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==Overview==
==Overview==
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Malignancy is often associated with neutropenia, due to impaired production from myelodysplastic syndromes and hematological malignancies with [[bone marrow]] infiltration, [[hemolysis]] and impaired production from cytotoxic chemotherapy, and antibody-mediated destruction of neutrophils.
Malignancy is often associated with neutropenia, due to impaired production from myelodysplastic syndromes and hematological malignancies with [[bone marrow]] infiltration, [[hemolysis]] and impaired production from cytotoxic chemotherapy, and antibody-mediated destruction of neutrophils.


Alternative etiologies include post-infectious neutropenia resulting from bacterial, fungal, or viral infections. While bacterial infections typically cause [[leukocytosis]], [[Salmonella enterica|salmonella]]<ref name="PMID9311642">{{cite journal |author=James J, Dutta TK, Jayanthi S.|title=Correlation of clinical and hematologic profiles with bone marrow responses in typhoid fever. |journal=Am J Trop Med Hyg. |volume=57|issue=3 |pages=313-6 |year=1997|pmid 9311642|doi=|url=https://www.ncbi.nlm.nih.gov/pubmed?term=9311642}}</ref> and [[shigella enteritis]]<ref name="PMID7068229">{{cite journal |author=Fried D, Maytal J, Hanukoglu A.|title=The differential leukocyte count in shigellosis. |journal=Infection. |volume=10|issue=1 |pages=13-4 |year=1982|pmid 7068229|doi=|url=https://www.ncbi.nlm.nih.gov/pubmed?term=7068229}}</ref>, [[brucellosis]]<ref name="PMID8449576">{{cite journal |author=al-Eissa Y, al-Nasser M.|title=Haematological manifestations of childhood brucellosis. |journal=Infection. |volume=21|issue=1 |pages=23-6 |year=1993|pmid 8449576|doi=|url=https://www.ncbi.nlm.nih.gov/pubmed?term=8449576}}</ref>, [[tularemia]]
Alternative etiologies include post-infectious neutropenia resulting from bacterial, fungal, or viral infections. While bacterial infections typically cause [[leukocytosis]], [[Salmonella enterica|salmonella]],<ref name="PMID9311642">{{cite journal |author=James J, Dutta TK, Jayanthi S.|title=Correlation of clinical and hematologic profiles with bone marrow responses in typhoid fever. |journal=Am J Trop Med Hyg. |volume=57|issue=3 |pages=313-6 |year=1997|pmid 9311642|doi=|url=https://www.ncbi.nlm.nih.gov/pubmed?term=9311642}}</ref> [[shigella enteritis]],<ref name="PMID7068229">{{cite journal |author=Fried D, Maytal J, Hanukoglu A.|title=The differential leukocyte count in shigellosis. |journal=Infection. |volume=10|issue=1 |pages=13-4 |year=1982|pmid 7068229|doi=|url=https://www.ncbi.nlm.nih.gov/pubmed?term=7068229}}</ref> [[brucellosis]],<ref name="PMID8449576">{{cite journal |author=al-Eissa Y, al-Nasser M.|title=Haematological manifestations of childhood brucellosis. |journal=Infection. |volume=21|issue=1 |pages=23-6 |year=1993|pmid 8449576|doi=|url=https://www.ncbi.nlm.nih.gov/pubmed?term=8449576}}</ref> [[tularemia]],<ref name="PMID3710592">{{cite journal |author=Syrjälä H.|title=Peripheral blood leukocyte counts, erythrocyte sedimentation rate and C-reactive protein in tularemia caused by the type B strain of Francisella tularensis. |journal=Infection. |volume=14|issue=2 |pages=51-4 |year=1986|pmid 3710592|doi=|url=https://www.ncbi.nlm.nih.gov/pubmed?term=3710592}}</ref> [[tuberculosis]], and [[rickettsial disease]]s, such as [[Rocky Mountain spotted fever]]<ref name="PMID286884">{{cite journal |author=Hall GW, Schwartz RP. |title=White blood cell count and differential in Rocky Mountain spotted fever. |journal=N C Med J. |volume=40|issue=4 |pages=212-4 |year=1979|pmid 286884|doi=|url=https://www.ncbi.nlm.nih.gov/pubmed?term=286884}}</ref> can present with neutropenia. Parasitic diseases with neutropenia include [[leishmaniasis]] with [[hemolysis]] and splenic sequestration and [[malaria]] due to hyperreactive malarial splenomegaly (HMS).<ref name="PMID4575057">{{cite journal |author=Dale DC, Wolff SM. |title=Studies of the neutropenia of acute malaria. |journal=Blood. |volume=41|issue=2 |pages=197-206 |year=1973|pmid 4575057|doi=|url=https://www.ncbi.nlm.nih.gov/pubmed?term=4575057}}</ref> Viral etiologies include [[HIV]], [[EBV]],<ref name="PMID6318560">{{cite journal |author=Schooley RT, Densen P, Harmon D, Felsenstein D, Hirsch MS, Henle W, Weitzman S. |title=Antineutrophil antibodies in infectious mononucleosis. |journal=Am J Med. |volume=76|issue=1 |pages=85-90 |year=1984 |pmid 6318560|doi=|url=https://www.ncbi.nlm.nih.gov/pubmed?term=6318560}}</ref> [[CMV]], HHV-6, viral [[hepatitis]], [[dengue fever]], [[yellow fever]], [[measles]], [[varicella]], and [[rubella]].
<ref name="PMID3710592">{{cite journal |author=Syrjälä H.|title=Peripheral blood leukocyte counts, erythrocyte sedimentation rate and C-reactive protein in tularemia caused by the type B strain of Francisella tularensis. |journal=Infection. |volume=14|issue=2 |pages=51-4 |year=1986|pmid 3710592|doi=|url=https://www.ncbi.nlm.nih.gov/pubmed?term=3710592}}</ref>, [[tuberculosis]], and [[rickettsial disease]]s, such as [[Rocky Mountain spotted fever]]
<ref name="PMID286884">{{cite journal |author=Hall GW, Schwartz RP. |title=White blood cell count and differential in Rocky Mountain spotted fever. |journal=N C Med J. |volume=40|issue=4 |pages=212-4 |year=1979|pmid 286884|doi=|url=https://www.ncbi.nlm.nih.gov/pubmed?term=286884}}</ref> can present with neutropenia. Parasitic diseases with neutropenia include [[leishmaniasis]] with [[hemolysis]] and splenic sequestration and [[malaria]]<ref name="PMID4575057">{{cite journal |author=Dale DC, Wolff SM. |title=Studies of the neutropenia of acute malaria. |journal=Blood. |volume=41|issue=2 |pages=197-206 |year=1973|pmid 4575057|doi=|url=https://www.ncbi.nlm.nih.gov/pubmed?term=4575057}}</ref> due to hyperreactive malarial splenomegaly (HMS). Viral etiologies include [[HIV]], [[EBV]]
<ref name="PMID6318560">{{cite journal |author=Schooley RT, Densen P, Harmon D, Felsenstein D, Hirsch MS, Henle W, Weitzman S. |title=Antineutrophil antibodies in infectious mononucleosis. |journal=Am J Med. |volume=76|issue=1 |pages=85-90 |year=1984 |pmid 6318560|doi=|url=https://www.ncbi.nlm.nih.gov/pubmed?term=6318560}}</ref>, [[CMV]], HHV-6, viral [[hepatitis]], [[dengue fever]], [[yellow fever]], [[measles]], [[varicella]], and [[rubella]].


Immunodeficiencies are frequently associated with neutropenia (38% in [[Hyper IgM syndrome]], 12% in [[CVID]], and 7% in [[X-linked agammaglobulinemia]]) as are autoimmune disorders including up to 50% of patients with systemic [[lupus erythematosus]], yet with lower overall prevalence. While rheumatoid arthritis infrequently presents with neutropenia, severe neutropenia can develop in the setting of large granular lymphocyte (LGL) leukemia or Felty syndrome <ref name="PMID6979979">{{cite journal |author=Bucknall RC, Davis P, Bacon PA, Jones JV |title=Neutropenia in rheumatoid arthritis: studies on possible contributing factors |journal=Ann Rheum Dis. |volume=41 |issue=3 |pages=242-7 |year=2009 |pmid=6979979 |doi=|url=https://www.ncbi.nlm.nih.gov/pubmed?term=6979979}}</ref>.
Immunodeficiencies are frequently associated with neutropenia (38% in [[Hyper IgM syndrome]], 12% in [[CVID]], and 7% in [[X-linked agammaglobulinemia]]) as are autoimmune disorders including up to 50% of patients with systemic [[lupus erythematosus]], yet with lower overall prevalence. While rheumatoid arthritis infrequently presents with neutropenia, severe neutropenia can develop in the setting of large granular lymphocyte (LGL) leukemia or Felty syndrome. <ref name="PMID6979979">{{cite journal |author=Bucknall RC, Davis P, Bacon PA, Jones JV |title=Neutropenia in rheumatoid arthritis: studies on possible contributing factors |journal=Ann Rheum Dis. |volume=41 |issue=3 |pages=242-7 |year=2009 |pmid=6979979 |doi=|url=https://www.ncbi.nlm.nih.gov/pubmed?term=6979979}}</ref>


Finally, nutritional deficiencies resulting in neutropenia are typically attributed to vitamin B12, folate, and copper and are related to inadequate dietary intake, pernicious anemia, bariatric surgery, and malabsorptive syndromes.
Finally, nutritional deficiencies resulting in neutropenia are typically attributed to vitamin B12, folate, and copper and are related to inadequate dietary intake, pernicious anemia, bariatric surgery, and malabsorptive syndromes.

Revision as of 19:13, 9 November 2016

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ogheneochuko Ajari, MB.BS, MS [2], Daniel A. Gerber, M.D. [3]

Overview

Neutropenia may be caused by drugs, cancer, radiation, vitamin B12 deficiency or folate deficiency. Marginalization and sequestration of neutrophils also can cause neutropenia following procedures such as hemodialysis.

Causes

The most common etiologies are constitutional or benign ethnic neutropenia (BEN) and drug-induced neutropenia.

Malignancy is often associated with neutropenia, due to impaired production from myelodysplastic syndromes and hematological malignancies with bone marrow infiltration, hemolysis and impaired production from cytotoxic chemotherapy, and antibody-mediated destruction of neutrophils.

Alternative etiologies include post-infectious neutropenia resulting from bacterial, fungal, or viral infections. While bacterial infections typically cause leukocytosis, salmonella,[1] shigella enteritis,[2] brucellosis,[3] tularemia,[4] tuberculosis, and rickettsial diseases, such as Rocky Mountain spotted fever[5] can present with neutropenia. Parasitic diseases with neutropenia include leishmaniasis with hemolysis and splenic sequestration and malaria due to hyperreactive malarial splenomegaly (HMS).[6] Viral etiologies include HIV, EBV,[7] CMV, HHV-6, viral hepatitis, dengue fever, yellow fever, measles, varicella, and rubella.

Immunodeficiencies are frequently associated with neutropenia (38% in Hyper IgM syndrome, 12% in CVID, and 7% in X-linked agammaglobulinemia) as are autoimmune disorders including up to 50% of patients with systemic lupus erythematosus, yet with lower overall prevalence. While rheumatoid arthritis infrequently presents with neutropenia, severe neutropenia can develop in the setting of large granular lymphocyte (LGL) leukemia or Felty syndrome. [8]

Finally, nutritional deficiencies resulting in neutropenia are typically attributed to vitamin B12, folate, and copper and are related to inadequate dietary intake, pernicious anemia, bariatric surgery, and malabsorptive syndromes.

Life Threatening Causes

Life-threatening causes include conditions which may result in death or permanent disability within 24 hours if left untreated.

Common Causes

Causes by Organ System

Cardiovascular No underlying causes
Chemical / poisoning Arsenic trioxide, gold salts, strontium-89
Dermatologic Chediak-Higashi disease, dyskeratosis congenita, x-linked, Elejalde syndrome , reticular dysgenesis, reticular dysplasia
Drug Side Effect 5-azacytidine, acetophenazine, aclarubicin, actinomycin D, acyclovir, aflibercept, albendazole, alemtuzumab, allopurinol, amantadine, amiloride, aminoglutethimide, aminoglutethimide, aminopyrine, amiodarone,amodiaquine, ampicillin, amsacrine, anakinra, anidulafungin, anti-thymocyte globulin, antibiotics, antipyrine, aprepitant, aripiprazole, arsenic trioxide, asenapine, atazanavir, atovaquone, auranofin, azacitidine, azathioprine, aztreonam, barbiturates, belinostat, benazepril, bendamustine, bevacizumab, blinatumomab, boceprevir, bortezomib, bosutinib, brentuximab, busulfan, cabazitaxel, cabozantinib, canakinumab, candesartan, capecitabine, captopril, carbimazole, carboplatin, carfilzomib, carmustine, cefaclor, cefadroxil, cefazolin, cefepime, cefixime, cefoperazone, cefotetan, cefotiam, cefoxitin, ceftaroline, ceftriaxone, cefuroxime, cephalexin, cephapirin, cephradine, cetuximab, chemotherapy, chlorambucil, chloramphenicol, chloroquine, chlorpromazine, chlorthalidone, cidofovir, cilazapril, cimetidine, cisplatin, cladribine, clarithromycin, clindamycin, clofarabine, clopidogrel, clozapine, colchicine, crizotinib, cromolyn, cyclophosphamide, cytarabine, cytosine arabinoside, dabrafenib,dacarbazine, daclatasvir, dactinomycin, dasatinib, daunorubicin, decitabine, deferasirox, deferiprone, delavirdine, desipramine, dexrazoxane, diatrizoate, diazepam, diazoxide, dicloxacillin, Diethylpropiondiflunisal, dipyrone, docetaxel, dolutegravir, doripenem, dothiepin, doxorubicin, doxycycline, efavirenz, eflornithine, elvitegravir, enalapril, enalaprilat, enfuvirtide, enzalutamide, epirubicin, eprosartan, eribulin, etanercept, ethacrynic acid, ethambutol, ethosuximide, ethotoin, etodolac, etoposide, everolimus, felbamate, fentanyl, fidaxomicin, flucytosine, fludarabine, fluorouracil, fluoxetine, fosamprenavir, foscarnet, fosinopril, ganciclovir, gefitinib, gemcitabine, gemifloxacin mesylate, glyburide, golimumab, griseofulvin, guanidinium, haloperidol, hydroxycarbamide, hydroxyurea, ibuprofen lysine, ibritumomab tiuxetan, ibrutinib, ibuprofen, idarubicin, idelalisib, iloperidone, imatinib, imipenem cilastatin, indinavir, indomethacin, infliximab, interferon alfa-2a, interferon alfa-2b, interferon alfacon-1, interferon beta-1b, irinotecan, isoniazid, isotretinoin, itraconazole, ixabepilone, lamivudine, lamotrigine, lansoprazole, lenalidomide, levamisole, levetiracetam, levomepromazine, lincomycin, linezolid, lisinopril, loxapine, lurasidone, maprotiline, maraviroc, meclofenamate, mercaptopurine, meropenem, mesalamine, methazolamide, methimazole, methotrexate, methyldopa, metolazone, mexiletine, mianserin, micafungin, mifamurtide, milnacipran, minocycline, mirtazapine, mitotane, mitoxantrone, moexipril, moxalactam, mycophenolate, mycophenolic acid, nafcillin, naproxen, nefazodone, nelarabine, nelfinavir, nevirapine, nilotinib, nilutamide, norfloxacin, nortriptyline, obinutuzumab, ofatumumab, ofloxacin, olanzapine, olaparib, olsalazine,omacetaxine, omeprazole, oprelvekin, oxacillin, oxaliplatin, paclitaxel, palbociclib, paliperidone, panobinostat, pantoprazole, pazopanib, peginterferon alfa-2a, peginterferon alfa-2b, pemetrexed, penicillamine, penicillin, penicillin G, pentamidine, pentostatin, peramivir, perazine, perindopril, pertuzumab, phenylbutazone, phenytoin, piperacillin, piperaquine, pipothiazine, piroxicam, pixantrone, pomalidomide, ponatinib, posaconazole, pralatrexate, prednisone, probenecid, procainamide, procarbazine, prochlorperazine, proguanil, propylthiouracil, pyrimethamine, quetiapine, quinapril, quinidine, quinine, radium chloride, raltitrexed, ramipril, ramucirumab, ranitidine, rasagiline, rasburicase, regorafenib, remoxipride, ribavirin, rifabutin, rifapentine, rifaximin, rilonacept, riluzole, risperidone, ritodrine, ritonavir, rituximab, romidepsin, ruxolitinib, saquinavir, satraplatin, secukinumab, sirolimus, sodium aurothiomalate, sofosbuvir, sorafenib, stavudine, stiripentol, succimer, Sulfacetamide, Sulfamethoxazole/Trimethoprim (oral),

sulfasalazine, sulfonamide, sulindac, sunitinib, suramin, tacrolimus, tedizolid, teicoplanin, temozolomide, temsirolimus, teniposide, tenofovir, terbinafine, teriflunomide, thalidomide, thiothixene, ticarcillin, ticlopidine, tipranavir, tocilizumab, tofacitinib, tolazamide, tolmetin, topotecan, tositumomab, trabectedin, trametinib, trandolapril, trastuzumab, trimethadione, trimethoprim, trimetrexate, valganciclovir, valproic acid, valrubicin, valsartan, vancomycin, vandetanib, vesnarinone, vincristine, vindesine, vinflunine, vinorelbine, zidovudine, zileuton, ziprasidone, ziv-aflibercept, zoledronic acid

Ear Nose Throat No underlying causes
Endocrine Hyperthyroidism
Environmental No underlying causes
Gastroenterologic Glycogen storage disorder, hypersplenism, Shwachman-Diamond syndrome
Genetic Barth syndrome, cartilage-hair hypoplasia, Chediak-Higashi disease, Cohen syndrome, Dubowitz syndrome, Elejalde syndrome , familial histiocytic reticulosis, Fanconi syndrome, fumarate hydratase deficiency, Griscelli syndrome type 1, methylmalonic aciduria, myelokathexis, propionic acidemia, propionyl-CoA carboxylase deficiency PCCA type, Shwachman-Diamond syndrome, WHIM syndrome
Hematologic Alloimmune neonatal neutropenia, alloimmune neutropenia in infancy, aplastic anemia, autoimmune neutropenia, chronic lymphocytic leukemia, cyclical neutropenia, familial histiocytic reticulosis, Hermansky-Pudlak syndrome, histiocytosis X, hypersplenism, Kostmann disease, myelodysplastic syndrome, myelofibrosis, pancytopenia, paroxysmal nocturnal haemoglobinuria, Shwachman-Diamond syndrome, x-linked agammaglobulinemia
Iatrogenic Hemodialysis, radiation therapy
Infectious Disease Brucellosis, cytomegalovirus, dengue, Epstein-Barr virus, hepatitis A, hepatitis B, hepatitis C, hepatitis, human granulocytic ehrlichiosis, human immunodeficiency virus, human monocytotropic ehrlichiosis, kala azar, Kostmann disease, lassa fever, Lyme disease, malaria, measles, rickettsiae, rickettsial infections, rocky mountain spotted fever, rubella, salmonella infection, sepsis, severe acute respiratory syndrome, shigellosis, tuberculosis, tularemia, varicella, visceral leishmaniasis, WHIM syndrome
Musculoskeletal / Ortho Cartilage-hair hypoplasia, metaphyseal chondrodysplasia, Mckusick type
Neurologic Fumarate hydratase deficiency
Nutritional / Metabolic Copper deficiency, glutathione synthase deficiency, glycogen storage disorder, glycogenosis type 1b, hereditary orotic aciduria, isovaleric acidemia, methylmalonic aciduria, propionic acidemia, propionyl-CoA carboxylase deficiency PCCA type, vitamin deficiencies
Obstetric/Gynecologic No underlying causes
Oncologic Chronic lymphocytic leukemia, hairy cell leukemia, histiocytosis X, leukemia, myelodysplastic syndrome, myelofibrosis
Opthalmologic No underlying causes
Overdose / Toxicity Alcoholism
Psychiatric No underlying causes
Pulmonary Severe acute respiratory syndrome
Renal / Electrolyte Fanconi syndrome
Rheum / Immune / Allergy Alloimmune neonatal neutropenia, alloimmune neutropenia in infancy, autoimmune lymphoproliferative syndrome type 1, autoimmune lymphoproliferative syndrome type 2, autoimmune neutropenia, common variable immune deficiency, Felty's syndrome, histiocytosis X, hyper-immunoglobulin M syndrome, lupus, rheumatoid arthritis, secondary autoimmune neutropenia, WHIM syndrome, x-linked agammaglobulinemia, x-linked hyperimmunoglobulin M syndrome
Sexual No underlying causes
Trauma No underlying causes
Urologic No underlying causes
Dental No underlying causes
Miscellaneous No underlying causes

Causes in Alphabetical Order

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3

References

  1. ↑ James J, Dutta TK, Jayanthi S. (1997). "Correlation of clinical and hematologic profiles with bone marrow responses in typhoid fever". Am J Trop Med Hyg. 57 (3): 313–6. Text "pmid 9311642" ignored (help)
  2. ↑ Fried D, Maytal J, Hanukoglu A. (1982). "The differential leukocyte count in shigellosis". Infection. 10 (1): 13–4. Text "pmid 7068229" ignored (help)
  3. ↑ al-Eissa Y, al-Nasser M. (1993). "Haematological manifestations of childhood brucellosis". Infection. 21 (1): 23–6. Text "pmid 8449576" ignored (help)
  4. ↑ Syrjälä H. (1986). "Peripheral blood leukocyte counts, erythrocyte sedimentation rate and C-reactive protein in tularemia caused by the type B strain of Francisella tularensis". Infection. 14 (2): 51–4. Text "pmid 3710592" ignored (help)
  5. ↑ Hall GW, Schwartz RP. (1979). "White blood cell count and differential in Rocky Mountain spotted fever". N C Med J. 40 (4): 212–4. Text "pmid 286884" ignored (help)
  6. ↑ Dale DC, Wolff SM. (1973). "Studies of the neutropenia of acute malaria". Blood. 41 (2): 197–206. Text "pmid 4575057" ignored (help)
  7. ↑ Schooley RT, Densen P, Harmon D, Felsenstein D, Hirsch MS, Henle W, Weitzman S. (1984). "Antineutrophil antibodies in infectious mononucleosis". Am J Med. 76 (1): 85–90. Text "pmid 6318560" ignored (help)
  8. ↑ Bucknall RC, Davis P, Bacon PA, Jones JV (2009). "Neutropenia in rheumatoid arthritis: studies on possible contributing factors". Ann Rheum Dis. 41 (3): 242–7. PMID 6979979.
  9. ↑ Andrès E, Zimmer J, Affenberger S, Federici L, Alt M, Maloisel F. (2006). "Idiosyncratic drug-induced agranulocytosis: Update of an old disorder". Eur J Intern Med. 17 (8): 529–35. Text "pmid 17142169" ignored (help)

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