The Difficulty of Diagnosing Lupus

Unpredictable nature of disease can complicate diagnosis

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Lupus (also known as systemic lupus erythematosus) is an autoimmune disorder in which the body’s immune cells attack its own tissues. It affects more than 200,000 Americans each year with symptoms affecting the joints, skin, kidneys, blood, brain, heart, and lungs.

The diagnosis of lupus can often be tricky insofar as the signs and symptoms closely mimic that of other diseases. Making a diagnosis requires the doctor to take in many factors including the person’s symptoms, medical history, lab results, and special assays used to evaluate the person’s immune system.

Even then, diagnoses can be difficult to confirm.

Why Lupus Can Is So Difficult to Diagnose

There are a number of things that can complicate a lupus diagnosis. Chief among them is the fact that lupus is not one disease but an array of different subtypes, each with their own causes and characteristics.  Among the many challenges facing clinicians:

  • Lupus is a relapsing-remitting condition, meaning that symptoms can and go.  Until a pattern is recognized, the disease can often go unrecognized.
  • There is not a single blood test that can be used on its own make the diagnosis.
  • Lupus is a "snowflake" condition, meaning that even if two people have the same subtype, their symptoms can be entirely different.
  • Lupus is relatively uncommon condition and, as a result, primary care physicians can often overlook or miss symptoms.

Common Signs and Symptoms of Lupus

Most symptoms of lupus are generalized and non-specific and can include things like fatigue, fever, and muscle or joint pain.

Slightly more telling the characteristic malar (butterfly-shaped) or discoid (disk-shaped) rashes seen in people with lupus or a condition called Raynaud's phenomenon in which the fingers turn a deep purple in the cold. Light sensitivity, facial swelling, and mouth ulcers may also provide clues.

Systemic lupus can impact multiple organs systems, often in characteristic ways, and can commonly affect:

ANA Testing to Diagnosing Lupus

There are a number of tests used to diagnose lupus including blood tests, chest X-rays, echocardiogram, and urinalysis. The aim of the tests is to find evidence of an autoimmune disorder to better support a lupus diagnosis. Based on certain values, the clinician can either confirm or rule out lupus as the cause of illness.

To this end, a test called the antinuclear antibody (ANA) assay can detect the presence of immune proteins called autoantibodies which incite the autoimmune response. The test also measures the titer (concentration) and the pattern (characteristics) of the cells under the microscope. Certain titer values and patterns are highly indicative of lupus, while others are less so.

With that being said, having an inconclusive or negative diagnosis doesn’t necessarily rule out lupus, while having a positive result doesn’t mean that some other type of autoimmune disorder (scleroderma, polymyositis, Sjogren's syndrome) might be behind the symptoms.

All told, 95 percent of people with lupus have a positive ANA.

Additional Tests Used to Confirm Lupus

Additional antibody tests may be used to confirm a positive ANA test if the clinical symptoms are vague or in the event the ANA is negative but lupus is still strongly suspected. By comparing the positive and negative results, a doctor can use best clinical judgment to make a diagnosis. The individual tests evaluate the presence of:

  • Anti-double-stranded DNA, a type of antibody found in 50 percent of lupus cases
  • Anti-Smith antibodies found in 40 percent of people with lupus which is also associated with mixed connective tissue disease (MTCD)
  • Anti-phospholipids antibodies found in 30 percent of lupus cases which are also present in syphilis (explaining why so many people with lupus have false-positive syphilis results)
  • Anti-Ro/SS-A and anti-La/SS-B antibodies also found in Sjogren's syndrome
  • Anti-histone antibodies, most frequently seen in drug-induced lupus
  • Anti-ribonucleic antibodies which are seen in high volumes in people with symptoms of multiple diseases, including lupus

Typically speaking, the combination of a positive ANA, anti-double-stranded DNA and anti-Smith antibodies is considered the "gold standard" for making a lupus diagnosis.


  • Kasper, D.; Fauci, A.; and Hauser, S. Harrison's Principles of Internal Medicine. New York: Mc Graw-Hill Education, 2015. Print.
  • Lam, N.; Ghetu, M.; and M. Bieniek. "Systemic Lupus Erythematosus: Primary Care Approach to Diagnosis and Management." American Family Physician. 2016; 94(4):284-94.