Cyclic neutropenia

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Cyclic neutropenia is a disorder that causes frequent infections and other health problems in affected individuals. People with this condition have recurrent episodes of neutropenia during which there is a shortage (deficiency) of neutrophils. Neutrophils are a type of white blood cell that plays a role in inflammation and in fighting infection. The episodes of neutropenia are apparent at birth or soon afterward. For most affected individuals, neutropenia recurs every 21 days and lasts about 3 to 5 days.

Neutropenia makes it more difficult for the body to fight off pathogens such as bacteria and viruses, so people with cyclic neutropenia typically develop recurrent infections of the sinuses, respiratory tract, and skin. Additionally, people with this condition often develop open sores (ulcers) in the mouth and colon, inflammation of the throat (pharyngitis) and gums (gingivitis), recurrent fever, or abdominal pain. People with cyclic neutropenia have these health problems only during episodes of neutropenia. At times when their neutrophil levels are normal, they are not at an increased risk of infection and inflammation.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Mutations in the ELANE gene cause cyclic neutropenia. The ELANE gene provides instructions for making a protein called neutrophil elastase, which is found in neutrophils. When the body starts an immune response to fight an infection, neutrophils release neutrophil elastase. This protein then modifies the function of certain cells and proteins to help fight the infection.

ELANE gene mutations that cause cyclic neutropenia lead to an abnormal neutrophil elastase protein that seems to retain some of its function. However, neutrophils that produce abnormal neutrophil elastase protein appear to have a shorter lifespan than normal neutrophils. The shorter neutrophil lifespan is thought to be responsible for the cyclic nature of this condition. When the affected neutrophils die early, there is a period in which there is a shortage of neutrophils because it takes time for the body to replenish its supply.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

Cyclic neutropenia is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.

In most cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Cyclic neutropenia is a rare condition and is estimated to occur in 1 in 1 million individuals worldwide.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Bone pain · Very frequent (99-80%)

An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) localized to bone.

Cyclic neutropenia · Very frequent (99-80%)

Abnormal decrease of the absolute number of neutrophils in the blood, per microlitre, compared to a reference range for a given sex and age-group, which occurs cyclically and then recovers without intervention.

Headache · Very frequent (99-80%)

Cephalgia, or pain sensed in various parts of the head, not confined to the area of distribution of any nerve.

Sinusitis · Very frequent (99-80%)

Inflammation of the paranasal sinuses owing to a viral, bacterial, or fungal infection, allergy, or an autoimmune reaction.

Cervical lymphadenopathy · Frequent (79-30%)

Enlarged lymph nodes in the neck.

Fatigue · Frequent (79-30%)

A subjective feeling of tiredness characterized by a lack of energy and motivation.

Gingivitis · Frequent (79-30%)

Inflammation of the gingiva

Lymphadenopathy · Frequent (79-30%)

Enlargement (swelling) of a lymph node.

Oral ulcer · Frequent (79-30%)

Erosion of the mucous mebrane of the mouth with local excavation of the surface, resulting from the sloughing of inflammatory necrotic tissue.

Periodic fever · Frequent (79-30%)

Episodic fever that recurs at regular intervals.

Pharyngitis · Frequent (79-30%)

Inflammation (due to infection or irritation) of the pharynx.

Recurrent fever · Frequent (79-30%)

Periodic (episodic or recurrent) bouts of fever.

Recurrent skin infections · Frequent (79-30%)

Infections of the skin that happen multiple times.

Recurrent tonsillitis · Frequent (79-30%)

Inflammation of the tonsils that has occurred repeatedly. The definition of recurrent may vary somewhat, but the criteria used recently as a measure of severity were five or more episodes of true tonsillitis per year, symptoms recurring for at least a year, and episodes that are disabling and that prevent normal functioning. In some cases recurrent tonsillitis may be related to immunosusceptibility. Evidence exists for a genetic predisposition for recurrent tonsillitis.

Other findings in the same source

From: Orphanet

Additional reported features include Respiratory tract infection (Frequent (79-30%)); Tooth abscess (Frequent (79-30%)); Abdominal pain (Occasional (29-5%)); Cellulitis (Occasional (29-5%)); Decreased eosinophil count (Occasional (29-5%)); Lymphopenia (Occasional (29-5%)); Opportunistic infection (Occasional (29-5%)); Otitis media (Occasional (29-5%)); Perianal abscess (Occasional (29-5%)); Periodontitis (Occasional (29-5%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Cyclic neutropenia is Allergy and Immunology, with a allergist / clinical immunologist as the relevant type of clinician. General physician / Family Medicine; paediatrician for children. Referral depends on symptoms.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Does the history suggest an allergy, an immune problem or another explanation?
• How would any proposed allergy or immune test change care?
• Is an individual emergency plan needed, and who should understand it?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Cyclic neutropenia. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.