the blood indicates the presence of pathology

The disease can increase ESR levels. Therefore, its increased value is a good reason for further examination of the patient for the development of inflammatory processes in the body.

There are a number of reasons why the ESR rate increases. A reaction caused by an increase in the rate of precipitation of red blood cells and the amount of their content in the blood most often indicates pathology. Therefore, it is necessary to monitor the sedimentation of these elements, as well as take measures after which the ESR does not increase.

The main cause of the disorder is a change in the physicochemical properties and composition of the blood. We are talking about such pathologies:

1. Shift in protein albumin-globulin ratio;
2. Increase in hydrogen value;
3. Excessive saturation of blood cells with hemoglobin.

An increase in ESR levels may be due to one of the following pathological conditions:

• Chronic and acute inflammatory processes that are infectious in nature;
• Rheumatoid polyarthritis;
• Diseases of the heart and blood vessels;
• Pathologies of the liver, kidneys and pancreas;
• Endocrine diseases;
• Hematological diseases;
• Damage to internal organs or individual tissues;
• Arsenic or lead poisoning;
• Pathologies that lead to the development of intoxication of the body;
• Malignant neoplasms;
• Increased cholesterol levels;
• The effect of certain medications on the body.

To understand exactly which disease led to an increase in ESR, it is necessary to conduct a number of additional studies.

Other laboratory tests to diagnose arthritis

A general blood test and immunological parameters help clarify the type of disease

To identify a patient with arthritis, it is necessary to study not only ESR, but also other indicators. If this disease is suspected, the specialist must prescribe the following diagnostic tests to the patient:

• General blood analysis;
• Blood chemistry;
• Study of immunological parameters.

It is mandatory to check the level of complement and specific immunoglobulins. ESR indicators in diagnosing arthritis are as important as the values ​​of specific antibodies that are necessary to suppress certain infectious processes in the human body.

If arthritis is suspected, genetic diagnosis is required. It is important for most varieties of the reactive type of this disease.