Cyclic Neutropenia

What is cyclic neutropenia?

Cyclic neutropenia involves having lower-than-normal levels of neutrophils (a type of white blood cell) in your blood. But the low levels occur periodically, not all the time. Neutrophils are important because they help fight infection. A shortage of neutrophils, or neutropenia, makes it harder for your immune system to fight harmful bacteria or viruses that can make you sick.

Cyclic neutropenia differs from other forms of neutropenia in that neutrophil levels drop and then return to normal on a fairly consistent, predictable schedule. Neutrophil levels drop for about three to five days, return to normal and then drop again around every three weeks.

Other names for cyclic neutropenia include periodic neutropenia or cyclic hematopoiesis. “Cyclic hematopoiesis” isn’t used much, and it might be used to indicate period deficiency (or drop) in platelets.

Is cyclic neutropenia an immune deficiency?

Yes. Neutrophils help your immune system protect you from infection. During periods when your neutrophils are low, your immune system has a harder time fighting germs. The lower your neutrophil count, the harder it is for your immune system to protect you.

How common is cyclic neutropenia?

It’s rare. Researchers estimate that only about 1 in every 1 million people has cyclic neutropenia.

What are the symptoms of cyclic neutropenia?

With cyclic neutropenia, symptoms appear on a consistent schedule. Although the timeline may differ from person to person, you’ll likely experience neutropenia for about the same number of days and at the same intervals separating periods of normal and low neutrophil levels.

During periods when your neutrophils are low, you’re more susceptible to infection and may experience associated symptoms. Symptoms may include:

• Fever.
• Fatigue.
• Sore throat.
• Mouth sores.
• Gum (periodontal) disease.
• Upper respiratory infections.
• Digestive system infections.
• Skin (cellulitis) infections.

Symptoms and symptom severity can vary throughout your life. For many people, symptoms often get milder after puberty. Adolescents and young adults are more prone to mouth sores and dental issues. Adults more commonly report symptoms like headaches and sinus infections (sinusitis).

What causes cyclic neutropenia?

Cyclic neutropenia results from a genetic mutation (change) in the ELANE gene. You can inherit the mutation from a biological parent, or it can arise during development. The ELANE gene contains instructions for making an enzyme that helps neutrophils work. Problems with this gene prevent neutrophils from working as they should to protect you from infection.

Neutropenia symptoms result when:

• Your body doesn’t produce enough neutrophils.
• Neutrophils die early.
• Neutrophils don’t work correctly.

How is cyclic neutropenia diagnosed?

Signs of cyclic neutropenia usually appear at birth. Healthcare providers diagnose most people in infancy. Your healthcare provider will consider various factors before making a diagnosis.

• Family health history: Most people with cyclic neutropenia inherit it. This means that other members of your biological family likely have it, too. Your provider may suspect cyclical neutropenia if another family member, like a parent, has the condition.
• Blood test results: Your provider will order blood tests to determine whether you have neutropenia. They’ll measure your neutrophil levels two to three times per week for about six weeks. Low levels are less than 200 neutrophils per microliter of blood.
• Symptoms: Your provider will consider how consistently your symptoms appear. Experiencing symptoms at around the same time (roughly every three weeks) can help your provider rule out other forms of neutropenia that aren’t cyclical.
• Genetic test results: Your provider may order genetic tests to see if you have a mutation in genes associated with cyclic neutropenia.

What are differential diagnoses for cyclic neutropenia?

An important part of diagnosis involves distinguishing cyclic neutropenia from other types of neutropenia that cause similar symptoms. Other types of neutropenia include:

• Severe congenital neutropenia (formerly known as Kostmann syndrome).
• Autoimmune neutropenia.
• Idiopathic neutropenia.

Neutropenia may also be a sign of a different condition. For example, certain types of cancer and cancer treatments, like chemotherapy, can cause low neutrophil levels. With these causes, even if your neutrophil levels fluctuate, they don’t often do so on a consistent cycle, as with cyclic neutropenia.

What are the treatments for cyclic neutropenia?

Treatment involves curing any infections and boosting your neutrophils to healthy levels to prevent future infections.

Treatments include:

• Antibiotics: Antibiotics fight bacteria that cause infections.
• Granulocyte colony-stimulating factor (G-CSF): G-CSF treatments, like filgrastim (Neupogen®), help your body make more neutrophils. Neutrophils form in your bone marrow. G-CSF is a safe, effective, long-term treatment for cyclic neutropenia.
• Stem cell transplant: Stem cells eventually mature into healthy blood cells, like neutrophils. A stem cell transplant can replace your unhealthy neutrophil cells with healthy ones. Almost all people don’t need stem cell transplants to treat cyclic neutropenia. Still, you may need this procedure if your symptoms are severe and you don’t respond to G-CSF.

What are the side effects of cyclic neutropenia treatments?

Antibiotics may cause minor side effects, like diarrhea or yeast infections.

G-CSF side effects vary depending on the specific type of medicine you’re receiving and the dosage. Often, healthcare providers can manage cyclic neutropenia with low doses of G-CSF that only cause mild side effects.

Side effects may include:

• Headache.
• Joint and bone pain.
• Nausea and diarrhea.
• Rupture of your spleen or an enlarged spleen (splenomegaly).

Ask your healthcare provider about any side effects you should be aware of during treatment. It’s a good idea to be aware of any side effects requiring emergency medical attention.

What is the outlook for people with cyclic neutropenia?

While untreated neutropenia can cause life-threatening infections, medicines like G-CSF have greatly improved cyclic neutropenia outcomes. You may need regular blood work to monitor your neutrophil levels, but often, people with cyclic neutropenia can live normal lives thanks to current treatments.

Can neutropenia turn into leukemia?

A different type of neutropenia called congenital neutropenia is associated with an increased risk of developing cancers called myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) over time. But cyclic neutropenia doesn’t pose the same risks.

When should I call my healthcare provider about cyclic neutropenia?

If you or your child has cyclic neutropenia, you should call your healthcare provider at once if you think an infection is developing. The signs include:

• Pain.
• Fever.
• Swelling or skin discoloration (redness).

How do I take care of myself?

Protect yourself from infection — especially when you know that your body doesn’t always make enough healthy neutrophils to protect you. You can:

• Wash your hands frequently.
• Practice good dental hygiene and see your dentist regularly.
• Get recommended vaccinations.
• Avoid touching your face, eyes and nose if you haven’t recently washed your hands.

Follow your healthcare provider’s guidance about how often you’ll need blood tests to monitor your neutrophil levels. Take all medicines as prescribed.