Introduction

Pyuria refers to the presence of an increased number of white blood cells (WBCs) in the urine. It is abnormal to have a high count of white blood cells in urine; therefore, it is usually a sign of an infection and inflammation present in the human body. Autoimmune diseases are commonly referred to as the immune system attacking and destroying cells in the body. Genetics is a primary predisposing factor for autoimmune conditions that affect various organ systems, with some of the most common conditions including Hashimoto’s thyroiditis, an underactive thyroid, systemic lupus erythematosus (SLE), and rheumatoid arthritis.¹ Autoimmune conditions have been associated with causing urinary complications. For example, lupus causes pyuria without an underlying infection.

Understanding pyuria

There are two types of pyuria: sterile pyuria refers to white blood cells present in urine with no sign of bacterial infection, and non-sterile pyuria, also known as infectious pyuria, develops when there are WBCs in urine with bacteria. Additionally, pyuria can be a signal for other conditions; however, the symptoms will be dependent on whether there is an underlying bacterial infection or not. General symptoms and indications of infectious pyuria include frequent urination, pain when urinating, and cloudy urine. 

Sterile pyuria can be difficult to distinguish from infections, such as urinary tract infections (UTIs), and is challenging to diagnose because it can occur in non-infectious conditions.² Non-infectious conditions affecting the kidneys and systemic lupus are known to be the main underlying causes of sterile pyuria. Particularly, conditions causing inflammatory responses and people with a history of bladder cancer, interstitial nephritis, and diabetes mellitus. Diagnosis methods include urinalysis, which reveals the presence of white blood cells in urine, and microbiological testing, such as urine culture, used to detect signs of bacteria and distinguish between sterile and non-sterile pyuria. The diagnosis for sterile pyuria is the detection of more than 10 WBCs/mm³ in urine samples through urinalysis tests.³ Additionally, a urine dipstick test could be a first line of testing for an infection in urine because it is a simple and efficient test that could be carried out by a healthcare professional.

Autoimmune diseases and the urinary system

Autoimmune conditions, such as SLE, affect multiple organs and tissues in the human body, specifically, the kidneys and joints. SLE causes lupus nephritis, which is a type of inflammation in the kidneys that releases high amounts of white blood cells into the urine, thus causing pyuria. Common symptoms of SLE are skin rashes, joint pain, and fatigue, which will vary from person to person.⁴ Additionally, 75% of biopsies taken from SLE patients showed active nephritis; therefore, pyuria is a clinical manifestation of SLE.⁵ 

Although SLE is considered to be one of the main causes of pyuria, there are other conditions that could cause pyuria, including tuberculosis (TB), sexually transmitted infections (STIs), and viral infections.⁶ Structural abnormalities, such as urinary tract obstruction caused by tumours and stones, could increase the risk of pyuria. Furthermore, transient pyuria, which is temporary, is commonly caused by medical instruments, including catheters or cystoscopes.

Sterile pyuria in autoimmune diseases

SLE is an example of an autoimmune disease that causes sterile pyuria, whereby immune cells attack urinary tissues, and WBCs are present in urine in the absence of an infection; therefore, the inflammation present is mediated by the immune system, not an infection. Lupus nephritis is a condition that affects SLE patients because the immune system attacks the kidneys, specifically the glomerulus, which could impair kidney function.⁷ The function of the kidneys in the body is to filter the blood and remove waste products, which is very important for maintaining health. The progression of this condition could cause kidney failure if it is not treated. Furthermore, lupus nephritis can present with conditions such as proteinuria and haematuria. Lupus nephritis is different from a UTI-based non-sterile pyuria because there would be no bacteria in the urine, even though there are elevated WBCs.

Diagnosing autoimmune-related pyuria

Testing for infection with urine culture would be an accurate diagnosis for sterile and non-sterile pyuria. Additionally, urinalysis would confirm whether pyuria is present; however, further testing is required to determine whether there is an autoimmune condition associated with pyuria. Furthermore, a medical history and related symptoms are useful when diagnosing autoimmune-related pyuria. Some of the pyuria symptoms include:

• Mouth ulcers
• Dry eyes and mouth
• Rashes on the skin 
• Joint pain 
• Persistent fatigue 
• Weight loss 

For lupus, autoantibody testing, such as antinuclear antibody (ANA), anti-dsDNA testing, and creatinine testing for kidney function, is required. These types of tests are diagnostic blood tests that confirm the presence of autoimmune disorders. ANA is a biomarker commonly used to test for rheumatic diseases, including SLE, through enzyme and multiplex immunoassays (to test for immune reactions).⁸ Additionally, anti-ds DNA testing is a more specific test that can be an indication for lupus nephritis.⁹ Additionally, testing for kidney function is useful for monitoring SLE and creatinine testing measures the amount of waste product in the blood and urine.

Treatment and management

Medications, including corticosteroids or immunosuppressants, are used to treat autoimmune conditions. For lupus in particular, hydroxychloroquine, non-steroidal anti-inflammatory drugs (NSAIDs) and steroids are used depending on the severity of the condition. Hydroxychloroquine is the most common drug used for the treatment of SLE because it can reduce the flare-up of lupus nephritis and skin problems.¹⁰ Additionally, completing a course of hydroxychloroquine decreases the chances of organ damage and is known to lower cholesterol.¹¹ Furthermore, hydroxychloroquine is an effective SLE treatment because it is taken orally and is safe for use by pregnant women under the supervision of a healthcare professional. 

NSAIDs are widely used for relieving symptoms associated with pain; however, if lupus nephritis is present, there is a risk of kidney injury.¹² Additionally, monitoring plays a big role in managing SLE. Regular urine and kidney function testing helps healthcare professionals to adjust the dosage of medication, to check the progression of the condition, and to assess whether there is any damage to the organs. 

FAQs

Can lupus cause bladder inflammation? 

Lupus can cause lupus cystitis, which is essentially inflammation of the lining of the bladder. 

What are the first signs of lupus nephritis?

The initial signs include swelling in the legs, ankles and around the eyes.

Can lupus mimic a UTI?

Lupus increases the risk of kidney infections, which can show symptoms similar to a UTI.

What happens if pyuria is left untreated?

If there is an infection present, then this could spread, leading to sepsis.

What does lupus urine look like?

 Lupus urine indicates kidney problems and is likely to be frothy and foamy.

What autoimmune disease causes white blood cells in the urine?

Lupus nephritis indicates a high count of white blood cells in urinalysis tests. 

Life expectancy of someone with lupus nephritis?

Someone with lupus nephritis can live a normal lifespan with appropriate treatment. 

Summary 

Autoimmune diseases, including lupus, can be the underlying cause of pyuria. However, it is important to distinguish whether pyuria is infectious or non-infectious because pyuria is not only present in cases with autoimmune conditions. While UTIs are the most common cause of pyuria, especially when accompanied by proteinuria, haematuria, or systemic lupus, therefore, symptom evaluation for autoimmune diseases is required. Accurate diagnosis is key for an effective treatment plan and management. Although medication is crucial for treating the symptoms of lupus, lifestyle changes and different approaches can help manage these symptoms. A combination of immunosuppressive medication and lifestyle adjustments can benefit patients.