Cyclic neutropenia: a rare cycling drop in white blood cells

Neutrophils are a type of white blood cell that plays a role in inflammation and in fighting infection, especially bacterial infection. Neutropenia means a shortage of them. In cyclic neutropenia the shortage comes and goes in a repeating pattern. NORD describes it as a rare blood disorder characterised by recurrent episodes of abnormally low levels of neutrophils, with symptoms that may include fever, a general feeling of ill health and sores (ulcers) of the mucous membranes of the mouth.

The cycle is regular. NORD says that in most cases episodes recur every 21 days, and that the cycling period usually remains constant and consistent in an affected person. MedlinePlus adds that the episodes are apparent at birth or soon afterwards, and that between episodes people are not at increased risk of infection.

No UK patient leaflet specific to cyclic neutropenia was available when this page was prepared, so the information below draws on MedlinePlus Genetics and NORD. In the UK, care is led by haematology teams, and a GP or haematologist is the right source for personal advice.

NORD lists fever, malaise, inflammation and deep ulceration of the mucous membranes of the mouth (aphthae and stomatitis), inflammation of the throat (pharyngitis), inflammation and degeneration of the tissues that support the teeth (periodontal disease) and loss of appetite. Periodontal disease may result in loosening of teeth and early tooth loss.

MedlinePlus says people typically develop recurrent infections of the sinuses, respiratory tract and skin, and often develop open sores in the mouth and colon, inflammation of the throat and gums, recurrent fever or abdominal pain. NORD says the bacterial infections often affect the skin, digestive tract and respiratory system, vary in severity and in some cases may cause life-threatening complications.

The pattern of fever and mouth ulcers that comes and goes every few weeks is often what prompts the diagnosis, especially in childhood. Keeping a simple diary of dates of fever, ulcers and infections can show the rhythm.

MedlinePlus says mutations in the ELANE gene cause cyclic neutropenia. The gene provides instructions for making neutrophil elastase, a protein in neutrophils. The abnormal protein appears to retain some function, but neutrophils that make it appear to have a shorter lifespan, and when they die early there is a period in which the supply is short because it takes time for the body to replenish it. That is thought to explain the cycle.

NORD says the disease is autosomal dominant and can be passed on from one affected parent, and that it affects males and females equally. Some cases arise without a family history. Genetic counselling is recommended for people with inherited forms and their families.

NORD says diagnosis is made from a detailed history and thorough clinical evaluation, and may be confirmed by monitoring the neutrophil count two or three times per week for six weeks, to show the cycle. It advises that individuals should be genetically tested for mutations in the ELANE gene.

There are many other causes of neutropenia, which NORD lists as viral infection, certain drugs, exposure to certain poisons, autoimmune neutropenia, chemotherapy and other primary disorders such as leukaemia. A haematologist will therefore consider these before concluding that the cycle is genetic. NORD also separates cyclic neutropenia from severe congenital neutropenia and says that, unlike severe congenital neutropenia, cyclic neutropenia is not associated with a risk of developing acute myeloid leukaemia.

NORD says prompt, appropriate treatment of the infections is important, which may include antibiotics, and that careful oral and dental care is required. It also advises avoiding activities that may cause minor injuries. Since 1987 recombinant human granulocyte colony stimulating factor (G-CSF) has been used to treat cyclic neutropenia and other severe chronic neutropenias. It says studies show long-term therapy can raise neutrophil numbers to the normal range in most individuals, reducing infections and other symptoms.

Careful evaluation before starting G-CSF and ongoing observation during therapy are essential, so treatment is supervised by a specialist team. Other treatment is symptomatic and supportive.

The sources used here do not set out fever instructions, but NORD stresses that bacterial infections in cyclic neutropenia can in some cases be life-threatening and need prompt treatment. People with a known neutropenia should follow the specific instructions their haematology team has given them about who to call and how fast. If you have not been given any, a fever is a reason to contact your GP or NHS 111 promptly, and 999 is appropriate for severe breathlessness, confusion or collapse.

The sources used here do not give firm statistics on how the condition changes over a lifetime, so it is best to discuss expectations with the haematology team. MedlinePlus emphasises that between episodes people are well. Good dental hygiene, regular dental review, prompt attention to ulcers and infections, and an agreed plan for fever are the practical foundations of day-to-day care.