Chronic Idiopathic Neutrophilia: Retrospective Analysis of Causes and Consequences
Authors: Arteta-Bulos Rafael , Weir Alva B. , Lewis James 
Published: October 2019

Abstract
Abstract 4717

Background:
Chronic idiopathic neutrophilia (CIN) is a poorly described disorder that must be distinguished from more serious disorders associated with neutrophilia in a cost-effective manner. The last thoroughly studied case review of CIN was published nearly 40 years ago (Ward HN, Reinhard Eh. Ann Internal Med 1971). Since this review, new testing capabilities, including JAK-2 mutation evaluation, bcr-abl testing and CT scans have become readily available, complicating the decision making process in the diagnostic evaluation of healthy patients with an elevated neutrophil count. The challenge to the diagnostician is how aggressive, inconvenient and expensive the search for a cause for elevated neutrophil counts in otherwise healthy individuals should be.

Objective:
To evaluate causes and consequences of CIN with a plan to develop effective diagnostic guidelines for the evaluation of CIN.

Patients and Methods:
We performed a retrospective 10-year review (1999-2008) of patients visiting a Veteran's Affairs Medical Center with ICD-9 codes suggesting the diagnosis of leukocytosis to ascertain the incidence of CIN and evaluate both causative factors and outcome over time. We also reviewed charts of patients presenting with codes suggesting the diagnosis of a myeloproliferative disorder from 2005 to 2010 to discover if their initial presentation might have been misdiagnosed as CIN. We classified patients as CIN if they fulfilled the following criteria: neutrophil counts of 8.0 × 109/L or greater on multiple determinations, persistence or recurrence of neutrophilia over a time period of greater than six months, followed medically for a minimum of two years, no unexplained abnormality in the red cell or platelet counts, and no identifiable medical illness or drug usage known to produce prolonged neutrophilia. Patients thus identified were evaluated for the following parameters: duration of neutrophilia, age, ethnicity, weight, smoking history, presence of immature neutrophils, thrombocytosis, erythrocytosis, basophilia, eosinophilia, monocytosis, development or discovery of a solid tumor or hematologic malignancy or myeloproliferative disorder, drugs known to cause neutrophilia (lithium, corticosteroids, beta agonists), chronic infection or inflammatory disorder, leukocyte alkaline phosphatase (LAP) score, bone marrow evaluation, CT scan evaluation, theater of military engagement, hepatitis B and C, diabetes, drug abuse, splenectomy, constitutional symptoms, incidence of myocardial infarction, stent or CABG, and psychiatric diagnoses.

Results:
Of 450 charts reviewed with diagnoses suggesting leukocytosis, 57 met criteria for CIN. They were followed for a mean of 7.3 years without progression to other serious disorders. Peak neutrophil counts ranged from 8.9 to 22.6 × 109/L. The mean peak neutrophil count was 12.1 × 109/L. None of the patients with CIN had evident chronic inflammatory disorders over a significant period of their neutrophilia. There was no increase in malignancy rate or myocardial infarction/CABG during follow up. Cigarette smoking stood out as a potential causative factor with (82.4%) of the 57 patients as active cigarette smokers compared to 27% of the patients cared for in our institution during the same time period. Of the 81 patients with myeloproliferative neoplasms, only chronic myeloid leukemia (CML) presented with laboratory data that might be confused with CIN (3 of 10). The average BMI of patients in our study was 29.5 kg/m2. The average BMI of all patients visiting VAMC Memphis in 2001 was 28 kg/m2, suggesting no significant difference. The average BMI of smokers with CIN in our series was the same at 29.9 kg/m2. However, the average BMI of never smokers and those who had quit smoking over ten years in our study was 35.5 kg/m2, suggesting obesity as an associated factor in non smokers.

Conclusion:
CIN occurs more commonly in white patients than in African Americans. Cigarette smoking and obesity are associated and possibly causative factors in the development of CIN. CIN is unlikely to be confused with an early myeloproliferative neoplasm, other than CML. Statistical analysis and guidelines for the diagnostic evaluation of neutrophilia in otherwise healthy patients will be presented.

Disclosures:
No relevant conflicts of interest to declare.