Autoimmune
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October 29, 2024

How is Lupus Diagnosed? Key Tests and Procedures You Should Know About

Medically Reviewed by
Updated On
November 1, 2024

Systemic lupus erythematosus (SLE), commonly referred to as lupus, is a chronic autoimmune condition that can impact almost any organ in the body. In lupus, the immune system, which typically defends against harmful pathogens, mistakenly targets and damages healthy tissues.

Lupus is often called ”the great imitator” due to its ability to mimic other conditions, making diagnosis difficult. Despite the complexity, early diagnosis is essential to prevent life-threatening complications.

In this article, we will explore how lupus is diagnosed, focusing on the key tests and procedures used by healthcare providers to confirm this complex condition.

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What is Lupus?

Lupus (SLE) is a chronic autoimmune disease where the immune system attacks healthy tissues, leading to inflammation and damage in the skin, joints, kidneys, and heart.

Symptoms vary widely but often include joint pain, fever, persistent fatigue, and the characteristic “butterfly rash” across the face. This complexity and its ability to mimic other diseases often lead to diagnostic delays.

If left untreated long enough, lupus can develop serious and even life-threatening complications including:

  • Lung Complications: inflammation of the lung lining (pleuritis) can lead to breathing difficulties or pulmonary embolism (blood clots in the lungs).
  • Blood Disorders: lupus can cause anemia (low red blood cells), low white blood cells, and low platelets.
  • Neurological Problems: lupus can lead to cognitive issues, mood disorders, and in severe cases, seizures or stroke. 

Early diagnosis and appropriate treatment can reduce lupus disease activity, improving patients’ quality of life and preventing severe and irreversible organ damage.

Why Diagnosing Lupus is Challenging

Lupus is often difficult to diagnose because its symptoms overlap with other conditions, such as rheumatoid arthritis, fibromyalgia, and other autoimmune diseases. The unpredictable nature of lupus—marked by periods of remission and flare-ups—further complicates diagnosis, as symptoms can vary in severity and timing.

The gradual onset of lupus symptoms often leads to misdiagnosis, especially when different doctors assess symptoms separately instead of evaluating the whole picture.

Research shows that diagnosing lupus can take several years, with some patients waiting up to six years for a definitive diagnosis. 

Patients with neuropsychiatric symptoms, which affect both the nervous system and mental health, often experience longer delays due to the complexity of these symptoms. These may include headaches, memory issues, mood changes, seizures, and stroke-like symptoms.

Despite the challenges, specific tests alongside clinical evaluations are necessary to make an accurate lupus diagnosis.

The Diagnostic Process: How is Lupus Diagnosed?

Diagnosing lupus typically begins with a comprehensive patient evaluation. Healthcare providers will gather a detailed medical history, paying close attention to the duration, severity, and patterns of symptoms such as joint pain, rashes, fatigue, fevers, and other systemic complaints. 

During the physical examination physicians often look for signs like skin lesions, joint swelling, and indicators of organ involvement, such as kidney or heart abnormalities.

There are two guidelines for diagnosing lupus, the joint European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR) 2019 diagnostic criteria, and the The Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) Group. 

Diagnostic requirements for each guideline overlap significantly; common tests are discussed below, along with differences.

Key Blood Tests for Lupus Diagnosis

Several blood tests are used to detect markers that indicate lupus or other autoimmune activity.

Antinuclear Antibody (ANA) Test

The ANA test is often the first step in diagnosing lupus. This blood test looks for antibodies that target the body’s own cells. 

While a positive ANA result suggests autoimmune activity, it does not definitively diagnose lupus, as other conditions can also trigger a positive ANA test. However, about 95% of lupus patients have a positive ANA test, making it an essential tool in the diagnostic process.

Anti-dsDNA and Anti-Smith Antibodies

These two antibodies are more specific to lupus. The anti-dsDNA (double-stranded DNA) antibody test is highly specific for lupus, demonstrating at least 90% specificity for SLE. It can also indicate more severe disease, particularly when kidneys are involved. 

Anti-Smith antibodies are another specific marker of lupus, though they are less commonly detected. If these antibodies are present alongside a positive ANA, they strongly support a lupus diagnosis.

Complement Levels (C3 and C4)

The complement system is one part of the immune system. Activating the complement system drives inflammation and tissue damage in lupus, ultimately contributing to organ damage.

Complement proteins, particularly C3 and C4, get “used up” rapidly during lupus flares as they get broken down or deposited in organs. Low levels of these proteins often indicate active lupus. 

Having either low C3 or low C4 supports a lupus diagnosis; having both components below normal is even stronger evidence for lupus.

Measuring complement levels can also help assess disease activity, as low levels often indicate ongoing inflammation and immune system activity against the body’s tissues.

Erythrocyte Sedimentation Rate (ESR) and C-Reactive Protein (CRP)

Both ESR and CRP are markers of general inflammation. While these tests are not specific to lupus, elevated levels of ESR and CRP can suggest an inflammatory process is present.

ESR is typically elevated in lupus patients and reflects general inflammation in the body. It can be useful in monitoring disease activity, especially in cases of active lupus, but it's non-specific and can be elevated in many other conditions.

CRP, on the other hand, tends to stay normal or only mildly elevated in lupus unless there is an infection or another inflammatory condition present. This contrasts with other autoimmune diseases like rheumatoid arthritis, where CRP is often significantly elevated during flares.

In the 2019 EULAR/ACR classification criteria for lupus, ESR and CRP are not included as formal criteria due to their lack of specificity. However, they can still be used in clinical practice to help monitor disease activity or detect infections, which are common complications in lupus patients.

Urine Tests for Kidney Involvement

One of the serious complications of lupus is lupus nephritis, a condition where the kidneys are affected by the disease. Detecting kidney involvement is crucial in managing lupus.

Urinalysis and Proteinuria

A simple urine test called a urinalysis (UA) can reveal important clues about kidney function. 

Proteinuria, or the presence of excess protein in the urine, is a component of the UA that is also a clinical indicator of lupus. 

Proteinuria is used as an indicator of kidney damage or active lupus nephritis, which can lead to significant complications if not monitored and managed.

The presence of blood in the urine can also suggest kidney involvement. These findings may prompt further testing to assess the severity of kidney damage and guide treatment decisions.

Imaging and Biopsies

Imaging tests and biopsies are sometimes necessary to assess organ damage in lupus patients.

Imaging Tests (X-rays, MRIs, and CT scans)

These imaging tools are not used to diagnose lupus, but they help doctors assess damage to vital organs such as the lungs, heart, and joints. 

X-rays and CT scans detect fluid around the lungs or lung issues like pneumonitis, interstitial lung disease, or pulmonary embolism; they may also be used to assess pericardial effusion, or fluid around the heart. X-rays can also be used to assess joint damage in lupus patients.

MRIs are used to spot brain and spinal cord problems related to neuropsychiatric lupus such as meningitis, optic neuritis, nerve damage, cerebral vasculitis, or strokes.

Echocardiograms help identify heart issues like fluid around the heart (pericardial effusion) or heart valve inflammation (Libman-Sacks endocarditis).

Skin and Kidney Biopsies

When lupus affects the skin or kidneys, a biopsy may be performed to confirm the diagnosis. 

A skin biopsy can help identify lupus-related lesions. A biopsy can show specific changes like inflammation at the skin’s deeper layers (interface vacuolar dermatitis) in acute or subacute cutaneous lupus, or a buildup of immune cells around blood vessels (perivascular infiltrates) in discoid lupus.

Kidney biopsies are especially important when diagnosing lupus nephritis, a type of lupus that affects the kidneys. 

The results of the biopsy are heavily used in determining if someone has SLE, especially when combined with a positive ANA test. 

Different types of kidney involvement are classified by severity, with more severe forms (class III/IV) being more critical for diagnosis than others.

Lupus Diagnosis Criteria: The EULAR/ACR and SLICC Guidelines

To formally diagnose lupus, healthcare providers often rely on established guidelines. Two commonly-used guidelines are the 2019 Joint European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) Criteria for Lupus Diagnosis and the Systemic Lupus International Collaborating Clinics (SLICC) Criteria.

2019 Joint EULAR/ACR Criteria for Lupus Diagnosis

To diagnose lupus under the 2019 EULAR/ACR guidelines, patients must score at least 10 points based on weighted criteria.

Key steps include:

Positive ANA Test: a positive antinuclear antibody (ANA) test is required to consider lupus. The ANA must be at least 1:80 or an equivalent positive test. Without a positive ANA, lupus cannot be diagnosed using these guidelines.

Additive Criteria: After a positive ANA, additional clinical and immunological criteria must be met to accumulate 10 points or more.

These criteria are grouped into:

Clinical Domains:

  • General Symptoms: unexplained fever.
  • Blood Disorders: low white blood cells, low platelets, or destruction of red blood cells.
  • Nervous System Issues: confusion, seizures, psychosis, or other neuropsychiatric symptoms.
  • Skin and Mouth Issues: mouth ulcers, hair loss, or lupus rashes.
  • Lung/Heart Inflammation: fluid around the lungs or heart, or heart lining inflammation.
  • Joint Problems: swollen, painful joints, often with morning stiffness.
  • Kidney Issues: lupus-related kidney disease or excess protein in urine.

Immunological Domains:

  • Antiphospholipid antibodies
  • Complement proteins (C3/C4)
  • Lupus-specific antibodies (anti-dsDNA, anti-Smith)

A renal biopsy showing class III or IV lupus nephritis automatically meets the 10-point threshold when combined with a positive ANA.

Systemic Lupus International Collaborating Clinics (SLICC) Criteria

The SLICC classification criteria for diagnosing Systemic Lupus Erythematosus (SLE) follow a simpler diagnostic process. SLICC criteria require either:

  • Meeting at least four unweighted criteria, with at least one clinical and one immunologic criterion, or
  • Having lupus nephritis confirmed by biopsy, along with a positive ANA or anti-dsDNA antibody.

Unlike the 2019 joint EULAR/ACR guidelines, an entry criterion (positive ANA) is not required. 

Specific clinical criteria include:

  • Acute or chronic lupus affecting the skin
  • Sores in the mouth (usually on the roof of the mouth)
  • Hair loss that doesn’t leave scars (thinning hair or fragile hair)
  • Joint issues: swelling in two or more joints or morning stiffness lasting 30 minutes or more
  • Inflammation around the lungs or heart
  • Kidney problems
  • Nervous system problems (like seizures or mental health issues)
  • Anemia caused by red blood cells breaking down
  • Low white blood cell count
  • Low platelet count

Immunologic Criteria:

  • Positive ANA test
  • Positive anti-dsDNA antibody test
  • Positive anti-Smith antibody test
  • Presence of antiphospholipid antibodies
  • Low complement levels 
  • Positive direct Coombs test (without anemia caused by red blood cells breaking down); the Coombs test assesses red blood cell destruction due to an immune attack

Challenges in Diagnosing Lupus Early

Lupus often goes missed, which can delay important treatments and reduce a patient’s risk of complications.

Mild Cases and Misdiagnosis

Early lupus symptoms often resemble conditions like rheumatoid arthritis, fibromyalgia, or chronic fatigue syndrome, which can lead to misdiagnosis and therefore ineffective treatments.

This makes it essential for clinicians to perform a thorough evaluation and consider lupus as a potential diagnosis, especially in patients with a wide range of unexplained symptoms.

Need for Specialist Evaluation

A rheumatologist or other specialists may be needed to confirm the diagnosis of lupus. 

Rheumatologists are experts in autoimmune diseases and are best equipped to manage the complexities of lupus, including disease activity monitoring and long-term treatment strategies.

What to Do After a Lupus Diagnosis

While a lupus diagnosis requires regular follow ups and certain lifestyle adjustments, there is hope for a happy, healthy life with lupus. 

Next Steps for Patients

Receiving a lupus diagnosis can be overwhelming. It’s important for patients to work closely with their healthcare providers to develop a personalized treatment plan that may include medications, lifestyle changes, and regular monitoring to track disease activity. 

Patients should also be educated about the potential for flare-ups and the importance of sticking to their treatment plans.

Finding Support

Support groups, both in-person and online, can be invaluable for patients with lupus. These communities provide emotional support, share experiences, and help patients navigate the challenges of living with a chronic illness. 

Receiving a lupus diagnosis can be overwhelming, but working with healthcare providers to develop a personalized treatment plan is key to managing the condition. 

Support groups and organizations like the Lupus Foundation of America provide resources and community support for patients.

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Key Takeaways

  • Lupus is a Complex, Multisystem Autoimmune Disease: systemic lupus erythematosus (SLE) affects various organs and involves symptoms like joint pain, fatigue, and skin rashes. It can lead to severe complications such as kidney failure, cardiovascular issues, and neurological problems if not diagnosed and treated early.
  • Challenges in Diagnosing Lupus: lupus is known as "the great imitator" due to its wide-ranging and fluctuating symptoms, which can resemble other conditions. Diagnosis is often delayed, sometimes taking years, especially when symptoms are mild or when neuropsychiatric symptoms are present.
  • Diagnostic Process Involves Specific Criteria and Tests: diagnosing lupus requires a combination of clinical evaluation and blood tests (like ANA, anti-dsDNA, and complement levels), and sometimes biopsies. Diagnostic guidelines from EULAR/ACR and SLICC help clinicians confirm lupus by using a scoring system based on specific symptoms and test results.
The information provided is not intended to be a substitute for professional medical advice. Always consult with your doctor or other qualified healthcare provider before taking any dietary supplement or making any changes to your diet or exercise routine.

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