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{{CMG}} {{AE}} {{Sahar}} <br>
{{SK}} [[Cyclic hematopoiesis]]
==Overview==
Cyclic neutropenia is a [[condition]] in which the [[neutrophil]] count periodically and regularly rises and falls. It is rarely observed in humans, but has been observed in the Grey Collie dog.
==Historical Perspective==
* Cyclic neutropenia first described in the year 1910 in an infant with recurrent [[fever]].<ref name="DaleBolyard2002">{{cite journal|last1=Dale|first1=David C.|last2=Bolyard|first2=Audrey Anna|last3=Aprikyan|first3=Andrew|title=Cyclic neutropenia|journal=Seminars in Hematology|volume=39|issue=2|year=2002|pages=89–94|issn=00371963|doi=10.1053/shem.2002.31917}}</ref>
==Classification==
* There is no established system for the [[classification]] of cyclic neutropenia.
==Pathophysiology==
* Normal [[neutrophil|neutrophilic]] counts is typically between 1500 to 8500 cells/μl after the age of one year.<ref name="ManroeWeinberg1979">{{cite journal|last1=Manroe|first1=Barbara L.|last2=Weinberg|first2=Arthur G.|last3=Rosenfeld|first3=Charles R.|last4=Browne|first4=Richard|title=The neonatal blood count in health and disease.I. Reference values for neutrophilic cells|journal=The Journal of Pediatrics|volume=95|issue=1|year=1979|pages=89–98|issn=00223476|doi=10.1016/S0022-3476(79)80096-7}}</ref>
* Cyclic neutropenia is caused by [[heterozygous]] [[mutation]] in the ELA2 (ELANE) [[gene]].<ref name="DaleBolyard2002">{{cite journal|last1=Dale|first1=David C.|last2=Bolyard|first2=Audrey Anna|last3=Aprikyan|first3=Andrew|title=Cyclic neutropenia|journal=Seminars in Hematology|volume=39|issue=2|year=2002|pages=89–94|issn=00371963|doi=10.1053/shem.2002.31917}}</ref><ref name="HorwitzCorey2013">{{cite journal|last1=Horwitz|first1=Marshall S.|last2=Corey|first2=Seth J.|last3=Grimes|first3=H. Leighton|last4=Tidwell|first4=Timothy|title=ELANE Mutations in Cyclic and Severe Congenital Neutropenia|journal=Hematology/Oncology Clinics of North America|volume=27|issue=1|year=2013|pages=19–41|issn=08898588|doi=10.1016/j.hoc.2012.10.004}}</ref>
* The [[disease]] occurs in [[autosomal dominant]] mode of inheritance.
* The culprit [[gene]] is responsible for encoding the [[neutrophil]] granule serine protease, neutrophil elastase.
* [[Mutation]] results in abnormal [[gene]] product that damages cells while they mature, leading to to failure of [[cell]] production.
* Theoretically, this [[disorder]] can be cured by [[bone marrow transplantation]]. This demonstrates its [[pathogenesis]]] as the [[stem cell]] abnormality.<ref name="pmid7036779">{{cite journal |vauthors=Lange RD, Jones JB |title=Cyclic neutropenia. Review of clinical manifestations and management |journal=Am J Pediatr Hematol Oncol |volume=3 |issue=4 |pages=363–7 |date=1981 |pmid=7036779 |doi= |url=}}</ref>
* This [[stem cell]] abnormality leads to the myelocyte maturation arrest during [[neutropenia]] episodes.
==Causes==
* Cyclic neutropenia is caused by [[heterozygous]] mutation in the ELA2 (ELANE) [[gene]].<ref name="HorwitzCorey2013">{{cite journal|last1=Horwitz|first1=Marshall S.|last2=Corey|first2=Seth J.|last3=Grimes|first3=H. Leighton|last4=Tidwell|first4=Timothy|title=ELANE Mutations in Cyclic and Severe Congenital Neutropenia|journal=Hematology/Oncology Clinics of North America|volume=27|issue=1|year=2013|pages=19–41|issn=08898588|doi=10.1016/j.hoc.2012.10.004}}</ref>
==Differentiating Cyclic neutropenia from Other Diseases==
* Cyclic neutropenia should be differentiated from other [[disorders]] manifesting with recurrent [[fever]], [[aphthous stomatitis]], and [[pharyngitis]]. These include [[PFAPA syndrome]], monogenic [[autoinflammatory disorders]] such as [[FMF]], [[CAPS]], and [[TRAPS]], as well as primary [[immunodeficiencies]].<ref name="AliSartori-Valinotti2016">{{cite journal|last1=Ali|first1=Nora S.|last2=Sartori-Valinotti|first2=Julio C.|last3=Bruce|first3=Alison J.|title=Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome|journal=Clinics in Dermatology|volume=34|issue=4|year=2016|pages=482–486|issn=0738081X|doi=10.1016/j.clindermatol.2016.02.021}}</ref>
*[[Shwachman-Diamond syndrome]] may also present with [[neutropenia]]. However, its [[diagnosis]] requires some [[dysmorphic]] features which are not present in patients with cyclic neutropenia.<ref name="pmid10393609">{{cite journal |vauthors=Ginzberg H, Shin J, Ellis L, Morrison J, Ip W, Dror Y, Freedman M, Heitlinger LA, Belt MA, Corey M, Rommens JM, Durie PR |title=Shwachman syndrome: phenotypic manifestations of sibling sets and isolated cases in a large patient cohort are similar |journal=J. Pediatr. |volume=135 |issue=1 |pages=81–8 |date=July 1999 |pmid=10393609 |doi=10.1016/s0022-3476(99)70332-x |url=}}</ref>
* For more information on cyclic neutropenia [[differential diagnosis]] please [[Neutropenia differential diagnosis|click here]].
==Epidemiology and Demographics==
* The incidence of cyclic neutropenia is 0.010-0.02 per 100,000 individuals worldwide.<ref name="pmid14962902">{{cite journal |vauthors=Bellanné-Chantelot C, Clauin S, Leblanc T, Cassinat B, Rodrigues-Lima F, Beaufils S, Vaury C, Barkaoui M, Fenneteau O, Maier-Redelsperger M, Chomienne C, Donadieu J |title=Mutations in the ELA2 gene correlate with more severe expression of neutropenia: a study of 81 patients from the French Neutropenia Register |journal=Blood |volume=103 |issue=11 |pages=4119–25 |date=June 2004 |pmid=14962902 |doi=10.1182/blood-2003-10-3518 |url=}}</ref>
* There is no [[racial]] predilection to cyclic neutropenia.
* Cyclic neutropenia affects [[men]] and [[women]] equally.
==Risk Factors==
* There are no established [[risk factors]] for cyclic neutropenia.
==Screening==
* There is insufficient evidence to recommend routine [[screening]] for cyclic neutropenia.
==Natural History, Complications, and Prognosis==
* Disease manifests in early years of life with episodes of [[fever]] occurring every 21 days (range from 14 to 35 days).<ref name="pmid11957190">{{cite journal |vauthors=Dale DC, Bolyard AA, Aprikyan A |title=Cyclic neutropenia |journal=Semin. Hematol. |volume=39 |issue=2 |pages=89–94 |date=April 2002 |pmid=11957190 |doi= |url=}}</ref>
* The hallmark of this [[disorder]] is the predictability of the fever episodes. 
* Patients may be asymptomatic or develop life-threatening infections depending on the severity of neutropenia.
* During episodes, [[patients]] are neutropenic and it increases their risk for [[dental]] and [[gingival]] [[complications]].<ref name="PalmerStephens1996">{{cite journal|last1=Palmer|first1=Susan E.|last2=Stephens|first2=Karen|last3=Dale|first3=David C.|title=Genetics, phenotype, and natural history of autosomal dominant cyclic hematopoiesis|journal=American Journal of Medical Genetics|volume=66|issue=4|year=1996|pages=413–422|issn=01487299|doi=10.1002/(SICI)1096-8628(19961230)66:4<413::AID-AJMG5>3.0.CO;2-L}}</ref>
* Although [[patients]] with cyclic neutropenia are not as immunodeficient as the post-chemotherapy [[patients]], they still should not be assumed normal.
* Serious [[complications]] of this disorder include [[pneumonia]], [[mastoiditis]], and [[bacterial]] [[cutaneous]] and [[subcutaneous infections]].<ref name="GlavanRoganović2015">{{cite journal|last1=Glavan|first1=Nedeljka|last2=Roganović|first2=Jelena|last3=Glavan-Gacanin|first3=Lana|last4=Jonjic|first4=Nives|title=Appendectomy in a child with cyclic neutropenia in profound neutropenic episode|journal=Therapeutics and Clinical Risk Management|year=2015|pages=1217|issn=1178-203X|doi=10.2147/TCRM.S89488}}</ref>
* Death induced by [[infections]] are a possible [[complication]] of this [[disorder]] and has been reported in 10% of the [[patients]].<ref name="DaleCottle2003">{{cite journal|last1=Dale|first1=David C.|last2=Cottle|first2=Tammy E.|last3=Fier|first3=Carol J.|last4=Bolyard|first4=Audrey Anna|last5=Bonilla|first5=Mary Ann|last6=Boxer|first6=Laurence A.|last7=Cham|first7=Bonnie|last8=Freedman|first8=Melvin H.|last9=Kannourakis|first9=George|last10=Kinsey|first10=Sally E.|last11=Davis|first11=Robert|last12=Scarlata|first12=Debra|last13=Schwinzer|first13=Beate|last14=Zeidler|first14=Cornelia|last15=Welte|first15=Karl|title=Severe chronic neutropenia: Treatment and follow-up of patients in the Severe Chronic Neutropenia International Registry|journal=American Journal of Hematology|volume=72|issue=2|year=2003|pages=82–93|issn=0361-8609|doi=10.1002/ajh.10255}}</ref>
==Diagnosis==
* [[Diagnosis]] of cyclic neutropenia is based on the clinical picture and the exclusion of other possible [[causes]] of [[neutropenia]].<ref name="pmid11957190">{{cite journal |vauthors=Dale DC, Bolyard AA, Aprikyan A |title=Cyclic neutropenia |journal=Semin. Hematol. |volume=39 |issue=2 |pages=89–94 |date=April 2002 |pmid=11957190 |doi= |url=}}</ref>
*[[ANC|Absolute necrophiliac count]] ([[ANC]]) should be <200/microL, usually for at least two to three days, in each of two to three regularly spaced cycles.
* [[Genetic analysis]] may be done for the confirmation of the [[diagnosis]]. However, it usually turns positive for [[gene mutation]] in 90% of the [[patients]].<ref name="pmid17053055">{{cite journal |vauthors=Horwitz MS, Duan Z, Korkmaz B, Lee HH, Mealiffe ME, Salipante SJ |title=Neutrophil elastase in cyclic and severe congenital neutropenia |journal=Blood |volume=109 |issue=5 |pages=1817–24 |date=March 2007 |pmid=17053055 |pmc=1801070 |doi=10.1182/blood-2006-08-019166 |url=}}</ref>
* [[Bone marrow aspiration]] is not considered helpful for the [[diagnosis]].
===Diagnostic Criteria===
* There is no [[diagnostic]] criteria for the [[diagnosis]] of cyclic neutropenia.
===History and Symptoms===
* [[Symptoms]] of cyclic neutropenia include [[fever]], [[malaise]], [[oral ulcers]], [[gingival]] [[inflammation]], edema, and [[sore throat]].<ref name="pmid8989458">{{cite journal |vauthors=Palmer SE, Stephens K, Dale DC |title=Genetics, phenotype, and natural history of autosomal dominant cyclic hematopoiesis |journal=Am. J. Med. Genet. |volume=66 |issue=4 |pages=413–22 |date=December 1996 |pmid=8989458 |doi=10.1002/(SICI)1096-8628(19961230)66:4<413::AID-AJMG5>3.0.CO;2-L |url=}}</ref><ref name="pmid7036779">{{cite journal |vauthors=Lange RD, Jones JB |title=Cyclic neutropenia. Review of clinical manifestations and management |journal=Am J Pediatr Hematol Oncol |volume=3 |issue=4 |pages=363–7 |date=1981 |pmid=7036779 |doi= |url=}}</ref>
===Physical Examination===
* [[Physical examination]] of [[patients]] with cyclic neutropenia include [[fever]], [[pharyngitis]], and [[gingival]] [[inflammation]] and [[edema]].<ref name="pmid8989458">{{cite journal |vauthors=Palmer SE, Stephens K, Dale DC |title=Genetics, phenotype, and natural history of autosomal dominant cyclic hematopoiesis |journal=Am. J. Med. Genet. |volume=66 |issue=4 |pages=413–22 |date=December 1996 |pmid=8989458 |doi=10.1002/(SICI)1096-8628(19961230)66:4<413::AID-AJMG5>3.0.CO;2-L |url=}}</ref>


==Overview==
===Laboratory Findings===
Cyclic neutropenia is a condition in which the [[neutrophil count]] periodically and regularly rises and falls. It is rarely observed in humans, but has been observed in the Grey Collie dog.
* Laboratory findings associated with the [[diagnosis]] of cyclic neutropenia include:<ref name="GlavanRoganović2015">{{cite journal|last1=Glavan|first1=Nedeljka|last2=Roganović|first2=Jelena|last3=Glavan-Gacanin|first3=Lana|last4=Jonjic|first4=Nives|title=Appendectomy in a child with cyclic neutropenia in profound neutropenic episode|journal=Therapeutics and Clinical Risk Management|year=2015|pages=1217|issn=1178-203X|doi=10.2147/TCRM.S89488}}</ref>
** Low [[absolute neutrophilic count]]
**[[Neutropenia]] may be mild or severe with a nadir of 100/μL for 3–6 days in each cycle. However, the duration of [[neutropenia]] varies between the [[patients]].
===Electrocardiogram===
* There are no [[ECG]] findings [[Association (statistics)|associated]] with cyclic neutropenia.
===X-ray===
* There are no [[x-ray]] findings [[Association (statistics)|associated]] with cyclic neutropenia.
===Echocardiography or Ultrasound===
* There are no [[echocardiography]]/[[ultrasound]] findings [[Association (statistics)|associated]] with cyclic neutropenia.
===CT Scan===
* There are no [[CT scan]] findings [[Association (statistics)|associated]] with cyclic neutropenia.
===MRI===
* There are no [[MRI]] findings [[Association (statistics)|associated]] with cyclic neutropenia.
===Other Imaging Findings===
* There are no other [[imaging]] findings [[Association (statistics)|associated]] with cyclic neutropenia.
===Other Diagnostic Studies===
* There are no other [[diagnostic]] studies [[Association (statistics)|associated]] with cyclic neutropenia.
 
==Treatment==
===Medical Therapy===
* The mainstay of treatment for cyclic neutropenia is medical therapy.<ref name="pmid2469956">{{cite journal |vauthors=Hammond WP, Price TH, Souza LM, Dale DC |title=Treatment of cyclic neutropenia with granulocyte colony-stimulating factor |journal=N. Engl. J. Med. |volume=320 |issue=20 |pages=1306–11 |date=May 1989 |pmid=2469956 |doi=10.1056/NEJM198905183202003 |url=}}</ref><ref name="pmid7529539">{{cite journal |vauthors=Bonilla MA, Dale D, Zeidler C, Last L, Reiter A, Ruggeiro M, Davis M, Koci B, Hammond W, Gillio A |title=Long-term safety of treatment with recombinant human granulocyte colony-stimulating factor (r-metHuG-CSF) in patients with severe congenital neutropenias |journal=Br. J. Haematol. |volume=88 |issue=4 |pages=723–30 |date=December 1994 |pmid=7529539 |doi=10.1111/j.1365-2141.1994.tb05110.x |url=}}</ref>
* It is recommended that all [[patients]] receive [[Granulocyte colony-stimulating factor]] ([[G-CSF]]). However, the mainstay of treatment is supportive.<ref name="pmid8989458">{{cite journal |vauthors=Palmer SE, Stephens K, Dale DC |title=Genetics, phenotype, and natural history of autosomal dominant cyclic hematopoiesis |journal=Am. J. Med. Genet. |volume=66 |issue=4 |pages=413–22 |date=December 1996 |pmid=8989458 |doi=10.1002/(SICI)1096-8628(19961230)66:4<413::AID-AJMG5>3.0.CO;2-L |url=}}</ref><ref name="pmid8589368">{{cite journal |vauthors=Heussner P, Haase D, Kanz L, Fonatsch C, Welte K, Freund M |title=G-CSF in the long-term treatment of cyclic neutropenia and chronic idiopathic neutropenia in adult patients |journal=Int. J. Hematol. |volume=62 |issue=4 |pages=225–34 |date=December 1995 |pmid=8589368 |doi= |url=}}</ref>
*[[G-CSF]] should be administered [[Subcutaneous|subcutaneously]] starting at 2 to 3 mcg/kg every one to two days.
* [[Patients]] with following features should receive [[G-CSF]]:
**[[Patients]] with recurrent [[symptoms]]
** [[Patients]] with evidence of [[gingival]] disease or severe [[infection]]
* Regular [[dental]] care is recommended.
===Surgery===
*[[Surgical]] intervention is not recommended for the [[management]] of cyclic neutropenia.
===Primary Prevention===
* There are no established measures for the [[primary prevention]] of cyclic neutropenia.
===Secondary Prevention===
* There are no established measures for the [[secondary prevention]] of cyclic neutropenia.


==References==
==References==
{{Reflist|2}}
{{Reflist|2}}
[[Category:Hematology]]

Latest revision as of 03:09, 23 September 2020

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Sahar Memar Montazerin, M.D.[2]
Synonyms and keywords: Cyclic hematopoiesis

Overview

Cyclic neutropenia is a condition in which the neutrophil count periodically and regularly rises and falls. It is rarely observed in humans, but has been observed in the Grey Collie dog.

Historical Perspective

  • Cyclic neutropenia first described in the year 1910 in an infant with recurrent fever.[1]

Classification

  • There is no established system for the classification of cyclic neutropenia.

Pathophysiology

Causes

Differentiating Cyclic neutropenia from Other Diseases

Epidemiology and Demographics

  • The incidence of cyclic neutropenia is 0.010-0.02 per 100,000 individuals worldwide.[7]
  • There is no racial predilection to cyclic neutropenia.
  • Cyclic neutropenia affects men and women equally.

Risk Factors

  • There are no established risk factors for cyclic neutropenia.

Screening

  • There is insufficient evidence to recommend routine screening for cyclic neutropenia.

Natural History, Complications, and Prognosis

Diagnosis

Diagnostic Criteria

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

X-ray

Echocardiography or Ultrasound

CT Scan

MRI

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Primary Prevention

Secondary Prevention

References

  1. ↑ 1.0 1.1 Dale, David C.; Bolyard, Audrey Anna; Aprikyan, Andrew (2002). "Cyclic neutropenia". Seminars in Hematology. 39 (2): 89–94. doi:10.1053/shem.2002.31917. ISSN 0037-1963.
  2. ↑ Manroe, Barbara L.; Weinberg, Arthur G.; Rosenfeld, Charles R.; Browne, Richard (1979). "The neonatal blood count in health and disease.I. Reference values for neutrophilic cells". The Journal of Pediatrics. 95 (1): 89–98. doi:10.1016/S0022-3476(79)80096-7. ISSN 0022-3476.
  3. ↑ 3.0 3.1 Horwitz, Marshall S.; Corey, Seth J.; Grimes, H. Leighton; Tidwell, Timothy (2013). "ELANE Mutations in Cyclic and Severe Congenital Neutropenia". Hematology/Oncology Clinics of North America. 27 (1): 19–41. doi:10.1016/j.hoc.2012.10.004. ISSN 0889-8588.
  4. ↑ 4.0 4.1 Lange RD, Jones JB (1981). "Cyclic neutropenia. Review of clinical manifestations and management". Am J Pediatr Hematol Oncol. 3 (4): 363–7. PMID 7036779.
  5. ↑ Ali, Nora S.; Sartori-Valinotti, Julio C.; Bruce, Alison J. (2016). "Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome". Clinics in Dermatology. 34 (4): 482–486. doi:10.1016/j.clindermatol.2016.02.021. ISSN 0738-081X.
  6. ↑ Ginzberg H, Shin J, Ellis L, Morrison J, Ip W, Dror Y, Freedman M, Heitlinger LA, Belt MA, Corey M, Rommens JM, Durie PR (July 1999). "Shwachman syndrome: phenotypic manifestations of sibling sets and isolated cases in a large patient cohort are similar". J. Pediatr. 135 (1): 81–8. doi:10.1016/s0022-3476(99)70332-x. PMID 10393609.
  7. ↑ Bellanné-Chantelot C, Clauin S, Leblanc T, Cassinat B, Rodrigues-Lima F, Beaufils S, Vaury C, Barkaoui M, Fenneteau O, Maier-Redelsperger M, Chomienne C, Donadieu J (June 2004). "Mutations in the ELA2 gene correlate with more severe expression of neutropenia: a study of 81 patients from the French Neutropenia Register". Blood. 103 (11): 4119–25. doi:10.1182/blood-2003-10-3518. PMID 14962902.
  8. ↑ 8.0 8.1 Dale DC, Bolyard AA, Aprikyan A (April 2002). "Cyclic neutropenia". Semin. Hematol. 39 (2): 89–94. PMID 11957190.
  9. ↑ Palmer, Susan E.; Stephens, Karen; Dale, David C. (1996). "Genetics, phenotype, and natural history of autosomal dominant cyclic hematopoiesis". American Journal of Medical Genetics. 66 (4): 413–422. doi:10.1002/(SICI)1096-8628(19961230)66:4<413::AID-AJMG5>3.0.CO;2-L. ISSN 0148-7299.
  10. ↑ 10.0 10.1 Glavan, Nedeljka; Roganović, Jelena; Glavan-Gacanin, Lana; Jonjic, Nives (2015). "Appendectomy in a child with cyclic neutropenia in profound neutropenic episode". Therapeutics and Clinical Risk Management: 1217. doi:10.2147/TCRM.S89488. ISSN 1178-203X.
  11. ↑ Dale, David C.; Cottle, Tammy E.; Fier, Carol J.; Bolyard, Audrey Anna; Bonilla, Mary Ann; Boxer, Laurence A.; Cham, Bonnie; Freedman, Melvin H.; Kannourakis, George; Kinsey, Sally E.; Davis, Robert; Scarlata, Debra; Schwinzer, Beate; Zeidler, Cornelia; Welte, Karl (2003). "Severe chronic neutropenia: Treatment and follow-up of patients in the Severe Chronic Neutropenia International Registry". American Journal of Hematology. 72 (2): 82–93. doi:10.1002/ajh.10255. ISSN 0361-8609.
  12. ↑ Horwitz MS, Duan Z, Korkmaz B, Lee HH, Mealiffe ME, Salipante SJ (March 2007). "Neutrophil elastase in cyclic and severe congenital neutropenia". Blood. 109 (5): 1817–24. doi:10.1182/blood-2006-08-019166. PMC 1801070. PMID 17053055.
  13. ↑ 13.0 13.1 13.2 Palmer SE, Stephens K, Dale DC (December 1996). "Genetics, phenotype, and natural history of autosomal dominant cyclic hematopoiesis". Am. J. Med. Genet. 66 (4): 413–22. doi:10.1002/(SICI)1096-8628(19961230)66:4<413::AID-AJMG5>3.0.CO;2-L. PMID 8989458.
  14. ↑ Hammond WP, Price TH, Souza LM, Dale DC (May 1989). "Treatment of cyclic neutropenia with granulocyte colony-stimulating factor". N. Engl. J. Med. 320 (20): 1306–11. doi:10.1056/NEJM198905183202003. PMID 2469956.
  15. ↑ Bonilla MA, Dale D, Zeidler C, Last L, Reiter A, Ruggeiro M, Davis M, Koci B, Hammond W, Gillio A (December 1994). "Long-term safety of treatment with recombinant human granulocyte colony-stimulating factor (r-metHuG-CSF) in patients with severe congenital neutropenias". Br. J. Haematol. 88 (4): 723–30. doi:10.1111/j.1365-2141.1994.tb05110.x. PMID 7529539.
  16. ↑ Heussner P, Haase D, Kanz L, Fonatsch C, Welte K, Freund M (December 1995). "G-CSF in the long-term treatment of cyclic neutropenia and chronic idiopathic neutropenia in adult patients". Int. J. Hematol. 62 (4): 225–34. PMID 8589368.
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