Autoimmune Neutropenia

What is autoimmune neutropenia (AIN)?

Autoimmune neutropenia (AIN) (pronounced “noo-troh-PEE-nee-uh”) is a blood disorder that involves your immune system attacking your body’s neutrophils (a type of white blood cell). Neutrophils are an essential part of your immune system. They destroy harmful bodily invaders that cause infections, like fungi and bacteria. With autoimmune neutropenia, your immune system mistakenly attacks these white blood cells. As a result, you have a lower-than-normal level of neutrophils in your blood.

AIN may be primary or secondary.

• Primary autoimmune neutropenia primarily affects infants and toddlers. It involves having a low neutrophil count that can’t be explained by other causes. Primary neutropenia usually resolves on its own within a few years.
• Secondary autoimmune neutropenia is more common in older children and adults. It involves having a low neutrophil count resulting from another condition, including infections, blood disorders, etc. Other autoimmune diseases often cause neutropenia. An autoimmune disease involves your immune system mistakenly attacking your body instead of protecting it. Secondary autoimmune neutropenia is usually chronic (long-lasting).

How low do your neutrophils have to be to be considered neutropenia?

Autoimmune neutropenia is just one type of neutropenia. Neutropenia is classified as mild, moderate or severe depending on how many neutrophils are in a microliter (microL) of blood.

• Mild neutropenia: 1,000 – 1,500 microL.
• Moderate neutropenia: 500 – 1,000 microL.
• Severe neutropenia: Less than 500 microL.

How does autoimmune neutropenia affect my body?

Your experience of AIN depends on multiple factors that you should discuss with your healthcare provider. Having too few neutrophils can put you at risk of getting infections. These infections may even be life-threatening without emergency medical attention. In other cases, autoimmune neutropenia may cause mild infections or no symptoms (asymptomatic).

Work with your healthcare provider to determine what’s causing your neutropenia. Based on the causes, your provider can monitor your condition to keep infections under control.

Who does autoimmune neutropenia (AIN) affect?

Primary autoimmune neutropenia mainly affects infants and young children. On average, it’s diagnosed around eight months old. Secondary autoimmune neutropenia is often due to another autoimmune disease, like lupus or rheumatoid arthritis. Most children with secondary AIN are diagnosed around age 10 (on average). Most adults diagnosed with secondary AIN are between the ages of 40 and 60.

How common is autoimmune neutropenia?

Primary autoimmune neutropenia is rare, occurring in about 1 out of 100,000 children under 10.

What are the symptoms of autoimmune neutropenia?

Autoimmune neutropenia doesn’t always cause noticeable symptoms. Or, you may notice signs of an infection, including:

• Ear infections (most common).
• Respiratory infections (most common).
• Mouth infections (ulcers, gingivitis).
• Skin infections.
• Pneumonia.
• Meningitis.
• Urinary tract infections (UTIs).
• Sepsis.

Infections associated with primary AIN are usually mild. More serious infections, like pneumonia, meningitis and sepsis, are more commonly associated with secondary AIN than primary AIN.

What causes autoimmune neutropenia?

AIN is classified as primary or secondary based on what’s causing low neutrophil levels.

Primary autoimmune neutropenia

With primary AIN, antibodies target and destroy neutrophils. Antibodies are proteins in your immune system that destroy harmful bodily invaders, like viruses and bacteria. Researchers aren’t sure what causes your body’s antibodies to attack neutrophils.

Secondary autoimmune neutropenia

The low neutrophil count associated with secondary AIN results from another cause or condition that prompts your immune system to destroy neutrophils.

Causes may include:

• Autoimmune diseases (rheumatoid arthritis, lupus, autoimmune hemolytic anemia).
• Cancer (large granular lymphocyte leukemia).
• Infections (HIV, Parvovirus, hepatitis B).
• Tumors (Wilms tumor, Hodgkin’s disease).
• Neurological diseases (multiple sclerosis).
• Kidney or bone marrow transplants.
• Medications, including specific chemotherapy drugs.

How is autoimmune neutropenia diagnosed?

Your healthcare provider may notice your low neutrophil levels during blood work to investigate potential causes of an infection or a fever. Diagnosing AIN can be tricky since it has multiple causes. Your provider may arrive at a diagnosis after ruling out other conditions that may be causing your low neutrophil levels.

Your healthcare provider may perform the following tests to diagnose or monitor autoimmune neutropenia.

• Complete blood count (CBC): A CBC shows the number of neutrophils in your blood. These levels can shift. To confirm your neutropenia, your provider will likely perform more than one CBC to check for consistently low neutrophil levels. Frequent CBCs can show whether your AIN is chronic.
• Peripheral smear: Looking at your blood under a microscope can assess neutrophil morphology and help point towards a diagnosis
• Vitamin B12, folate and copper tests: These tests can reveal deficiencies associated with neutropenia. Your body requires these to make neutrophils.
• Liver function tests: Your provider may evaluate your liver function and screen you for viral hepatitis.
• HIV and other viral studies: HIV and other viral infections may cause low white counts and therefore can be a part of the initial workup
• Flow cytometry: Flow cytometry is a lab test that allows your provider to examine cells for signs of disease. It may be used to determine if an autoimmune condition is causing your neutropenia.
• Imaging: You may receive an MRI or a CT scan if your provider suspects that lymphoma may be causing your AIN.
• Bone marrow aspiration and biopsy: During a bone marrow aspiration and biopsy, your provider removes a small sample of bone marrow to test for signs of disease. These procedures can show if your neutropenia is related to blood cancer, like leukemia.

Your provider may order a blood test to check for signs of antibodies in your blood that are attacking your neutrophils. The most common tests are I-GIFT and GAT:

• Indirect granulocyte immunofluorescence test (I-GIFT).
• Granulocyte agglutination test (GAT).

Unfortunately, these tests aren’t always reliable for diagnosing AIN. Depending on what’s causing your neutropenia and the timing of your test, these tests may not detect the antibodies or produce false-positive results. A false-positive means that the test detected the antibodies when they aren’t present.

Your healthcare provider may order additional tests if they suspect a specific condition is causing your neutropenia.

How is autoimmune neutropenia treated?

Treatment depends on how severe your condition is. For instance, asymptomatic infants with neutropenia may need more frequent CBCs to monitor their neutrophil levels, but they may not need immediate treatments. Your provider may prescribe prophylactic antibiotics if your child is getting frequent infections. While antibiotics treat infections, prophylactic antibiotics prevent them.

With secondary AIN, your provider will treat the underlying condition causing your low neutrophil count to prevent infections. They may also prescribe:

• Granulocyte colony-stimulating factor (G-CSF): G-CSF is the primary treatment for more severe forms of neutropenia. It spurs your body to make more neutrophils. G-CSF can also prevent frequent infections associated with primary AIN.
• Corticosteroids: Corticosteroids, like prednisone, can limit your body’s immune response so that antibodies don’t attack your neutrophils.
• Other treatment: Additional agents have also been used to treat those critically ill with severe autoimmune neutropenia include IVIG, rituximab and alemtuzumab.

How can I prevent autoimmune neutropenia?

Neither primary nor secondary autoimmune neutropenia is preventable. Still, you can prevent complications associated with autoimmune neutropenia by taking precautions to avoid infections.

What can I expect if I have autoimmune neutropenia?

Primary autoimmune neutropenia usually resolves on its own. In approximately 95% of children with AIN, neutrophil counts return to normal by ages two or three. Almost all cases of primary AIN resolve by age 11.

Otherwise, your prognosis depends on multiple factors, like what underlying condition may be causing your neutropenia. Treating the underlying disease and preventing infections can help boost your neutrophils to their normal levels.

When should I seek care?

See your provider immediately if you have a severe form of autoimmune anemia and develop a fever. Sometimes, your provider may prescribe an antibiotic for you to have on hand in case you develop a fever. You’ll likely receive treatment in a hospital.

Your provider can discuss symptoms you should be aware of and actions you should take to prevent complications if you have a severe, chronic form of autoimmune neutropenia.

A note from Cleveland Clinic

Work with your healthcare provider to determine what an AIN diagnosis means for you or your child. Although symptoms and causes vary, the good news is that treatments like G-CSF are very effective at boosting neutrophil levels. If your child has AIN, follow your provider’s guidance on how frequently they’ll need blood tests. Be on the lookout for signs of infection and get treatment as soon as possible to prevent possible complications.