I was called not long ago by a dear friend whose daughter has been struggling for years with a vaguely defined febrile illness that has recently been diagnosed as cyclic neutropenia. This prompted me to read up about this condition and it is indeed a curious and interesting although rare condition.
Cyclic Neutropenia is a condition where an individual’s absolute neutrophil count (ANC) cycles about every 21 days (range 14-35 days, but 90% of patients have approximately 21 day cycles) so that they have 3-6 days per cycle with an extremely low ANC of 0.2 neutrophils/ microliter of blood (normal 4-11). These severe drops in ANC are due to markedly reduced neutrophil production in the bone marrow. Most cases of cyclic neutropenia are hereditary, and have recently been discovered to be due to a defect in the gene coding for ELA2, a proteinase enzyme in the azurophil granules of the neutrophil that are released to destroy bacteria and host tissue in fighting infections. During these cycles of severe neutropenia patients tend to develop fevers and infections, usually fairly mild, but at times life threatening.
The diagnosis can be suspected when fever and illness seems to cycle every 3 weeks or so, and is tentatively diagnosed by getting differential white blood cell counts (essentially a CBC) three times weekly for 6 weeks, to show two cycles of severe neutropenia. Hereditary cyclic neutropenia is a rare autosomal dominant disorder, occurring in 1-2/ million children (1) . It usually presents in early childhood, and sometimes improves after adolescence. As is typical of an autosomal dominant disorder it can occur in several siblings in a family, but can also be a spontaneous mutation and occur sporadically. In the young child the differential diagnosis includes PFAPA (Periodic Fever with Apthous Stomatitis, Pharyngitis and Adenitis) where there is periodic high fever every few weeks, and relatively asymptomatic shallow apthous ulcers often under the lips, and sometimes Pharyngitis (sore throat) and adenitis (swollen nodes). In this condition the neutrophil count is normal during febrile episodes, and the child usually grows out of the condition by about age 8 years. PFAPA is much more common than cyclic neutropenia, and is probably under-diagnosed.
Cyclic neutropenia can be treated with the Granulocyte Colony Stimulating Factor G-CSF drugs more commonly used to treat chemotherapy induced neutropenia. This is marketed in the US as Neupogen, and can induce the bone marrow to increase production and release of neutrophils into the blood stream. Other treatments that have been used to treat cyclic neutropenia include splenectomy (not likely effective), testosterone, and danazol. Bone marrow transplantation has been used with some success in animal models, but to my knowledge has not been done in humans.
As a family physician I’m unlikely to ever see a case of cyclic neutropenia, but I’m glad this call prompted me to look into this condition and learn something new and interesting. Have any of you out there had any experience with this condition? Leave comments please.
My dental patients with cyclic neutropenia also have more severe periodontal disease (aggressive periodontitis). Most physicians are not aware of the association of cyclic neutropenia to dental disease. The physician should also inquire about the dental health of the patient, and ask if periodontal disease is prevalent in the family. (Genetics and periodontal disease).
My 10 yr old has battled with low wbc counts, fevers and horrible mouth ulsers for 2yrs now. last week she was hospitaized for the 2nd time in 2 mnths. some drs think she has cn but others arent covinced. They began treating her with gcsf. As a mom this has been hard. Can anyone help me with rhings
Elizabeth, I was diagnosed with cyclic neutropenia by a hematologist when I was 18 years old after a series of blood tests. My father was diagnosed with lupus when he was 40, and it seems that other autoimmune problems such as crohns disease run in my immediate family. It would be interesting to find out more about the relationship between lupus and disorders such as cyclic neutropenia.
I would also love to know more specific preventative actions that those with CN could take to increase neutrophil count and strengthen the immune system.
Hi there, I live in a small town called East London in South Africa, my son who turned 10 yesterday, was born with cyclic neutropenia and according to our peadiatritian here my son will never out grow this disorder and will in all likely pass it onto his child/children.
I would love to correspond with parents / families whose children also have this disorder
Ive been sick with cn since I was 9 months old, David Wilson from the University of Kentucky diagnosed me at around 9 yrs old. Ive been treated by Susan Desmond in the past with the nuprogen shots which caused horrible pain in my back and chest. I am now 42 layin on the couch suffering with this horrible illness. I only treat my symtoms now but some cycles are worse than others. Id love a cure before I pass.
I was told I had Cyclic neutropenia when I was in 10th grade, way pass the age of 8. And I’m 23 now and Im still fighting this. But I can’t seem to find out why my disorder came later in life than earlier. Can you help me?
There is an international registry
http://depts.washington.edu/registry/index.html
I was diagnosed with this disease when I was five and have shown no symptoms since the age of 11. I just found out I am pregnant. Would I be considered a high risk pregnancy?
Dear Dr. Pullen,
In our case, it is our 2nd daughter who suffers from c.n. from her 20th (!) ans still suffers from it now she is 31. F-CSF didn’t help her and that’s it. So, we think it is not hereditary because it exposed itself at adolescence age – although we have many cases of cancer in my family, like leukemia.
The problem is the total absence of a more or less effective treatment. The patient group simply is too small for industry to develop a medecine?
It woulde be good to know how many children/people suffer from it globally (around the whole world) and bring ot to the attention of industry.
Four years ago, my son, 11 yrs old at the time, became sick with fever, headaches, occasionally sore throat, lethargic, loss of appetite, every 9 days. We knew he wasn’t faking not feeling well because of the fevers, some of them very high. Our family doctor did blood work but did not find anything and referred me to an infectious disease doctor because he kept getting sick. After 3 1/2 months, he started to become sick every 12 to 14 days. The infectious disease doctor drew more blood and ex rays but didn’t find anything. He then drew blood when he was sick and still did not find anything wrong with him. We had several visits and he did say it was like his bone marrow would work and then it wouldn’t. He wanted to recommend him to a pediatric infectious disease doctor 2 hours away in Grand Rapids Mi. By now it is 7 months after he started getting sick. We have done some other alternative health care and decided to seek that route. By ten months he was better, whether he out grew what ever was wrong or the other route worked, I am not sure. It sounds somewhat like this cyclic neutropenia. Even to this day, he will become run down and run a fever. We homeschooled before, but last year, first year of public school he missed 15 days, most of those were due to a fever and being tired. Have you or any heard of this before.
Tone: I have no specific info for you about physicians in Norway or support groups. I’d consider contacting one of the major medical centers for advice, possibly John Hopkin’s or maybe the CDC. DrP.
I just got the message that me daughter has cyclic neutropenia. I am from Norway and I almost cant find any informasjon about these illness and the doctors here seems to know almost nothing. Susan: I am also looking for a support group or other families with children with this illness.
My mother in law, husband, 1 of his 2 sisters, and 2 of our 3 children have cyclic neutropenia. You could say it runs in the family.
I am looking for a support group or other families that have children with the disorder.
Also, I am trying to see if anyone has went on disability due to this disorder and what their experience was with that.
It is a livable disorder, but it will keep you on your toes and make you a germaphobe. Its tough being sick all the time.
I know of no relationship between Lupus and Cyclic neutropenia. Good thought though.
I was told that my son had Cyclic Neutropenia back when he was 3 years old. He is now 10. I still watch him very closely. When he was 3, he was having night sweats and his fever was up to 104. When his temp. hit that high I took him to the hospital. They took blood from him and found out that his WBC was 1.7 and his ANC was 187. The doctor at the hospital I went to thought he had leukemia so I took my son to Children’s hospital in Cincinnati. They told me that he didn’t have cancer he had cyclic Neutropenia. My son was giving IV antibiotics every day and had blood test 3 times a day to see if his ANC was coming up. They released him and his ANC was up to 1200. I wasn’t for sure what Cyclic Neutropenia so I went home and did some research and found some things about it. I also saw on one web site that it was basically my fault because I have SLE. I didn’t know that Lupus could cause my son to have health problems. Now I have done more investigating but no where does it now say that a child with cyclic neutropenia stems from mothers that have Lupus. So now I am asking anyone that I can find if Lupus can contribute to the diagnosis of cyclic neutropenia.