Systemic lupus erythematosus (lupus) is a complex autoimmune condition where the body’s immune system mistakenly attacks its own healthy tissues. This can lead to widespread inflammation and tissue damage in various organs. Because lupus symptoms can resemble those of many other conditions, achieving an accurate diagnosis is challenging. A standardized set of criteria is necessary to help doctors distinguish lupus from other illnesses, ensuring correct evaluation and management.
The Antinuclear Antibody Test Gateway
Under the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria, a positive Antinuclear Antibody (ANA) test is the mandatory initial step for a lupus diagnosis. If a patient’s ANA test is negative, systemic lupus erythematosus is unlikely, and further diagnostic criteria are not applied. The ANA test detects autoantibodies, which are immune proteins that target components within the nucleus of a cell.
While a positive ANA test is a necessary initial step, it does not confirm a lupus diagnosis on its own. These antibodies can also be present in other autoimmune diseases or in some healthy individuals. Therefore, a positive ANA result indicates the immune system is producing these autoantibodies, prompting further investigation to determine if lupus or another condition is present. Its role is to filter for individuals who warrant a more in-depth assessment for lupus.
Clinical Domains and Symptoms
Following a positive ANA test, medical professionals evaluate a patient’s signs and symptoms, grouped into specific “clinical domains” under the 2019 EULAR/ACR criteria. Each of these domains represents a different body system that lupus can affect, and the presence of criteria within these domains contributes to the diagnostic score. Only one criterion with the highest score counts per domain, and criteria should not be counted if explained by other conditions.
Constitutional
The Constitutional domain includes fever of 100.4°F (38°C) or higher, not attributed to infection.
Skin and Hair
The Skin and Hair domain includes non-scarring hair loss (diffuse or thinning), oral ulcers (typically painless sores in the mouth or nose), and specific types of cutaneous lupus, such as acute cutaneous lupus (e.g., malar “butterfly” rash) and chronic discoid lupus.
Joints
The Joints domain includes arthritis, characterized by tenderness or swelling in two or more joints, often affecting the hands or feet.
Serosal Linings
Inflammation of the Serosal Linings involves conditions like pleurisy (inflammation around the lungs causing chest pain) or pericarditis (inflammation around the heart leading to chest discomfort). These conditions indicate inflammation of the membranes surrounding internal organs.
Kidney
Kidney involvement, known as lupus nephritis, is detected through abnormalities in urine tests indicating kidney damage, or confirmed by a kidney biopsy.
Neurologic
The Neurologic domain includes central nervous system manifestations such as seizures, psychosis, or delirium, which are not explained by other medical conditions or medications.
Hematologic (Blood)
The Hematologic (blood) domain includes abnormalities like low white blood cell counts (leukopenia), low platelet counts (thrombocytopenia), or autoimmune hemolytic anemia, a condition where red blood cells are destroyed by the immune system.
Immunologic Laboratory Evidence
Beyond the initial ANA test, the 2019 EULAR/ACR criteria incorporate specific blood tests that provide immunologic evidence, distinct from clinical symptoms. These tests identify specific autoantibodies or other immune system markers that suggest lupus. This category contributes to the overall diagnostic score alongside clinical findings.
Antiphospholipid Antibodies
Antiphospholipid Antibodies are autoantibodies that target phospholipids, a type of fat molecule found in cell membranes. Examples include anti-cardiolipin antibodies, anti-beta-2-glycoprotein I antibodies, and a positive lupus anticoagulant test. Their presence can indicate an increased risk of blood clots or pregnancy complications in lupus patients.
Complement Proteins
Complement Proteins are also assessed, including low levels of C3 and C4, components of the immune system’s complement cascade. Low levels of these proteins indicate active immune system consumption, a feature of lupus flare-ups or disease activity. This reduction suggests the immune system is actively attacking tissues.
Lupus-Specific Antibodies
The most specific antibodies for lupus are Lupus-Specific Antibodies, namely anti-double-stranded DNA (anti-dsDNA) and anti-Smith (anti-Sm) antibodies. Anti-dsDNA antibodies are specific and often correlate with kidney involvement. Anti-Sm antibodies are also specific for lupus, though found in fewer patients. Detecting either provides immunological evidence supporting a lupus diagnosis.
Applying the Scoring System for Diagnosis
The 2019 EULAR/ACR criteria synthesize clinical and immunologic information using a weighted scoring system for diagnosis. Each criterion within the clinical and immunologic domains is assigned a specific point value, ranging from 2 to 10 points based on its diagnostic significance. These points are added together to reach a total score.
To be classified as having systemic lupus erythematosus under these criteria, a patient must first have a positive ANA test. Following this, they must accumulate a total score of 10 or more points from the various clinical and immunologic domains. It is also required that at least one clinical criterion is present, meaning symptoms observed by the patient or doctor must contribute to the score.
This scoring system serves primarily as a classification tool, useful in clinical research to ensure consistency across studies. However, it is also used to support a clinical diagnosis in everyday practice. Ultimately, these criteria are a guideline, and a final diagnosis is always made by a qualified rheumatologist. The rheumatologist considers the entire clinical picture, including a patient’s medical history, physical examination findings, and all laboratory results, rather than relying solely on the numerical score.