Original Article

Chronic Idiopathic Neutrophilia: Experience and Recommendations

Authors: Alva B. Weir, MD, FACP, James B. Lewis Jr, MD, FACP, Rafael Arteta-Bulos, MD

Abstract

Objectives: To distinguish chronic idiopathic neutrophilia (CIN) in a cost-effective manner from neutrophilia caused by important underlying illnesses.


Methods: This was a retrospective review of patients visiting a Veterans Affairs Medical Center over the last 10 years with a diagnosis of leukocytosis or myeloproliferative disorder. Of this group, fifty-seven patients from 1999 to 2008 were identified with CIN. Clinical and laboratory parameters were examined to identify CIN and establish its course. Eighty-one patients who presented from 2005 to 2010 with myeloproliferative disorders were also studied at time of diagnosis to determine any possible confusion with CIN.


Results: The patients with CIN were followed for a mean of ≥7.3 years without progression to other serious disorders. Compared to non-CIN patients evaluated for neutrophilia, in multiple logistic regression analyses, smoking (P = .001) and increased BMI (P = .004) were significantly associated with CIN. No CIN patient developed a clinically apparent myeloproliferative disorder other than chronic myeloid leukemia (CML). Of the patients with myeloproliferative neoplasms reviewed at the time of their initial diagnosis, only CML occasionally presented with a picture consistent with CIN. For nonsmokers, the BMI of CIN patients was significantly higher than the average VA population (P < .001).


Conclusion: Cigarette smoking and obesity are confirmed as factors associated with CIN and may be causative. CIN is unlikely to develop into a clinically recognizable myeloproliferative neoplasm other than CML. Cost-effective guidelines for the diagnostic evaluation of neutrophilia in otherwise healthy patients are presented.

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References

1. Ward HN, Reinhard EH. Chronic idiopathic leukocytosis. Ann Intern Med 1971;75:193-198.
 
2. Stemmelin GR, Doti CA, Shanley CM, et al. Smoking as a cause for mild chronic neutrophilia. Blood 2004;104. Abstract 3796.
 
3. Parry H, Cohen S, Schlarb JE, et al. Smoking, alcohol consumption and leukocyte counts. Am J Clin Pathol 1997;107:64-67.
 
4. Corre F, Lellouch J, Schwartz D. Smoking and leukocyte counts. Results of an epidemiological survey. Lancet 1971;2:632-634.
 
5. Noble RC, Penny BB. Comparison of leukocyte count and function in smoking and nonsmoking young men. Infect Immun 1975;12:550-555.
 
6. Smith MR, Kinmonth A, Luben RN, et al. Smoking status and differential white cell count in men and women in the EPIC-Norfolk population. Atherosclerosis 2003;169:331-337.
 
7. Herishanu Y, Rogowski O, Polliack A, et al. Leukocytosis in obese individuals: possible link in patients with unexplained persistent neutrophilia. Eur J Haematol 2006;76:516-520.
 
8. Suzuki K, Kitagawa S. Chronic idiopathic leukocytosis. Ryoikibetsu Shokogun Shirizu 1998;21(Pt 2):17-18.
 
9. Schwartz J, Weiss S. Host and environmental factors influencing the peripheral blood leukocyte count. Am J Epidemiol 1991;134:1402-1409.
 
10. Koury MJ, Mahmud N, Rhodes MM. Origin and development of blood cells. In: Greer JP, Foerster J, Rodgers GM, et al (eds): Wintrobe's Clinical Hematology. 12th ed. Philadelphia, PA: Wolters Kluwer/Lippincott Williams & Wilkins; 2009:95.
 
11. Campbell PJ, Green AR. The myeloproliferative disorders. N Engl J Med 2006;355:2452-2466.
 
12. Spivak JL, Silver RT. The revised World Health Organization diagnostic criteria for polycythemia vera, essential thrombocytosis, and primary myelofibrosis: an alternative proposal. Blood 2008;112:231-239.
 
13. Quintás-Cardama A, Cortes JE. Chronic myeloid leukemia: diagnosis and treatment. Mayo Clin Proc 2006;81:973-988.
 
14. Tefferi A, Barbui T. Bcr/abl-negative, classic myeloproliferative disorders: diagnosis and treatment. Mayo Clin Proc 2005;80:1220-1232.
 
15. Komrokji RS, Zhang L, Bennett JM. Myelodysplastic syndromes classification and risk stratification. Hematol Oncol Clin North Am 2010;24:443-457.
 
16. Van Eeden SF, Hogg JC. The response of human bone marrow to chronic cigarette smoking. Eur Respir J 2000;15:915-921.
 
17. Francus T, Romano PM, Manzo G, et al. IL-1, IL-6, and PDGF mRNA expression in alveolar cells following stimulation with a tobacco-derived antigen. Cell Immunol 1992;145:156-174.
 
18. Wannamethee SG, Lowe GDO, Shaper AG, et al. Associations between cigarette smoking, pipe/cigar smoking, and smoking cessation, and haemostatic inflammatory markers for cardiovascular disease. Eur Heart J 2005;26:1765-1773.
 
19. Yanbaeva DG, Dentener MA, Creutzberg EC, et al. Systemic effects of smoking. Chest 2007;131:1557-1566.
 
20. Laharrague P, Oppert JM, Brousset P, et al. High concentration of leptin stimulates myeloid differentiation from human bone marrow CD34+ progenitors: potential involvement in leukocytosis of obese subjects. Int J Obesity 2000;24:1212-1216.
 
21. Reichard KK, Larson RS, Rabinowitz I. Chronic myeloid leukemia. In: Greer JP, Foerster J, Rodgers GM, et al (eds): Wintrobe's Clinical Hematology. 12th ed. Philadelphia, PA: Wolters Kluwer/Lippincott Williams & Wilkins; 2009:2009.
 
22. Athens JW, Raab SO, Haab OP, et al. Leukokinetic studies. III. The distribution of granulocytes in the blood of normal subjects. J Clin Invest 1961;40:159-164.
 
23. Bremner JD, Krystal JH, Southwick SM, et al. Noradrenergic mechanisms in stress and anxiety: II. Clinical studies. Synapse 1996;23:39-51.
 
24. Arranz L, Guayerbas N, De la Fuente M. Impairment of several immune functions in anxious women. J Psychosom Res 2007;62:1-8.
 
25. Grann V, Ziv E, Joseph C, et al. Duffy (Fy), DARC, and neutropenia among women from the United States, Europe, and the Caribbean. Br J Haematol 2008;143:288-293.