Cyclic Neutropenia

What is Cyclic Neutropenia?

Neutrophils are a type of cell that help protect our bodies by consuming and destroying harmful microorganisms. If they aren’t able to perform this task, it weakens our immune defenses and can lead to frequent infections. Main reasons for a decrease in neutrophils, known as neutropenia, are autoimmune diseases, reactions to drugs, chemotherapy, and inherited disorders.

One rare blood condition connected to neutropenia is called cyclic neutropenia. This involves regular changes in the number of neutrophils in the blood, resulting in a recurring drop in neutrophils every 21 days. This is usually caused by a mutation in the ELANE gene, which is passed down through families.

The symptoms and appearances of cyclic neutropenia can vary from mild to severe, depending on how low the neutrophil count gets and how long it stays low. Sometimes, the neutrophil count can drop all the way to zero and stay extremely low for up to three to five days.

What Causes Cyclic Neutropenia?

New advancements in molecular biology have allowed scientists to find the genetic reasons behind many inherited diseases. By looking at the genetic makeup of patients with a condition called cyclic neutropenia, they have found changes in a specific location of a gene responsible for producing neutrophil elastase, an important protein. This gene is now known as ELANE. These changes in the gene are always found in patients suffering from cyclic neutropenia, but not in their family members who do not have the disease. Because of this, some experts prefer to call this disease “ELANE-associated neutropenia”.

Risk Factors and Frequency for Cyclic Neutropenia

Cyclic neutropenia is a genetic disease that affects both males and females equally. It’s often found in young children and lasts for their entire lives. There are also instances where people acquire the disease later in their life. This condition can be passed down in families.

Signs and Symptoms of Cyclic Neutropenia

Cyclic neutropenia is a condition where patients have a recurring decrease in the count of a type of white blood cell, called neutrophils. This leads to a cycle of symptoms including regular fevers, mouth ulcers, and respiratory tract infections. During periods when the neutrophil count is low, patients may experience more unusual, or “opportunistic”, infections. These may present as fevers, sores in the mouth, inflamed gums, tonsillitis, throat infection, skin infections, and swollen glands. They also often suffer from a form of gum disease with loss of jaw bone from early childhood.

• Regular fevers
• Mouth ulcers
• Respiratory tract infections
• Opportunistic infections during low neutrophil count
• Gum inflammation
• Tonsillitis
• Throat Infection
• Skin Infections
• Swollen glands
• Specific gum disease resulting in loss of jaw bone

It’s been noted that the recurring fevers seen in cyclic neutropenia tend to lessen after adolescence. However, adult patients still often have mouth ulcers, gum inflammation, the specific gum disease, and other infections. Infections in patients with cyclic neutropenia tend to respond well to antibiotics and it’s rare for them to get severe infections. That said, a few serious complications have been noticed in long-term follow-ups which include spontaneous peritonitis, a type of abdominal infection, segmental bowel necrosis which is death of part of the intestine, and septicemia, a life-threatening infection that can spread throughout the body.

Testing for Cyclic Neutropenia

Cyclic neutropenia is diagnosed and evaluated through a set of components such as clinical symptoms, length of the disease, history of the condition in the family, and white blood cell counts, among other factors. Other investigations can include a full blood count, a bone marrow biopsy, microscopic tissue studies, checking for cancer markers, and applying tests to measure the levels of a substance called granulocyte-colony stimulating factor.

In addition to these tests, you might get a chest x-ray, an ultrasound, and a CT scan to help rule out other potential immune system disorders. DNA tests can also help confirm genetic disorders, including cyclic neutropenia. So these tests can give a more broad and complete understanding of the condition being assessed.

Treatment Options for Cyclic Neutropenia

The main way to manage this condition is by regularly checking blood counts, preventing and controlling infections with cautious use of antibiotics, taking care of oral health, and educating the patient. Some patients with recurring signs and symptoms have been successfully treated using corticosteroid medication every other day. For most kids dealing with severe inborn neutropenia, a treatment involving a long-term use of a substance called granulocyte-colony stimulating factor (G-CSF) is needed. G-CSF has been regarded as a particularly safe and effective treatment for preventing infections and boosting the quality of life for those suffering from cyclic neutropenia. Recent research suggests that combining G-CSF with high-dose immunoglobulin might be a strong treatment for cyclic neutropenia. For patients who don’t improve with G-CSF treatment, a procedure called hematopoietic stem cell transplantation (HSCT) serves as the ultimate treatment solution. This process can permanently correct cyclic neutropenia, providing the best long-term option.

What else can Cyclic Neutropenia be?

Cyclic neutropenia, a condition that leads to recurring instances of low neutrophil levels in the blood, often shares its symptoms with several other medical conditions that also cause recurrent fevers. These conditions include: recurrent tonsillitis, infectious diseases, juvenile idiopathic arthritis, Behçet’s disease, and familial Mediterranean fever syndrome.

There are also some uncommon conditions that present symptoms similar to cyclic neutropenia, such as:

• Marshall syndrome: This is a condition characterized by recurrent fevers that come back every 3 to 8 weeks. Symptoms of Marshall syndrome also include swelling in the neck’s lymph nodes, throat inflammation, and canker sores. This syndrome is usually diagnosed when other conditions have been ruled out.
• PFAPA syndrome: Also known as periodic fever, aphthous stomatitis, pharyngitis, and adenitis, this is a type of non-hereditary condition that contributes to inflammation in the body. This condition produces recurring fevers that last between 3 to 6 days along with canker sores, throat inflammation, tonsillitis, and swelling in the neck’s lymph nodes.

What to expect with Cyclic Neutropenia

Cyclic neutropenia is typically milder than other conditions involving a low level of neutrophils, a type of white blood cell.⁸ Systemic symptoms of cyclic neutropenia, including recurring fevers, usually lessen after the teenage years. However, even adults with this condition often suffer from mouth ulcers, gum inflammation (gingivitis), gum disease (periodontitis), and other infections.¹⁵ Many patients, particularly children, may experience gum disease with a loss of alveolar bone, the bone that holds the teeth in place.

Possible Complications When Diagnosed with Cyclic Neutropenia

Research indicates that people with cyclic neutropenia, a condition that causes low levels of certain white blood cells, might experience serious health problems over time. These include:

• Bloodstream infections (septicemia)
• Inflammation of the thin tissue that lines the abdomen and covers most of the organs within (spontaneous peritonitis)
• Death of a portion of the intestinal wall (segmental bowel necrosis)

Preventing Cyclic Neutropenia

Teaching patients about proper mouth and tooth care, along with the appropriate use of antibiotics, is crucial in managing cyclic neutropenia, a condition affecting white blood cells. Patients should be informed about the need for good oral hygiene and the importance of regular dental check-ups every month.