Summary
Neutrophil disorders are a group of conditions that affect the body’s ability to fight bacterial and fungal infections. Neutrophils are a type of white blood cell that clear bacteria and fungi from the body. They are also called granulocytes or pus cells.
Neutrophils are produced in bone marrow and released into the blood. They control infection by travelling into body tissues to kill microorganisms, such as bacteria and fungi. Neutrophils destroy bacteria and fungi through a process called phagocytosis. This process involves the neutrophils engulfing infected cells and using granules (small particles) and chemicals to destroy the bacteria and fungi. Neutrophils also produce chemical signals that attract other neutrophils at sites of infection, and an accumulation of neutrophils forms pus.
There are many different conditions that are grouped under the heading neutrophil disorders. However, people affected by a neutrophil disorder have:
- a reduced number of neutrophils, owing to a defect in the production of neutrophils, or
- neutrophils that don’t function properly, or
- low numbers of neutrophils, associated with another disorder.
If you have a neutrophil disorder it means that you can’t fight infections as well as people with normal levels of functioning neutrophils. Some neutrophil disorders affect both males and females, and the severity of the condition can vary. From an early age, patients may have severe, recurrent bacterial and fungal infections, such as pneumonia, meningitis, sepsis and abscesses.
The aim of treatment is to reduce the risk of infection by practising good hygiene, including dental hygiene and skin care, and to treat promptly any infections with antibiotics and antifungal agents.
More specialised treatments depend on the condition and may include stimulation of the bone marrow to produce more neutrophils (using G-CSF ((granulocyte colony-stimulating factor) injections) and, if appropriate, a stem cell transplant.
The outlook for patients with neutrophil disorders depends on the severity of the disease, how much damage has occurred before diagnosis and how successfully infections can be prevented and treated in the future.
This information focuses on inherited genetic conditions that affect the production of neutrophils or the way neutrophils work.
There are two common causes of low numbers of neutrophils (neutropenia). The first is chemotherapy given to patients in the treatment of cancer. The second is an autoimmune condition, such as lupus. Neutrophil disorders caused by an autoimmune condition are called autoimmune neutropenias, owing to the body producing antibodies to its own neutrophils, or to the bone marrow stem cells from which neutrophils are derived.
This information focuses on inherited genetic conditions that affect the production of neutrophils or the way neutrophils work (see the table below). These conditions come under the heading primary immunodeficiencies and can be passed down from one generation to the next.
Some types of neutrophil disorders can be inherited from one parent who has a faulty gene. Other types of neutrophil disorders are inherited only if both parents have a faulty gene. Further types are X-linked, which means that the condition usually affects males only.
The faulty genes can affect the production or the function of neutrophils. The way the genes are inherited often means that the parents are themselves unaffected. This has implications for family planning, and families may need genetic counselling.
Immunodeficiency UK has a separate leaflet devoted to the genetics of primary immunodeficiency.
Table 1. Types of neutrophil disorders and their Inheritance
*Further information on CGD can be found at https://www.cgdsociety.org
Several other primary immunodeficiency conditions may be associated with low neutrophil numbers.
Common features, which you may recognise in yourself or your child, include:
- Skin and surface tissues – abscesses, cellulitis, infected lymph nodes, infected belly button (umbilicus), poor wound healing, fungal infections (including persistent thrush and fungal rashes).
- Mouth – ulcers, gingivitis, dental abscesses, stomatitis (inflammation of the mouth and lips).
- Lungs – pneumonia, abscesses, bronchiectasis.
- Gut – colitis, inflammatory bowel disease, diarrhoea, liver abscesses, peri-anal abscesses, inflammation of the caecum (typhlitis).
- Blood – in addition to infections, other symptoms can include anaemia, and bleeding and bruising tendencies, and can sometimes be associated with types of leukaemia.
Recurrent infections will lead a doctor to look for underlying causes, but as infections are common at any age, the clues may not always be apparent. A clinical history of severe, recurrent infections, a possible family history of immune deficiency and slowing of growth or development are important factors to consider.
A careful physical examination will also alert the doctor to the possibility of a neutrophil disorder, which can be confirmed by the following tests:
- A full blood count (FBC) – to measure the numbers of neutrophils and other white blood cells, plus red blood cells, platelets and haemoglobin. Repeat tests are often necessary as sometimes the neutropenia occurs in cycles
- Autoimmune tests – to look for evidence of autoimmune diseases which may explain neutropenia
- Tests for specific autoantibodies against neutrophils
- Specialist genetic tests – to see which genes may be affected
- Microbiology tests – to look for the specific organism causing an infection. This involves taking samples of body fluids including sputum, stools, skin and throat/nasal swabs
- Bone marrow biopsy – a sample of bone marrow is usually taken from the top of the pelvic bone, just below the waist, using a thick needle. A local anaesthetic and a sedative are often given to minimise any discomfort.
Further tests may include X-rays and scans (e.g. chest X-rays, ultrasound scans, CT scans) depending on which part of the body is affected.
The priority is to treat any serious bacterial or fungal infections with antibiotics or antifungal medicines. Some people need to take prophylactic medicines – a regular dose to prevent infections from flaring up.
Other preventative measures are good skin and dental hygiene, and constant vigilance for signs of infection. Regular dental checks are important, and your dentist should be made aware of your condition. Please see our leaflet ‘Keeping well and healthy when you have an immunodeficiency’.
Infections should be treated promptly and vigorously, and your GP should be aware of this.
Where the number of neutrophils is low, injections of G-CSF are given under the skin to stimulate the bone marrow to produce and release neutrophils.
Haematopoietic stem cell transplant (HSCT), also known as a bone marrow transplant (BMT), can offer a permanent cure for those with inherited disease which does not respond to G-CSF injections. Ideally, HSCT is carried out before the cycles of repeated infection and inflammation take their toll on the body. Further information about what is involved in having a HSCT/BMT and its risks will be provided by the BMT centre, and families will have a chance to discuss this treatment option in detail with an immunologist and BMT consultant on several occasions.
Gene therapy aims to correct the underlying genetic abnormality by replacing the faulty gene in immune cells with a normal copy. It is currently undergoing clinical trials in selected patients who have certain neutrophil disorders, including CGD and LAD.
Additional treatments may be required for those with complications. If lung problems, such as bronchiectasis, have developed, then physiotherapy may be needed to remove excessive mucus from the airways.
A healthy diet is important and advice from a dietician may be advisable, especially if you have gut symptoms.
It is important not to smoke. If you are a smoker, then your GP can offer support for you to stop smoking.
You will usually be under the care of an immunology team comprising doctors and specialist nurses. Monitoring is by regular appointments, blood tests and involvement of other specialists if necessary. It is a good idea to note down any concerns and questions you may have before each appointment. Please see our leaflet ‘Making the most of your appointments’.
Not all vaccines are safe to be given to people with neutrophil disorders.
You should discuss any recommended vaccinations with your immunology team before receiving a vaccine.
Without treatment, patients remain at risk of serious infections and inflammation. With HSCT, people with inherited neutrophil disorders can be cured and live a normal life.
If the condition is inherited, then you and your family may be offered genetic counselling. Genetic counselling both for affected people and for family members is important once the genetic cause is known.
Reference
Neutrophil disorders and their management. R Lakshman and A Finn. Journal of Clinical Pathology (2001) January; 54(1): 7–19. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1731272/pdf/v054p00007.pdf
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