Cyclic neutropenia is a rare blood condition that causes regular drops in neutrophils, which are white blood cells that help fight infection. Many people with cyclic neutropenia have repeated fevers, mouth sores, swollen gums, sore throat, or skin infections, and the early signs of cyclic neutropenia often begin in infancy or childhood. Cyclic neutropenia can continue for life, but some people have milder patterns as they get older. Not everyone will have the same experience, and serious infection can sometimes be dangerous or rarely life threatening if treatment is delayed. Treatment for cyclic neutropenia often includes careful infection care and medicines such as G-CSF to raise neutrophil levels and lower the risk of infections.
How many people live with Cyclic neutropenia?
Cyclic neutropenia is very rare and is estimated to affect about 1 in 1 million people, which works out to roughly 8,000 people worldwide (MedlinePlus Genetics, 2024; United Nations, 2024). Using the same rate, it would affect about 340 people in the United States, but that is an estimate rather than a direct national count (MedlinePlus Genetics, 2024; U.S. Census Bureau, 2024).
Overview
Cyclic neutropeniaSymptoms
Cyclic neutropenia causes recurring spells of low white blood cells, often every 3 weeks. During these times, people may have fever, mouth sores, swollen gums, sore throat, or tiredness. Infections can happen more easily, especially in the skin or sinuses.
Outlook and prognosis
With cyclic neutropenia, outlook is usually good when infections are recognized early and blood counts are followed over time. Many people live full, active lives, though they may have repeated mouth sores, fevers, or infections during low-count cycles.
Causes and risk factors
Cyclic neutropenia is usually caused by a change in the ELANE gene, often inherited from a parent but sometimes new in the child. Risk is mainly genetic; lifestyle and environment do not cause cyclic neutropenia, though infections can worsen its effects.
Genetic influences
Genetics are central to cyclic neutropenia. In many people with cyclic neutropenia, changes in the ELANE gene are the main cause, and different variants can affect how often episodes happen and how severe they are.
Diagnosis
Cyclic neutropenia is diagnosed by repeated blood counts over several weeks to show regular drops in neutrophils. Doctors also review infection patterns and mouth sores. Genetic diagnosis of cyclic neutropenia may be confirmed with genetic tests, often for ELANE changes.
Treatment and drugs
Treatment for cyclic neutropenia focuses on preventing infections and helping neutrophil counts recover. Many living with cyclic neutropenia receive G-CSF shots to boost white blood cells. Infections are treated quickly, sometimes with antibiotics and careful follow-up.
Symptoms
Cyclic neutropenia often shows up as repeat stretches of fever, mouth sores, and infections that seem to come and go, with many people feeling fairly well in between. These episodes happen when infection-fighting white blood cells called neutrophils drop, usually on a rough cycle of about 21 days, though the timing can vary. The early features of cyclic neutropenia may look like ordinary childhood bugs or repeated canker sores at first. Features can vary from person to person and can change over time.
These problems often flare for 3 to 5 days, then settle, and return again after a fairly regular gap. Many people with cyclic neutropenia feel well or much better between episodes.
Fevers can come back every few weeks, often with chills, aches, or a generally unwell feeling. During these days, even school, work, or simple errands can feel much harder.
Painful mouth ulcers and inflamed gums are among the most common features of cyclic neutropenia. Eating, drinking, or brushing teeth can become surprisingly uncomfortable during a flare.
Sore throat, swollen tonsils, and repeated sinus or ear infections can show up during low-count days. It may seem like one infection clears and another returns a few weeks later.
How people usually first notice Cyclic neutropenia?
How cyclic neutropenia is first noticed often becomes clear when a child or sometimes an adult has fevers, painful mouth sores, swollen gums, or repeated infections that seem to come and go in a pattern, often about every 3 weeks. During these low points, many living with cyclic neutropenia may also have sore throats, skin infections, or unusual tiredness, while between episodes they can seem completely well, which is an important clue. Doctors often first suspect the condition when blood tests done during these recurring illness spells show the neutrophil count, a type of infection-fighting white blood cell, dropping very low and then rising again.
Types of Cyclic neutropenia
No distinct types of cyclic neutropenia are widely recognized.
Can I slow down the onset of symptoms?
No, there is no good evidence that lifestyle changes can meaningfully delay the start of symptoms in cyclic neutropenia, because the regular drops in infection-fighting white blood cells are part of the condition itself. Healthy habits like good sleep, careful dental care, handwashing, and getting infections treated early may help lower the chance of complications when blood counts are low, but they do not prevent the cycles, and research has not shown that diet, exercise, or supplements can stop symptoms from starting. If symptoms are frequent or severe, regular blood count checks and a doctor-prescribed medicine that helps the body make more white blood cells can reduce infections and make episodes milder, so while you may not be able to delay onset, good care can still help a lot.
What genetics can tell you about symptoms
Genetics can tell you quite a bit about symptoms in cyclic neutropenia because changes in the ELANE gene are a well-known cause, and they help explain why neutrophil levels repeatedly drop in cycles. These genetic changes can affect how often low counts happen and how severe problems may be, so some people have mainly mouth sores, fevers, and frequent infections, while others have milder symptoms. Genetics may also help explain when symptoms begin, often in childhood, but the exact pattern can still vary from one person to another, even within the same family.
Causes and risk factors
Most cases of cyclic neutropenia are caused by a change in the ELANE gene. This gene change can be inherited from a parent, or it can happen for the first time in a child. Some risks are written in our DNA, passed down through families. When it comes to risk factors for cyclic neutropenia, family history is the main one, and lifestyle or environmental factors do not usually cause it. Still, smoking, poor mouth care, close exposure to germs, or other illnesses can make times of low white blood cell counts harder and raise the chance of infection.
What are the most common causes or risk factors?
Cyclic neutropenia is most often caused by a change in a gene called ELANE, which affects how the body makes neutrophils, the white blood cells that help fight infection. This gene change can be passed down in families or can happen for the first time in a child with no family history. The main risk factor is having a parent or close relative with the condition, and there are no well-known lifestyle or environmental causes.
Environmental and biological risk factors
For cyclic neutropenia, the list of proven environmental and non-genetic biological risk factors is very short. Most cases are tied to an internal change that begins before birth, rather than something in day-to-day surroundings. Awareness of both biological and environmental influences helps you feel prepared. So far, researchers have not confirmed that common exposures, routine pregnancy factors, infections, or birth events directly cause cyclic neutropenia.
Genetic risk factors
Cyclic neutropenia is usually linked to a change in ELANE, a gene involved in how certain infection-fighting white blood cells develop. These genetic changes can make neutrophil counts rise and fall in a repeating pattern, which is why infections, mouth sores, or fevers may come and go over time. Carrying a genetic change doesn’t guarantee the condition will appear, and even within the same family, symptoms can vary.
ELANE changes: The main genetic cause of cyclic neutropenia is a change in ELANE. This gene helps neutrophils mature, and certain changes can disrupt that process in a rhythmic way.
Family history: Cyclic neutropenia often runs in families in an autosomal dominant pattern, which means one changed copy of the gene can be enough to cause it. If a parent carries the change, each child has a 1 in 2, or 50%, chance of inheriting it.
New variants: Some people with cyclic neutropenia have a new genetic change that started in them and was not inherited from either parent. This means the early symptoms of cyclic neutropenia can show up even when no one else in the family has had the condition.
Lifestyle risk factors
Lifestyle habits do not cause cyclic neutropenia, but they can influence how often infections develop, how severe symptoms feel, and how well the body recovers between low-neutrophil periods. When people ask how lifestyle affects cyclic neutropenia, the most important issues are lowering exposure to everyday infection sources and supporting healing. Diet, activity, sleep, and oral care can all make a practical difference in day-to-day management.
Mouth ulcers and gum infections can flare more easily during neutropenic periods. Gentle brushing, regular dental care, and prompt attention to mouth sores may reduce pain and lower the chance of bacteria entering the bloodstream.
Raw or undercooked foods, unwashed produce, and poor kitchen hygiene can increase exposure to germs that may cause more serious illness in cyclic neutropenia. Safe food handling and choosing lower-risk foods during vulnerable days can help reduce infection episodes.
Poor sleep and chronic stress can impair immune regulation and make it harder to cope with fatigue, fevers, and recurrent infections. Consistent sleep and stress-management habits may improve resilience during symptomatic cycles.
Skipping meals or eating a low-quality diet does not cause cyclic neutropenia, but it can slow recovery from infections and worsen weakness or poor wound healing. Adequate protein, calories, fluids, and key vitamins support tissue repair and overall health during recurrent flare periods.
Risk prevention
Cyclic neutropenia cannot usually be prevented because it is most often linked to an inherited change that affects how the body makes certain infection-fighting white blood cells. Prevention is about lowering risk, not eliminating it completely. For many living with cyclic neutropenia, the main goal is to prevent infections, catch problems early, and reduce complications during the times when white blood cell counts drop. This can matter in everyday life, such as when a small mouth sore or mild fever turns into something more serious than expected.
Many people with cyclic neutropenia have symptoms that come and go in a fairly regular pattern, often every few weeks. Tracking fevers, mouth sores, sore throat, or infections can help you and your doctor plan extra caution during low-count days.
Careful handwashing lowers the chance of picking up germs during vulnerable periods. This is especially helpful before eating, after using the bathroom, and after being in crowded places.
Try to limit close contact with people who are sick when your counts are likely to be low. Good food safety, prompt cleaning of cuts, and avoiding unnecessary exposure to high-risk settings can also reduce infection risk.
Gentle daily brushing and regular dental visits can help prevent mouth infections, which are common in cyclic neutropenia. If gums bleed easily or mouth ulcers keep coming back, let your care team know early.
Can you prevent Cyclic neutropenia?
No, cyclic neutropenia usually cannot be prevented because it is most often caused by an inherited or spontaneous gene change that makes infection-fighting white blood cells drop very low in a repeating pattern. While you cannot stop the condition itself from happening, careful infection prevention, good dental care, and getting medical help quickly for fever or signs of infection can help lower the risk of complications.
Transmission
How cyclic neutropenia is inherited is very different from how infections spread: it is not contagious and does not pass through coughing, kissing, sharing food, or everyday contact. Instead, cyclic neutropenia is usually passed from parent to child through a changed gene that affects how neutrophils, a type of white blood cell, are made.
In many families, one changed copy of the gene is enough to cause the condition, so each child of an affected parent has a 1 in 2, or 50%, chance of inheriting it. Some people with cyclic neutropenia are the first in their family to have it because the gene change happened new in them, so there may be no earlier family history.
When to test your genes
If you have repeated episodes of fever, mouth sores, infections, or very low neutrophil counts that seem to come in cycles about every 3 weeks, genetic testing is worth discussing. It can confirm cyclic neutropenia, guide monitoring and treatment, and help assess risk in relatives.
Diagnosis
People with cyclic neutropenia often come to medical attention because infections keep returning in a pattern, such as mouth sores, fever, or feeling run-down every few weeks. The diagnosis of cyclic neutropenia usually depends on noticing this repeating rhythm and then confirming it with blood tests over time. It’s natural to worry when symptoms don’t have a clear explanation. Some diagnoses are clear after a single visit, while others take more time.
Doctors ask about repeated episodes of fever, mouth ulcers, sore throat, swollen gums, or skin infections that seem to come and go. A symptom diary can help show whether these problems return at fairly regular intervals, which is an important clue.
The main test is a complete blood count, also called a CBC, repeated several times over weeks. In cyclic neutropenia, these tests show that neutrophils, a type of white blood cell that fights infection, drop very low in a repeating cycle.
To confirm the pattern, blood counts are often checked two to three times a week for about 6 to 8 weeks. This is a key part of how cyclic neutropenia is diagnosed because a single normal test can miss the low points.
Doctors usually begin with a careful review of infections, fevers, mouth problems, and any past hospital visits or antibiotic use. A detailed family and health history can help because some conditions have a genetic link and may run in families.
How is Cyclic neutropenia diagnosed?
Cyclic neutropenia is usually diagnosed with repeated blood tests over several weeks, often 2 to 3 times a week for about 6 to 8 weeks, to show a regular pattern where the level of infection-fighting white blood cells drops and then rises again. Doctors also look at the pattern of symptoms, such as repeated fevers, mouth sores, or infections that seem to come and go on a schedule, and they may do other tests to rule out other causes of low white blood cells. In some cases, a genetic test can help confirm the diagnosis, especially if there is a family history or the blood test pattern strongly suggests it.
Stages of Cyclic neutropenia
Cyclic neutropenia does not have defined progression stages. That is because it usually comes and goes in repeated cycles, rather than steadily moving from one stage to the next over time. People with cyclic neutropenia often have symptom-free periods between low white blood cell counts, then episodes with fever, mouth sores, sore throat, or infections when the count drops. Doctors usually start with a conversation about symptoms and timing, and how cyclic neutropenia is diagnosed usually involves repeated blood tests over several weeks to show the regular pattern.
Outlook and prognosis
The outlook for people with cyclic neutropenia is generally good, especially with careful monitoring and prompt treatment of infections. Many affected individuals have recurrent episodes of fever, mouth ulcers, sore throat, skin infections, or more serious bacterial infections during neutropenic periods, but these risks are greatly reduced by granulocyte colony-stimulating factor therapy and appropriate antibiotics when needed. Unlike severe congenital neutropenia, cyclic neutropenia is not usually associated with a high risk of myelodysplastic syndrome or leukemia. Most people can achieve a near-normal life expectancy and maintain normal daily activities with ongoing care. Mortality is low in treated patients, but severe sepsis can rarely be life-threatening if infections are not recognized and managed quickly.
Long-term effects
For many people, the long-term effects of cyclic neutropenia are tied to repeated drops in infection-fighting white blood cells. This can lead to a pattern of flare-ups every few weeks, with periods of feeling fairly well in between. Long-term effects vary widely, and they often depend on how low the white blood cell count falls and how often infections happen.
The main long-term effect of cyclic neutropenia is a higher chance of infections that keep coming back over time. These often affect the mouth, throat, skin, sinuses, or lungs, especially during low-count periods.
Many living with cyclic neutropenia develop repeated mouth sores, gum inflammation, or painful infections around the teeth. Over time, this can make eating uncomfortable and may affect dental health if episodes are frequent.
Cyclic neutropenia often causes recurring fever episodes that follow the same rough timing as the blood count cycle. In some people, what seem like the early symptoms of cyclic neutropenia are actually these repeated fever and mouth flare-ups.
In children with cyclic neutropenia, frequent infections can sometimes affect growth, weight gain, or energy over time. This is more likely when episodes are severe or happen often enough to interrupt eating and normal daily life.
How is it to live with Cyclic neutropenia?
Living with cyclic neutropenia can feel unpredictable because there are recurring stretches, often every few weeks, when infection-fighting white blood cells drop and everyday problems like mouth sores, fever, sore throat, or skin infections can suddenly disrupt school, work, sleep, and social plans. Many people with cyclic neutropenia learn to pay close attention to early signs of infection and may need regular blood tests, fast medical care for fever, and sometimes ongoing treatment to lower the risk of serious illness, but between low-count periods they may feel quite well. For family members and other close contacts, this can mean extra planning, worry during fever episodes, and being more alert about infection exposure, while also helping keep daily life as normal, active, and reassuring as possible.
Treatment and drugs
Cyclic neutropenia is usually treated by lowering the risk of infections during the times when neutrophil counts dip, since those are the days when mouth sores, fevers, or skin infections are most likely to flare. The main treatment for many people with cyclic neutropenia is a medicine that helps the bone marrow make more infection-fighting white blood cells, and doctors may also use antibiotics quickly if signs of infection appear. Treatment often looks different for each person, and some may only need careful monitoring and fast treatment of infections, while others need regular medicine to prevent the early symptoms of cyclic neutropenia from disrupting daily life. Good dental care, tracking fever or mouth ulcers, and regular blood tests also play an important part, and in rare severe cases a specialist may discuss more intensive options.
Can you cure Cyclic neutropenia?
There is usually no permanent cure for cyclic neutropenia, but it can often be managed well. Treatment may include medicine that helps the body make more infection-fighting white blood cells, along with fast treatment for infections and regular blood tests. In rare, very severe cases, a bone marrow transplant may be considered, but this is not common because it carries serious risks.
Non-drug treatment
Living with cyclic neutropenia often means planning around times when infection risk rises, even if you feel well between episodes. Non-drug treatments focus on lowering exposure to germs, spotting problems early, and protecting areas that commonly get infected, such as the mouth, skin, and gums. Managing this condition often includes practical daily habits, regular check-ins, and a clear plan for when fever or sores appear.
Careful handwashing, avoiding close contact with people who are sick, and sensible food safety can help lower infection risk during low-count days. For many, this is a big part of how to prevent infections in cyclic neutropenia.
A written plan for fever, chills, mouth sores, or new pain can help you get urgent care quickly when it matters most. Because infections can become serious fast, many living with cyclic neutropenia are advised not to wait and see if symptoms pass.
Regular dental visits and gentle daily mouth care can help prevent gum disease, mouth ulcers, and painful infections. A soft toothbrush and early attention to bleeding gums or sores may make eating and speaking easier.
Small cuts, scrapes, and irritated skin should be cleaned promptly and watched closely for redness, warmth, swelling, or drainage. Simple routines—like handwashing or gentle wound care—can have lasting benefits.
Your genes may have an impact on how drugs work for you
In cyclic neutropenia, the genetic change that causes the condition can also affect how severe the low white blood cell cycles are, which can influence how often someone needs treatment and how well they respond to white blood cell-boosting shots or antibiotics for infections. For example, some people have milder patterns with fewer infections, while others need closer dose adjustments because their counts drop more deeply or more often. In day-to-day care, doctors usually base treatment on blood count results and infection history rather than on special drug-response genetic testing, because that kind of testing is not a routine part of care for this condition.
Pharmacological treatments
Living with cyclic neutropenia often means planning around repeated stretches when infection risk rises, especially during the lowest white blood cell days. The main drug treatment for cyclic neutropenia is a white blood cell growth factor, most often filgrastim, which helps the body make more infection-fighting neutrophils. Not everyone responds to the same medication in the same way. Other medicines, such as antibiotics or antifungals, may be added when infections keep coming back or need urgent treatment.
Filgrastim is the standard first-line medication for cyclic neutropenia and is the drug used most often for long-term treatment. It helps the bone marrow make more neutrophils, which can shorten low-count periods and reduce infections, mouth sores, and fevers.
Pegfilgrastim is a longer-acting version of the same type of growth factor and may be considered in some people with cyclic neutropenia. It is used less often than filgrastim, and dosing needs careful follow-up because response can vary.
Antibiotics are used to treat bacterial infections quickly when neutrophil counts drop and symptoms such as fever, sore throat, or skin infection appear. In some people with frequent infections, doctors may also use preventive antibiotics for part of the cycle as part of treatment for cyclic neutropenia.
Antifungal medicines may be needed if fungal infections develop, especially with repeated mouth or throat problems during neutropenic periods. They are not routine for everyone, but they can be important when infections are persistent or severe.
Genetic influences
Repeated fevers, mouth sores, or infections that seem to come and go on a schedule can make families wonder why this keeps happening. It’s natural to ask whether family history plays a role. In cyclic neutropenia, genetics are a major factor, and many cases are caused by a change in the ELANE gene, which helps the body make certain infection-fighting white blood cells. Cyclic neutropenia usually follows an autosomal dominant inheritance pattern, meaning one changed copy of the gene from either parent can be enough to cause the condition, although the gene change can also happen for the first time in a child. Even within the same family, the condition can look different from one person to another, with some having milder cycles and others having more noticeable symptoms. Genetic testing can help confirm the diagnosis and may be useful when doctors are evaluating early symptoms of cyclic neutropenia or checking whether other relatives could be affected.
Is Cyclic neutropenia genetic?
Genetics are central to cyclic neutropenia. In many people with cyclic neutropenia, changes in the ELANE gene are the main cause, and different variants can affect how often episodes happen and how severe they are.
Having a genetic risk is not necessarily a diagnosis
Genetic variants are a normal part of being human and are widely seen across the population. Most do not directly affect health and are simply one part of natural human diversity. For many genes, carrying a variant associated with a condition suggests a possible connection, not a certain diagnosis, especially when several genes and environmental factors are involved. In some cases, though, one well-understood variant in a particular gene can be enough to confirm a diagnosis.
Pharmacogenetics—how genetics influence drug effects
When fevers, mouth sores, or repeated infections keep returning in a cycle, treatment often has to be adjusted around those low white blood cell days. In many people with cyclic neutropenia, a change in the ELANE gene helps confirm the diagnosis, and that can steer doctors toward the right long-term plan instead of treating it like a one-time drop in blood counts. Many living with the condition ask how genetics affect treatment for cyclic neutropenia, and the answer is usually more about guiding care than picking a single drug. Genetics is only one factor, but the gene finding can help doctors judge how closely to monitor infections, when to use a white blood cell growth medicine such as filgrastim, and how much follow-up is needed over time. Unlike some other conditions, there is no widely used gene test that reliably predicts the exact dose or side effects of filgrastim or antibiotics in cyclic neutropenia, so treatment is still adjusted mainly by symptoms, blood counts, and infection history. Family testing may also help identify relatives who share cyclic neutropenia and could benefit from monitoring and early treatment planning.
Interactions with other conditions
People with cyclic neutropenia can seem fairly well for part of the month, then suddenly become much more vulnerable to problems when their neutrophil count drops. During those low-count periods, common infections such as sinus infections, sore throats, skin infections, mouth sores, or gum disease can start more easily and may become more severe than expected. Another important aspect is how it may link with other diseases: any condition that weakens the immune system, affects the mouth or gut, or causes frequent inflammation can make the pattern harder to manage. For many living with cyclic neutropenia, this can mean that early symptoms of infection need extra attention, especially if they also have asthma, inflammatory bowel disease, diabetes, or another illness that raises infection risk or slows healing. Medicines used for other conditions can matter too, because some drugs can further lower white blood cells or mask signs of infection such as fever. If you have cyclic neutropenia and another long-term condition, coordinated care helps your doctors judge which symptoms belong to the neutropenia cycle and which may signal a separate illness that needs treatment.
How genes can cause diseases
Humans have more than 20,000 genes, each carrying out one or a few specific functions in the body. One gene instructs the body to digest lactose from milk, another tells the body how to build strong bones and another prevents the body's cells from beginning to multiply uncontrollably and developing into cancer. As all of these genes combined are the building instructions for our body, a defect in one of these genes can have severe health consequences.
Through decades of genetic research, we know the genetic code of any healthy/functional human gene. We have also identified that in certain positions on a gene, some individuals may have a different genetic letter from the one you have. We call these hotspots "Genetic Variations" or "Variants" in short. In many cases, studies have been able to show that having the genetic letter "G" in the position makes you healthy, but having the letter "A" in the same position disrupts the gene function and causes a disease. Genopedia allows you to view these variants in genes and summarizes all that we know from scientific research, which genetic letters (Genotype) have good or bad consequences on your health or on your traits.
What other conditions can cause similar symptoms to Cyclic neutropenia?
Other problems can look a lot like cyclic neutropenia because they also cause repeated fevers, mouth sores, and infections, including other conditions that lower the infection-fighting white blood cells, such as severe congenital neutropenia and autoimmune neutropenia. Short-term drops in these white blood cells after a virus or from certain medicines can also cause similar episodes, and doctors may also need to rule out bone marrow illnesses such as aplastic anemia or leukemia. In children, PFAPA, a condition that causes repeated fever attacks, can sometimes be confused with it too.
History
Long before blood tests could map changes from week to week, families and doctors noticed that some people had a striking pattern: they would seem fairly well for a time, then every few weeks develop mouth sores, fever, swollen glands, or repeated infections, only to improve again and later go through the same cycle. For many living with cyclic neutropenia, that stop-and-start pattern can shape daily life in very practical ways, like missing school during one week of the month and feeling much better the next.
Early medical reports in the late 19th and early 20th centuries described recurring infections and low white blood cell counts, but it took time to realize these episodes were not random. As doctors began checking blood counts repeatedly instead of only once, they saw a regular rise-and-fall pattern in neutrophils, the white blood cells that help fight bacteria. That pattern helped separate cyclic neutropenia from other causes of frequent infection and made the condition easier to recognize when people came in with the same symptoms over and over.
In recent decades, awareness has grown as better lab testing allowed doctors to confirm the cycle more clearly and to understand why symptoms can come and go. This also helped explain why early symptoms of cyclic neutropenia were sometimes missed or mistaken for unrelated infections, especially in children, since a single blood test could look different depending on the day it was taken. Researchers later identified a genetic cause in some families, but the key historical step was learning to connect the repeating pattern of illness with the repeating change in blood counts.
The history of cyclic neutropenia is really a story of pattern recognition. What once may have looked like “someone who gets sick a lot” became understood as a distinct blood disorder with a recognizable rhythm. That shift has mattered for patients and families, because it made diagnosis more accurate, reduced confusion, and opened the way to better monitoring and treatment.