Cyclic Neutropenia Symptoms, Diagnosis, and Treatment

Cyclic neutropenia is an inherited condition where the neutrophil count (white blood cell that fights bacterial infections) becomes severely low on a cycle of approximately every 21 days. It usually presents in the first year of life.

The cycles decrease with age and it can disappear in some adult patients.

Symptoms

Symptoms generally lag behind the neutropenia (low neutrophil count), meaning the neutrophil count has already been extremely low for a couple of days prior to the development of symptoms. Unlike with other congenital forms of neutropenia (severe congenital neutropenia, Shwachman Diamond Syndrome, etc.), birth defects are not seen.

Symptoms include:

• Aphthous ulcers (ulcers in the mouth)
• Throat inflammation (pharyngitis)
• Gum inflammation (gingivitis)
• Skin infections
• Fever

Who Is at Risk?

Cyclic neutropenia is congenital, meaning the person is born with the condition. It is passed down in families in an autosomal dominant fashion, meaning only one parent has to be affected to pass it on to their children. Not all family members may be affected similarly and some may or may not have any symptoms.

Diagnosis

Cyclic neutropenia can be challenging to diagnose as the severe neutropenia only lasts 3 to 6 days during each cycle. In between these cycles, the neutrophil counts are normal. Recurrent oral infections and fever every 21 to 28 days should raise suspicion for cyclic neutropenia.

In order to catch the cycle of severe neutropenia, an absolute neutrophil count (ANC), a part of acomplete blood count (CBC), is performed two to three times per week for six to eight weeks.

The absolute neutrophil count (ANC) reveals your neutrophil levels. Neutropenia is indicated when levels fall below 1,000 neutrophils/mcL; severe cases are associated with levels less than 500 neutrophils/mcL.

In addition to the severe neutropenia, there can be a decrease in the immature red blood cells (reticulocytopenia) and/or platelets (thrombocytopenia). The monocyte count (another type of white blood cell) often increases during the time of severe neutropenia.

If cyclic neutropenia is suspected based on serial blood counts, genetic testing can look for mutations in the ELANE gene (on chromosome 19). Nearly all patients with cyclic neutropenia have an ELANE mutation.

Mutations in the ELANE gene have been associated with cyclic neutropenia and severe congenital neutropenia. Given the clinical presentation and confirmatory genetic testing, ​bone marrow biopsy is not required but is often performed during the work-up of neutropenia.

Treatments

Although cyclic neutropenia is considered a benign condition, deaths secondary to serious infections have occurred. Treatment is geared toward preventing and/or treating infections.

• Granulocyte colony-stimulating factor (G-CSF, also called filgrastim): G-CSF stimulates the bone marrow to produce more neutrophils. It is used to prevent the neutrophil count from dropping below 500 cells/mL. G-CSF has been shown to decrease the severity of the neutropenia and decrease the number of infections. G-CSF is usually administered subcutaneously (just beneath the skin) every day, or sometimes less frequently. Some patients may be able to discontinue G-CSF as an adult because sometimes the neutropenia gets milder with age.
• Preventative dental care: Because many of the infections occur in the mouth, it is important to maintain good oral hygiene. Antibacterial mouthwashes may be recommended.
• Evaluation for fever: Because patients with cyclic neutropenia can develop severe bacterial infections, it is important that episodes of fever be evaluated carefully. Sometimes, the episodes will require hospitalization with intravenous (IV) antibiotics until serious infection can be ruled out.